Wardwise Treatment Guidelines


Wardwise Treatment Guidelines

Edited By :

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Dr.Salim Al Mamun
MBBS(Raj);CCD(BIRDEM);
CMU(DU)
Medical officer
Tenglahata Uposhastha Kendro
Kazipur , Sirajganj.

drsalimalmamun@gmail.com
http://www.drsalimalmamun.wordpress.com
Management of some poisoning
Poisoning in Medicine Ward

1. Sedative poisoning
Diagnostic tools:
1. H/O of taking sedatives e.g. Sedil, lexotanil, Bopam etc.
2. Pt. may be disoriented or drowsy or in deep sleep.
3. Respiration is normal or depressed.
4. Planter reflex is normal or extensor.
5. Pupils mid dilated & sluggish reaction to light.
Management:
1. Diet- normal, plenty of tea, coffee by mouth if Pt. can swallow
2. NPO till recovery, If pt. is in deep sleep.
3. O2 inhalation 1-4 L/min, if respiration is depressed.
4. Infusion 5% DNS 1000 i/v @ 10 drops/ min.
5. Activated charcoal (Tab. Ultracarbon 2+2+2), if pt. present with in 1 hour.
6. Antidote of Benzodiazepine- Flumazenil, slowly IV, dose 0.2 mg over 30–60 seconds, repeated in 0.5 mg increments as needed up to a total dose of 3–5 mg.
Flumazenil is a benzodiazepine receptor-specific antagonist; it has no effect on ethanol, barbiturates, or other sedative-hypnotic agents.
Flumazenil should not be used in pt. with H/O seizures or in patients with preexisting seizure disorder, toxin induced cardio toxicity, co-ingestion with TCA. The duration of action of flumazenil is short (2–3 hours) and resedation may occur, requiring repeated doses.
Activated Charcoal: Activated charcoal effectively adsorbs almost all drugs and poisons. Poorly adsorbed substances include iron, lithium, potassium, sodium, mineral acids, and alcohols.
(Ref. CMDT 2010)
2. Tricyclic antidepressant poisoning (Tryptin)

Clinical features
1. H/O taking TCA drugs in over doses ie. Amitryptylin
2. Dilated pupil, ileus, and retention of urine.
3. Respiration may depressed.
4. Presence of arrhythmias in ECG may present
5. Hypotension may occur
6. Hyperreflexia with extensor plantar, coma, and seizures.
7. Improvement can be expected within 24 h.

Management
1. NPO till further order or recovery.
2. IV fluids infusion (5% DNS1000cc +5% DA1000cc i.v. @20 drops/min. stat & daily)
3. Gastric lavage may be given after delayed presentation.
4. Tab. Ultracarbon 2+2+2
5. Treatment of arrythmias
6. If convulsion present Diazepam and phenytoin.
7. ECG monitoring during the first 24 h and until ECG changes have disappeared for 12 h.
8. If acidosis present- IV sodibicarb
Note: Sodibicarb available at 7.5% 25 ml
Tips:
• Gastric elimination may be useful for 24 h after ingestion because tricyclics slow gastric emptying.
• Cardiac arrhythmias are more common if there is acidosis. Bicarbonate should be used to achieve an arterial pH of 7.5 urgently.
• If arrhythmias occur with no acidosis and fail to respond to treatment with amiodarone or phenytoin, bicarbonate (25-50 mL 8.4% IV) may still be useful with in 20 min.
• If VT compromising cardiac out put, Lidocaine 50-100mg i.v. should be given.
(Ref. Oxford American Hand book of critical care + Parvin Kumar & M. Clark)

3. Stupifying poisoning (unknown poisoning)
Diagnostic tools:
1. H/O of poisoning during traveling or ingestion or inhalation of foods or other substances by unknown person.
2. Pt. in deep sleep or drowsy
3. Pupil constricted or dilated and light reaction normal or absent
4. Circulation (Pulse & BP) usually normal
5. Respiration normal.
(Contradictory-in OPC poisoning pupil is constricted but bradycardia hypotension & crepitation present in lungs).

Management:
1. NPO till further order
2. Iv fluid Infusion
3. Inj. Omeprazole (40mg) 1 vial i/v slowly stat and daily
4. Continued catheterization (antibiotic if catheterization is done)
5. Monitor vital signs

(Ref. National guideline for management of poisoning)

4. Corrosive Poisoning (strong acid & alkali)
Management:
1. NPO TFO
2. Clearing of the airways
3. O2 inhalation 4-6 L/min
4. Irrigate exposed eyes with sterile cold water or saline at least for 20 minutes and continue until the pt. returns to normal
5. Infusion 5% DNS 1000 + 5% DA 1000 cc i/v @ 20 drops/ min.
6. Inj. Diclofen 1 amp. im stat. & SOS
7. Inj. Omeprazole 40 mg IV slowly stat. & B.D.

Tips:
1. Dilution or neutralization, induction of emesis, gastric aspiration and lavage are contra-indicated.
2. Emulcents- egg white, olive oil, butter, cold milk should be avoided.
3. As there is no specific antidote, symptomatic treatment is to be provided. Neutralization with alkali now a days is not done.
4. Surgical treatment must be considered for any pt grade ll or lll esophageal injury.
5. Diagnostic Endoscopy should be performed within 12-24 hours of alkali ingestion.
6. Corticosteroids have no role in the management of a case and complication. It is rather harmful.
7. Soluble calcium tablet followed by 10% ca gluconate IV can be given in acid ingestion.
8. 1% NaHCO3 irrigation may be given in eye involvement with steroid eye drops.
( Ref. National guideline for management of poisoning)

5. Dhatura Poisoning
Management:
1. NPO TFO
2. Stomach wash with in 1 hour
3. Clearing of the airways
4. O2 inhalation 4-6 L/min
5. Infusion 5% DNS 1000 + 5% DA 1000 cc i/v @ 20 drops/ min.
6. Inj. Omeprazole 40 mg iv slowly stat. & B.D.
7. Physostigmine 0.5 mg to 1 mg s/c stat.
8. Paracetamol suppository
9. Tepid sponging
10. Catheterization done for urinary retention. (antibiotic if catheterization is done).

Tips:
1. If stomach is full, no forceful emesis should be tried.
2. Specific antidote: (l) Physostigmine 0.5 mg to 1 mg s/c to antagonise atropine in a single dose. (ll) Prostigmine is more effective and less toxic than physostigmine in same dose. (lll) Pilocarpine 5 mg s/c, though useful, does not counteract the action of Dhatura on brain, can be repeated 2 hourly at early stage of poisoning.
3. Delirium can be treated with short acting barbiturates.
4. To control marked excitement chlorolhydrate or paraldehyde in moderate dose may be given.
5. Repeated purgation is not recommended.
6. Forced diuresis is not encouraged.
7. Light diet, mainly liquid or semi-liquid should be given if the condition is mild.
8. Other symptomatic treatments.

(Ref. National guideline for management of poisoning)

6. Methanol Poisoning
Management:
1. NPO TFO
2. Stomach wash with in 1 hour
3. Clearing of the airways
4. O2 inhalation 4-6 L/min
5. Infusion 5% DNS 1000 + 5% DA 1000 cc i/v @ 20 drops/ min.
6. Inj. Omeprazole 40 mg iv slowly stat. & B.D.
7. Antidode : Ethanol.
Loading dose: 10% ethanol 7.5 ml/kg IV over 30 to 60 mins
Maintaining dose: 10% ethanol 1.96 ml/kg/hr IV.
If IV not available, then
Orally: 95% ethanol, 0.8 ml/kg followed by 0.1 ml/kg/hr can be given.
Maintaining dose : 0.2 ml/kg/hr. This alcohol should be diluted in water or fruit juice.
Tips:

1. Should be hospitalized and must be treated by an ophthalmologist for his visual problems.
2. Stomach wash although advocated, there is no evidence of affectivity with it.
4. In severe cases pt should be incubated and mechanical respiration should be given.
7. Acidosis should be controlled by infusing sodium bi-carbonate.
8. Sedation can be given cautiously to prevent delirium and restlessness.
9. The antidote for methanol poisoning is ethanol.

(Ref. National guideline for management of poisoning.)

7. Puffer fish poisoning
Management:
1. NPO TFO except medication
2. Stomach wash with in 1 hour with 2% sodibicarb
3. Clearing of the airways
4. O2 inhalation 4-6 L/min
5. Infusion 5% DNS 1000 + 5% DA 1000 cc i/v @ 20 drops/ min.
6. Inj. Omeprazole 40 mg iv slowly stat. & B.D.
7. Tab. Ultracarbon 2+ 2 + 2
8. Atropinization and inj. neostigmine has been used for come round from unconsciousness and restoring neurogenic power both sensory and motor.
Tips:
There is no specific antidote, so only symptomatic treatment:
1. Artificial respiration with oxygen inhalation by mask in mild cases and direct ventilatory support and sedation in severe cases.
2. Purgation and forced diuresis to lessen absorbed poison is not recommended.
3. Steroids for life saving measure although contra-indication persists.
( Ref. National guideline for management of poisoning)

8. Opiate Poisoning
Management:
a. NPO TFO except medication
b. Infusion 5% DNS 1000 cc + 5% DA 1000 cc iv @ 20 d/min
c. Tab Ultracarbon 2 + 2 + 2
d. Inj. Omeprazole 40 mg iv slowly stat. & daily
e. Naloxone can be given to reverse the sign of severe poisoning (coma, respiratory depression or convulsion) within a few minutes but it has a short life and the pt may relapse.

Dose: Administer 0.4–2 mg intravenously, and repeat as needed to awaken the patient. Very large doses (10–20 mg) may be required for patients intoxicated by some opioids (eg, propoxyphene, codeine, fentanyl derivatives).
Caution: The duration of effect of naloxone is only about 2–3 hours; repeated doses may be necessary for patients intoxicated by long-acting drugs such as methadone. Continuous observation for at least 3 hours after the last naloxone dose is mandatory.
9. Paracetamol Poisoning
Management
1. NPO TFO except medication
2. Infusion 5% DNS 1000 cc + 5% DA 1000 cc iv @ 20 d/min
3. Tab Ultracarbon 2 + 2 + 2
4. Inj. Omeprazole 40 mg iv slowly stat. & daily
5. Special antidote: N-Acetylcysteine (NAC), Methionine.
Dose:
 Adult: 150 mg/kg IV in 200 ml of 5% DA over 15 mins, followed by
 50 mg/kg IV in 500 ml dextrose over 4 hours, followed by
 100 mg/kg IV in 1000 ml 5% DA over 16 hours.

With established hepatotoxicity, continue NAC treatment 50 ml/kg in 500 ml of 5% DA over 8 hours.
Repeat until prothrombin time and liver enzyme begin to return to normal.

(Ref. National guideline for management of poisoning.)

10. Savlon poisoning
Diagnostic tools:
1. H/O of ingestion of savlon
2. Burning sensation in throat and upper abdomen.
Management:
1. NPO till further order except medication
2. Irrigate exposed eyes with sterile cold water or saline at least for 20 minutes and continue until the pt. returns to normal.
3. Inj. Omeprazole (40mg) 1 vial i/v slowly stat and daily
4. Inj. Amoxicillin (500mg) 1 vial i/v stat & 8 hourly
5. IV infusion
11. OPC poisoning
Management:
1. External decontamination with water.
2. Remove clothing. Avoid contamination with other personnel.
3. Gastric lavage if pt. resent within 1 hour
4. NPO TFO
5. O2 inhalation 4-6 L/min
6. Tab Ultracarbon 2 + 2 + 2 if present within 1 hour
7. Assisted ventilation as appropriate if respiratory failure
8. Infusion 5% DNS 1000 cc + 5% DA 1000 cc iv @ 20 d/min
9. Inj. Amoxicillin 500 mg iv stat. & 8 hourly
10. Inj. Omeprazole 40 mg iv stat. & daily
11. Atropine 0.6-2 mg repeats after 10-25 min upto atropinasation occurs.
12. Pralidoxime chloride 2 g IV over 4 min, repeated at 4-6 hourly
13. Continued catheterization
14. Monitor vital sign

12 Poisonous snake bite
Polyvalent antisnake venom is effective against the following snake’s venom
1. Cobra
2. Krait
3. Russel’s viper
4. Saw scaled viper
Indication of Polyvalent antisnake venom:
1. Neurotoxic signs
2. Rapid extension of local swelling
3. Acute renal failure
4. Cardiovascular abnormalities
5. Bleeding abnormalities
6. Haemoglobinuria / myoglobinuria

Management:
Assesment
Look for sign of envenometion
1. Polyvalent antisnake venom 10 vial + 100 cc 5% DNS or NS iv @ 60 drops/min
2. If Neurotoxic features- Inj. Atropine 1 amp. iv stat. & 4 hourly, then after 15 min. inj. Neostigmine 4 amp. Subcutaneously 4 hourly.
3. Antibiotic- if risk of infection or Endotrachael intubation done.
4. If features of resp. failure-endotracheal intubation.
5. Follow up 15-30 min. interval by- pulse, BP, Respiratory rate, respiratory movement, adverse effects of antivenom
6. In case of haemostatic abnormalities
• Strict bed rest
• Avoid I/M injection.
• Fresh blood transfusion.
• Avoid NSAID or Aspirin for pain
7.Inj. TT & TIG
8. Iv infusion
Criteria for repeating the initial dose of antivenom:
• If no improvement or deterioration after 1-2 hours
• Persistence or recurrence of blood incoagulability after 6 hours.

Non-poisonous snake bite
Management:
• Symptomatic
• No NSAID ( Analgesic Paracitamol)
• No Sedative & anxiolytics
• Follow up 30 min. interval by- pulse, BP, Resp. rate, resp. movement, features of envenomation.
• After 24 hours if no features of envenomation then discharge the pt.

Respiratory System

1. Allergic rhinitis
Diagnostic tools
1. Frequent sudden attack of sneezing
2. Profuse watery nasal discharge
3. Nasal obstruction.
Management:
Following management either singly or in combination..
1. Antihistamine such as Loratidine
2. Sodium cromoglycate nasal spray
3. Nasal steroid spray e.g. Beclomethason diproprionate, Fluticasone or Budesonide
4. Systemic steroid –in which symptoms are severe.

2. Pneumonia
Diagnostic tools:
1. Fever high grade with cough with sputum (rusty)
2. Chest pain- pleuritic
3. On exam. –feature of consolidation like bronchial breath sound present, vocal resonance increased.
Management:
Uncomplicated CAP (community acquired pneumonia)
1. Antibiotic for 7-10 days
Amoxicilin 500 mg 8 hourly or
Clarithromycin 500 mg 12 hourly
2. Tab. Paracetamol

Severe CAP (2 weeks)
1. Diet- Normal
2. Inj. Ceftriaxone (1gm) 1 vial i/v stat. & B.D
3. Tab. Clarin (500mg) 1+0+1
4. Tab. Paracetamol (500mg) 1+1+1
5. If Chest pain NSAID- Diclofenac sodium
6. Assessment of severity
7. Mechanical ventilation if needed
-Respiratory rate 70 5 5

Category -II management

Pre-treatment wt (kg) Intensive phase Continuation phase
Daily
(First 3 months) Daily
(First 2 months) Daily
(Next 5 months)
Numbers of 4FDC tablets Injection
Streptomycin Numbers of
2 FDC tablets Numbers of
Ehambutol (400 mg) tablets
30-37 2 500 mg 2 2
38-54 3 750 mg 3 3
55-70 4 1 gm* 4 4
>70 5 1 gm* 5 5

4FDC means- 4 fixed drug combination. These 4 drugs are….
1. Rifampicin (R) 150mg
2. Isoniazide (H) 75 mg
3. Ethumbutal (E) 400 mg
4. Pyrazinamide (Z) 275 mg

2 FDC means – 2 fixed drug combination. These 2 drugs are-
1. Rifampicin (R) 150 mg
2. Isoniazid (H) 75 mg.

Q. Why 4 drugs are used in intensive phase?
Ans: To kill rapidly proliferating Mycobacteria.

Q. Why 2 drugs are used in continuation phase?
Ans: To kill the dormant bacteria.

9. Antitubercular drug induced hepatitis
Diagnostic tools
1. H/O of taking Anti TB drugs
2. Yellow coloration of eye & urine
3. Anorexia, nausea & vomiting
4. Investigation- S. Bilirubin- Increased, SGPT-Increased, Alkaline phosphatase- normal, Exclusion of other causes of hepatitis- by HBsAg, AntiHBC, AntiHBE and USG of hapato billiary system & Bil >1.2 mg/dl, SGPT>2 times than normal
Management:
Treatment is symptomatic
1. Stop the offending drugs till hepatitis subside
2. Complete bed rest
3. Diet- normal
4. Tab. Domperidone(10mg) 1+1+1 (1/2 hour before meal, if vomiting)
5. Cap. Omeprazole (20mg) 1+0+1 (1/2 hour before meal)

Tips:
a) Treatment should be restarted when pt. symptomatically well and S. Bilirubin and SGPT become normal.
b) Where there is no scope to do S. Bilirubin and SGPT then Rx. Can be restarted 14 days after the urine or eye become normal.
Ref: Nation guideline of management of tuberculosis.

10. Pneumothorax
Management:
1. Bed rest
2. O2 inhalation
3. Treatment of the underlying cause if any e.g. Pnemonia, COPD etc.
4. Water sealed drainge(percutaneous needle aspiration)- Indication:
i. Immediate decompression prior to definitive therapy in tension pneumothorax
ii. In open or close pneumothorax- Pt. age 15% of hemithorax or significant dysponea.
5. Intercostal tube drainge
i. Tension pneumothorax
ii. Pneumothorax with underlying chronic lung disease e.g. COPD
iii. In open or close pneumothorax -Pt. age > 50 years with >15 % of hemithorax or significant dysponea
iv. When >2.5 L air aspirated or Pneumothorax persists after percuteneous needle aspiration (water seal drainage).
Indication of Surgery in pneumothorax:
1. In all pt. following a second pneumothorax
2. Following first episode of primary pneumothorax
Surgeries are
-Pleurodosis. (Can be achieved by pleural abrasion or parietal pleurectomy at thoracotomy or thoracoscopy).

Advice:
1. Stop smoking
2. Avoid flying 1-2 weeks following full inflation of lung

11. Empyema thorasics
Management
1. Draining of the pus- intercostals tube drainge
2. Antibiotic iv co-amoxiclav or Cefuroxime plus metronidazole
3. Surgical intervention- if IT tube not providing drainge, when the pus is thick or loculated.
4. Surgical decortication of lung – if gross thickening of the visceral pleura is preventing re-expansion of lung.

12. Sarcoidosis
Diagnostic tool
1. Erythema nodosum
2. CXR (P/A)- Bilateral hilar lymphadenopathy
Management:
1. Avoid sun light exposure
2. NSAID for erythema nodosum
3. Steroid-Prednisolone 20-40 mg/day
Indication:
a) Symptoms severe
b) Hypercalcaemia
c) Pulmonary impairement
d) Renal impairement
e) Uveitis

4. Inhaler corticosteroid in asymptomatic parenchymal sarcoid
5. Topical steroid for mild uveitis
6. Severe disease – MTX 10-20 mg / week
-Azathioprine 50-150 mg/day
-Specific TNF alpha inhibitor
7. Cuteneous sarcoid
a) Chloroquine
b) Hydroxychloroquine
c) Low dose thalidomide

13. Pulmonary hypertension
Management:
1. O2 inhalation
2. All pt. should be anticoagulant with warfarin
3. Diuretics
4. Digoxin
5. Specific treatment
d) High dose calcium channel blocker e.g. Amlodipine
e) Prostaglandins such as epoprostenol (prostacyclin) or iloprost therapy
f) PDE inhibitor Sildenafil
g) Oral endothelin antagonist- Bosentan
6. Atrial septostomy
7. Pulmonary thromboendarterectomy
8. Heart- lung transplantation.

14. Acute severe Asthma
Diagnostic tools:
1. Past H/O of asthma
2. Severe breathlessness with cough
3. Patient unable to talk due to breathlessness
4. On exam. Pulse > 110/min, R.rate- > 25/ min, Pt. May be cyanosed, bilateral poly phonic rhonchi present, but chest may be silent.

Management:
1. Diet- normal
2. O2 inhalation 2-5 L/min
3. Propped up position
4. Nebulization with Normal saline 1.5 cc + Salbutamol solution 0.5 cc stat. and 20 min interval for 1 hour then 1-4 hourly.
5. Inj. Hydrocortisone 100 mg 2 vial iv stat. then 4-6 hourly.
6. Inhaler Salbutamol 200 µgm 2 puff stat. & 6 hourly
7. Inhaler Beclomethasone 250 µgm 2 puff 12 hourly (Gargling after use)
8. Tab. Theophylline 400 mg ½ + 0 + ½.

 NB: IV hydrocortisone can be replaced by oral steroid after 24-48 hours.
 Costly regimen- Inhaler Salmetrol & Fludicasone combination. 2 puff 12 hourly. (gargling after use).
 If pt. can buy only one inhaler then give steroid inhaler.
15. Acute exacerbation of COPD
Diagnostic tools:
1. Age > 40 years
2. Smoking H/O
3. Severe breathlessness with cough
4. Previous H/O of hospitalization
5. On exam. Pulse > 100/min, R.rate- > 25/ min, Pt. May be cyanosed, Breath sound vesicular with prolonged expiration,bilateral poly phonic rhonchi & creps present (if infection).

Management:
3. Diet- normal
4. O2 inhalation 1-2 L/min
5. Propped up position
6. Nebulization with Normal saline 1.5 cc + Salbutamol solution 0.5 cc + Ipratropium bromide solution 0.5 cc stat. and 20 min interval for 1 hour then 1-4 hourly.
7. Inj. Hydrocortisone 100 mg 2 vial iv stat. then 4-6 hourly.
8. Inhaler Salbutamol & Ipratropium bromide combination 2 puff stat. & 6 hourly
9. Inhaler Beclomethasone 250 µgm 2 puff 12 hourly (Gargling after use)
10. Tab. Theophylline 400 mg ½ + 0 + ½.
11. Tab. Azithromycin 500 mg 1 + 0 + 0

NB:
 IV hydrocortisone can be replaced by oral steroid after 24-48 hours.
 Costly regimen- Inhaler Salmetrol & Fludicasone combination. 2 puff 12 hourly. (gargling after use).
Antibiotic should be other than the previous one that was used in last 3 month

Renal system

1. Acute glomerulonephritis (Nephritic Syndrome)
Diagnostic tool
1. Swelling of face, leg & eyelid
2. H/O of skin lesion 1-4 weeks before
3. Oliguria, haematuria, fever
4. On exam. –Puffy face, BP-high, leg edema present
-Bed side urine exam. – proteinuria.
– Haematuria
Management
Treatment is supportive, with control of hypertension, edema, and dialysis as needed. Antibiotic treatment for streptococcal infection should be given to all patients and their cohabitants in poststreptococcal AGN.
1. Diet – Normal, protein, salt, fruit, fluid restricted (previous day out put + 400cc)
2. Tab. Cefuroxime axetil (250mg) (in post streptococcal GN then Phenoxymethyl penicillin)
1+o+1
3. Tab. Frusemide (40mg)
1+1+0
4. Tab. Ramipril (1.25mg)
0+0+1 (gradually increasing the dose to titrate BP)
5. Please maintain input out put chart.
 The inflammatory glomerular injury may require corticosteroids and cytotoxic agents.
 Postinfectious Glomerulonephritis- Corticosteroids have not been shown to improve outcome.
(Ref: Harrison’s principle of Internal Medicine)

2. Nephrotic syndrome
Diagnostic tool
1. Generalized edema
2. Massive proteinuria- Frothy urine
3. 24 hours total urinary protein > 3.5 gm
4. Urin volum- normal
5. Usually haematuria absent
Management
1. Diet – Normal, protein, salt, fruit, fluid restricted (previous day out put + 400cc)
2. Tab. Cefuroxime (250mg)
1+o+1
3. Inj. Frusemide(20mg)
1 amp. I/v stat & 1 amp at 8 a.m. & 4 p.m.
5. Tab. Ramipril (1.25mg)
0+0+1 (gradually increasing the dose)
6. Prednisone, 1 mg/kg/d orally
7. Tab. Atrovastatin (10mg) 0 + 0 + 1 after meal (if hypercholesterolemia)
8. Please maintain input output chart.
Tips:
a) Duration of steroid- usually shorter duration (8 weeks) in children but in adult it may take 20- 24 weeks.
b) Patients with frequent relapses and corticosteroid resistance may need cyclophosphamide or chlorambucil to induce subsequent remissions.
(Ref: Harrison’s principle of Internal Medicine +Ref. CMDT 2010)

3. Acute pyelonephritis
Diagnostic tool
1. High fever with chills & rigor
2. Loin pain, dysuria, haematuria, frequency of micturition
3. On exam. – Temperature high
– Renal angle tenderness present.
Management:
1. Diet –normal
2. Antibiotic 1st line (duration10 days)
-Ciprofloxacin (500mg)
-Co-amoxyclav (500/125mg)
3. Tab. Paracetamol if fever
Antibiotic 2nd choice in seriously ill pt. (duration 7-14 days)
• Cefuroxime iv (750mg) 8 hourly
• Gentamycin iv
(Ref: Davidson’s principle & practice of Medicine 21st edition, page 471)
4. Urinary Tract Infection (UTI)
Diagnostic tools:
1. Dysuria, haematuria, frequency of micturition with fever with chills & rigor
2. Urine R/E- pus cell > 5/HPF
3. C/s- growth > 105

Management:
Antibiotic- 3 days in women, 10 days in men
A. First choice
Trimethoprim 200 mg 12 hourly

B. 2nd choice
• Amoxicilin 500 mg 8 hourly or
• Nitrofuratoin 50mg 6 hourly or
• Ciprofloxacin 100mg 12 hourly or
• Co-amoxyclav (250/125mg) 8 hourly
C. In Pregnancy 7 days
• Cephalexin 250mg 6 hourly or
• Amoxicilin 250mg 8 hourly

(Ref: Davidson’s principle & practice of Medicine 21st edition, page 471)

5. Acute renal failure
Diagnostic tools
• H/O of vomiting or diarrhoea or massive blood loss
• Oliguria or anuria
Management:
1. Diet: Protein, salt, fruit restricted
2. Fluid restricted- fluid intake previous day output + 400 cc
3. Infusion Normal saline if pt. dehydrated
4. Antibiotic in case of infection.
5. Cap. Omeprazol (20mg) 1+0 +1
6. Inj. Frusemide (20mg) 2 amp iv stat. and daily (if feature of fluid retension)
7. Maintain input & output chart
Follow up:
• Pulse
• BP
• Hydration status
• Urine out put
• S. creatinine & blood urea
• ECG
Indication of Renal replacement therapy (dialysis or transplantation) in acute renal failure:
1. Hyperkalaemia K+ >6 mmol/L
2. Fluild overload & pulmonary edema
3. Metabolic acidosis
4. Increased plasma urea and creatinine (urea > 180 mg/dl & creatinine >6.8 mmol/L)
5. Uraemic pericarditis/ uraemic encephalopathy
6. Chronic renal failure
Diagnostic tools:
1. H/O of Hypertension or diabetes
2. Pt. complain of anorexia, vomiting, generalized weakness
3. On exam.- Anaemia present
c) Hypertension present
4. S. creatinine- raised.
Management:
1. Diet: Protein, salt & fruit restricted protein 60 gm daily
2. Tab. Calcium carbonate (500mg) 1+0+1
3. Cap. Cholicalciferol (0.25 µgm) 0+1+0
4. Tab. Ferrous sulphate 1+0+1
5. Treatment of the underlying cause like Hypertension, DM etc.
6. If anemia persists after iron therapy then
Inj. Epoietin (25-50IU/kg body wt. once or twice in a week).

Antihypertensive used in CRF
1. First choice- ACEI, ARB, Non-dihydropyridines CCB (Amlodipin)
2. Alpha receptor blocker
3. Betablocker (Atenolol)
N: B: 1-2 week after giving ACEi or ARB if s.creatinine increased 25 % than previous record then stop ACEi or ARB).
Indication of dialysis in CRF (WHO criteria)
1. Uraemic pericarditis
2. Uraemic encephalopathy or neuropathy
3. Pulmonary edema unresponsive to diuretics
4. Severe hypertension if not control by medical management
5. Severe hyperkalaemia not control by medical management
6. Severe bleeding diathesis
7. S. Creatinine > 12 mg/dl or BUN > 100mg/dl
Tips:
Ccr (creatinine clearance) can be estimated from the formula of Cockcroft and Gault:
Ccr = (140- age) × body weight / 72 × S. creatinine (mg/dl)
For women, the creatinine clearance is multiplied by 0.85 because muscle mass is less.
Staging of CKD
Stages of CKD GFR (ml/min/1.73m2)
Stage 1 ≥90 (with evidence of kidney damage)
Stage 2 60-89
Stage 3 30-59
Stage 4 15-29
Stage 5 <15 or dialysis

N: B: kidney damage means pathological abnormalities or marker of damage, including abnormalities in urine tests or imaging studies. Two GFR values 3 months apart are required to assign stage.

CVS diseases
1. Vasovagal syncope
Diagnostic tools
1. Syncope triggered by reduction in venous return due to
a) Prolonged standing
b) Excessive heat
c) Large meal
2. Head up tilt test +Ve.
Pt. is asked to lie on a table that is then tilted to an angel of 60 to 700 for up to 45 min. while ECG & BP are monitored. A positive test is characterized by bradycardia and/ or hypotension associated with typical symptoms.
Management:
I. Life style modifications
i) Salt supplementation
ii) Avoid prolonged standing
iii) Correct dehydration
iv) Avoid missing meal
II. Pt. resistant to life style measure
i) Fludrocortisone
ii) Beta blockers
iii) Disopyramide
3. Dual chamber pace maker if symptoms due to bradycardia.

2. Acute pulmonary oedema
Management:
1. Propped up position
2. O2 high flow 4-6 L/min via face mask
3. Administer Nitrates such as iv GTN 10-200 µg/min or buccal GTN 2-5 mg titrated upwards every 10 min, until clinical improvement occurs or systolic BP falls to 100 mm of Hg.
In other pt. diuretics should be stopped for 24 hours & the ACEi start at low dose.

ACEi Starting dose Target dose
i) Enalapril 2.5 mg 12 hourly 10 mg 12 hrly
ii) Ramipril 1.25 mg daily 10 mg daily.

4. ARB Have similar effect to that of ACEi
Starting dose Target dose
Losarton 25 mg/day 100 mg/day.

5. Combined ACEi & ARB
Indication-HF pt. in those with recurrent hospitalization for HF.
6. Beta blocker therapy
More effective than ACEi in reducing mortality. Bisolol starting dose at 1.25 mg daily increase gradually over 12 weeks to a target maintainance dose of 10 mg daily.
7. Digoxin
To provide rate control
Also in NYHA III, IV
8. Amiodarone
– Effective in pt. of symptomatic arrhythmia
– Should not be used in asymptomatic arrhythmia.
4. Valvular heart disease

Mitral stenosis
Management
Medical management of all valvular diseases is almost same
1. Diet- normal
2. Avoid strenuous exercise
3. O2 inhalation sos
4. Tab. Penoxymethyl penicillin (250mg) 1 + 0 + 1
5. Tab. Frusemide (40mg) 1+0+0
6. Tab. Digoxin 0.25mg 0+0+1 if Atrial fibrillation
7. Tab. Ecospirin (75mg) 0+1+0 (P/C) if Atrial fibrillation
8. In MR ACEI should be given
9. In AR systolic BP should be controlled with Nifedipine or ACEi
Indication of surgery in Mitral stenosis
1. Patient symptomatic despite medical treatment
2. If pulmonary hypertension develops
3. Severe mitral stenosis
4. Pregnancy
2 types of surgery can performed in Mitral stenosis
1. Valvuloplasty
2. Valve replacement
Indication of mitral valvuloplasty in mitral stenosis
1. Significant symptom
2. Isolated MS
3. No (trivial) MR
4. Mobile, non-calcified valve/ subvalve apparatus on Echocardiogram
5. Left atrium free of thrombus
Indication of mitral valve replacement in mitral stenosis
1. MS with MR
2. Rigid & calcified mitral valve cups
Contraindication of surgery
1. Active rheumatic carditis

Mitral regurgitation
Indication of surgery in Mitral Regurgitation (valve replacement or repair)
1. Worsening symptoms
2. Progressive cardiomegally
3. Echocardiographic evidence of deteriorating left ventricular function.

Aortic stenosis
Indication of surgery in Aortic stenosis
1. Development of angina
2. Development of syncope
3. Symptoms of low cardiac output
4. Heart failure
Pt. with moderate to severe stenosis is evaluated every 1-2 year with Doppler Echocardiography to detect progression of severity.

Indication of surgery in aortic regurgitation
1. Symptomatic pt.
2. Asymptomatic pt. should be followed up annually with Echo for evidence of increasing ventricular size, if this occurs or if the end systolic dimension increases to ≥ 55mm the aortic valve replacement should undertaken.

5. Myocardial infarction
Diagnostic tools
1. Classical chest pain > 30 min.
2. ECG changes
3. Biochemical markers e.g. Troponin I.
For diagnosis 2 criteria should be present.
• ECG changes
 ST elevation
 New onset left bundle brunch block
 Evolution of ‘Q’ wave
ECG changes may be isolated or in combination
• Biochemical markers
 CK-MB > 2 fold increase
 Troponin I or T raised level indicate myocardial necrosis.
Management:
1. Complete bed rest
2. Diet- liquid to semisolid
3. O2 inhalation 4-6 L/min
4. GTN spray 2 puff sublingually stat. & sos
5. Tab. GTN SR 2.6 mg 1/2 + 0 + 1/2 + 0
6. Tab. Ecospirin (75mg) 4 tab. Stat. & Tab. Clopidogrel (75mg) 4 tab. Stat.
Then
Tab. Clopidogrel & Aspirin 0 + 1 +0 (after meal)
7. Cap. Omeprazole (20mg) 1 + 0 + 1 ( before meal)
8. Tab. Metoprolol (50 mg) ½ +0 + ½
9. Tab. Ramipril ( 1.25 mg) 0 + 0 +1
10. Tab. Atrovastatin 10 mg 0 + 0 + 1 after meal
11. Inj. Morphine 3 mg iv stat. & SOS (may be repeated after 15 min.)
12. Inj. Stemetil 1 amp. Im stat. Along with Morphine
13. If pt. present with in 12 hours then thrombolysis with Streptokinase or PCI
14. Management of Risk factors e.g. Hypertension, DM etc.
15. Continuous monitoring with pulse rate, rhythm & BP

Mobilization and rehabilitation
 In uncomplicated cases
a) Sit on chair on 2nd day
b) Walk to toilet on 3rd day
c) Return to home on day 5 to 7
d) Gradually increasing activity & return to normal work in 4 to 6 week
 In complicated cases
-Process of mobilization & rehabilitation varies & depends upon the pts functional capacity.

Endocrine system
1. Hypoglycemia
Diagnostic tools
1. H/O of diabetes Mellitus
2. H/O of treatment with Insulin or Secretogogues (e.g. Secrin, Consucon, Limpet etc)
3. H/O of missed or delayed meal
4. Pt. complain headache, dizziness, profuse sweating, palpitation, confusion, drowsy, unconscious
5. On exam.- Bilateral planter extensor
6. Urgent Blood glucose- < 45 mg/dl or 14mmol/L, Keton body on urine present.

Other urgent investigation
I. S. Electrolytes
II. Blood & Urine keton bodies
III. S. creatinine
IV. CBC & Blood culture

Management:
1. NPO TFO
2. O2 inhalation 4-6 L/min
3. Infusion Normal saline
1 L over 30 min.
1 L over 1 hour
1 L over 2 hour
1 L over next 2-4 hours
4. When blood glucose <15.00 mmol/L (270mg/dl) then switch to 5% DA 1 Litre 8 hourly
If pt. still dehydrated then contd. Normal saline and add 5% DA 1 litre 12 hourly
4. Short acting insulin
a) If infusion pump,is available then infuse @ 3-6 units / hour
b) If pump not available 10-20 units IM stat. then 5-10 units hourly. Hourly fall of blood glucose is in the range of 3-4 mmol/L
c) Usual subcutaneous regimen of insulin may be started when the pt. is stable clinically & biochemically & able to take oral food.

5. Potassium replacement
a) None in the first Litre of i.v. fluid unless <3mmol/L
b) If plasma potassium 5.5 mmol/L do not give potassium
6. Broad spectrum antibiotic
7. Continued catheterization
8. Change the posture 2 hourly.

3. HONK (hyperosmolar non-ketotic coma)

Diagnostic tools
1. H/O of DM
2. H/O of irregular treatment or missed dose of Insulin or drugs
3. Stressful condition e.g. infection, trauma, pregnancy
4. On exam. – Severe dehydration, pulse-tachycardia, BP- Hypotension.
5. Investigation- Blood sugar- > 33 mmol/L
a. No keton body in urine
b. Hyperosmolality (> 320 mOsm/ kg)

Hyperosmolality can be calculated by
= 2[Na+] + 2[K+] + [glucose] + urea (all in mmol)
{ Normal osmolality is 280-300 mOsm/kg}

Management:
Same as DK but less insulin is required.
(Ref: Davidson’s principle & practice of Medicine)

4. Cushing syndrome
Management:
Medical treatment before surgery
1. Metyrapone and ketokonazole- the dose should be titrated against 24 hour free urine cortisol level.
2. Treatment of the underlying cause.

Cushing disease
1. Transphenoidal surgery
2. If unsuccessful then bilateral adrenalectomy
Nelson syndrome can be prevented by pituitary irradiation.
5. Addisons disease
Management:
1. Diet- normal
2. Tab. Hydrocortisone 15 mg at morning & 5 mg at 6pm
3. Fludrocortisone 0.05-0.1mg daily

Follow up:
1. Pulse
2. BP
3. S. electrolytes

Advice:
1. If fever double the dose
2. In vomiting inj. Should be given if can not swallow tablet
3. Minor surgery Inj. Hydrocortisone 100 mg im with premedication.
4. Major surgery- Inj. Hydrocortisone 100 mg im 6 hourly until able to take oral tablet
5. Pt. should carry steroid card
6. Bracelet.
6. Addisonian crisis
Management
1. NPO TFO
2. O2 inhalation
3. Infusion normal saline 1000 cc iv @ 30d/min.
4. Infusion 10 % DA 1000cc iv @ 20d/min.
5. Inj. Hydrocortisone 100mg iv stat then im 6 hourly
6. Antibiotic
7. Treatment of the underlying cause.

7. Phaeochromocytoma
Management
a. Definitive treatment is surgery
b. Preparation of pt. before surgery minimum for 6 week
c. Control of HTN by Alpha blocker Phenoxybenzamine 10-20mg orally 6-8 hourly. If tachycardia occurs add betablocker –Propanolol or Labetalol
d. During surgery- Sodium Nitroprusside & short acting alpha antagonist Phentolamine are used to control HTN
e. Postoperative period Hypotension should be managed by -Fluid & Noradrenaline infusion.
8. Hypopituitarism
Management
1. Glucocorticoid replacement
2. Thyroxine 100-150 µgm daily (before this steroid must be given)
3. Sex hormone in men of any age & in female <50 years
4. GH in children & adolescent S/C inj.
5. Treatment of the underlying cause.

9. Prolactinoma
Management:
1. Dopamine agonist (Bromocryptine 1st line drug)
2. Surgery 2nd line treatment.

10. Acromegaly
Management:
1. 1st line treatment is surgery
2. 2nd line treatment is…..
a) Bromocryptine
b) Somatostatin analogue (Octreotide, Lanreotide) slow releasing inj. Every few weeks interval
c) GH receptor antagonist Pegvisomant indicated in whom GH & IGF1 fail to suppress sufficiently by Somatostatin analogue.
11. Diabetes insipidus
Management:
Cranial DI
1. Desmopressin nasal spray 5 µgm in morning & 10 µgm at night. In sick pt. im inj.

Nephrogenic DI
1. Bendroflumethazide 5-10mg/day
2. Amiloride 5-10mg/day
3. Indomethacin 15 mg 8 hourly.

12. Amenorrhoea
Management:
1. Exclude physiological cause e.g. Pg. Menopause etc.
2. Decrease exercise, work load
3. Weight gaining if under weight.

13. Thyrotoxic storm
Management
1. Diet – normal
2. Infusion Normal saline 1000c iv @ 20d/ min
3. Tab. Propanolol 80 mg 6 hourly or 1-5 mg iv 6hourly
4. Sodium ipodate 500mg orally or Dexamethasone 2 mg 6 hourly + Amiodarone
5. Carbimazole if can not take orally then give per rectally
6. Antibiotic
1. Thyrotoxicosis
Management
1. Pt. under 40 years- Tab. Carbimazole 40 -60 mg daily, when pt. euthyroid then 5-20mg for 18 months. If replase occur then –surgery.Subtotal thyroidectomy. Pt. should make euthyroid before surgery by Potassium iodide 60 mg 8 hourly for 2 weeks.
2. If pt. over 40 years – Radio 131I ablation.
Antithyroid drugs
I. Carbimazole 40-60mg daily
II. Methimazole
III. Propylthiouracil (400-600mg daily)

3. Surgery is indicated
Larg goiter.

Note:
 Subjective improvement occur 10-14 days
 Patient biochemically euthyroid at 3-4 weeks. At this time carbimazole should be given at a dose of 5-20mg daily for 12- 15 months.

Thyrotoxicosis in pregnancy
1. Tab. Propylthiouracil 150 mg/day (larger dose cause fetal hypothyroidism).
2. Surgery- if poor compliance. It should be done at 2nd trimester.

15.Graves opthalmopathy
Management
1. Reassurance
2. Methylcellulose eye drop & gell
3. Side shield attached spectacle
4. Prednisolone
5. Sometimes orbital irradiation
6. If loss of visual acquity then urgent surgical decompression.
16. Hypothyroidism
Management
1. Diet – normal
2. Tab. Thyroxine (50µgm) 1 + 0 + 0 ( ½ hour before breakfast)
After 3 weeks
2 + 0 + 0 (½ hour before breakfast)
After 6 week do T3, T4, and TSH then adjust dose of Thyroxine level.
3. Antilipid drugs if hyperlipidaemia.

Note:
1) pt. feel better wuth in 2-3 weeks
2) Reduction in weight & periorbital puffiness occurs quickly
3) Restoration of skin & hair texure and resolution of any effusion take 3-6 months.

Hypothyroidism in IHD
Management
1. Diet- normal, avoid fatty & salty food
2. Tab. Thyroxine (50µgm) 1/2 + 0 + 0 ( ½ hour before breakfast)
Starting dose should be minimum because it can aggravate or precipitate IHD.
Hypothyroidism in Pregnancy
Management
Extra 50µgm/day is required than maintenance dose . Because placenta metabolise thyroxine & increase Thyroxine binding globulin in pregnancy.
T3, T4 & TSH should be assessed in every trimester.
Increased dose of thyroxine is required in the following condition
1. Anticonvulsant drugs
2. Rifampicin
3. Chloroquine
4. Sertraline
5. Aluminium hydroxide
6. Ferrous sulphate
7. Calcium carbonate
8. Malabsorption
9. Pregnancy
17. Myxoedema coma
Diagnostic tools
1. Elderly pt.
2. H/O hypothyroidism
3. Altered consciousness
4. Temperature as low as 25oC.
Management
1. Slow rewarming
2. NG tube feeding
3. O2 inhalation
4. Infusion 5% DNS/ NS
5. Broad spectrum antibiotics
6. Inj. Triiodothyronine (20 µgm) iv stat & 8 hourly, when pt. can take orally then Tab. Thyroxine (50µgm) 1 + 0 + 0 ( ½ hour before breakfast)
7. Inj. Hydrocortisone 100mg im 8 hourly.

Infectious disease
1. Chicken pox in adult or in children
Management
1. Diet – normal
2. Antihistamine
3. Antibiotics
4. Antiviral- oral Aciclovir 800mg 5 times daily for 5 days
In immunocompromised host/ pregnant women Aciclovir 5 mg/kg 8 hourly until pt. improving then complete therapy with oral therapy until all leishon crusting over.
 Visceral involvement (non- CNS) – Aciclovir 5 mg/kg 8 hourly for 7 days.
 Severe complications like encephalitis/ disseminated infection- Aciclovir 10 mg/kg 8 hourly for 14-21 days.
 Lotion claamilon-apply loacaly

2. Shingles or Herpes Zoster
Management
1. Diet – normal
2. Antiviral- oral Aciclovir 800mg 5 times daily
3. Tab. Amitryptylline 25-100mg daily
4. Analgesic –NSAID
Treatment & doses as for chicken pox but typically duration 7-10 days.

3. Infectious Mononeucleosis
Management
1. Diet – normal
2. Antibiotic- penicillin, Avoid Amphicillin or Amoxicillin
3. Steroid – inj. Hydrocortisone 100 mg iv stat. & 6 hourly if pharyngeal edema
4. Return to work governed by pt. physical fitness.

4. Dengue fever
Management
1. Diet – normal, plenty of fluid & home made fruit juice intake
2. Tab. Paracetamol
3. Avoid NSAID, Steroid
4. Fluid management

5. Leptospirosis
Management
1. Diet- normal, salt, fruit. Protein restricted
2. BT if bleeding manifestation
3. Treatment of renal failure
4. Cap. Doxicycline 100 mg 1 + 0 + 1 0r inj. Ceftriacone 1 gm daily
5. If uveitis then oral steroid.
6. Tab. Paracetamol

6.Enteric fever
Management
1. Diet- normal
2. Tab. Paracetamol
3. Antibiotic
Antibiotics that can be used in Enteric fever are—
1. Co-trimoxazole 2 tab. 12 hourly
2. Ciprofloxacin 500 mg 12 hourly
3. Ceftriaxone 2 gm 12 hourly
4. Azithromycin 500 mg daily
Duration of treatment is 14 days.

7. Leprosy
Management
Paucibacillary
1. Diet- normal
2. Tab. Daposone 100mg 1 +0 + 0 ….6 months
3. Tab. Rifampicin 600mg 1 + 0 + 0 one Tab. Monthly for 6 months

Multibacillary
Monthly basis for 12 months
1. Tab. Rifampicin 600mg 1 + 0 + 0
2. Tab. Clofazimine 300mg 1 + 0 + 0
Daily basis for 12 months
1. Tab. Dapsone 100mg 1 tab. daily
2. Tab. Clofazimine 50mg 1tab. daily.
Paucibacillary with single lesion
1. Tab. Ofloxacin 400mg- single dose
2. Tab. Rifampicin 600mg-single dose
3. Tab. Minocycline 100mg- single dose.
8. Rickettsial infection
Management
1. Tetracycline 500mg 6 hourly Or
2. Doxycyclline 100mg 12 hourly Or
3. Chloramohenicol 500mg 6 hourly Or
4. Blood transfusion if haemorrhage
5. Sedation if delirium occurs
Duration of treatment is 7 days.
9. Giardiasis
Management
1. Tinidazole 2 gm stat.
Or
Metronidazole 400mg 8 hourly for 10 days.

10. Filariasis
Management
1. DEC 6 mg /kg daily in 3 divided doses for 12 days.
2. In tropical pulmonary eosinophillia same dose of DEC for 14 days.
Or
3. 300mg DEC single dose
11. Syphilis
Management
Antibiotic- choice Penicillin
Doxicycline if allergic to penicillin except in pregnancy
Azithromycin is a further alternative.

Cure indicated by resolution of clinical sign & decline of non-treponemal test (VDRL) usually to undetectable levels with in 6 months of primary syphilis & 12- 18 months of 2ndary syphilis.
Syphilis in pregnancy
Penicillin is choice.
Erythromycine if allergic to penicilline.
Ceftriaxone 250mg im for 10 days.

12. Gonorrhoea
Management
Uncomplicated
Cefixime 400mg stat. or
Ciprofloxacin 500mg stat. or
Ofloxacin 400mg stat.
Complicated
Quinolone resistance
Ceftriaxone 250 mg im stat or
Spectinomycin 2 gm im stat
In pregnancy & breastfeeding
Cefixime
Ceftriaxone

13. Chlamydial infection
Management
Standard regimen
Azithromycin 1gm single dose or
Doxycycline 100mg B.D. for 7 days.
Alternative regimen
Erythromycin 500mg 6 hourly for 7 days or
Ofloxacin 200 mg 12 hourly for 7 days.

14. Malaria
Uncomplicated
Management:
1. Diet –normal
2. Tab. Artemether & Lumefentrin (Coartem) 4+0+ 4 (for 3 days) (1st line drug)
3. Tab. Paracetamol (500mg) 1+1+1
 Situations where Coartem can not be given…..
a) Pregnancy in first trimester
b) Children 25 kg body wt.) 50 mg morning and evening after meal
• Patients (95%.
Treatment D:
Sodium Antimony Gluconate for PKDL cases
Dose:
20 mg/kg/day in IM route.
Total 6 cycles.
Each cycle consists of 20 days treatment.
Should be an interval of 10 days in between 2 cycles.
Essential to weight the pt every time before starting a new cycle.

Ref: National guideline of diagnosis & management of Kala-azar.

Alimentary tract Disease:

1. Hiccup
Management:

1. Eating 1 TSF of dry granulated sugar.
2. Interruption of the respiratory cycle by breath holding, Valsalva maneuver or rebreathing into a bag.
3. Irritation of the diaphragm by holding knees to chest
4. Tab. Baclofen 1 + 1 + 1
5. Inj. Chlorpromazine 25mg/ml 1 amp. i.m. stat. & B.D. (Before giving LFT & Renal function test should be done)
6. Treatment of the underlying cause.
Other drug can be used treatment
1. Other agents -phenytoin, carbamazepine, benzodiazepines (lorazepam, diazepam), metoclopramide, baclofen, gabapentin, and occasionally general anesthesia.

( Ref. CMDT 2010)

2. Oral ulcer
Management
1. Topical steroid- 0.1% Triamcinolone in orabase (Kenacort oral base )
Or
Choline salicylate 8.7% gel
2. Rarely pt. with very severe recurrent apthous ulcer may need oral steroid.

3. Oral Candiasis
Diagnostic tools
1. Occurs usually in immunocompromised pt. like DM, cytotoxic drugs, steroid, old age etc.
2. White patch in mouth
Management:
1. Nystatin or Amphotericin suspension or Lozens
2. Resistant cases or immunocompromised pt. may require oral fluconazole.

4. Achalasia Cardia
Treatment option:
1. Endoscopic force full pneumatic dilatation
2. Endoscopically directed Botulinum toxin inj. In to the lower oesophageal sphincter
3. If replase occur then surgery- myotomy (Heller’s operation either laparoscopically or open).

5. Gastro Esophagial Reflux Disease( GERD)
Management
1. Omeprazole 20 mg 1 + 0 +1
6. Peptic Ulcer Disease (PUD)
Management
1. Avoid smoking, Aspirin, NSAID
2. H. pylori eradication therapy… duration 7- 14 days.
Cap. Omeprazole 20 mg 1 + 0 +1 ½ hour before meal
Cap. Amoxicillin 500mg 2 + 0 + 2
Tab. Clarithromycin 500mg 1 + 0 + 1
3. Maintainance dose of Omeorazole 20 mg daily.
7. Zolinger- Ellusion syndrome
Diagnostic tools:
1. Severe upper abd. Pain, diarrhea, statorrhoea
2. Poor response to ulcer therapy
3. Endoscopy shows- severe & multiple ulcer in post bulbar duodenum, jejunum & oesophagus.
Management:
1. PPI- larger dose 60- 80mg daily
2. Somatostatin analogue- Inj. Octreotide subcutenously
3. If localized tumor found then resection of the tumor.

8. Non-ulcer dyspepsia (NUD)
Diagnostic tools:
1. Age 6 cm
2. Those whose clinical & Laboratory measurements deteriorate
3. Those not respond after 7-10 days maximal medical treatment.

Maintainance of remission
1. Oral aminosalicylates- Mesalazine or Balsalazine
Sulphalazine has higher side effects but choice in pt. with associated arthopathy. Pt. who frequently relapses despite Aminoslicylate is treated with thiopurines.

13. Irritable bowel syndrome ( IBS)
Diarrhea predominant
Management:
1. Reassuarrance
2. Avoid legumes & excessive dietary fibre
3. Still symptomatic –Loperamide 2-8 mg daily
4. Still symptomatic- Amitryptylline 10 -25 mg at night
5. Still symptomatic-
i) Relaxation therapy
ii) Biofeedback
iii) Hypnotherapy
Constipation predominant
Management:
1. Reassurance
2. High roughage diet
3. Still symptomatic- ispagula, Lactulose
4. Still symptomatic-
i. Relaxation therapy
ii. Biofeedback
iii. Hypnotherapy

Pain & bloating
ManageMent:
1. Mebevarine
2. Peppermint oil
3. Alverine
4. Still symptomatic- Amitryptylline 10- 25 mg at night, Probiotics, Dietary change
5. Still symptomatic-
a. Relaxation therapy
b. Biofeedback
c. Hypnotherapy
14. Anal fissure
Management:
1. Avoid constipation
2. Increase fluid intake
3. Nitric oxide & 0.2% GTN or deltiazem ointment
4. Resistant case- inj. Botulinum toxin
Surgery- Lateral internal anal sphincterotomy or advancement anoplasty.

Haematology
1. Blood transfusion reaction
a) Febrile reaction
Diagnostic tools
 Pt. complain of fever, chills & rigor
 Pt. otherwise normal
Management:
1. Stop the transfusion
2. Paracetamol tab. Or suppository
3. Restart the transfusion at a slower rate
4. Observe the pt. more frequently.

b) Urticaria
Mild allergic reaction
1. Stop the transfusion
2. Give chlorpheniramine 10 mg iv slowly
3. Restart BT at a slower rate
4. Observe frequently.

c) Severe allergic reaction
Diagnosttic tools
1. Bronchospasm, abdominal pain
2. Angioedema, hypotension
Management:
1. Discontinue the transfusion
2. Give Chlorpheniramine 10 mg iv slowly
3. O2 inhalation
4. Nebulize with Salbutamol
5. If severe bronchospasm or hypotension then give inj. Adrenaline 0.5 mg i.m.
6. Send clotted blood sample to the transfusion laboratory
7. Take down blood unit & giving set & return intact to blood bank with all other used/ unused unit.

d)ABO incompatibility
Management:
1. Take down blood unit & giving set & return intact to blood bank with all other used/ unused unit
2. Start i.v. saline infusion
3. Monitor urine out put- maintain urine out >100ml/ hour. Give Frusemide if urine output fall
4. Treat DIC with appropriate blood products
5. Inform hospital transfusion department immediately.
3. Iron deficiency anemia
Management:
1. Diet- iron containing foods like Lal sak, kochu sak etc
2. Tab. Ferrous sulphate 200mg 8 hourly for 3-6 months. If pt. intolerant to ferrous sulphate then Ferrous sulphate 12 hourly or Ferrous gluconate 300 mg 12 hourly
3. Blood transfusion-indication
i) If pt. have angina
ii) Heart failure
iii) Evidence of cerebral anoxia
4. Parentral iron-indication
i) Malabsorption
ii) Chronic gut disease

Follow up:
1. Hb%- Hb% should be rise 1 gm/dl/week
2. Reticulocyte count- Reticulocytosis is evident after 7-10 days.
4.Megaloblastic anaemia
Management:
1. Diet- normal
2. Inj. Hydroxycobalamine 1000 µg i.m. five doses 2-3 days apart then 3 monthly life long
3. Tab. Folic acid 5 mg 1 tab daily for 3 week, then 1 tab. Weekly for life long
4. Ferrous sulphate 200 mg 8 hourly, if initial responses is not maintained & PBF is dimorphic.

5.Spleenectomized Pt.
Management:
1. Vaccinate the pt.
 Pnemococcal
 H.inluenza type B
 Meningococcus C
 Influenza
Vaccination should be done 2-3 weeks before elective surgery. If emergency surgery is done then vaccination should be done after surgery.
2. Pneumococcal reimmunization should be done every 5 yearly
3. Influenza reimmunization should be done yearly basis.
4. Penicillin V 500 mg 12 hourly life long
5. Should carry Bracelet or card.

6.Autoimmune Haemolytic anaemia
Management:
1. Steroid –prednisolone 1 mg/kg/day orally, when Hb% normalized, reticulocytosis resolved dose of steroid should be reduced over 10 weeks
2. Blood transfusion- when developed heart failure or unabated fails in Hb%
3. Splenectomy- if haemolysis fails to respond to steroid or can only be stablished by larger doses.
4. Azathioprine or cyclophosphamide-if splenectomy is not appropriate.

7.Paroxyamal nocturnal haemoglobinuria (PNH)
Diagnostic tools:
 Pt. complain –red brown color urine particularly in morning
 Urine R/E- haemoglobinuria

Management:
1. Diet- normal
2. Blood transfusion
3. Treatment of thrombosis
4. Recently anticomplement C5 monoclonal Ab Ecluzimab is used.

8. Sickle cell anemia
Management:
1. Tab. Folic acid 5 mg 1+ 0 + 0
2. Tab. Penicillin V
3. Hydroxycarbamide
4. Vaccinate against Pneumococcus, H. influenza & Hepatitis B.
Treatment of vaso-occlusive crisis
1. O2 inhalation
2. Rehydration with Normal saline
3. Antibiotic
4. Analgesia with opiate
5. Exchange transfusion
 in life threatening crisis
 Or to prepare the pt. for surgery.

9. Chronic myeloid leukaemia
Chronic phase
1. First line therapy- Imatinib,
If fail to response or progress on therapy- Dasatinib or Nalatinib, Bone marrow transplantation (allogenic)
Or
Hydroxyurea or Hydroxycarbamide or Interferon.
2. Hydroxyurea- if pt. can not afford Imatinib.
Accelerated or blast crisis phase
1. Imatinib
2. Hydroxycarbamide & low dose cytarabine. If fail to response or progress on therapy- Dasatinib or Nalatinib, Bone marrow transplantation (allogenic).

10. Chronic Lymphatic leukaemia
Stage A
No treatment is required.
Stage B & C
1. Chlorambucil, recently Fludarabine plus Cyclophasphamide
2. Corticosteroid- in bone marrow failure or autoimmune cytopenias
3. Blood transfusion if anaemia or thrombocytopenia
4. Antibiotic – infection
5. Radiotherapy-if lymph node causing discomfort or local obstruction & symptomatic splenomegally
6. Splenectomy- to decrease autoimmune destruction of RBC, Hypersplenism & to relieve massive splenomegally.

11. Myelodysplastic syndrome
Management:
1. Blood transfusion
2. Platelet transfusion
3. Erythropoietin & GCSF
4. Allogenic bone marrow transplantation in younger pt.

12. Multiple myeloma
Management:
Asymptomatic –no treatment is required
Symptomatic
1. Plenty of fluid intake
2. NSAID to relieve pain
3. Bisphosphonates
4. Allopurinol
5. Plasmapharesis-in hyperviscosity
6. Chemotherapy
1st line –Thalidomide
Older pt. – Thalidomide plus Melphalan & Prednisolone
In younger pt. -Thalidomide plus allogenic BMT.
7. Radiotherapy- localized bone pain not responding to simple analgesic & pathological fracture, spinal cord compression.

13. Aplastic anaemia
Management:
1. Diet- normal
2. Antibiotic
3. Immune suppressive therapy for older pt. with-Ciclosporin & Antithymocytic globulin
4. Younger pt. < 30 years – allogenic BMT.
14. Myelofibrosis
Management:
1. Diet- normal
2. Tab. Folic acid
3. Blood transfusion
4. Hydroxycarbamide
5. Splenectomy- if symptomatic pancytopenia, enlarged spleen, hypersplenism
6. Allogenic BMT in younger pt.
15. Polycythaemia Rubra vera
Management:
1. Diet- normal
2. Venesection 400-500 ml every 5-7 days until PCV 30 thousand do not require treatment
2. First line therapy for pt. with spontaneous bleeding
A. Prednisolone 1 mg/ kg daily
B. If response to steroid is slow & severe haemostatic failure
 Prednisolone & IVIg
Or
Intravenous anti D
C. Persistent or potentially life threatening bleeding should be treated with platelet transfusion in addition to other therapies
D. Splenectomy- if 2 relapses or primary refractory disease
E. If significant bleeding persists despite splenectomy- low dose steroid, immunosuppressive therapy with Rituximab, ciclosporin & Tacrolimus.
17. Haemophilia
Haemophillia A
1. Resting of the bleeding site by bed rest or splint
2. In severe hemophilia A intravenous infusion of factor VIII concentration
3. In mild to moderate hemophilia A Vasopressin receptor agonist DDAVP 0.3 µg/ kg iv or subcutaneously. Alternatively same effect can be achieved by intranasal administration of 300 µg.
4. Prophylaxis – Factor VIII can be administered 2 or 3 times per week.
Haemophillia B
Factor IX concentration intravenous infusion.
18. Acute leukaemia
Diagnostic tool
1. Fever high grade
2. Generalized weakness
3. Bleeding manifestations e.g.- gum bleeding, epistaxis, etc.
4. On exam. –Anaemia, Lymphadenopathy, Bony tenderness, Hepato-splenomegally.

Urgent Investigation:
1. CBC with PBF

Management:( Supportive)
1. Diet- normal
2. Blood transfusion (before BT PBF should be done)
3. Inj. Eracef (1gm) ivial i/v daily
4. Tab. Paracetamol (500mg) 1+1+1
5. If menorrhagia Tab. Premulate N 2+2+2

For specific management referred to Haematologist.

19. Haemolytic anaemia
Diagnostic tool
1. Generalized weakness
2. No fever, bleeding manifestation
3. On exam.
 No lymphadenopathy, No bony tenderness
 Hepatosplenomegally.

Management:
1. Diet – normal
2. BT
3. Tab. Folison 1+0+0

Dietary advice:
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An approach to diagnosis of Anaemia from examination findings:
 Anaemia + Bleeding manifestation + No lymphadenopathy + No bony tenderness + No Hepatosplenomegally ¬– Aplastic anaemia.
 Anaemia + No Bleeding manifestation + No lymphadenopathy + No bony tenderness + Hepatosplenomegally ¬– Haemolytic anaemia.
 Anaemia + Bleeding manifestation + lymphadenopathy + bony tenderness + Hepatosplenomegally ¬– Acute leaukaemia.

MUSCULO-SKELETAL DISEASES
1. Low back pain (LBP)
Management:
1. Reassurance, explanation
2. Analgesic- paracetamol, NSAID, Muscle relaxants
3. Discourage bed rest
4. Low dose TCA e.g. Amitryptylline
5. Refered for Physiotherapy or manipulation- if return to normal physical activity has not been achieved by 6 weeks.
2. Osteoarthritis
Management:
1. Full explanation of the condition
 Established structured changes are permanent
 Pain & function can be improved
2. Exercise- strengthening & aerobic exercise
3. Hot or cold compression
4. Reduction of adverse mechanical factors
– Weight loss if obese
– Shock absorbing foot wear
– Use of walking stick for painful knee or hip OA.
5. Drug
– Paracetamol
– Topical NSAID
– Oral NSAID
6. Intraarticular inj. Of corticosteroid to relieve pain of knee & thumb base OA
7. Surgery
Indication:
i) OA whose pain, stiffness & reduced function impact significantly on their quality of life
ii) Refractory OA (refractory to non-surgical & adjunctive treatment).
Surgeries are- Osteotomy & joint replacement for knee & hip joint OA.
3. Rheumatoid arthritis
Diagnostic tools:
1. Polyarthritis -3 or more joints pain
2. Hand joint involvement
3. Symmetrical arthritis
4. Rheumatoid nodule
5. Morning stiffness > 1 hour
6. Rheumatoid factor (RA test Positive)
7. Radiological changes
8. Symptoms for more than 6 weeks.

4 or more criteria suggest diagnosis of RA.

Management: (ward or practical mx.)
1. Diet : Normal
2. Cap. Indomethacin (25mg) 1+1+1 (after meal)
3. Cap. Omeprazole (20mg) 1+0+1 ( before meal)
4. Tab. MTX (2.5mg) 3+0+0 ( every saturday)
5. Tab. Folic acid 1+0+0 (every sunday)

Rheumatoid arthritis
Management:(Ideal)
1. Rest
2. Passive exercise
3. NSAID
4. DMARD
5. Anti TNF therapy-if disease activity persists despite adequate trial of 2 DMARD including Methotrexate
6. Corticosteroid-Prednisolone 7.5-10 mg daily. To cover delayed onset of action of DMARD
7. Surgery-indication-when medical treatment fail to pain relief or to prevent tendon rupture.
8. Surgeries are
Synovectomy (wrist or finger tendon sheath)
Osteotomy
Arthodosis or arthoplasty
Follow up in pt. getting MTX initially monthly, then every 3 month
1. Clinical improvement
2. Full blood count and LFTs
4. Ankylosing spondylosis
Management:
Non-pharmacological:
1. Explanation & education
2. Daily back extension exercise including a morning ‘warm up’ routine
3. Avoid prolonged period of inactivity work like driving, computer work etc.
4. Swimming is the best exercise.
Pharmacological treatment:
1. NSAID
2. MTX or sulphasalazine if peripheral arthritis
3. Anti TNF therapy for disease inadequately controlled with above measure
4. Oral corticosteroid- in acute uveitis
Surgery
In severe hip, knee, shoulder joint restriction.
5. Reactive arthritis
Management:
1. Rest
2. NSAID
3. Tetracycline
4. Intraarticular inj. for marked synovitis
5. DMARD
 Persistent marked symptom
 Recurrent arthritis
 Severe keratoderma blenorrhagica
6. Ant. Uveitis- topical, oral, subconjunctival steroid.
6. Psoriatic arthritis
Management:
1. Avoid splint & prolonged rest
2. NSAID
3. Intrarticular inj. of steroid to control synovitis
4. DMARD- Methotrexete
5. Anti TNF therapy in whom DMARD fail
6. Retinoid acitretin
7. Photochemotherapy & methylpsoralin and long wave UV light.

7. Gout
Management:
Acute attack
1. Application of ice pack
2. NSAID
3. Oral Colchicine 0.5 mg 6/8/12 hourly
4. Joint aspiration & intraarticular inj. Of steroid
5. For severe oligo-polyarticular attack- parentral corticosteroid.
Long term management:
1. Correction of predisposing factors
2. Weight loss & reduction of excess alcohol intake especially bear
3. Diuretics should be stopped if possible
4. Avoid sea food, read meat
5. Allopurinol initial dose 100 mg daily (50 mg in elderly), gradually increase the dose up to 900 mg daily.
Follow up:
S. uric acid should be measured 3-4 weeks interval.
Advice to the pt:
During initiation of urate lowering drug acute attack may occur but drug should not be stopped.
Tips:
Acute attack during initiation of urate lowering therapy; oral cholchicine or NSAID can be added.

8. Septic arthritis
Urgent investigation:
1. Synovial fluid for Gram staining & culture
2. Blood for FBC & culture
3. Consider sputum, urine culture
Management:
1. Intavenous Flucloxacillin 2 gm 6 hourly for 2-3 weeks then oral for 6 weeks. Change according to C/S
2. If Penicillin allergy then-Clindamycin 450-600 mg 6 hourly
3. If high risk for Gram negative infection then add Cephalosporin
4. Serial needle aspiration 1-3 times per day
5. Pain relieved by- local ice pack, oral or iv analgesic
6. Physiotherapy from the first day
-Regular passive movement progressing to active movement.
9. SLE
General management:
1. Educate the pt.
2. Avoid sun & UV light exposure, employ sun block
3. Avoid smoking
4. Control hypertension & dyslipidaemia
Mild disease (restricted to skin & joints)
1. NSAID
2. If necessary Hydroxy chloroquine 200-400 mg daily
3. Short course of steroid for rash, synovitis, pleurisy & pericarditis.
Life threatening disease
Affecting kidneys, CNS or CVS requires high dose steroid plus immune suppression.
1. A commonly used regimen- Pulse Methyl prednisolone 500 mg -1 gm iv coupled with cyclophosphamide 2 mg/kg iv repeated at 2-3 weekly interval on 6-8 occasion.
Alternatively in renal involvement Cyclophosphamide can be replaced with Mycophenolate mofetil(MMF) with fewer side effects.
2. Folowing control- prednisolone 40-60 mg daily & Azathioprime, MTX or MMF
3. Co-trimoxazole 960 mg thrice weekly to prevent P. carinii infection due to cyclophosphamide
4. Mesna is given with bolous Cyclophosphamide to reduce risk of haemorrhagic cystitis
5. Lupus nephritis with Antiphospholipid syndrome who have had previous thrombosis require life long warfarin.

10. Systemic sclerosis
A) Raynaud’s syndrome with digital ulcer
1. Avoid cold exposure
2. Use of mittens (heated mittens are available)
3. Calcium antagonist or ARB
4. Antibiotic
a. Intermitten infusion of epoprostenol may benefit severe digital ischaemia
B) Ooesophageal reflux
 PPI
 Metochlopramide or domperidon
 Antibiotic for bacterial overgrowth
C) Hypertension-ACEi even also in renal impairement
D) Joint involvement-Analgesic
E) Pulmonary hypertension- Endothelin-1 antagonist ‘ Bosentan’
F) Corticosteroid & cytotoxic drug are indicated in pt. with
– co-existing myositis or
– fibrosing alveolitis.

11. Polymyositis & Dermatomyositis
Management:
1. Oral corticosteroid 40-60 mg daily
2. iv Methylprednisolone 1 gm daily for 3 days in pt. with respiratory or pharyngeal weakness. If thre is a good response steroid should be reduced by approximately 25% per month to maintain dose of 5-7.5 mg
3. Most pt. require additional treatment with Azathioprine & MTX
4. iv immuneglobulin may be effective in refractoryces.

12. Bechet’s Syndrome
Diagnostic tools
1. Oral ulcer deep & multiple
2. Genital ulcer
3. Skin leishon-erythema nodusum or acneform leishon
4. Migratory thrombophlebitis
5. Anterior or posterior uveitis
6. Neurological sign-brain stem involvement, pyramidal tract signs etc.
Management:
1. Oral ulcer- topical steroid preparation
2. Colchicine for erythema nodusum & arthalgia
3. Thalidomide 100-300 mg daily for 28 days & effective for resistant oral & genital ulcer
4. Corticosteroid & immunosuppressive for systemic disease.

13. Polymyalgia Rheumatica (PMR)
Management:
1. Prednisolone 20-30 mg daily gradually reduce the dose 10-15 mg by about 8 weeks ultimately 5-7.5 mg for 12-14 weeks
2. Immunosuppressive like MTX, Azathioprine when steroid require > 7.5 mg/day.

14. Giant cell arteritis
Management:
1. Prednisolone 60 mg daily

15. Osteoporesis
Non-pharmacological treatment
1. Cessation of smoking
2. Moderation of alcohol intake
3. Dietary calcium intake
4. Exercise
Drug treatment
Indication
1. BMD T score below -2.5 or below -1.5 in corticosteroid induced osteoporeis
2.Vertebral fracture irrespective of BMD (except traumatic vertebral fracture)
Drugs used
1. Alendronate 70 mg/ week or Risedronate 35 mg/ week. Orally on empty stomach & no food should be taken up to 30-45 min. of administration
2. Calcium & vit-D
3. PTH- Teriparatide. Superior to Alendronate. It is expensive, rserve for
a) Szevere osteoporesis BMD T score -3.5 to – 4.0 or below
b) Failure to respond adequately to other treatment.
Duration 24 months, after that Bisphosphonate should be used to maintain BMD. Teriparatide should not be used simultinously with Bisphosphonate.
4. Calcitonin- has analgesic properties. Sometimes used short to medium time in pt. with acute vertebral fracture. Dose s/c or im 100-200 U daily or intranasal spray 200 micro units daily.
5. HRT-primarily indicated for prevention of osteoporesis in women with an early menopause & for treatment of women with osteoporesis in their early fifties who have troublesome menopausal symptoms
6. Calcitrol-recently licensed for treatment of osteoporesis
Surgery
 Hip replacement- total or partial, indicated for intracapsular fracture of femoral neck.
 Kyphoplasty-indicated for acute vertebral compression fracture where there is a significant degree collapse & severe pain.
 Vertebroplasty- indicated for painful vertebral fracture which fails to settle by medical treatment.
Follow up:
1. BMD repeat after 2-3 years
2. NTX (N-Telopeptide) respond quickly than BMD.

16. Osteomalasia & Rickets
Management:
1. Respond quickly to treatment with ergocalciferol 250-100 µgm daily.
After 3-4 months treatment can generally be stopped or the dose of vit-D reduce to maintainance level of 10-20 µgm Cholecalciferol daily except in pt. with Malabsorption in whom higher dose may required.
Follow up:
1. Clinical improvement
2. Elevation in 25(OH)D
3. Reduce in PTH.

Neurology
1. Tension type Headache
Management:
1. Explanation of symptoms
2. Avoid precipitation
3. Analgesics-NSAID
4. Muscle relaxation
5. Amitryptyline
6. Phycotherapy.

2. Migrain
Acute attack
1. Identification & avoidance of precipitating or exacerbating factors such as OCP, smoking
2. Analgesic-NSAID or Paracetamol
3. Metochlopramide or domperidon
4. Severe attack- Sumatryptan, 5-HT agonists
5. Frequent attack are prevented with
 Propanolol
 TCA
 Sodium valproate 300-600mg/day or Topiramate 50 -100 mg/day.
3. Status epilepticus
Management:
Clearing the airway
O2 inhalation

Inj. Diazepam 10mg (Sedil) iv or rectally
Can be repeated after 15 min.

If seizure continued after 30min. then
i.v. Fosphenytoin 15mg/kg at 100mg/min.
Or
i.v. Phenobarbital 10mg/kg at 100mg/min.

If seizure still continued after 30min. then
Start treatment for refractory status with intubation with general anaesthesia with Propofol or Thiopental.

Once status controlled start longer term anticonvulsant medication with one of the following-
a) Sodium valproate 10mg/kg i.v. over 3-5 min. Then 800-2000mg/day.
b) Carbamazepine 400mg by NG tube then 400-1200mg/day.

Guideline for choice of Antiepileptic drugs
Epilepsy type 1st line 2nd line 3rd line
1. Partial or 2ndary GTCS Carbamazepine Sodium valproate Phenobarbital
(200-2000mg/day) Phenytoin
2-3 dose/day

2. Primary GTCS Sodium valproate Lamotrigine Phenobarbital
400-2500/day 60-180mg/day 1-2 dose/day
1-2 dose/day Phenytoin
Carbamazepine
4. Acute stroke
Diagnostic tools
• Sudden onset of weakness of one side of the body or loss of consciousness
• No H/O of fever
• On exam. Hemiplegia and planter extensor in that side.
Management:
1. NG tube feeding
2. O2 inhalation 2-4 l/min
3. Infusion Normal saline 1000cc iv @ 10 drops/min
4. Syrp. Amoxicillin 2 TSF TDS
5. Omeprazole sachet 1 sachet dissolve in ½ glass water then take via NG tube 12 hourly
6. Paracetamol suppository (500mg) 1 stick P/R stat. and SOS
7. Cold tepid sponging
8. Continued catheterization
9. Change the posture 2 hourly
10. Care of the mouth, eye, bowel
11. Treatment of underlying cause like DM, Dyslipidaemia etc.

• If pt. is known hypertensive and taking drug regularly then contd. the drug.
• If pt. is not known hypertensive & BP is high then not give antihypertensive. Antihypertensive should be given in the following condition
-In Ischaemic stroke if BP >220/120 mm of Hg
-In Haemorrhagic stroke > 180/ 110 mm of Hg
• If pt. is Diabetic then start insulin
• If pt. is not known diabetic but blood sugar is >11.1 mmol/L then start insulin.

5. Tetanus
Management
1. O2 inhalation stat 4-6 L/min
2. Nurse in a quite room
3. Avoid unnecessary stimuli
4. NG tube feeding 200 ml 2 hourly
5. Infusion 5% DNS 1000 cc i.v. daily
6. Inj. Benzylpenicillin 600mg iv 6 hourly Or inj. Metronidazole if allergic to Penicillin
7. Inj. TIG 12 amp. i.m. stat.
8. Inj. Diazepam (10mg) 1 amp. i.v. stat & B.D.
9. Change the posture 2 hourly

6. Meningo-encephalitis
Diagnostic tools
1. Fever, Headache
2. Alteration of consciousness
3. On exam.- Neck rigidity present
1. Kernig’s sign present
Management:
1. NG tube feeding 200 ml 2 hourly in sitting posture & maintain the posture for 10 min.
2. Inj. Ceftriaxone (2gm) 1 vial i.v. stat & BD
3. Inj. Dexamethasone 2 amp. i.v. 20 min before giving antibiotics stat & 6 hourly for 3 days
4. Omeprazole sachet 1 packet dissolve in ½ glass water through NG tube BD
5. Continued catheterization
6. Change the posture 2 hourly
7. Care of mouth, eye & bowel
8. If short H/O of fever then add Tab. Acyclovir (400mg) 2+2+2+2+2

Pyogenic Meningitis Choice of antibiotic
1. Pt. present with typical meningococcal rash- Inj. Benzylpenicillin 2.4gm iv 6 hourly
2. Adult aged 18-50 years without typical meningoccal rash – Cefotaxime 2 gm iv 6 hourly or Ceftriaxone 2 gm iv 12 hourly.
3. Pt. in whom penicillin resistant pneumococcal infection is suspected- as for (2) but add Vancomycin 1 gm iv 12 hourly or Rifampicin 600mg iv 12 hourly
4. Adult aged over 50 years and those in whom Listeria monocytogen infection is suspected (Brainstem sign, immunosuppression, diabetic, alcoholic)- as for (2) but add Ampicillin 2 gm iv 4 hourly or Co trimoxazole 50mg /kg iv in 2 divided dose.

7. Encephalitis
Diagnostic tools
4. Fever, Headache
5. Alteration of consciousness
6. On exam. – No Neck rigidity
-No Kernig’s sign.
Management:
1. Same as Mningo-encephalitis
2. If convulsion occurs then add Tab. Carbamazepine (200mg) 1+1+1.

8. Trigeminal neuralgia
Management:
a. Carbamazepine up to 1200 mg daily should be started at low dose. Who can not tolerate it add Gabapentin or Pregabaline.
b. Inj. of Alcohol or Phenol in to a peripheral branch of the nerve.
9. Restless leg syndrome
Management:
1. Clonazepam (0.5-2mg) at night
2. Levodopa 100-200 mg or dopamine agonist at night.

10. Subarachonoid Haemorrhage
Management:
1. Nimodipine 30-60 mg iv for 5-14 days followed by 360 mg for further 7 days.
2. Definitive treatment
a. Insertion of platinum coil in to an aneurysm via endovascular procedure
Or
b. Surgical clipping of the aneurysm neck.
AV malformation –surgical removal, ligation, injection of material to occlude the fistula or draining veins.

11. Transverse Myelitis
Management:
1. Diet – normal
2. Inj. Methylprednisolone 1 gm daily for 3 days
3. Omeprazole
4. Continued catheterization

12. Dementia/ Alzheimer;s disease
Management:
1. Donepezil 10 mg daily
2. Antidepressant in depressive pt.

13. Wernick- Korsakoff disease
Diagnostic tools
1. H/O alcoholism, malabsorption, malnutrition, Hyperemesis gravidarum
2. Acute confusional state (W.encephalopathy)
3. Brain stem sign e.g. ataxia, nystigmus & extraocular muscle weakness particularly lateral rectus.
Management:
1. Intravenous Thiamine 2 vial 8 hourly for 48 hours, then oral Thiamine 100 mg 8 hourly
2. Treatment of the underlying cause.

14. Parkinsonism
Management:
1. Levodopa –carvidopa, 50 mg 8 or 12 hourly increased up to 1000 mg/day. This drug improve bradykinesia & rigidity
2. Anticholinergic-improve tremor & rigidity
3. Trihexyphenidyl (benzhexol 1-4 mg 8 hourly)
4. Orphenadrine 50 -100 mg 8 hourly
3. Dopamine receptor agonist
5. Bromocryptine 1 mg initially then 2.5 mg 8 hourly up to 30 mg/day
6. Pergolide 50 µgm (starting dose) increased to 250 µgm 8 hourly up to 3000 µgm/day.
4. Amantadine
-Use in early of the disease when more potent treatment is not required
-To control dyskinesia produced by dopaminergic treatment.
Dose 100 mg 8 or 12 hourly.
5. COMT inhibitors
Entacapone 200 mg with each dose of levodopa. This prolonged the effect of levodopa & allows levodopa dose to be reduced & given less frequently.
6. Surgery
Stereotactic thalamotomy to treat tremor. Now a days need relatively infrequently
7. Physiotherapy & speech therapy.

15. Huntington’s disease
Symptomatic management
7. Tetrabenazine or dopamine antagonists such as sulpride
8. Antidepressants for depressive pt.
9. Psycological support
10. Genetic counselling for the relatives
16. Rabies
Management:
Established disease
1. ICU support
2. Sedation with Diazepam 10 mg 4-6 hourly
3. Chlorpromazine 50-100 mg if necessary
4. Nutrition & fluid by iv or gastrostomy.
Prevention
Pre-exposure prophylaxis – protection is afforded by 2 intradermal injection of 0.1 ml human diploid cell vaccine or 2 intramuscular inj. Of 1 ml, given 4 weeks apart, followed by yearly booster.
Post exposer vaccination before development of sign symptom. For maximum protection hyperimmune serum and vaccine are required.
Safest antirabies antiserum is human rabies immune globulin, the dose is 20 U/kg, half should be infiltrated around the bite and half im at adifferent site from vaccine.
Safest vaccine is human diploid cell vaccine 1 ml is given intramuscularly on days 0, 3, 7,14, 30 and 90.

17. Cerebral abscess
Treatment:
1. Diet – normal
2. Antibiotic
3. Anticonvulsant- Carbamazepine SR 200 mg B.D.
4. Paracetamol if fever
5. Surgery
Burr-hole aspiration or excision-where presence of a capsule may lead to a persistent focus of infection.

Antibiotic choice is guided by following condition
Frontal lobe
Cefuroxime 1.5 gm iv 8 hourly
Plus
Metronidazole 500 mg 8 hourly.
Temporal lobe & Cerebellum
-Ampicillin 2-3 gm iv 8 hourly
Plus
-Metronidazole 500 mg 8 hourly
Plus
Either Ceftazidime 2 gm iv 8 hourly or Gentamycin 5 mg/ kg iv daily.
Any site
H/O penetrating injury
-Flucloxacillin 2-3 gm iv 6 hourly
Or
– Cefuroxime 1.5 gm iv 8 hourly
Multiple abscesses
-Benzylpenicillin 1.8 – 2.8 gm iv 6 hourly if endocardits or cyanotic heart disease.
– Otherwise Cefuroxime 1.5 gm 8 hourly
Plus
Meteronidazole 500 mg 8 hourly.

18. Idiopathic intracranial hypertension
Management:
1. Weigh reducing diet
2. Avoid any precipitating condition or medication
3. Carbonic anhydrase inhibitor-Acetazolamide
4. Repeated LP
5. Optic nerve fenestration or lumbo-peritoneal shunt if
-Pt. failing to respond
-Chronic papilloedema threatens vision.

19. Lumber disc herniation
Management:
1. Back strengthening exercise
2. Early mobilization
3. Analgesic
4. Inj. Of local anaesthetic agent or corticosteroid, if symptoms due to ligamentus injury or joint dysfunction
5. Surgery
-No response to conservative treatment
-progressive neurological deficits develops
-Central disc herniation with bilateral symptoms & signs & distrubnance of sphincter function require urgent surgical decompression.

20. Fascial nerve palsy
Management:
1. Artificial tear & ointment
2. Eye should be tapped shut overnight
3. Prednisolone 40-60 mg daily for 7 days (should be started with in 72 hours).

21. Guillain-Barre Syndrome
Management:
1. Regular monitoring of the pt. with respiratory function, VC & ABG
2. Artificial ventilation if VC 15 mg/dl
c) Prolonged prothrombin time
d) Co-morbidities- like DM, IHD
Criteria of hospital discharge-
a) Substantial symptomatic improvement
b) A significant downward trend in the serum aminotransferase and bilirubin values and
c) A return to normal of the PT
d) Mild aminotransferase elevations should not be considered contraindications to the gradual resumption of normal activity.
( Ref: Harrison’s principle of Internal Medicine + CMDT 2010)

3. Acute liver failure
Hyperacute liver failure- if jaundice to encephalopathy time 2gm/dl in 24 hours).
5. Close monitoring of the pt. with Pulse, BP, and urine out put and Hb%.
6. If bleeding continues then Therapeutic Endoscopy.
Tips
 A systolic blood pressure less than 100 mm Hg identifies a high-risk patient with severe acute bleeding.
 A heart rate over 100 beats/min with a systolic blood pressure over 100 mm Hg signifies moderate acute blood loss.
 A normal systolic blood pressure and heart rate suggest relatively minor hemorrhage.
 In actively bleeding patients, platelets are transfused if the platelet count is under 50,000/mm3 and considered if there is impaired platelet function due to aspirin or clopidogrel use (regardless of the platelet count).
 Uremic patients (who also have dysfunctional platelets) with active bleeding are given three doses of desmopressin (DDAVP), 0.3 mcg/kg intravenously, at 12-hour intervals.
 Fresh frozen plasma is administered for actively bleeding patients with a coagulopathy and an INR > 1.5.
 In the face of massive bleeding, 1 unit of fresh frozen plasma should be given for each 5 units of packed red blood cells transfused.
 Predictor of rebleeding- clinical predictors of increased risk of rebleeding and death include
a. Age > 60 years,
b. Co morbid illnesses,
c. Systolic blood pressure 100 beats/min, and
e. Bright red blood in the nasogastric aspirate or on rectal examination.
Features of active bleeding: Patients with active bleeding manifested by hematemesis or bright red blood on nasogastric aspirate, shock, persistent hemodynamic derangement despite fluid resuscitation, serious co-morbid medical illness, or evidence of advanced liver disease require admission to an intensive care unit (ICU). Urgent Endoscopy should be performed after adequate resuscitation, usually within 12 hours.
(Ref. CMDT 2010)
6. Acute pancreatitis
Diagnostic tool
1. Severe constant upper abdominal pain may radiate to back relieve by sitting and leaning forwards.
2. Fever & vomiting
3. On exam. – Upper abdominal tenderness but no rigidity and rebound tenderness.

Urgent Investigation
1. S. amylase
2. S. lipase ( if Pt. present after 48 hours)
3. ECG
4. USG of whole abdomen
Management
1. NPO TFO
2. O2 inhalation 4-6 L/ min
3. Infusion Normal saline 1000 cc + 5% DNS 1000 cc i/v @ 20 drops/ min stat and daily
4. Antibiotic-Imipenem (500 mg every 8 hours intravenously) and possibly cefuroxime (1.5 g intravenously three times daily, then 250 mg orally twice daily) administered for no more than 14 days
5. Inj. Omeprazole (40mg) 1 vial i/v stat. & daily
6. Inj. Tramadol HCl (100mg/ml) 1 amp. i.m. stat & 8 hourly
7. NG suction if paralytic illus develops
8. Close monitoring of the pt. with Pulse, BP, and urine out put.
N: B:
• If cause of acute pancreatitis is gall stone then Surgery should be performed after 2 weeks of recovery.
• Oral intake of fluid and foods can be resumed when the patient is largely free of pain and has bowel sounds (even if the serum amylase is still elevated).
(Ref. CMDT 2010 + Oxford American Hand book of critical care.)
7. Chronic pancreatitis
Management:
1. Avoidance of alcohol
2. Analgesia with NSAID or Opiate
3. Oral pancreatic enzyme supplement
4. Dietary fat restriction
5. PPI
6. Coeliac plexus neurolysis or minimally invasive thoracoscopic splaniectomy sometimes required.
(Ref: Davidson)
8. Variceal bleeding
Management:
1. NPO TFO
2. Normal saline 1-2 liter
3. Prophylactic antibiotic – Cephalosporin iv
4. PPI
5. Vasopressor (Terlipressin)-2 mg iv 6 hourly until bleeding stops then 1 mg 6 hourly for further 24 hours
6. Endoscopic procedure to stop variceal bleeding
 Band ligation
-Should be repeated 1-2 week until varices are obliterated. Regular follow up endoscopy is required to identify & treatment of any recurrence of varice.
 Ballon tamponade- Sengstaken-Blakemore tube
7. TIPSS- pt. in whom other treatment is not successful & those with good liver function.
8. Oesophageal transection
– When TIPSS is not available
– Bleeding can not be controlled with other therapies.
9. Portal hypertension
Management:
1. Management of variceal bleeding
2. Primary prevention of variceal bleeding
3. Propanolol 80-160 mg daily or nadalol.( administration of these drugs at doses which reduces heart rate 25% has shown to be effective in primary prevention).
4. Secondary prevention- Beta blocker following banding.

10. Alcoholic liver disease
Management:
1. Cessation of alcohol
2. Nutrition
3. Steroid
Indication:
– Severe alcoholic hepatitis, Maddreys discrimination score >32
Contraindication:
i) Existing sepsis
ii) Variceal haemorrhage
If bilirubin has not fallen 7 days after starting therapy in treatment with steroid, then steroid is unlikely to reduce mortality & should be stopped.
4. Pentoxifylline
5. Use in severe alcoholic hepatitis
6. It appears to reduce incidence of hepato-renal failure
7. Its use is not complicated by sepsis.
5. Liver transplantation

11. NAFLD
Management:
1. Reduce BMI
2. Metformine- 1st line treatment in pt. with DM & NAFLD.
Pioglitazone also improve inflammation & fibrosis.

12. Haemochromatosis
Primary
1. Weekly venesection of 500 ml of blood (250 mg of iron) until S. iron is normal; this may take up to 2 year or more. The aim is to reduce ferittin 1000 µg/ L
Asymptomatic disease is also treated by venesection
4. Screening of HCC by USG

13. Wilson’s disease
Management:
1. Penicillamine –most pt. require 1.5 gm/day (1-4gm/day). The dose can be reduce once the disease is in remission.
Treatment should be continued through out the life including pregnancy. Abrupt discontinuation may precipitate acute liver failure
2. Trientrine dihydrochloride 1.2-2.4 gm/day & Zinc 50 mg 8 hourly, if side effects of penicillin occur.
3. Liver transplantation
– In fulminant liver failure
– Advance cirrhosis with liver failure.
4. Siblings & children of pt. with Wilson’s disease must be investigated & treatment should be given to all affected individual even if they are asymptomatic.

14. Autoimmune Hepatitis
Management:
Prednisolone 40 mg daily
– Dose can be reduced as the pt. & LFT improve. Maintainance therapy is required for at least 2 years after LFT have returned to normal & withdrawl of treatment should not be considered unless liver biopsy is also normal.
– Azathioprine 1-1.5 mg/kg/day allows the dose of prednisolone to be reduced.

15. Primary billiary cirrhosis
Diagnostic tools:
1. Female patient
2. Middle age
3. Flactuating jaundice
4. History of itching.
Asymptomatic
Require monitoring on a yearly basis to assess the onset of symptom & also the disease.
Symptomatic
1. UDCA 13-15 mg/kg/day
2. Liver transplantation if
– Liver failure
– Intractable pruritus
3. Pruritus (Cause- up regulation of opoid receptor & increase endogenous opoid)
Managed by
i) Cholestyramine 4-16gm/day, the powder mixed in orange juice then taken before & after breakfast. It is ineffective in complete billiary obstruction.
ii) Alternative treatment
8. Rifampicin 300 mg/day
9. Naltrexone (opoid antagonist) 25 mg/ day up to 300 mg /day
10. Plasmapheresis
11. Liver support device.
4. Fatigue –no treatmnent , exclude depression & Hypothyroidism
5. Supplementation of fat soluble vitamins
6. Bone disease
Replacement of calcium & vit.D3
Bisphosphonate if evidence of Osteoporesis.

16. Acute cholecystitis
Management:
1. NPO
2. Fluid IV
3. Analgesic-moderate pain-NSAID
4. Severe pain-Pethidine
5. Antibiotic-Cephalosporin (cefuroxime), severely ill add Metronidazple.
6. NG aspiration- if persisting vomiting
7. Surgery should be performed after 6 weeks.

Electrolytes imbalance
1. Ward management of Hyponatraemia
In the ward maximum case of hyponatraemia are hypovoluemic hyponatraemia.
Normal Na+ 135- 145 mmol/L
Hyponatraemia if Na+ 125 mmol/L then oral correction
If Na+ is < 125 mmol/L then iv correction.
 1 TSF table salt contain 96 mmol/L Sodium
 1 L Normal saline contain 154 mmol/L Sodium
 500 ml 3% Sodium contain 512 mmol/L Sodium.

Problem: A pt. present with vomiting followed by unconsciousness. His Na+ is 110 mmol/L. How we will correct his Na+?
Total deficiency = (135 – 110) × 50 × 0.6 mmol/L (His weight is 50 kg).
= 750 mmol/L
Daily correction = 750/3
= 250 mmol/L
So, we have to give 1 L of Normal saline and 1 TSF Table salt daily (approximately) for 3 days.

1. Ward management of Hypenatraemia
Choice of type of fluid for replacement
Hypernatremia with hypovolemia
 Hypovolemic patients should receive isotonic (0.9%) saline to restore the volume deficit and to treat the hyperosmolality.
 After adequate volume resuscitation with normal saline, 0.45% saline or 5% dextrose (or both) can be used to replace any remaining free water deficit.
 Milder volume deficits may be treated with 0.45% saline and 5% dextrose.
Hypernatremia with euvolemia
Water ingestion or intravenous 5% dextrose will result in the excretion of excess sodium in the urine. If the glomerular filtration rate (GFR) is decreased, diuretics will increase urinary sodium excretion.
Hypernatremia with hypervolemia
 Treatment includes 5% dextrose solution to reduce hyperosmolality. Loop diuretics may be necessary to promote natriuresis and lower the total body sodium.
 In severe rare cases with kidney disease, hemodialysis may be necessary to correct the excess total body sodium and water.
3. Treatment of hypocalcaemia
Management:
a) In hyperventilation- rebreathing expired air in a paper bag or administer 5% CO2 in oxygen
b) Inj. 20 ml of 10% solution of Calcium gluconate i.v. slowly stat.
Or
Inj. 20 ml of 10% solution of Calcium gluconate i.m. may be given to obtain a prolonged effect.

4. Treatment of severe hypercalcaemia of malignancy
Management:
1. Rehydration with Normal saline as much as 4-6 L/min. (May need monitoring with CVP in old age or renal impairment)
2. Bisphosphonates e.g. Disodium Pamidronate 90 mg i.v. over 4 hours
3. Additional rapid therapy
a) Forced diuresis with saline & Frusemide
b) Prednisolone 40mg daily
c) Calcitonin
d) Haemodialysis
5. Hypokalaemia
Normal K+ is 3.5-5.5 mmol/L
Hypokalaemia if 2.5 mmol/L.
Intravenous potassium is indicated for patients with severe hypokalemia and for those who cannot take oral supplementation & if K+ is 5.5 mmol/L
Management:
1. iv Calcium gluconate 10 ml of 10 % solution
2. Nebulization with Salbutamol solution
3. iv glucose 50 ml of 50 % (in ward we use 25 % glucose 100 ml) plus inj. Actrapid 5 IU.
These 3 are commonly practiced in the ward. Other treatment options-
1. Inj. Iv Sodium bicarbonate
2. iv Frusemide and Normal Saline
3. Ion –exchange resin (e.g. resonium orally or rectally)
4. Dialysis.

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Bone Anatomy


Bone Anatomy

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Introduction:

There are lots of clinical symptoms in elderly patient’s. Among these problems, low back pain is one of the most common and agonizing symptoms, some times that becomes a chronic one. Back pain is considered chronic when there is no relief after months of pain, which requires an accurate diagnosis to determine the treatment that is most likely to help.1

The skeleton is not only an adaptable and well articulated frame, but also a dynamic mineral reserve bank in which the body stores its calcium and phosphorus in a metabolically stable and structurally useful way. In 1993 experts of osteoporosis consensus development conference in Hong Kong define osteoporosis as a metabolic disease characterized by low bone mass and micro architectural deterioration of bone tissue leading to enhanced bone fragility and consequent increase in fracture risk.2 The World Health Organization (WHO) defines osteoporosis as a bone density more than 2.5 standard deviation (SDs) below the young adult mean value (T-score < – 2.5). Values between 1 & 2.5 SDs below the young adult mean are termed “osteopenia”.3

In normal individuals bone mass increases during skeletal growth to reach a peak between the ages of 20 and 25 but fall there after in both sexes.4 Increased sex hormone production at puberty is required for skeletal maturation, which reaches maximum mass and density in early adulthood. Nutrition and life style also play an important role in growth, though genetic factors are the major determinants of peak skeletal mass and density. Peak bone mass is often lower among individuals with a family history of osteoporosis. After the age of 30 to 45, however the resorption and formation process become imbalanced, and resorption exceeds formation.5

Aging is a natural process. Osteoporosis is a major age related disease. Menopause is associated with decline in ovarian production of estrogen. Trabecular or cortical bone loss accelerates in women after natural menopause.

In most cases, osteoporosis remaining a silent disease, until a fracture of femur or lumber vertebra occurs. Its mains clinical significance lies in the predisposition to fracture, particularly of the wrist, vertebra, and proximal femur. It is well known that the development of one osteoporotic fracture markedly increases the relative risk of a second fracture as much as 20 folds.7

As the risk of fracture increases exponentially with age, changing population demographics will increase the burden of disease (currently costing almost 1 billion pound annually in the U.K.). The lifetime risk of hip fracture for white women at age 50 is around 15%, 5% for men, with equal risk around 11-13% for colles’ or vertebral fracture. Of those surviving to 80 years of age, 30% of women and 15% of men will suffer hip fracture.3

Bone strength is closely correlated with bone mineral density (BMD). In recent years, Prospective study have been shown that BMD can predict fracture risk more early than any other conventional investigating modalities.8 It is not possible to learn how strong or weak ones bone are from a blood test or a risk factor quantification. The only way to determine osteoporotic changes in the skeleton is to measure bone density directly, for which Dual energy X-ray absorptiometry (DEXA) bone mineral densitometry is very much useful non-invasive method.9

The prevalence of osteoporosis seems daunting, and the consequences, especially in elderly peoples, appear inevitable, it is still not a high enough health care priority in developing countries like Bangladesh.

The present study was conducted among the elderly patient’s admitted with low back pain to evaluate the frequency of osteoporotic changes in skeleton, and the associated risk factors which could have bearings in prevention and reduction of morbidity & mortality of osteoporosis in Bangladesh.

 

 

 

BONE ANATOMY AND PHYSIOLOGY  

 

Normal skeletal system:

The skeletal system is a vital to life as any organ system because it plays an essential role in mineral homeostasis, houses hematopoietic elements, provides mechanical support for movement, and protects and determines the attributes of body size and shape. The skeletal system is composed of 206 bones that vary in size and shape (trabecular, flat, cuboid), and this diversity is an example of how form reflects function. The bones are interconnected by a variety of joints that allow for a wide range of movement while maintaining stability. 10

 

Bone embryology-

The skeletal system develops from mesenchyme, which is derived from the mesodermal germ layer and from neural crest. Some bones, such as the flat bones of the skull, undergo membranous ossification: that is mesenchyme cells are directly transformed in to osteoblast. In most bones, such as the long bones of the limbs, mesenchyme condenses and form hyaline cartilage models of bones. Ossification centers appear in these cartilage models, and bone gradually ossifies by endochondrial ossification.

The skull consists of the neurocranium and viscero cranium (face). The neurocranium includes a membranaous portion, which forms the cranial vault, and cartilaginous portion (chondrocranium), which form the base of the skull. Neural crest cell from the face, most of the cranial vault, and prechordal part of the chondrocranium (the part that lies rostal to the notochord). Paraxial mesoderm form the remainder of the skull.

Limbs form as buds, along the body wall that appear in the fourth weak Lateral plate mesoderm forms the bones and connective tissue, while muscle cell migrate to the limbs from the somites of the AER regulates limbs out growth and ZPA controls antero posterior patterning.

The vertebral column and ribs develop from the sclerotome compartment of the somites, and the sternum is derived form mesoderm in the ventral body wall. A definitive vertibra is formed by condensation of the caudal half of one sclerotome and fusion with the cranial half of the subjacent sclerotome.11

In endochondral ossification , in which an initial cartilage template is invaded by vascular tissue containing osteoprogenitor cells. The cartilage in them replaced by bone that extends from the centers of ossification situated in the middle and ends of the developing bone. A thin remnant of cartilage remains at each end of the bone during child hood, and is referred to as the growth plate or epiphysis. Growth depends on division of chondrocytes with in the epiphysis. Cell division takes place in the proliferative zone nearest the end of the long bone, and newly formed chondrocytes migrate downwards and enlarge in the hypertropic zone, chondrocyte death ensues and surrounding matrix calcifies before being removed and replaced by mature bone. During puberty, the rise in circulating levels of sex hormones halts cell division in growth plate. The cartilage remnant then disappears as the epiphysis fuse, and longitudinal bone growth ceases. 4

Bone Anatomy & Histology-

Bone is a type of vascularized dense connective tissue with cell embedded in a matrix composed of organic material, mainly collagen fibers, and inorganic salt rich in calcium & phosphate.12

Types of bone-

Gross observation of bone in cross section shows dense areas without cavity-corresponding to compact bone and areas with numerous interconnecting cavities corresponding to cancellous (spongy) bone. Under microscope, however both compact bone and trabeculae separating the cavites of cancellous bone have the same basic histologic structure.

In long bone, the bulbous end called epiphysis, are composed of spongy bone covered by a thin layer of compact bone. The cylindrical part- diaphysis is almost totally composed of compact bone, with a small component of spongy bone on its inner surface around the bone marrow cavity. Short bones usually have a core of spongy bone completely surrounded by compact bone. The flat bone that form the calvaria have two layers of compact bone called plates (table), separated by layer of spongy bone called the diploe. 13  Cortical bone constitute roughly 80% of the adult skeleton and predominates in the shaft of the long bone. 14

Microscopic examination of bone shows two varieties: primary, immature, or woven bone and secondary, mature or lamellar bone. Primary bone is the first bone tissue to appear in embryonic development and in fracture repair and other repair processed, it is characterized by random deposition of tissue collagen fibers, in contrast to the organized lamellar deposition of collagen in secondary bone.

Primary bone tissue –

Primary bone tissue is usually temporary and is replaced in adults by secondary bone tissue except in a very few places in the body. e.g. near the suture of the flat bones of the skull, in tooth sockets and in the insersion of some tendons.

Secondary bone tissue –

Secondary bone tissue is the variety usually found in adult. It characteristically shows collagen fibers arranged in lamellae. The whole complex of concentric lamellae of bone surroundings a canal containing blood vessels, nerves and loose connective tissue is called Haversian system or osteon. In compact bone lamellae exhibit outer circumferential lamellae.

Each Haversian system is a long, often bifurcated cylinder parallel to the long axis of the disphysis. It consists of a central canal surrounded by 4-22 concentric lamellae. The Haversian canals communicate with the marrow cavity, the periosteum and one another through transverse or oblique Volkmann’s canal. Volkmann’s canals do not have concentric lamellae; instead, they perforate the lamellae. 13

Bone marrow-

The medullary cavity in long bones and the interstices of cancellous bone are filled with red or yellow marrow. At birth all the marrow of all the bones is red, active haemopoiesis is going on every where. As age advanced the red marrow atrophies and is replaced by yellow, fatty marrow with no power of haemopoiesis. This change begins in the distal parts of the limbs and gradually progresses proximally. By young adult life there is little red marrow remaining in the limb bones, and that only in their cancellous ends; ribs, sternum, vertebrae and skull bones contain red marrow throughout life.12

Periosteum & endosteum-

 

The outer surface of the bones is covered with a thick layer of vascular fibrous tissue. This layer is the periosteum and nutrition of the underlying bone substance depends on the integrity of its blood vessels. The periosteum is osteogenic, its deeper cell differentiating into osteoblast when required. In the growing individual new bone is laid down under the periosteum, and even after growth has ceased the periosteum retains the power to produce new bone when it is needed. eg. in the repair of fracture. The periosteum is united to the underlying bone by collagen (Sharpey’s) fibers, particularly strongly over the attachment of the tendon and ligaments. Periosteum does not, of course, cover the articulating surface of the bones in synovial joints, it is reflected from the articular margins to join the capsule of the joint. The single layered endosteum that lines inner bone surface (marrow cavity and vascular canals) is also osteogenic and contributes to new bone formation.4

Composition of bone –

Cellular component – bone is composed of cellular and non cellular components. The three most specialized cell types necessary for metabolic activities of bone are osteoblasts, osteoclasts and osteocytes. 14

Osteoblasts – are derived from pleuripotential bone marrow stem cells that are capable of differentiation into fibroblastic, adipocytic, or chondrocytic / osteoblastic lineages. A critical signal for osteoblastic differentiation is provided by expression of the transcription factor cbfa-1. When dormant osteoblasts  ( bone-lining cell) on the bone surface are activated to mature osteoblasts, they synthesize uncalcified bone matrix, or osteoid, and then  promote its subsequent mineralization. Osteoblasts express specific receptor  for parathyroid hormone (PTH), 1, 25 – dihydroxy vitamin D (1,25 [OH]2 D), insulin like growth factor 1, insulin, interleukin-1, interleukin-6, interleukin-11, thyroid hormone, estrogen, androgen, and glucocorticoids.14 Some osteoblasts  are gradually surrounded by newly formed matrix and become osteocyte. During this process a space called lacuna is formed. Lacunae are occupied by osteocytes and their extension. 13

Osteocytes – Osteocytes which derive from osteoblasts, lie in the lacunae situated between lamellae of matrix. Only one osteocyte is found in each lacuna.5  They communicate with each other and surface cells via an intricate network of tunnels through the matrix known as canaliculi. The osteocytic cell processes traverse the canaliculi, and their contracts along gap junctions allow the transfer of surface membrane potentials and substrates. The large number of osteocytic processes and their distribution through out bone tissue enable them to be the prime cell in several biological processes. Osteocytes  also have the capability to detect mechanical forces and translate them in to biologic activity, including the release of chemical mediators by signal transduction pathways involving cyclic adenosine monophosphate.15

Osteoclasts – The osteoclast is the cell responsible for bone resorption is derived from haematopoietic progenitor cell that also give rise to monocytes and macrophages. Cytokines crucial for osteoclast differentiation and maturation include interleukin (IL)-1, IL-3, IL-6, IL-11, tumor necrosis factor (TNF), granulocyte – macrophage colony stimulation factor (GM-CSF), and macrophage colony stimulating factor (M-CSF).16  Osteoclasts and their progenitors appear to lack receptor for PTH, various cytokines, vitamin D, and other hormones that regulate osteoclastogenesis.17 Osteoclast are very large, branched motile cells.  Dilated portion of the cell body contain from 5 to 50 (or more) nuclei. In areas of bone undergoing resorption, osteoclasts lie within Howship’s lacunae. In active osteoclasts, the surface facing bone matrix is folded in to irregular often subdivided projections, forming a ruffled border. Surrounding the ruffled border is a cytoplasmic zone –  the clear zone that is devoid of organelles, yet rich in actin microfilaments. This zone is a site of adhesion of osteoclast to the bone matrix and creates a micro environment in which bone resorption occurs. The osteoclast secretes collagenase and other enzymes and pumps protons in to a sub cellular pocket, promoting the localized digestion of collagen and dissolving calcium salt crystals. 18

Non cellular components :- The non cellular components of bone include the organic matrix and inorganic matrix, which comprise roughly one third and two third respectively of total bone mass.14  The organic matter is mainly protein.19 Type -1  collagen, the most abundant structural protein in bone, make up 90% of the organic matrix. Other proteins in bone include small amounts of other collagens and a host of non collagenous proteins, including osteonectin, osteocalcin, osteopontin, fibronectin, thrombospondin, bone sialo protein, proteoglycans, and serum protein.20 The non collagenous protein of bone are bound to the matrix and grouped according to their functions as adhesion protein, calcium binding proteins, mineralization proteins, enzymes, cytokines, and growth factors.21 Of these only osteocalcin is unique to bone. It is measurable in the serum and used as a sensitive and specific marker for osteoblast activity.22 Osteonectin, a bone specific protein linking mineral to collagen.23   Inorganic matter represent about 50% of the dry weight of bone matrix. Calcium and phosphorus are especially abundant, but bicarbonate, citrate, magnesium, potassium, and sodium are also found. Calcium and phosphorus form hydroxyapatite crystals with the composition Ca10 (PO4)6(OH)2. Significant quantities of amorphous (non crystalline) calcium phosphate are also present. In electron micrographs, hydroxyapatite crystals of bone appear as pales that lie along side the collagen fibrils but are surrounded by ground substance. The surface ions of hydroxyapatite are hydrated, and a layer of water and ions forms around the crystal. This layer , the hydration shell, facilitates the exchange of ions between the crystal and the body fluid.24

Bone modeling and remodeling: – Osteoblasts and osteoclasts act in coordination and are considered the functional unit of bone known as the basic multicellular unit. The process of bone formation and resorption are tightly coupled, and their balance determine skeletal mass at any point in time.16  Throughout the life, bone is being constantly reabsorbed and new bone is being formed. The calcium in bone turns over at a rate of 100% per year in infants and 18% per year in adults. About 5% of bone mass is being remodeled in human skeleton at any one time. The renewal rate for bone is about 4% per year for compact bone and 20% per year for trabecular bone.25 In the formation and maintenance of skeletal system, osteoblast provides much of the local control because it not only produce bone matrix, but also plays an important role in mediating osteoclast activity. Many of the primary stimulators of the bone resorption, such as parathyroid hormone, parathyroid hormone- related protein (PHRP), IL-1 and TNF have minimal or no direct effect on osteoclast. The osteoblast has receptors for these substances, and evidence suggests that once the osteoblast receives the appropriate signals it release a soluble mediator that induces osteoclast bone resorption. The cytokine and growth factor, especially TGF-β, released from the matrix during its digestion act as a feedback loop and trigger the formation and activation of osteoblast to synthesize and deposit an equivalent amount of new bone in the resorption pit1. Osteoclast mediated resorption of bone takes place in scalloped spaces ( Howship’s lacunae) where the osteoclasts are attached through a specific αv β3 integrin to components of the bone matrix such as osteopontin. The osteoclast form a tight seal to the underlining matrix and secrets protons, chloride, and proteinases in to a confined space linked to an extra cellular lysosome. The active osteoclast surface forms a ruffled border that contains a specialized proton-pump ATPase, which secretes acid and solubilizes the mineral phase. Carbonic anhydrase with in the osteoclast generates the needed protons. The bone matrix is reabsorbed in the acid environment adjacent to the ruffled border by proteases that act as low PH,  such as cathepsin-k.

New bone, whether formed in infants or in adult during repair, has relatively high ratio of cell to matrix and is characterized by coarse fiber bundle of collagen that are interlaced and randomly dispersed (woven bone). In adult, the more mature bone is organized with fiber bundles regularly arranged in parallel or concentric sheets (lamellar bone). In long bones, deposition of lamellar bone in a concentric arrangement around blood vessels forms the Haversian system. The growth in length of bones is dependent on proliferation of cartilage cells and on the endochondrial sequence at the growth plate. Growth in width and thickness is accomplished by formation of bone at the periosteal surface and by resorption at the endosteal surface, with the rate of formation exceeding that of resorption. In adult, after the growth plate close, growth in length and endochondral bone formation cease, except for some activity in the cartilage cells beneath the articular surface.

Remodeling of bone occurs along lines of force generated by mechanical stress. This signal from these mechanical stresses is sensed by osteocytes, which transmit signals to osteoclasts or osteoblast or their precursors. A bowing deformity increase new bone formation at concave surface and resorption at convex surface, seemingly designed to produce the strongest mechanical structure. Bone plasticity reflects the interaction of cells with each other and with the environment. The product of osteoblast and osteoclast activity can assist in the diagnosis and management of bone disease. Osteoblast activity can be assessed by measuring serum bone specific alkaline phosphatase.  Similarly, osteocalcin, a protein secreted from osteoblast, is made virtually only by osteoblast. Osteoclast, activity can be assessed by measurement of products of collagen degradation.

The cycle of bone remodeling is carried out by the basic multicellular unit (BMU), comprising a group of osteoclasts and osteoblasts. In cortical bone , the BMUs tunnel through the tissue, where as in cancellous bone, they move across the trabecular surface. The process of bone remodeling is initiated by contraction of the lining cell and recruitment of osteoclast precursors. These precursors fuse to form multinucleated, active osteoplast that mediate bone resorption. Osteoclast adheres to bone and subsequently remove it by acidification and proteolytic digestion. As the BMU advances, osteoclast leave the resorption site and osteoblast move into cover the excavated area and begin the process of new bone formation by secreting osteoid, which is eventually mineralized in to new bone. After osteoid mineralization, osteoblast flatten and form a layer of lining cells over new bone.5. On completing the cycle (about 120 days), remodeling is balanced if there has been no net change in the amount of bone.3

Blood and nerve supply of the bone:-

One or two nutrient arteries enter the shaft of a long bone obliquely and usually directed away from the growing end. Within the medullary cavity they divided into ascending and descending branches. Near the ends of bone, they are joined by branches from the neighboring systemic vessels and from periarticular vascular arcades. Cortical bone receives blood supply from periosteum and from muscular vessels at their attachment. Vein are numerous and large in the cancellous red marrow bone (e.g. the basi vertebral veins) Lymphatics are present, but scanty; they drain to the regional lymph nodes of the part.

Subcutaneous periosteum is supplied by the nerves of the overlying skin. In deeper parts of the local nerves, usually the branches to nearby muscle provide the supply. Periosteum in all parts of the body is very sensitive. Other nerves, probably vasomotor in function, accompany nutrient vessels into bone.

 

Peak bone mass:-

Peak bone mass (PBM) can be defined as the amount of bony tissue present at the end of the skeletal maturation. The precise age at which peak bone mineral density is a acquired is still unknown and may be site dependent. In general, accepte that up to 90% of peak bone mass is acquired by age 18 in girl and by age 20 in boys, which makes youth the best time to invest in bone health. There after, bone mass increase slightly during the third decade of life and reaches its peak around age 30 years. So, peak bone mass is achieved during adulthood. Its magnitude is determined largely by hereditary factors, especially the allele for the vitamin D receptor molecule. Physical activity, muscle strength, diet, and hormone state however all contribute.26. Factors that may affect peak bone mass- sex, race, genetic factors, gonadal steroids, growth hormone, timing of puberty, calcium intake, exercise, etc.14

Sex and race: White woman have lighter skeletons, than white man or black women, where as black men have the heaviest skeleton.27 The skeleton of Asians appear to be intermediate between those of blacks and whites. In all the three races, women have lower peak bone mass than men. Because initial bone mass is an important determinant of bone mass latter of life, these difference may partially explain observed racial and sexual difference in the incidence of osteoporoses and fractures. However, such generalization should not obscure the fact that some white have high   bone mass, where as individual non-whites may have low bone mass and fracture. Moreover, there seem to be exceptions to the general pattern: Hispanics appear to have hip fracture rate that are even lower than American black. Whereas the Bantu people of South Africa have extremely low fracture rate but also low bone mass. 28

 

Genetic factors: The impact of genetic factors on bone density has been demonstrated in several ways. For example, bone density is lower in daughters of women with osteoporosis than in the daughters of women without osteoporosis. Moreover, the concordance of bone density is much higher among monozygotic twins than dizygotic twins.29 Several genes, including the vitamin D receptor gene, the genes encoding type-1 procollagen, and the estrogen receptor gene, have been implicated in the pathogenesis of osteoporosis, but no conclusive genetic linkages have been demonstrated.14 The type of vitamin D receptor molecule that is inherited accounts for approximately 75% of the maximal peak mass achieved. Polymorphism in the vitamin D receptor or molecule is associated with either a highest or lower maximal bone mass.

Nutrition: Calcium is essential for healthy bone development, and increasing the calcium intake in children and adolescent increase bone growth. Calcium deficiency in young people can account for a 5 to 10 percent different in peak bone mass and can increase the risk for hip fracture latter in life. The skeleton appears to be more responsive to calcium supplementation before the onset of puberty than after puberty has started. It has been shown that adolescent girls (but not boys) have insufficient calcium intake levels in the diet. The calcium deficiency occurs during a period of rapid bone growth, stunting the peak bone mass ultimately achieved; thus, these individual are at greater risk of developing osteoporosis.10 Milk and other dairy products are the most abundant source of calcium. In addition to calcium, protein plays a key role in bone mass acquisition. Besides adequate amount of vitamins C,D,K and minerals such as magnesium, zinc, are also important for bone health. Adolescents with average nutritional calcium intake bellow 1000 mg/day for boys and 850mg/day for girls will probably not reach optimal bone mass. The national osteoporosis foundation describes bone mass as analogous to a bank account in to which, during persons childhood, adolescents, and early adult hood, new bone ‘deposits’ are made to the skeleton faster than old bone is ‘withdrawn’. After the age 30, the rate of withdrawal exceeds the rate of deposit; therefore, establishing healthy bone mass in childhood and early adult hood is crucial.30

Physical activity: girls and boys and young adults who exercise regularly generally achieve greater peak bone mass than those who do not. Physical activity is a determinant of peak bone mass31. Sufficient exercise during childhood and adolescent, particularly the pre pubertal years, is more effective for increasing bone mass and strength than exercise in adulthood. 32  Whether benefits achieved before puberty are sustained into adult hood remains to be determined by appropriate longitudinal studies. In healthy adults, vigorous exercise programs and resistance training of moderate to high intensity can preserve bone density33. Weight bearing physical activity is important for maintenance of bone mass, and activities that increase muscles strength are also safe and beneficial, particularly for bones of the upper limb.34 An optimal, exercise program should include activities for increasing strength, balance, flexibility and coordination of the upper and lower limbs and trunk. To influence BMD, physical activity undertaken 2-3 times per week and maintained for 20 to 60 minutes has been found to be helpful. Training intensity between 70 to 80 % of the functional capacity, or maximum strength can preserve bone density, but remain to be determined whether these are optimal for influencing BMD.35 Low intensity exercise such as walking has minimal effect on BMD.36 In adults, any skeletal benefit accrued from a exercise program will not be sustained, if an individual returns to a secondary life style.32

 

Hormonal factor: sex hormone, including estrogen and testosterone, are essential for the development of bone mass. Beside growth hormone, thyroid hormone, PTH and calcitonin also play crucial roles. The pubertal growth spurt is related to the production of estrogen- the major female hormone. A certain content of body fat may be required to induce the onset of puberty. Adipose tissue mass is correlated tightly with whole body density in women but not in man. This fact brings into focus the notion that dietary indiscretions can have a profound effect on the overall process of fat production, menarche and estrogen protection. Women with eating disorders such as anorexia nervosa or bulimia have diminished body fat as well as abnormalities in menstrual function. These women develop insufficient bone mass either as a result of  loss of bone or as a result of deficient formation.37,38


PATHOLOGICAL BASIS OF LOW BONE DENSITY

 

Definition of osteoporosis: The word osteoporosis is from the Greek osteon for “bone” & porous for “pore” or “passage”.  Indeed osteoporosis literally makes bone more porous. Osteoporosis is a generic term referring to a state of decreased mass per unit volume (density) of normally mineralized bone. Clinically, osteoporosis is synonymous with low bone density. In 1991, a panel of experts arrived at a consensus definition of osteoporosis as a systemic disease characterized by low bone mass and micro architectural  deterioration of the skeleton, leading to enhance bone fragility and increased fracture risk39 This definition encompasses the two important skeletal changes in osteoporosis namely, diminished bone mass and diminished bone quality. However, this is not a practical definition for patient care, because the only means of assessing bone quality (other than fragility fracture) is histologic study of bone biopsy specimens.

The short comings of this definition led the World Health Organization (WHO) to convene a new panel of experts to define just what is meant by the term “low bone mass”40. The group began its deliberations by agreeing on two basic concepts. First, they assumed that fracture risk must be lowest when BMD is highest – sometimes between ages 20 and 40 in healthy people. The relative risk for fracture in this reference group was arbitrarily set at 1.0. Second, the expert panel agreed, on the basis of several studies41 that relative risk for fracture double for each standard deviation (SD) decrement in BMD. Thus, in patient’s in whom BMD is 1SD below the mean for peak bone mass, the relative risk is 2.0. If the value is 2 SD below the mean, the risk double 4.0. The relationship between BMD and fracture risk is continuous, and there is no fracture threshold. With these concepts in mind, the WHO panel developed the following working definitions:-

v         Normal is defined as BMD less than or equal to 1.0 SD below the mean for peak bone mass.

v         Low bone mass (osteopenia) is defined as more than 1.0 but less than or equal to 2.5 SD below the mean.

v         Osteoporosis is defined as more than 2.5 SD below the mean.

These definitions were developed for epidemiologic studies but have been adapted as “Diagnostic Criteria” in much the same way that arbitrarily selected cut points are used to define hypercholesterolemia and hypertension.

 

Prevalence of osteoporosis:– Women of all races and ethnic origin are susceptible to osteoporosis and fracture. But whites, especially of northern European descent, and Asian are at increase risk for osteoporosis., Osteoporosis is not a just a disease of women, and there are compelling reasons for men to join the fight for better access to screening and more equitable reimbursements for screening. Two million of the total 10 million individuals diagnosed with osteoporosis in 1995 were male. Another 3 million men are at risk. Studies completed in 1994 showed that a 50 year old man has a remaining life time risk of osteoporotic fracture of 13% and experiencing such a fracture has more direct implication for man than women: while the rate of hip fracture is two to three times higher in women then men, the one year mortality following a hip fracture is nearly twice as high for men as for women. The statistics paint a chilling portrait of the future for men suffering from osteoporosis. Each year, men suffer 1/3 of all hip fracture that occurs, and 1/3 of these men will not survive more than a year. Over 100,000 men have a hip fracture every year, 1/3 of these men will die of complication from their hip fracture within a year. Of the survivors, more then a quarter will not walk again without assistance. In addition to hip fracture, men also experience painful and debilitating fracture of the spine, wrist, and other bones due to osteoporosis. In type 1 and type 2 osteoporosis, women are affected more than the men, with female to male ratio of 6:2 and 2:1 respectively. In secondary osteoporosis, both sexes are equally affected. The peak incidence of type 1 osteoporosis is in people aged 50 to 70 years, and peak incidence for type 2 is in people aged 70 years or older. Secondary osteoporosis can occur in persons of any age. Accordingly to US census bureau, international database, 2004, 1.45 crore people among 14.13 crore population of Bangladesh are suffering from osteoporosis, which is 10.26 percent of total population. 6.62% patient’s of osteoporosis are under diagnosed world wide and in Bangladesh 0.93 crore are undiagnosed which is 64.13 % of the total osteoporotic patient. Recent National Health and Nutrition Examination Survey (NHANES III, 1988-1994)42 review dual energy x-ray absorptiometry measurements of femoral BMD in a non-Hispanic white population. This snapshot determined peak bone mass in 382 men and 409 women 20 to 29 years of age. According to the WHO criteria, 13% to 18% of women aged 50 or older had osteoporosis, another 37 % to 50% had low bone mass. From the most recent US census data, this translates to 4 to 6 million women with osteoporosis and 13 to 17 million with low bone mass; in men over age 50, the corresponding members are 1 to 2 million with osteoporosis and 4 to 9 million with low bone mass.43 The definition of low bone mass includes persons in whom risk of fracture is at least double that for healthy young adults. Therefore, about 22 million to 34 million Americans aged 50 are currently at increased risk for fracture.

Costs of care: Complication of osteoporosis are major community health problem in terms of both people and healthcare dollars. The estimated cost fractures complicating osteoporosis in 1995 was a staggering $13.8 billion.44  Most of this money ($10.3 billion, or 75%) was spent for treatment of fracture in white women.45 These investigation confirmed the well recognized observation that osteoporosis is principally a problem of ageing white women. Nonetheless, a full 23% of health care expenditures for this disease were incurred by white men (18%) and non-white women (5%). Even the group least susceptible to osteoporotic fracture, non-white men, required $200 million in osteoporosis care in 1995. Most money (63%) went for care of hip fracture, but 37% dollars were spent on other types of fractures. While every effort was made to capture relevant data, fractures other than hip fractures were probably under reported, because most of them do not require hospital admission44.

Morbidity and mortality from hip fractures: Some studies have documented substantial in hospital mortality in patient’s with hip fracture; estimates range from 4% to 11.5%.46 Other studies have shown that this mortality rate remains high for several years after a fracture. In one report, excess in death per 100 cases was 14 during the 5 years after fracture to patient’s who had little functional impairment or low co morbidities before fracture. The fact that the patient’s general health status is important in assessing the risk of mortality after hip fracture is obvious.47

In one study, the 3month mortality was 13.5%, compared with 2.6% in a match Cohort. However, if the fracture occurred in an institution the 3 months mortality was 23%, compared with 10% for institutionalized patient’s who did not sustain a hip fracture. 48

Serving a hip facture is not the end of the study. A Mayo clinic study of men who do had broken hips showed that more than half needed to be discharged to nursing homes. Among those who survived, 97% still resided in nursing homes or in for terminal care facilities or required home health care 1 year later. Only 41% of these men had recovered their pre fracture functional status after 1 year.49 Given this high morbidity and mortality, a great deal of attention has been paid to factors that influence the out comes from hip fractures. The findings are predictable: out come are poorest for patient’s over age 85 years, these with coexisting functional problems, and those with scores of 3 or 4 on the American society of anesthesiologists rating of operative risk. For as yet in unexplained reasons, being male is predictor of unexplained hip fractures that carry a poor prognosis.

Most in hospital death (65%) result from cardiovascular events, and a history of congestive heart failure, angina, or chronic pulmonary obstructive disease contributes substantially to mortality. According to one study, postoperative aspirin administration reduced the risk of dying in hospital by 75%, an important observation that requires additional verification.

In another study of relatively healthily population sustaining hip fracture in their own homes and discharged to their homes, gait and balance were reviewed 2 months after fracture. A 17% increase in 2year mortality was shown for each unit decrease in the balance score (range, 0 to 17), but poor gait were not associated with an increased likelihood of readmission to hospital. However, both poor balance and poor gait ware associated with a substantially increased likelihood of nursing home admission.50

Pathogenesis of osteoporosis:

Skeletal fragility can result from: (a) failure to produce a skeleton of optimal mass and strength during growth; (b) excessive bone resorption resulting in decreased bone mass and micro architectural deterioration of skeleton; (c) an inadequate formation response to increased resorption during bone remodeling. In addition, the incidence of fragility fractures, particularly of the hip and wrist, is further determined by the frequency and direction of falls.

To understand how excursive bone resorption and inadequate formation result in skeletal fragility, it is necessary to understand the process of bone remodeling, which is the major activity of bone cell in the adult skeleton. The bone remodeling or bone mullicellular unit (BMUs) described many years ago by Frost and others51 can occurs either on the surface of trabecular bone as irregular Howship lacunae or in cortical bone as relatively uniform cylindrical Haversian systems. The process begins with the activation of hematopoietic precursors to become osteoclasts, which normally requires an interacuion with cells of the osteoblastic lineage. Because the resorption and reversal phases of bone remodeling are short and the period required for osteoblastic replacement of the bone is long any increase in the rate of bone remodeling will result in a loss of bone mass. Moreover, the larger member of unfilled Howship lacunae and Haversian canals will further weaken the bone. Excessive resorption can also result in complete loss of trabecular structures, so that there is no template for bone formation. Thus, there are multiple ways in which an increase in osteoclastic resorption can result in skeletal fragility. However, high rate of resorption are not always associated with bone loss; for example, during the pubertal growth spurt. Hence an inadequate formation response during remodeling is an essential component of the pathogenesis of osteoporosis.

Central role of estrogen: The concept that estrogen deficiency is critical to the pathogenesis of osteoporosis was based initially on the fact that post menopausal women, whose estrogen level naturally decline, are at highest risk for developing the disease. Morphologic studies and measurement of certain biochemical markers have indicated that bone remodeling is accelerated at the menopause as both markers of resorption and formation increased.52 Hence, contrary to Albright’s original hypothesis, an increase in bone resorption, and not impaired bone formation, appears to be the driving force for bone loss in the setting of estrogen deficiency. But rapid and continuous bone loss that occurs for several years after the menopause must indicate an impaired bone formation response, since in younger individuals going through the pubertal growth spurt, even faster rates of bone resorption can be associated with an increase in bone mass. However, the increased bone formation that normally occurs in response to mechanical loading is diminished is estrogen deficiency, suggesting estrogen is both anticatabolic and anabolic.53

Estrogen deficiency continues to play a role in bone loss in women in their 70 s and 80s, as evidenced by the fact that estrogen treatment rapidly reduces bone breakdown in these older women. More over, recent studies in humans have shown that the level of estrogen required to maintain relatively normal bone remodeling in older post menopausal women is lower than that required to stimulate classic target tissue such as the breast and uterus. Fracture risk is inversely related to estrogen level in post menopausal women, and as little as one-quarter of the dose of estrogen that stimulate the breast and uterus is sufficient to decrease bone resorption and increase bone mass in older women. This greater sensitivity of the skeleton may be age related.54

Estrogen is critical for epiphyseal closure in puberty in both sexes and regulates bone turnover in men as well women. In fact, estrogen has a greater effect than androgen in inhibiting bone resorption in men; although androgen may still play a role.55 Estrogen may also be important in the acquisition of peak bone mass in men. Moreover, osteoporosis in older men is more closely associated with low estrogen than with low androgen levels.56

Estrogen deficiency increases and estrogen treatment decreases, the rate of bone remodeling, as well as the amount of bone lost with each remodeling cycle. Studies in animal models and in cell culture have suggested that this involves multiple sites of estrogen action, not only on the cells of the BMU but on other marrow cells. Estrogen acts through 2 receptors: Estrogen receptor  (ER) and ER . ER appears to the primary mediator of estrogen’s actions on the skeleton.53 Osteoblast do express ER but actions of ER agonist on bone are less clear. Some study suggest that the effect of estrogen signaling through ER and ER are in opposition, while other study suggest that activation of this two receptors has similar effects on bone.57

Single nucleotide polymorphisms (SNPs) of ER may affect bone fragility. In largest study to date, 1 of the SNPs for this receptor was associated with a significant reduction in fracture risk, independent of bone mineral density (BMD). Other studies have suggested that SNPs of ER can affect BMD and rates of bone loss as well as fracture risk in both men and women.58

An orphan nuclear receptor, estrogen receptor related receptor  (ERR), with sequence homology to ER and ERR, is also present in bone cells.59 Despite its inability to bind estrogens, this receptor may interact with ER and ER or act directly to alter bone cells function. A regularly variant of the gene encoding ERR was recently found to be associated with a significant difference between lumbar spine and femoral neck BMD in premenopausal women.60

Sex hormone-binding globulin (SHBG), the major protein for sex steroids in plasma, may not only alter the bioavailability of estrogen to hormone-responsive tissues but also affect its entry in to cells. Epidemiologic studies suggest that SHBG may have a effect on bone loss and fracture risk independent of the effect as a binding protein.61

While estrogen can act on cells of the osteoblastic lineage, its effect on bone may also be dependent on actions on cell of the hemotopoietic lineage, including osteoclast precursors, mature osteoclasts and lymphocytes. Local cytokines and growth factors may mediate these effects. The effects of estrogen on cytokine production may be mediated by T cells.  A direct effect of estrogen in accelerating osteoclast apoptosis has been attributed to increased TGF- production.62

Calcium, Vitamin D, and parathyroid hormone:

The concept that osteoporosis is due to primarily to calcium deficiency particularly in the elderly, was initially put forward as a counter proposal to Albright’s estrogen deficiency theory. Decreased calcium intake, impaired intestinal absorption of calcium, due to aging or disease, as well as vitamin D deficiency can result in secondary hyperparathyroidism.  The active hormonal form, 1, 25, dihydroxy vitamin D (calcitriol), is not only necessary for optimal intestinal absorption of calcium and phosphorus, but exerts atonic inhibitory effect on parathyroid hormone (PTH) synthesis, so that there are dual path ways that can lead to secondary hyperparathyroidism.63 Vitamin D deficiency and secondary hyperparathyroidism can contribute not only to accelerated bone loss and increasing fragility, but also to neuromuscular impairment that can increase the risk of fall.64 Clinical trial involving older individuals at high risk for calcium and vitamin D deficiency indicate that supplementation of both can reverse secondary hyperparathyroidism, decrease bone resorption, increase bone mass, decrease fracture rate, and even decrease the frequency of falling.63 However, in a large recent study, calcium and vitamin D supplementation did not reduce fracture incidence significantly, perhaps because this population was less deficient in Vitamin D.65

Polymorphisms of the VDR have been studied extensively, but the results have been variable. This may be in part because the effect of a given polymorphism in this receptor is dependent on an interaction with the environment, particularly with calcium.66 VDR polymorphism are also associated with deficiency in the response to therapy with calcitriol.67 There is also evidence for an effect on fracture risk independent on bone density and bone turnover, which might be due to an alteration in the frequency of falls.68

Secondary hyperparathyroidism present when there is relative insufficiency of vitamin D, that is, where the level of circulating form-25- hydroxy vitamin D- fall below 30ng/ml, suggesting that the target for vitamin D supplementation should be at this level or higher.69 The seasonal decrease in fractures, independent of the increase in rate of falls.70 In addition, increase PTH level are associated with increased mortality in the frail elderly, independent of bone mass and vitamin D status. The precise mechanism underlying this relationship have not yet been determined, but the risk of cardiovascular death was increased.71 Polymorphism of the calcium sensing receptor, which regulates calcium secretion by suppression of PTH translation and PTH secretion, have not yet been associated with any alteration in bone phenotype.

Receptor activator of NF-, its ligand, and osteoprotegerin:

The concept that stimulation of bone resorption requires an interaction between cells of the osteoblastic and osteoclastic lineages was put forward many years ago, but its molecular mechanism was only identified recently.72 Three members of the TNF and TNF receptor super family are involved; Osteoblast produce RANKL, a ligand for receptor activation of NF-B (RANK) on haemopoietic cells, which activates the differentiation of osteoclasts and maintain their function. Osteoblasts also produce and secrete osteoprotegerin (OPG), a decoy receptor that can block RANKL/RANK interactions. Stimulators of bone resorption have been found to increase RANKL expression in osteoblasts, and some also decrease OPG expression.73 Bone cell appear to express the membrane-bound form of RANKL, and thus, osteoblasts must physically interact with osteoclasts precursors in order to activate RANK. Soluble RANK can be produced by activated T lymphocytes and is as active as membrane-bound RANKL in binding to RANK.74 Recently a monoclonal antibody against RANKL was shown to produce prolonged inhibition of bone resorption in post menopausal women.75 It was also shown that RANKL level were increased on the surface of bone marrow cells for early post menopausal women who were estrogen deficient.76 However, it has been difficult to demonstrate a role for OPG deficiency in the pathogenesis of osteoporosis. Since OPG levels are not consistently altered, OPG level increase with age, and it is possible that OPG production rises as a homeostatic response to limit the bone loss that occurs with an increase in other bone resorbing factors.77 Polymorphism in the OPG gene have been associated with osteoporotic fracture and differences in BMD.78 OPG Polymorphisms have also been linked to coronary artery disease.79

The RANKL/RANK interaction is critical for both differentiation and maintenance of osteoclast activity and hence represents a final common pathway for any pathogenetic factor in osteoporosis that acts by increasing bone resorption, while it is assumed that cells of the stromal / osteoblastic lineage are the major source of RANKL in physiologic bone remodeling, other cells may act as a source of RANKL in pathologic states; for example, T cell production may play a role in osteoporosis as well as inflammatory bone loss. 80

Recently a second system that might affect the interaction between osteoblast  and osteoclast has been identified.81 This involves the membrane adapter DNAX-activating protein 12 and Fc receptor common chain. Deletion of this molecule results in severe osteoporosis in mice. The molecules are involved in signaling through the immunorecptor tyrosine-based activation motif (ITAM). Co-operation between RANKL and ITAM signaling may be essential for osteoclastogenesis, for which nuclear factor of activated T cells (NFAT) is the master transcription factor.

 

Genes determining osteoblast differentiation and function:

Recent discoveries of signal transduction pathways and transcription factors critical for osteoblast differentiation and function have opened up new approaches to understanding the pathogenesis of osteoporosis. Gene deletion studies have shown that absence of runt-related transcription factor 2 (Runx2) or a downstream factor, osterix, are critical for osteoblast differentiation.82 Interestingly, over expression of Runx2 leads to a decrease in bone mass. 83 A role for polymorphism of these transcription factors in osteoporosis had not yet been identified.

The recent identification of the critical role for the Wnt signaling pathway in regulating osteoblast function is of particular interest, since it has been shown to play an important role in determining bone mass and strength. LDL-receptor-related protein 5 (LRP5) interacts with the frizzled receptor to transduce signaling by Wnt ligands. A mutation of LRP5 that leads to constitutive activation can result in an increase in bone density.84 The phenotype of families with LRP5 activating mutations varies considerably, although all show a striking absence of fractures. Some have normal skeletal structure, while others show abnormalities due to skeleton overgrowth.85 Deletion of LRP5 results in a severe osteoporotic syndrome associate with abnormal eye development.86 Polymorphism of LRP5 have been associated with differences in bone mass and fractures.87 Mutation of LRP5 have been identified in a few patient’s with idiopathic juvenile osteoporosis.88 However, Wnt signaling it also critical in bone development and can affect peak bone mass. 89 The inhibition of skeletal growth by glucocorticoids may be mediated by effects Wnt signaling. The precise mechanism whereby Wnt signaling alters osteoblast function are not fully understood, but there is evidence that the canonical-catenin pathway is involved and that there is an interaction with bone morphogenetic protein 2 (BMP2).90 There are a number of inhibitors that have been shown to interact with BMP2 and with the Wnt signaling pathway. One of these, Sclerostin, the product of the SOST Gene, has been shown to inhibit both BMP2 and Wnt signaling. Another potential inhibitory factor is the production of secreted frizzled-related protein (SFRP) by osteoblasts.91

Local and systemic growth factor:

Remodeling imbalance, characterized by an impaired bone formation response to increased activation of bone remodeling, is an essential component of the pathogenesis of osteoprosis.92 This may be due, in part, to an age-related decrease in the capacity of osteoblasts to replicate and differentiate. However, it seems likely that specific defects in the production or activity of local and systemic growth factor which also contribute to impaired bone formation BMPs as well as other members of the TNF family have been implicated. IGF, which is both a systemic and local regulator, as well TGF-, can also alter bone formation. There are some association between BMD and the incidence of the osteoporotic fracture and polymorphisms in the genes encoding IGF-1 and TGF-.93 But the largest study to date, in Icelandic and Danish Cohorts, suggests that polymorphisms of the BMP2 gene are linked to low BMD and fracture risk.94 Inhibition of local IGF-1 production may be an important component of glucocorticoid- induced osteoporosis as well as inhibition of growth in childhood.95

Cytokines, prostaglandin’s, NO, and leukotrienes:

The concept that locally produced cytokines such as IL-1 and prostaglandin such as prostaglandin E2 (PGE2) can affect bone in more than 30 years old.96 Subsequently, many cytokines were found to either stimulated or inhibits bone resorption and formation.97 Prostaglandins have both stimulatory and inhibitory actions; however, the predominant effect of PGE2, which is the major prostaglandin produced by bone cells, is to stimulate both resorption and formation.98 The possibility that these factors might also be involved in the pathogenesis of osteoporosis is based largely on animals studies of bone loss after ovariectomy.99 However, there is evidence that polymorphisms of IL-1, IL-6, TNF- and their receptors can influence bone mass in human.100

Postaglandins, particularly PGE2, are produced by bone cells largely through the action of inducible cyclooxygenase 2 (COX2). COX2 is induced by most of the factors that stimulates bone resorption and thus may enhance the response to these agents.98 Treatment with COX-2 inhibitor blunt the response to impact loading and fluid shear stress, indicating that prostaglandins play an important role in the response of mechanical forces, and this may be enhanced by estrogen,101 In epidemiologic studies, small increases in BMD and decrease in fracture risk have been reported in individuals using NSAIDS, 102

NO is produced by bone cells and is a cofactor for the anabolic response to mechanical loading.103 However, unlike prostaglandins, NO may inhibit bone resorption, perhaps by increasing OPG production.104 This effect may be responsible for the increase in BMD that has been demonstrated in patient’s treated with isosorbide mononitrate and other activators of the NO pahway.105

Leukotrienes, the products of lipoxygenase, can affect bone by stimulating resorption and inhibiting formation.106 Recently, arachidonate15-lipoxygenase, was identified as a negative regulator of bone density in mice,107 and polymorphisms in the human gene, ALOX15, were found to be associated with differences in peak BMD in postmenopausal women. 108

Collagen abnormalities:

A Polymorphism of the first intron of the gene coding for the type 1 collagen 1 chain and increased level of homocysteine can influence fracture risk independent of BMD.109 This may be due to differences in helix formation or cross-linking of collagen, challenging the concept that mineral and matrix composition are normal in osteoporosis and that only structural abnormalities account for skeletal fragility.

Leptin and neural pathways:

Leptin deficiency or resistance is associated with high BMD in mice despite the fact that gonadal function is diminished.110 This has been attributed to a central effect on adrenergic signaling. Increased  adrenergic activity can decrease bone mass, but other neural pathways may be involved.111 Some, but not all, epidemiologic studies suggest that -adrenergic blockers can decrease fracture risk and increase BMD.112 Another neural pathway has recently been implicated by the finding that mice in which the canabinoid  type-1 receptor is activated, as well as mice treated with antagonist of this receptor, are protected from ovariectomy-induced bone loss.113

Risk factors for low BMD:      

Bone mass reflects the mass accumulated during growth, less any bone mass that has been lost since the adult peak was attained. A strong genetic component is apparent in peak bone mass. In addition, maximum bone mass is influenced by diet (calcium, protein) and exercise. Children with many disease or condition that interferes with growth, nutrition, and exercise have suboptimal bone mass. Recent studies suggest that use of long-acting contraceptives, such as medroxyprogesterone acetate, may limit skeletal growth during puberty, but this observation requires confirmation.114

In women, BMD is stable from the mid-20s to the earliest stages of the climacteric and then declines as estrogen production falls. In men, the timing and mechanism of normal bone loss are less well understood. Many circumstances shorten the time during which peak BMD is stable (table-1). Most of these are not influenced by changes in diet and life style alone, which is an important difference between osteoporosis and hypertension on hypercholesterolemia. Exceptions are cigarette smoking,115 and excessive use of alcohol, which have adverse effect on skeleton as well as on most other organ systems. Each of the circumstances listed in the table has an impact on the skeleton at any time in life. The effect is aggravated if coupled with lower estrogen level after menopause.

Table-1 Disease and conditions associated with low bone mass

Hormone excess

Parathyroid hormone, primary and secondary

Thyroxin, endogenous and exogenous

Cortisol, endogenous and exogenous

Hormone deficiency

Estrogen, premenopause (may be linked with anorexia, bulimia, athletic amenorrhoea, premature menopause, prolactinoma, hypopituitarism)

Estrogen, postmenopause

Testosterone, primary and secondary testicular failures.

Vitamin D metabolites, inadequate intake or malabsorption

Miscellaneous (not necessarily mediated by hormonal abnormalities)     

Medical conditions

v  Gastrectomy

v  Idiopathic hypercalciuria

v  Systemic mastocytosis

v  Prolonged immobilization (paraplegia, quadriplegia)

Lifestyle factors

v  Cigarette smoking

v  Excessive ingestion of caffeine

v  Excessive sodium intake (promotes hypercalciuria)

Medications

Heparin, warfarin, cyclosporine

One condition that requires special mention is idiopathic hypercalciuria in a patient with a calcium containing kidney stone. The ‘reflex’ response is to restrict dietary calcium intake so urinary calcium excretion declines and the risk of additional stone formation falls. This is not necessarily a good idea, since many such patient’s have a renal calcium leak that is not influenced by diet. This renal leak promotes a negative calcium balance, and the skeleton pays the price in an attempt to preserve balance. Eliminating calcium from diet exacerbates the negative calcium balance and further compromises the skeleton.

Corticosteroids are best known of the medications that decrease BMD. Long term experience with inhaled Corticosteroids does not yet confirm that they are less detrimental to the skeleton than other Corticosteroids, but initial studies suggest this might be the case.116

Thyroid disease also can cause problems with bone mass. Many women are receiving thyroid replacement therapy for hypothyroidism, which is appropriate if the disease is well documented and if replacement is not excessive (ie, serum thyrotropin level remains within the normal range and is not suppressed). Otherwise, chronic mild, symptomatic iatrogenic hyperthyroidism probably increases bone loss, and long-term overmedication with thyroxin result in low BMD.

 

Other risk factors for fracture:

A history of fracture, apparently even traumatic fractures before menopause but especially low-impact fractures after menopause, substantially increase the risk.117 A family history of fragility fractures (after trauma equal to or less than a fall from a standing height) is a significant contributory to fracture risk. Given the scant attention paid to osteoporosis until recently, this information is often missing from or incorrect in the patient history.

Body habitus is also an important factor in hip fracture risk with fractures being more than twice as likely in women 5ft 8in, or taller than women 5ft 2in, or shorter.118 the corresponding heights for men are 6ft and 5ft 9in.119

 

Women in the lowest quartile for body weight are also at increased risk for fracture, whilewomen who gained weight after age 25 are at lower risk of fracture.120

Iatrogenic hip fractures probably occurs, and the risk increases with use of long acting benzodiazepins.121 On the positive side, reasonable evidence suggests that thiazide diureric therapy offers some protection against hip fractures in elderly patient’s.122 This does not imply that thiazides should be prescribed to treat osteoporosis or prevent hip fractures. However, if a diuretic is indicated is a patient at risk for fracture because of age and low bone density, thiazides should be considered.

The high incidence of vitamin deficiency, even in the well elderly in the United States, is receiving a great deal of attention.123 A prospective, controlled study in France showed that daily supplementation with 100 mg of calcium and 800IU of vitamin D significantly decrease the incidence of hip fracture in a nursing home population. Whether this occurs through an effect on BMD or because of the known beneficial effects of vitamin D on striated muscle was not established. This investigation did demonstrate that the supplements corrected mild hyperparathyroidism. 124

Other studies have shown that a high rate of bone turnover may be associated with an increased hip fracture risk independent of BMD. The effects of high bone turnover and low BMD were additive in terms of risk fracture. Thus, it would seem cost effective to provide 1,000 mg of calcium and 800 IU of vitamin D daily to everyone in the United States age 75 or older.125, 126

Many simple, objective measures of frailty can help assess the risk of hip fracture. These include ability to rise from a chair without use of the arm, depth perception, contrast sensitivity, and gait and balance assessment. Simply put, any condition that increase the risk of falling in the elderly increase the risk of fracture.127

Types of osteoporosis: 

Osteoporosis may be either a primary or a secondary form. Primary osteoporosis is the more common form and due to the typical age related loss of bone from skeleton. Primary osteoporosis is classified as type-1 and type-2. Secondary osteoporosis results from the presence of other disease or conditions that predispose to bone loss and is classified as type-3.

Type-1: Type-1 or postmenopausal osteoporosis occurs in 5% to 20% women, affecting those within 15 to 20 years of menopause,128 with a peak incidence in the 60s and early 70s. The incidence in women is eight times higher than that in men.129 The frequency of postmenopausal osteoporosis accounts for the overall female-male ratio of 2 : 1 to 3 : 1.

Estrogen deficiency is thought to underlie this from of osteoporosis, rendering skeleton more sensitive to parathyroid hormone (PTH) resulting in increased calcium resorption from bone. This in turn decreases PTH secretion, 1-25 -dihydroxy-vitamin D production, and calcium absorption and ultimately causes loss of trabecular bone, leading to vertebral crush fracture and colles’ fracture.

Women can loss around 2% to 3% of their bone per year for the first 5 years after menopause. Because of the low estrogen production, women loss nearly 50% of their trabecular bone and 35% of their cortical bone through their life time, whereas men loss only 25% of both types of bone. At least 75% of bone loss that occurs in women during the first two decades after menopause can be attributed to lack of estrogen rather than aging. Bone loss associated with menopause dose not begins with the onset of amenorrhoea but may occur 1 to 3 years before the actual cessation of menstrual periods.130

Type-2: Type-2 osteoporosis or senile osteoporosis occurs in women or men more than 70 years of age and usually is associated with decreased bone formation along with decreased ability of the kidney to produce1,25,(OH)2D3. The vitamin D deficiency results in decreased calcium absorption, which increases parathyroid hormone (PTH) level and therefore, bones resorption. In type-2 osteoporosis, cortical and trabecular bone is lost, particularly leading to increased risk of hips, long bones, and vertebral fractures.

Type-3: Type-3 or secondary osteoporosis occurs equally in men and women and at any age. In men, most cases are due to disease or to drug therapy, but in 30% to 45% of affected individuals no cause can be identified.131 In various series of osteoporotic patient’s, secondary osteoporosis accounts for about 40% of the total number of osteoporotic fracture seen by a physician.132

This type of osteoporosis is associated with variety of conditions, including hormonal imbalance (eg. Cushing’s syndrome); cancer (notably multiple myeloma); gastrointestinal disorders (especially inflammatory bowel disease causing malabsorption); drug use (eg. corticosteroid, cancer chemotherapy, anticonvulsants, heparin, barbiturates, valproic acid, gonadotrophin-releasing hormone (GnRH), excessive use of aluminum containing antacids); chronic renal failure; hypothyroidism, hypogonadims in men; immobilization; osteogenesis imperfecta and related disorder; inflammatory arthritis (particularly Rheumatoid arthritis); and poor nutrition (including malnutrition due to eating disorders).133, 134, 135


CLINICAL PRESENTATION OF LOW BONE DENSITY

 

Symptoms:

Osteoporosis is a clinically silent but progressive disease until fracture occurs. Since low bone density alone dose not cause symptoms, many patient’s with quite advanced osteoporosis remain asymptomatic until a fracture occurs. These fractures typically affect the forearm (Colles’ fracture), spine (vertebral fracture) and femur (hip fracture). Colles’ fracture and vertebral fracture most often occurs in women age 55 and above, where as hip fracture affect older individuals (aged 70+). Osteoporotic limb fractures are usually precipitated by falls, where as the precipitating factor in vertebral fracture is often being lifted or lifting a heavy weight. The clinical presentation of vertebral fracture is highly variable. Common clinical presentation include; increasing dorsal kyphosis (Dowager’s hump), loss of weight and back pain. Skeletal back pain may also be a symptom. Radiograph may show osteopenia. This finding indicates that at least 30% of bone mass has been lost.

Assessment:

The assessment of osteoporosis should include a through medical history to identify risk factor for low bone density and fracture, routine laboratory test to rule out secondary causes, a physical examination to identify signs and symptoms of fractures, and bone mineral density (BMD) testing.

History and physical examination:

The history and physical examination are neither sensitive enough nor sufficient for diagnosing primary osteoporosis. However, they are important in screening for secondary forms of osteoporosis and directing the evaluation. A medical history provides valuable clues to the presence of chronic conditions, behaviors, physical fitness, and the long term use of medications that could influence bone density.

Those already affected by complications of osteoporosis may complain of upper or mid thoracic back pain associated with activity, aggravated by long periods of sitting or standing, and easily relived by rest in the recumbent positions. The history should also assess the likelihood of fracture. Low bone density, a propensity to fall, grater height and prior fracture are indications of increased fracture risk.

The physical examination should be through for the same reasons. For example, lid lag, and enlargement or nodularity of the thyroid suggests hyperthyroidism. Moon faces, thin skin and buffalo hump suggest Cushing’s syndrome. Cachexia mandates screening for an eating disorder or malignancy. A pelvic examination is necessary for the complete evaluation of women. Osteoporotic fractures are a late physical manifestation. Common fracture sites are vertebrae, forearm, femoral neck, and proximal humerus. The presence of a Dowager’s hump (Spinal curvature) in elderly patient’s indicates multiple vertebral fractures and decreased bone volume.

Complications:

Vertebral fracture, a well recognized complication of osteoporosis, is the most common osteoporotic fracture. Less than one third of these fractures are clinically identified. Regardless of whether they are symptomatic or identified on imazing, vertebral fractures are associated with increased mortality and morbidity rates. Complications include back pain and decreased mobility, with consequent days of bed rest. Compression fracture of the vertebrae varies in degree from mild wedges to complete compression.

Disfiguring kyphosis (Dowager’s hump) is usually related to multiple wedge fracture of the dorsal vertebrae. Abdominal protrusion, which occurs as consequences of the kyphosis is an unrecognized aspect of osteoporosis. Height loss occurring as a consequence of vertebral fractures is one of the most distressing aspects of osteoporosis in many women.

Decreased pulmonary capacity is a known complication of kyphosis; if severe, this may lead to shortness of breath and pulmonary symptoms of restrictive lung disease. Also, the incidence of esophagitis is increased in patient’s with kyposis because of changes in the abdominal cavity. Once vertebral fracture occurs, the process may be relentless with ongoing further vertebral fractures and height loss despite correction of BMD. 136, 137

 

 

Differential Diagnosis:

Endocrinologic diseases

Endocrinologic deceases include the following.

  • Hypogonadism in men and women.
  • Cushing’s syndrome
  • Corticosteroid –induced osteoporosis
  • Hyperthyroidism.
  • Severe primary hyperparathyroidism

In patient’s with acromegaly, the effects of growth hormone excess on bone mass are controversial. Some studies show increase bone mass, and some studies show reduced bone mass. The latter findings may reflect accompanying hypogonadism, a frequent finding in acromegaly. However the data about bone mass and fracture in diabetes, acromegaly and endometriosis are conflicting.

A rare form of osteoporosis occurs during pregnancy or shortly after delivery. The presentation usually includes severe back pain and multiple vertebral fractures. About 70% of cases occur in first pregnancies, and recurrences are unusual. Most cases resolve spontaneously, and bone mass increases after the termination of breastfeeding. In many women, bone mass normalizes after 3 years. Only a small number of patient’s are disabled for months or years. Patient’s with osteoporosis of pregnancy are at increased risk for postmenopausal osteoporosis.

Osteoporosis occurring late in pregnancy may be related to poor diet or calcium and vitamin D deficiency, where as cases occurring during lactation seem to be related to excessive secretion of PTH-related peptide, which is responsible for calcium transport in the breast and for the mobilization of calcium from bone to milk.

 

Nutritional Deficiencies:

Nutritional deficiencies affect the skeleton by impairing the supply of calcium and vitamin D, leading to secondary hyperparathyroidism and osteomalacia. Such deficiencies can occur after gastric resection and in patient’s with short- bowel syndrome. In those with anorexia nervosa, nutritional deficiency is exacerbated by amenorrhea.

Immobilization:

Immobilization, either temporary or from permanent neurological deficit may cause bone loss from disuse.

Medication use:

Long term corticosteroid use constitutes the most common form of secondary osteoporosis in both men and women. Corticosteroids cause impaired osteoblast function and changes in calcium homeostasis, which lead to accelerated bone loss and fracture. In patient’s treated with prednisolone doses exceeding 7.5mg/d for more than 6 months, the prevalence of vertebral fracture 30-50%.

Agonist of gonadotropin-releasing hormone reduces circulating estrogen levels and thereby causes excessive bone loss. In premenopausal women, tamoxifen and Raloxifene interfere with the binding of estradiol to nuclear receptors and thereby impair the cellular action of the hormone.

In vitro experiments have shown that heparin reduces osteoblastic activity and decreases osteoblast adhesion to matrix proteins. Long-term treatment with heparin is a known cause of osteoporosis.

Both aluminum and lithium interfere with intracellular signaling, and aluminum also impairs osteoblast function and causes osteomalasia. Antiepileptic drugs, especially phenytoin, have been shown to interfere with vitamin D metabolism and to increase the risk of osteoporotic fractures.

 

Juvenile osteoporosis:

This type of osteoporosis affects children and is therefore unlikely to be confused with involutional osteoporosis. Juvenile osteoporosis is characterized by the occurrence of primarily vertebral and metaphysial fractures that lead to back pain and difficulty in walking. In most publications, boys are predominantly affected, but most children recover fully.

The National Institutes of Health (NIH) consensus Development Panel on Osteoporosis prevention, Diagnosis, and Therapy asserts that secondary causes of bone loss are more common in men and perimenopausal women than in postmenopausal women. According to the panel’s estimates, secondary cause are responsible for 30% to 60% of osteoporosis in men (mostly due to hypogonadism, glucocorticioid use, and alcoholism) and more than 50% of osteoporosis in perimenopausal women (mostly due to hypoestrogenemia, glucocorticoid use, excessive levels of thyroid hormone, and anticonvulsant use).138

Laboratory Test:

Basic chemical analysis of serum is indicated when the history suggests other clinical conditions influencing the bone density. The tests presented in tables2139 and 3140 are appropriate for excluding secondary causes of osteoporosis.139 These tests provide specific clues to serious illness that may otherwise have gone undetected and which, if treated, could result in resolution or modification of bone loss. Specific biochemical markers (human osteocalcin, bone alkaline phosphatase, immunoassays for pyrinoline cross-links and type 1 collagen-related peptides in urine) that reflect the overall rate of bone formation and bone resorption are now available. These markers are primarily of research interest and are not recommended as part of the basic workup for osteoporosis. They have a high degree of biologic variability and diurnal variation and do not differentiate causes of altered bone metabolism.141-143

For example, measures of bone turnover increase and remain elevated after menopause but do not necessarily provide information that can direct management.

Table-2

Evaluation of secondary osteoporosis

Abnormal study result

Suggested pathology

Increased creatinine level Renal disease
Increased hepatic transaminase level Hepatic disease
Increased calcium level Primary hyperparathyroidism or malignancy
Decreased calcium level Malabsorption, vitamin D deficiency
Decreased phosphorus level Osteomalacia
Increased alkaline phosphatase level Liver disease, Paget’s disease, fracture, other bone pathology.
Decreased albumin level Malnutrition
Decreased TSH level Hyperthyroidism
Increased ESR Myeloma
Anemia Myeloma
Decreased 24 hour calcium excretion level Malabsorption, vitamin D deficiency
TSH= Thyroid stimulating hormone; ESR= erythrocyte sedimentation rate.

Table-3

Direct laboratory assessment for secondary osteoporosis

Cause

Finding/test

Hypogonadism Decreased testosterone level in men

Decreased estrogen level in women

Increased gonadotropin level (LH and FSH)

Hyperthyroidism Decreased TSH level

Increased T4 level

Hyperparathyroidism Increased parathyroid hormone level.

Increased serum calcium level.

Increased 1, 25, hydroxyvitamin D level

Vitamin D deficiency Decreased 25- hydroxy calciferol level
Hemochromatosis Increased serum iron level

Increased ferritin level.

Cushing’s syndrome 24 hours urine free cotisol excretion

Over night dexamethason suppression test

Multiple myeloma Serum protein electrophoressis-M spike and Bence Jones proteinuria

Increased ESR

Anemia

Hypercalcemia

Decreased parathyroid hormone

LH=luteinizing hormone; FSH= Follicule- stimulating hormone; TSH= thyroid- stimulating hormone; T4= thyroxin; ESR= erythrocyte sedimentation rate.

Methods for BMD measurement:

BMD is determined by measuring the amount bone mineral (calcium hydroxyapatite) per unit volume of bone tissue. X-rays or gamma rays are offen use to quantify BMD. In quantitative terms, BMD is the amount of calcium hydroxyapatite, or Ca10 (PO4)6(OH) 2, perunit volume of bone tissue examined.

Common methods conventional radiography, quantitative CT (QCT), single- photon absorptiometry (SPA), dual-photon absorptiometry  (DPA), quantitative ultrasonography (QUS), and dual-energy X-ray absorptiometry (DEXA).

Bone density measurements can be performed by using X-ray methods, such as DEXA, QCT, and ultrasonic methods. The most accurate way to diagnosis osteoporosis is by measuring bone mass. DEXA scans can be used to detect small changes in bone mass by comparing the patient’s bone density to that of healthy adults (T score) and to age-matched adults (Z score).

A number of methods have been developed for the in vivo determination of bone density in patients at risk of osteoporosis. Two of the most frequently used methods are based on measuring the attenuation of a beam of electromagnetic radiation or ultrasound when it passes through the bone. Ultrasonic measurement of velocity through the bone has also been used to determine bone density.

Currently, DEXA is the most accurate and recommended method for BMD measurement. It is a sensitive technique and can detect changes in bone density only 6-12 months after a previous measurement is obtained. Density measurements of the spine or hip are used. The procedure takes approximately 20-30minutes. The radiation exposure is low at approximately 2.5 mrem.

Bone biopsy may be useful in unusual forms of osteoporosis, such as osteoporosis in young adults. Biopsy provides information about the rate of bone turnover and the presence of secondary form of osteoporosis, such as myeloma and systemic mastocytosis. Patient’s with high turnover usually respond better to antiresorptive drugs than other treatments. Bone turnover can also be evaluated by estimating certain biochemical markers, such as osteocalcin and deoxypyridinoline.144

X-ray (plain x- ray):-

Conventional radiographs are relatively insensitive for demonstrating osteoporosis. At least 30% of the bone mass must be lost before it is recognized. At this stage, the radiographic changes of generalized osteoporosis are more prominent in the axial skeleton than elsewhere.

In the spine, the accentuated primary trabecular pattern produces a vertically striated appearance in the vertebral bodies. Likewise, the loss of trabecular mass causes accentuation of the cortical outline, which is described as picture framing of the vertebral bodies. The vertebral bodies may develop a biconcave shape or compression fractures. In trabecular bones, the loss of   trabecular bone may cause the metaphyses to appear radiolucent. Pathologic fractures may occur at multiple sites.

In trabecular bones, bone resorption may be distinguished in 3 sites: endosteal   envelope, intracortical (Haversian) envelope, and periosteal envelope. These changes are best depicted with magnification radiography and quantitated with radiogrametry.

Other radiographic manifestation of osteoporosis includes the following:

–          Involvement of the lower dorsal and lumber spine, proximal humerus, femoral neck, and ribs (These sites are most commonly affected).

–          Increased radiolucency of bones

–          Decreased number and increased thickness of trabeculae

–          Cortical thinning

–          Juxtra- articular osteopenia with trabecular prominence

–          Bone bars (reinforcement lines)

–          Insufficiency fractures

–          Vertebral wedge fractures, fish vertebrae, decreased heights of vertebrae and accentuation of the cortical outlines (also called picture framing)

The assessment of a reduced radiological shadow density varies from physician to physician. So, the sensitivity and reliability of standard radiography to assess BMD are poor and as a result, this technique can not be used to diagnose osteoporosis. Radiography of the thoracic and lumbar spine is indicated only to identify and confirm the presence of fracture or to exclude possible metastasis.145

QCT Scan (Quantitative Computerized tomography):

QCT is generally used to measure bone density in the lumbar spine, though it can be applied to other parts of the skeleton, such as the forearm. The accuracy and scanning time depends on the type of CT scanner used. This technique is the only BMD-measurement method to provide a true volumetric measurement of bone density (in milligrams/cubic centimeters) and a separate measurement of trabecular and cortical bone density.

QCT has been used to assess vertebral fracture risk. It has been found to be superior to other methods for assessing age-related bone loss, for distinguishing fractures, and for diagnostic classification.

Recent development in the CT technology allows 3-dimensional (3D) Volumetric BMD analysis of the proximal femur and high-resolution CT (HRCT) allows the analysis for trabecular structure. QCT bone density measurement of the lumber spine can be performed on standard CT scanners with provision of specialized software, and peripheral QCT measurement can be obtained on specially designed small-bore CT scanners.

The measurements are accurate and precise and require a comparatively low radiation dose in comparison with that needed for a standard diagnostic CT procedure. QCT is more accurate than DEXA in measuring BMD, especially in the spine in the older population group, as CT avoids the effect of degenerative disease and extraneous calcification. Resent development in 3D QCT allows assessment of the hip and complicated situation in the spine, as when both scoliosis and vertebral fracture are present.

False positives/negatives: One major disadvantage of QCT is that artifacts hamper the CT data, reducing its accuracy. The usual sources of error include beam hardening, detected scatter, and system drift. The accuracy of QCT reading can be improved with careful attention to detail. Patient’s should be well centered and scanned by using consistent settings. Another limitation of QCT is a significantly higher radiation dose than that of DEXA.

The presence of excess fat in the marrow in trabecular bone in aging population introduces an error in the BMD measurement of 7-15% per 10% of fat. This problem can be resolved by using dual energy, but at the expense of double the radiation exposure to the patient. The accuracy error and precision of QCT are 5-8%.146, 147

SPA (Single photon absorptiometry) Study: –

SPA was established in 1963 for the bone densitometric evalution of the appendicular skeleton. SPA uses a single-energy source of gamma rays (iodine 125; photon energy, 27.3 keV) or Am-241 (60keV) to produce a collimated pencil beam, which is tracked across the measurement site. The half-life of 125I is approximately 60 days, resulting in a useful life of around 6 months. The transmitted photons are counted by using a sodium iodide crystal/photomultiplier for each point along the track.

Because of the low photon flux and energy source, the technique is usually applied to a peripheral skeletal site, such as the forearm and, less commonly, the heel. The forearm chosen is the nondependent arm. To allow correction for soft tissue, the forearm must be placed in a water bath. The mean photon count through the water bath without the interposed limb is used as baseline value. A reduction in the photon count below this baseline is assumed to be due to the bone. Muscles of the forearm have attenuation effect similar to that of water. The effects of varying muscle mass are thus eliminated by the water bath.

Degree of confidence:

Although SPA was widely used and although provide valuable a research data, the radionuclide source is a disadvantage. The energy source is subject to decay and must be replaced regularly. The low photon flux can cause the scanning time to be long (up to 40min), and spatial resolution tends to be poor. SPA machines repeatedly scanned in a single line and were limited (because of the physics of their operating principle) to measuring bone sites that could be either immersed in water or embedded in material with adsorption properties equivalent to soft tissue (to stimulate homogenous overlying soft tissue)

False positives / Negatives:

The precision error (coefficient of variation) is 1% for SPA. The precision error is affected not only by the measurement of technique but also subject characteristics. Precision error tends to increase in an elderly or osteoporotic population due to factors such as greater difficulty in repositioning and lower mean BMD.148

 

DPA (Dual Photon Absorptiometry) study               

DPA is an extension of the SPA principle that was developed to compensate for errors in SPA bone-mass measurement due to varying composition and thickness of surrounding soft tissues. This deficiency of SPA was over come by using 2 distinct photon energies, usually gadolinium153. Photons of different energy are differentially attenuated by bone and soft tissue. Therefore, their absorption by bone, and hence bone density, can be calculated by measuring the percentage of each transmitted beam and then by applying simple simultaneous equations. The source of photons is 153Ga, which emits photons of 2 discrete energies (44 and 100 keV). The scanning approach is similar to that of SPA.

 

Degree of confidence:

DPA represents an improvement over SPA in that it allows the direct measurement vertebral or femoral bone density. DPA eliminates the need for a constant soft tissue thickness across the scanning path (allowing its use in areas such as the spine and femur). DPA can be used to quantify changes in patient’s with metabolic bone disease or in those undergoing treatment with drugs that alter bone mineral content.

The desirable characteristics of DPA include its capability in assessing vertebral, proximal femoral or total body bone content; its independence from effect of marrow fat and other soft tissue, and its relatively low radiation dose. However, it is more expensive than other techniques, it has a lower scanning time, and it is not as widely available as SPA.

False Positive/ Negative:

With DPA, the error of precision and accuracy is 2-3%. One unavoidable source of error in the dual-photon technique is the fat distribution in the path of the radiation beam. It is possible to correct for an evenly distributed fat layer across the scanning path, but an uneven distribution introduces error in to the measurements.149

Ultrasound Measurement of Bone Density:                   

Finding: In 1984, Langton first described the measurement of broadband ultrasound attenuation (BUA) in the calcaneous as a potential indicator of hip fracture risk. The concept is based on the knowledge that the speed of sound and attenuation of sound wave are affected by density, compressibility, viscosity, elasticity, and structure of the material it is traveling though. This technique marked a departure from the conventional methods of bone density that used ionizing radiation. Ionizing radiation is attenuated at atomic level, whereas ultrasound is attenuated at the macroscopic structural level.  Some therefore, suggest that broadband ultrasound attenuation (BUA) depend on the macroscopic structure of cancellous bone in addition to the BMD assessed by using the ionizing radiation techniques.

BUA measurement in the calcaneus requires 1 transducer with 2 broadband ultrasound transducer components: one acts as a transmitter, and other acts as receiver. For a given material, ultrasound attenuation in always the same; this is known as the BUA index. To determine the attenuation index of any material (including bone) a broadband ultrasound frequencies is passed through the full thickness of material. The amplitude spectrums of the received signal in then compared with the spectrum of a reference material (water). By recording the frequency spectrum through water with and without the heel in position, a plot of attenuation with frequency is achieved. The difference between the 2 spectra is then plotted against frequency, giving a straight-line graph, the slope of which is the BUA index (in decibels per megahertz). The ultrasound frequencies used in the range of 0.1-1MHz. This range has become known as BUA.

Degree of confidence: QUS for bone analysis is a non-ionizing method in which the calcaneus as the measurement site. This technique is both a cost effective and accurate for identifying patients at risk of osteoporotic fracture. QUS has been scientifically validated in both fundamental in vitro studies and clinical in vivo studies. Clinical studies have shown that QUS parameters are sensitive to age related changes; they may be useful in distinguishing osteoporotic subject, and they offer a prospective prediction of fracture risk comparable to that of axial DEXA.

False positives/ Negatives: A number of factors can affect the accuracy and precision of BUA and produce false-positive or false-negative results. The anatomically incorrect placement of the region to be examined is 1 of these factors. Other factors are patient’s specific and may affect bone measurements; these are variability in bone width and soft tissue thickness or composition, marrow composition, and temperature. Error in measurement can be introduced by diffraction, which affect both attenuation and velocity measurements and is device specific.

 

DEXA (Dual Energy X-ray Absorptiometry):

DEXA is the method of choice to measure bone mineral density in elderly patient’s and others at risk of osteoporosis. Early detection is an important because fractures represent an enormous health burden. Central bone mineral density (BMD) measurement using DEXA is currently the gold standard for the diagnosis of osteoporosis.150 DEXA measurement can be completed by in about 15 to 20 minutes with minimal radiation exposure (about one tenth that of a standard chest X-ray).

Peripheral DEXA scans are inexpensive and are useful in screening large populations such as at health fair. The peripheral DEXA device is simple to operate. However, the sensitivity of peripheral DEXA for detecting osteoporosis is lower than that of central DEXA. Moreover, issues such as a lack of consensus on how results from peripheral sites are interpreted, poor correlation among the different machines, and precision errors prohibiting monitoring the patient’s who are receiving osteoporosis therapy limit the clinical utility of this technology.

Indication for obtaining a DEXA scan

Menopausal women should be evaluated clinically for osteoporosis risk in order to determine the need for BMD testing. All woman aged 65 or older, younger postmenopausal women with risk factors, and men aged 70 or older should undergo bone density testing. Risk factors include dementia, poor health, recent falls, prolonged immobilization, smoking, alcohol abuse, low body weight (<127 lb), history of fragility fracture in a first degree relative, estrogen deficiency at an early age (<45 years), and steroid use for more than 3 months.151

Adult who have a history of fragility fractures, have diseases associated with bone loss, or take medication that causes bone loss should also have DEXA scans.152 DEXA scans are also appropriate for monitoring a patient’s response to osteoporosis therapy.151

Site of measurement of BMD

The International Society for Clinical Densitometry recommends obtaining BMD measurements of the posteroanterior spine and hip. The lateral spine and ward’s triangle region of the hip should not be used for diagnosis, because these sites overestimate osteoporosis and results can be false positive. T-scores represent the standard deviations (SDs) comparing a patient’s BMD to that of a young adult (control), whereas Z-scores compare a patient’s, BMD to that of age matched controls. The World Health Organization (WHO) defines osteoporosis as T-score of 2.5 or below is either the spine or the hip.40

In the spine, the BMD of L1 through L4 should be reported unless there are vertebrae affected by severe degenerative changes or compression fractures. These should be excluded from the analysis because they falsely increased BMD. Most DEXA devices measure and report BMD of the total hip, femoral neck, and trochanter. The diagnostic classification of a patient is based on the lowest T-score of any of these hip sites.

Evidence suggest that the femur is the optimum site for predicting the risk of hip fracture153 and the spine is the optimum site for monitoring response to treatment.154 In very obese patient’s, those with primary hyperparathyroidism, or those in whom the hip or the spine, or both, can not be measured or interpreted, BMD may be measured in the forearm, using a 33% radius on the nondominant forearm.151

Interpretation of DEXA scans:   

Primary care physicians are usually not directly involved in the performance and interpretation of DEXA scans but should be familiar with the information on DEXA scan reports and how it applies to patient’s management.155 T-scores are used to diagnose osteoporosis, and Z-scores give the physician a sense of the age-appropriateness of bone loss. A Z-score of 2.0 or lower suggests a secondary cause and should trigger the search for underlying causes.156 In our practice, patient’s with a Z-scores below 1.0 are frequently found to have secondary causes, and such a score initiates a comprehensive search for these causes.

Although, postmenopausal osteoporosis is clearly the most common bone disease, secondary causes of osteoporosis are also quite common. Physicians need to actively look for these causes, either by thorough history taking or with biochemical studies.

Initiation of treatment:

Evidence showing an unacceptably high risk of fracture with T-scores of 2.5 and below and a significant reduction in fracture risk with treatment has made this threshold the initial criterion for the diagnosis of osteoporosis.155,156 However, the National Osteoporosis Foundation recommends initiating treatment to reduce fracture risk in women with T-scores below 2.0, even in the absence of risk factors, and in women with T-scores below 1.5 in the presence of one or more risk factors.157 Regardless of the T-score, patient’s with previous vertebral or hip fracture are classified as severely osteoporotic and should be treated. Recently the National Osteoporosis Risk Assessment study found osteoporotic fractures among patient’s who were classified as oeteopenic on the basis of the WHO criteria. There is now a move toward establishing a global fracture risk score that includes risk factors and BMD as a possible basis for initiating therapy.158

Monitoring response to treatment:

DEXA scans are useful in determining response to osteoporosis therapy. Under ideal conditions, the same technologist should perform DEXA scans on the same densitometer and under similar circumstances.

It is important to note that antiresorptive drug therapy leads to significant reduction of fracture risk, which can be obtained with very little improvement in BMD. Moreover, in interpreting serial DEXA scans, the actual BMD (in gm/cm2) should be compared and not the T-scores.

BMD remain the best and most useful marker for fracture risk reduction in clinical practice. The interval between BMD testing should be determined according to each patient’s clinical status. BMD measurements to monitor response to osteoporosis therapy should generally be obtained every year until stability is established, then at longer intervals, such as every 2 years.151 The posteroanterior lumbar spine is the optimum site to monitor therapy, and significant changes may be seen in a year or more, depending on the therapy used.154 Medicare permits physicians to repeat DEXA scans every 2 years157 or, in patient’s who are being monitored while on therapy, every year.

Osteoporosis in men:

The focus of osteoporosis management has been on postmenopausal women. However, osteoporosis in men is not rare.159 The estimated lifetime risk of fracture ranges from 13% to 25%.160 The three major causes of osteoporosis in men are alcohol abuse, glucocorticoid excess (from either endogenous Cushing’s syndrome or long-term glucocorticoid therapy), and hypogonadism.160,161 Bone density testing should be considered in men with fragility fractures; those taking drugs that may cause bone loss, such as androgen deprivation therapy for prostate cancer162; and men with multiple risk factors.

The International Society for Clinical Densitometry recommends that in men aged 65 years or older, osteoporosis should be diagnosed if T-scores are at or below 2.5. Between age 50 and 65years, osteoporosis should diagnosed if T-score are at or below 2.5 and other risk factors for facture are identified. In men under the age 50 years, diagnosis of osteoporosis should not be made on the basis of T-scores. Osteoporosis may be diagnosed clinically in men at any age with secondary causes of low BMD supported by the finding of low BMD.

It is important to know that the WHO classification, with its associated implications for fracture risk, was derived from a database composed purely of postmenopausal white women. Most densitometry devices now use the third National Health and Nutrition Examination Survey (NHANES III) database, which provide appropriate sex-matched controls for hip BMD.

Artifacts:

Certain conditions can artificially elevate the BMD, obscuring osteoporosis and leading to underestimation of fracture risk.163 These include degenerative changes seen in osteoarthritis and ankylosing spondylitis, structural abnormalities such as compression fracture164 and scolosis,165 aortic calcification, high-density objects on clothing, surgical implants,164 laminectomy,165 and retained radiopaque contrast agents.164 Vertebrae  with abnormal conditions should be excluded from the spine analysis. Similarly, BMD at the proximal femur can be altered by degenerative arthritis, degree of internal rotation, placement of soft tissue gluteal silicon implants,166 and overlying soft tissue thickness or fat.167 Patient’s positioning and appropriate placement of region of interest are paramount for precision and reproducibility.165 Physician should visually assess DEXA scans for artifacts that could affect BMD values. Going down the spine, the vertebrae become larger and have grater BMD (L1<L2<L3), and T-scores of individual vertebrae should be within approximately 1SD of each other. This observation does not apply to the hip, where differences greater than 1SD between regions may occurs because of different rates of loss cancellous and cortical bone from different hip sites.155

Automated analysis of spine scans in enhanced with the introduction of computer-aided densitometry, a software feature that assists physicians in the indentification of concealed osteoporosis or osteopenia in spine scans adversely affected by conditions that cause an artificial elevation in BMD.

Material and Methods:

The study was conducted in the Department of Medicine, Rajshahi Medical College Hospital from October 2005 to July 2006. 30(thirty) male and 30(thirty) female (total 60) patient’s were studied whose ages were >45years, H/O menopause >2years, low back pain, no pathological fracture of bone. Detailed history was taken from the patient’s. They were examined physically and requisite investigations were done. Their age, sex, occupation, height, weight, and special attention was given to the back pain, morning stiffness for at least 1 hour, heat intolerance, appetite, and alteration of bowel habit.

They were also asked about past history and drug history specially prednisolone, personal history specially smoking, family history especially non traumatic fracture of bone of their mother, any history of hypertension, diabetes mellitus.

During physical examination, along with examination of the locomotor system, general physical examination and a brief examination of all other systems also were done.

Plain X-ray of the lumbar spines and hip were done in all patient’s, using DEXA Bone Densitometer (XR36, Norland, USA), the spines and proximal femurs were studied in all patient’s. The results were then compared with the reference population data for individuals of the same age, sex, and ethnic background. The comparison was verified by age matched (Z-score) and Young reference (T-score). The interpretation was done by computer generated soft ware program following WHO recommendation (Table-4).

Table: 4 World Health Organization Definitions of osteoporosis based on Bone Density levels.

Normal Bone density within 1SD (+1SD or – 1SD) the young adult mean.
Low Bone mass (Osteopenia) Bone density within 1 to 2.5 SD (-1SD or – 2.5SD) below the young adult mean.
Osteoporosis Bone density 2.5 SD or more (> – 2.5 SD) below the young adult mean.
Severe Osteoporosis Bone density more than 2.5 SD below the young adult mean and there have been one or more osteoporotic fractures.

Completed blood count was done in all patient’s, other investigation like serum calcium level, urinary calcium level, serum albumin, X-ray skull, urinary benze Jones protein, and other necessary investigations were done in relevant cases to exclude secondary causes of osteoporosis.

Results:

Among the 60 cases, the mean age incidence was 58years, the youngest patient was 45 years and the oldest patient was 81 years. The maximum of cases were found in their 7th decades. The result is shown in Table-5.

In male patient’s, the maximum number of patient’s was in age group 60 & up years and also in female patient’s, the maximum number of patient’s, was in age group 60 & above years. This is shown in Table-6.

Among the 60 cases, the mean height incidence was 163.1 cm. The maximum number of cases was found in height group (cm) 160-169. This is shown in Table-7.

In male group, maximum number of patient’s, was in height group (cm) 160 –169; also in female group, the maximum number of patient’s was in height group (cm) 160 –169. This is shown in Table-8.

Among the 60 cases, the mean weight was 51.2 kg, the lowest weight was 30 kg, and the highest weight was 87 kg. The maximum number of cases was found in <50kg group. This is shown in the Table-9.

In male patient’s group, the maximum number of patient’s was in weight group <50 kg & also, the maximum number of patient’s, in female group, was in weight group <50 Kg. This is shown in Table-10.

Among 60cases, the mean Body mass Index (BMI) was 19.7kg/m2 The highest BMI was 33.1kg/m2 and the lowest BMI was 13 kg/m2. The maximum number of cases was found in BMI group<18.5 kg/m2. This is shown in Table-11.

In male group, the maximum number of patient’s were in BMI group 18.5 – 24.9, where as in female group, the maximum of patient’s were in BMI group <18.5. This is shown in Table-12.

Among 60 cases, 16 cases from urban and 44 cases from rural. This is shown in Table-13.

Both male and female patient’s were maximum from rural group. This is shown in Table-14.

Among 60 cases, incidence of bone mineral losses, was maximum in poor socioeconomic condition. This is shown in Table-15.

Maximum incidence of bone mineral losses among male and female groups, were also in poor socioeconomic conditions. This is shown Table-16.

Among 30 female patient’s, all of their occupations were house, wife, but in male patient’s, the incidence was maximum in other’s occupation (like landlord). This is shown in Table-17.

Among 30 male patient’s, 23 (76.7%) were smoker & among 30 female patient’s, 1 (3.3%) were smoker.  This is shown in Table-18.

No male patient’s had history of non traumatic fracture of the bone of their mothers. But among female patient’s, only eight patients had history of non-traumatic fracture of bone of their mothers. This is shown in Table-19.

Among male patient’s, only 1 patient had diabetes mellitus, and among female patient’s only 1 patient had diabetes mellitus. This is shown in Table-20.

Among 30 female patient’s, maximum patient’s were in 5-10 years group of menopausal durations. This is shown in Table-21.

Among 60 patient’s, the maximum patient’s were in back pain duration >1year. This is shown in Table-22.

Among male patient’s, maximum 19 patients had back pain duration >1year and among female patients, maximum 16 patient’s had back pain duration < 1 year. This is shown in Table-23.

The bone mineral densities are shown in Table-24. Four patient’s (male-3; Female-1) were found to have normal bone density, whereas the rest 56 patient’s had shown different grades of bone mineral loss. Among the 56 patient’s, 17 patient’s (Male-10; Female-7) suffered from osteopenia. Fourteen patients (Male-4; Female-10) had shown osteoporosis in both femoral neck and lumbar vertebra. The rest 25 patient’s (Male-13; Female-12) had shown combined osteopenic & osteoporotic changes either in lumber vertebra and / or femur. This is shown in Table-25.

BMD was higher in all sites in male than female. Osteophytes, which were common in older people, may have influenced lumber spine BMD result. This is shown in Table-26.

Among 4 normal BMD presentation patient’s, 1(25%) was in 50-54 years group & 2 (50%) were in 55-59 years group & 1 (25%) was in 60 & up years group. Among 17 osteopenic BMD presentation patient’s, 8 (47%) were in 45-49 years group & 1 (5.9%) was in 50-54 years group & 3 (17.6%) in 55-59 years group & 5 (29.4%) in 60 & up years group. Among 14 osteoporotic BMD presentation patient’s, 1 (7.1%) in 55-54 years group, & 1 (7.1%) in 55-59 years group & 12 (85.7%) in 60 & up years group. Among 25 combined BMD presentation patient’s, 2 (8%) in 45-49 years group & 5 (20%) in 50-54 years group & 6 (24%) in 50-59 years group & 12 (48%) in 60 and up years group. This is shown in Table-27.

Among 4 normal BMD presentation patient’s, 1 (25%) in 50-59 kg group & 3 (75%) in 60-69 kg group. Among 17 osteopenic BMD presentation patietns, 5 (29.4%) in < 50kg group & 4 (23.5%) in 50-59 kg group & 4 (23.5%) in 60-69kg group & 4 (23.5%) in 70 & up kg group. Among 14 osteoporotic BMD presentation patient’s, 11 (78.6%) in <50kg group & 3 (21.4%) in 50-59kg group & among 25 combined BMD presentation patient’s, 16 (64%) in<50kg group & 5 (20%) in 50-59 kg group & 3 (12%) in 60-69 kg group & 1 (4%) in 70 & up kg group. This is shown in Table-28.

Among 60 patient’s, 1 (25%) normal BMD presentation patient’s was in 150 –159 cm group & 3 (75%) were in 160 –169 cm group. 3 (17.6%) osteopenic BMD presentation patient’s are in height group 150-159 & 11(64.7%) osteopenic BMD presentation patient’s are in height group 160 –169 cm & 3 (17.6%) osteopenic BMD presentation patient’s are in height group 170 & up cm group. In osteoporotic BMD presentation patient’s, 1 (7.1%) are in height group <150cm, & 5(35.7%) are in height group 150-159 cm group, & 7 (50%) are in 160-169 cm & group, & 1 (7.1%) are in height group 170 & up cm. In Combined BMD presentation patient’s group, 5 (20%) are in height group 150-159cm, and 16 (64%) are in height group 160-169 cm, & 4 (16%) are in height group 170 & up cm. This is shown in Table-29.

In normal BMD presentation patient’s, 2 (50%) have BMI in 18.5-24.9 kg / m2  group, & 2 (50%) have BMI in 25-29.9 kg/m2 group. In osteopenic BMD presentation patient’s 3 (17.6%) patient’s BMI in < 18.5kg/m2 group, and 10 (58.8%) in 18.5-24.9kg/m2 BMI group, & 2 (11.8%) in 25-29.9 kg/m2 BMI group & 2 (11.8%) in 30 & up kg/m2 BMI group. In osteoporotic BMD patient’s, 11(78.1%) in < 18.5kg/m2 BMI group & 3 (21.4%) in 18.5-24.9kg/m2 BMI group. In combined BMD presentation patient’s, 13 (52%) in < 18.5kg/m2 BMI group & 11 (44%) in 18.5 –24.9kg/m2 BMI group & 1 (4%) in 25-29.9kg/m2 BMI group. This is shown in Table-30.

In normal BMD presentation patient’s, 1 (25%) are poor & 3 (75%) are in middle class. In osteopenic BMD presentation patient’s, 10 (58.8%) are poor & 6 (35.3%) are in middle class & 1 (5.9%) are in rich group. In osteoporotic BMD presentation patient’s, 8 (57.2%) are poor & 5 (35.7%) are in middle class & 1 (7.2%) are in rich group. In combined BMD presentation patient’s, 14 (56%) are poor & 11 (44%) are middle class. This is shown in Table-31.

Among 30 female patient’s, all were housewives. Among 30 male patient’s, in normal BMD presentation patient’s, 1 (33.3%) patient’s occupation was service & 2 (66.7%) patient’s occupation were others. In osteopenic BMD presentation male patient’s 1(10%) patient occupation was labor & also same number patient occupation, is business & 8 (80%) patient’s occupation were others. In osteoporotic BMD presentation male patient’s, 2 (50%) patient’s occupation were business & also same number of patient’s occupations was other. In combined BMD presentation male patient’s, 2 (15.4%) patient’s occupation were labor & also same number of patient’s occupation were service, business & 7 (53.8%) patient’s occupation were others. This is shown in Table-32.

Among 60 patient’s, in normal BMD presentation patient’s, 2 (50%) patient’s were in urban & 2 (50%) patient’s were in rural. In osteopenic BMD presentation patient’s, 4 (23.5%) were in urban & 13 (76.5%) patient’s were in rural. In osteoporotic BMD presentation patient’s, 3 (21.4%) patient’s were in urban & 11 (78.6%) patient’s were in rural. In combined BMD presentation patient’s, 7(28%) patient’s were in urban & 18 (72%) patient’s were in rural. This is shown in Table-33.

In normal BMD presentation patient’s, 2(50%) have smoking history. In osteopenic BMD presentation patient’s, 8 (47%) have smoking history. In osteoporotic BMD presentation patient’s, 4 (28.6%) have smoking history. In combined BMD presentation patient’s, 10(40%) have smoking history. This is shown Table-34.

Among 30 male patient’s, none of them have family history (non traumatic fracture of the bone of their mother). But among 30 female patient’s, in osteopenic BMD presenting female patient’s, 2 (28.6%) patient’s have family history positive. In osteoporotic BMD presenting female patient’s, 1 (10%) have family history positive. In combined BMD presenting female patient’s, 5 (41.7%) patient’s have family history positive. This is shown in Table-35.

Among the 60 patient’s, 2 patient’s were diabetic. In the normal BMD presetting patient’s 01 (25%) patient is diabetic, which is 25%, and in combined BMD presenting patient’s, 1(4%) patient is diabetic. So, incidence of diabetics with normal BMD presenting patient’s is higher. This is shown in Table-36.

Among the 30 female patient’s, normal BMD presenting patient’s, 1 (100%) patient menopause duration was 5-10years group. In osteopenic BMD presenting female patient’s, 4 (57.1%) patient’s menopausal duration was < 5years group and 2 (28.6%) patient’s menopausal duration was 5-10years group and 1(14.3%) patient’s menopausal duration was 10 & up years group in osteoporotic BMD presenting female patient’s, 3 (30%) patient’s menopausal duration was 5-0 years group, and 7 (70%) patient’s menopausal duration was 10 & up years group. In combined BMD presenting female patient’s, 2 (16.7%) patient’s menopausal duration was <5years group & 7 (58.3%) patient’s menopausal duration was 5-10 years group, & 3 (25%) patient’s menopausal durations was 10 & up years group. This is shown in Table-37.

In normal BMD presenting patient’s, 2 (50%) patient’s back pain duration was <1 year group, & 2 (50%) patient’s back pain duration was >1 year group. In osteopenic BMD presenting patient’s, 9(52.9%) patient’s back pain duration was <1year group, & 8 (47%) patient’s back pain duration was >1year. In osteoporotic BMD presenting patient’s, 6(42.8%) patient’s back pain duration was <1year group, & 8(57.2%) patient’s back pain duration was> 1year group. In Combined BMD presenting patient’s, 10(40%) patient’s back pain duration was < 1year group, & 15 (60%) patient’s back pain duration was > 1year group. This is shown in Table-38.

In normal BMD presenting patient’s, 25% have systolic blood pressure was < 140mm of Hg and 75% patient’s blood pressure were in 140-160 mm of Hg group. In osteopenic BMD presenting patient’s, 52.9% patient’s have systolic B.P. <140 mm of Hg group and 47.1% patient’s have systolic B.P. in 140-160 mm of Hg group. In osteoporotic BMD presenting patient’s, 57.1% paitents have systolic B.P.  was < 140 mm of Hg group and 42.9% patient’s have systolic B.P was 140 –160 mm of Hg group. In combined BMD presenting patient’s, 48% patient’s systolic B.P. equally was in < 140 mm of Hg and 140 – 160 mm of Hg group and 4% patient’s systolic B.P. was in > 160mm of Hg group. This is shown in Table-39.

In normal BMD presenting patient’s, 25% patient’s diastolic B.P. was in <90mm of Hg & 75% patient’s diastolic B.P was in 90-100 mm of Hg group. In osteopenic BMD presenting patient’s, 82.4% patient’s diastolic B.P. was in <90mm of Hg & 17.6% patient’s diastolic B.P was in 90-100 mm of Hg group. In osteoporotic BMD presenting patient’s, 71.4% patient’s diastolic was < 90 mm of Hg group & 28.6% patient’s diastolic B.P was in 90-100 mm of Hg group. In combined BMD presenting patient’s, 76% patient’s diastolic B.P was in < 90mm of Hg group & 24% patient’s diastolic BP was in 90-100 mm of Hg group. This is shown in Table-40.

Among the male patient’s, 24(80%) patient’s have degenerative changes and 4(13.3%) patient’s have osteoporotic changes and 2 (6.7%) patient’s have normal finding on X-ray L-S spine. In female patient’s, 3 (10%) have normal finding and 9(30%) patient’s have osteoporotic changes & 10 (30.3%) patient’s have degenerative changes and 8 (26.7%) patient’s have combined changes on X-ray L-S spine. This is shown in Table-41.

Sensitivity of the X-ray in assessing BMD is 39%. This is shown in Table-42.

Table- 5

Age incidence

Total patient’s = 60

Age group (years)

Number of Patient’s

Percentage

45 – 49

10

16.7%

50 – 54

8

13.3%

55 – 59

12

20%

60 & up

30

50%

Table-6

Age incidence between male & female group

Age group (years)

45 – 49

50 – 54

55 – 59

60 & up

No of pt

%

No of pt

%

No of pt

%

No of pt

%

Male       No =30

6

20

4

13.3

2

6.7

18

60

Female No= 30

4

13.3

4

13.3

10

33.3

12

40

Table-7

Height incidence

Total patient’s=60

Height group (cm)

Number of Patient’s

Percentage

< 150

1

1.7%

150 – 159

14

23%

160 – 169

37

61%

 170 & up

8

13%

Table-8

Height incidence between male & female group

Height group (cm)

< 150

150 – 159

160 – 169

170 & up

No of pt

%

No of pt

%

No of pt

%

No of pt

%

Male       No =30

5

16.7

17

56.7

8

26.7

Female No= 30

1

3.3

9

30

20

66.7

Table-9

Weight incidence

Total patient’s=60

Weight group (kg)

Number of Patient’s

Percentage

< 50

32

53.3%

50 – 59

13

21.7%

60 –69

10

16.7%

 70 & up

5

8.3%

Table-10

Weight incidence between male & female group

Weight group (kg)

< 50

50 – 59

60 – 69

70 & up

No of pt

%

No of pt

%

No of pt

%

No of pt

%

Male       No =30

13

43.3

8

26.7

6

20

3

10

Female No= 30

19

63.3

5

16.7

4

13.3

2

6.7

Table-11

BMI incidence

Total patient’s=60

BMI group (kg/m2)

Number of Patient’s

Percentage

< 18.5

27

45%

18.5 – 24.9

26

43.3%

25 –29.9

5

8.3%

30 & up

2

3.3%

Table-12

BMI incidence between male & female group

BMI group (kg/m2)

<18.5

18.5 – 24.9

25 –29.9

30 & up

No of pt

%

No of pt

%

No of pt

%

No of pt

%

Male       No =30

12

40

13

43.3

4

13.3

1

3.3

Female No= 30

15

50

13

43.3

1

3.3

1

3.3

Table-13

Address incidence

Total patient’s 60

Address

Number of Patient’s

Percentage

Urban

16

26.7%

Rural

44

73.3%

Table-14

Address incidence between male & female group

Address

Urban

Rural

No of pt

%

No of pt

%

Male       No =30

5

16.7

25

83.3

Female No= 30

11

36.7

19

63.3

Table-15

Incidence in different socioeconomic condition

Total patient’s=60

Socioeconomic condition

Number of Patient’s

Percentage

Poor

33

55%

Middle Class

25

41.7%

Rich

2

3.3%

Table-16

Socioeconomic incidence between male & female group

Socioeconomic condition

Poor

Middle Class

Rich

No of pt

%

No of pt

%

No of pt

%

Male       No =30

17

56.7

12

40

1

3.3

Female No= 30

16

53.3

13

43.3

1

3..3

Table-17

Occupational Status in male patient’s

 

Occupation

Number of patient’s (No =30)

Percentage (%)

Labor

3

10%

Service

3

10%

Business

5

16.7%

Others

19

63.3%

 

Table-18

Smoking incidence in different sexes

Patient’s

Number of patient’s

Percentage (%)

Male               No = 30

23

76.7%

Female          No = 30

1

3.3%

Table-19

Family history incidence

Patient’s

Family history positive

Percentage (%)

Female          No = 30

8

26.7

Table-20

Patient’s

Diabetic history

Percentage (%)

Male               No = 30

1

3.3%

Female          No = 30

1

3.3%

Table-21

Menopausal duration incidence

Menopausal duration (Years)

Number of Patient’s

Percentage

<5

6

20%

5 – 10

13

43.3%

10 & up

11

36.7%

Table-22

Back pain duration incidence

Back pain duration (Years)

Number of Patient’s

Percentage (%)

< 1

27

45%

> 1

33

55%

Table-23

Back pain duration incidence in different sexes

Back pain duration (Years)

< 1

> 1

No of pt

%

No of pt

%

Male       No =30

11

36.7

19

63.3

Female No= 30

16

53.3

14

46.7

Table-24

Bone mineral density (in gm/cm2) of lumbar vertebrae

and femoral neck in different categories.

Normal

No = 4

Osteopenia

No = 17

Osteoporosis

No = 14

Combined                    No = 25

Osteopenia

Osteoporosis

Site

LV

FN

LV

FN

LV

FN

LV

FN

LV

FN

BMD (SD)

1.2000

.05

1.0128

.02

.8396

.03

.7731

.06

.5860

.04

.5976

.03

.8250

.03

.8170

.01

.5484

0

.6502

.03

T-Score

(SD)

.73

.07

.48

.01

1.56

.02

1.88

.05

3.19

.01

3.52

.01

1.73

.01

2.05

.02

3.42

0

3.26

.09

* LV = lumbar vertebrae; FN= Femoral Neck; * Combined= Osteoporosis + osteopenia.

Table-25

Bone Mineral losses in different sexes.

Patient’s

Normal

No = 4

Osteopenia

No = 17

Osteoporosis

No = 14

Combined

No = 25

No of pt

%

No of pt

%

No of pt

%

No of pt

%

Male       No=30

3

10

10

33.3

4

13.3

13

43.3

Female No=30

1

3.3

7

23.3

10

33

12

40


Table-26

Comparison of male (M) and female (F) population for lumbar spine and femoral neck bone mineral densities stratified by age groups.

Age (years)

No

Spine (gm/cm2)

[mean SD]

Femur (gm/cm2) [mean SD]

45 – 49

M (6)

.9043 .09

.8432  .08

F (4)

.8850  .14

.7654  .07

50 – 54

M (4)

.9840 .16

.9147  .12

F (5)

.7497  .18

.6602  .07

55 – 59

M (2)

.9076 .004

.7697  .01

F (9)

.7912  .21

.6984  .01

60  & up

M (18)

.8470 .19

.7440  .16

F (12)

.6387  .15

.5737  .08

Table-27

Association with age

Presentation

45 – 49 years

50 – 54 years

55 – 59 years

60 & up years

No of pt

%

No of pt

%

No of pt

%

No of pt

%

Normal           No=4

1

25

2

50

1

25

Osteopenia     No=17

8

47

1

5.9

3

17.6

5

29.4

Osteoporosis  No=14

1

7.1

1

7.1

12

85.7

Combined       No=25

2

8

5

20

6

24

12

48

Table-28

Association with weight

Presentation

< 50 kg

50 – 59 kg

60 – 69 kg

70 & up kg

No of pt

%

No of pt

%

No of pt

%

No of pt

%

Normal           No=4

1

25

3

75

Osteopenia     No=17

5

29.4

4

23.5

4

23.5

4

23.5

Osteoporosis  No=14

11

78.6

3

21.4

Combined       No=25

16

64

5

20

3

12

1

4


Table-29

Association with Height

Presentation

< 150 cm 

150 – 159cm

160 – 169 cm

170 & up cm

No of pt

%

No of pt

%

No of pt

%

No of pt

%

Normal           No=4

1

25

3

75

Osteopenia     No=17

3

17.6

11

64.7

3

17.6

Osteoporosis  No=14

1

7.1

5

35.7

7

50

1

7.1

Combined       No=25

5

20

16

64

4

16

Table-30

Association with BMI

Presentation

< 18.5 kg/m2 

18.5 – 24.9 kg/m2

25 – 29.9 kg/m2

30 & up kg/m2

No of pt

%

No of pt

%

No of pt

%

No of pt

%

Normal           No=4

2

50

2

50

Osteopenia     No=17

3

17.6

10

58.8

2

11.8

2

11.8

Osteoporosis  No=14

11

78.6

3

21.4

Combined       No=25

13

52

11

44

1

4

Table-31

Association with Socioeconomic condition

Presentation

Poor

Middle Class

Rich

No of pt

%

No of pt

%

No of pt

%

Normal           No=4

1

25

3

75

Osteopenia     No=17

10

58.8

6

35.3

1

5.9

Osteoporosis  No=14

8

57.2

5

35.7

1

7.2

Combined       No=25

14

56

11

44

Table-32

Association with Occupation

Presentation

Labor

Service

Business

Others

No of pt

%

No of pt

%

No of pt

%

No of pt

%

Normal           No=3

1

33.3

2

66.7

Osteopenia     No=10

1

10

1

10

8

80

Osteoporosis  No=4

2

50

2

50

Combined       No=13

2

15.4

2

15.4

2

15.4

7

53.8

Table-33

Association with address

Presentation

Urban

Rural

No of pt

%

No of pt

%

Normal             No=4

2

50

2

50

Osteopenia        No=17

4

23.5

13

76.5

Osteoporosis     No=14

3

21.4

11

78.6

Combined         No=25

7

28

18

72

Table-34

Association with Smoking

Presentation

No of pt

%

Normal             No=4

2

50

Osteopenia        No=17

8

47

Osteoporosis     No=14

4

28.6

Combined         No=25

10

40

Table-35

Association with Family history

Presentation

No of pt

%

Normal             No= 1

Osteopenia        No= 7

2

28.6

Osteoporosis     No= 10

1

10

Combined         No= 12

5

41.7

Table-36

Association with D.M.

Presentation

No of pt

%

Normal             No= 4

1

25

Osteopenia        No= 17

0

0

Osteoporosis     No= 14

0

0

Combined         No= 25

1

4

 

Table-37

Association with duration of menopause

Presentation

< 5 years 

 5 – 10 years 

10 & up years

No of pt

%

No of pt

%

No of pt

%

Normal           No=1

1

100

Osteopenia     No=7

4

57.1

2

28.6

1

14.3

Osteoporosis  No= 10

3

30

7

70

Combined       No= 12

2

16.7

7

58.3

3

25

Table-38

Association with duration of back pain

Presentation

< 1 Year 

> 1 Year

No of pt

%

No of pt

%

Normal             No=4

2

50

2

50

Osteopenia        No=17

9

52.9

8

47

Osteoporosis     No=14

6

42.8

8

57.2

Combined         No=25

10

40

15

60

 

Table-39

Relation with systolic BP

Presentation

< 140  mm of Hg

140 – 160 mm of Hg

> 160  mm of Hg

No of pt

%

No of pt

%

No of pt

%

Normal           No=4

1

25

3

75

Osteopenia     No=17

9

52.9

8

47.1

Osteoporosis  No=14

8

57.1

6

42.9

Combined       No=25

12

48

12

48

1

4

Table-40

Relation with diastolic BP

Presentation

< 90  mm of Hg

90 – 100 mm of Hg

> 100  mm of Hg

No of pt

%

No of pt

%

No of pt

%

Normal           No=4

1

25

3

75

Osteopenia     No=17

14

82.4

3

17.6

Osteoporosis  No=14

10

71.4

4

28.6

Combined       No=25

19

76

6

24

Table-41

X- ray finding in different sexes.

Patient’s 

X-ray L-S spine

Normal

Osteoporotic changes

Degenerative changes

Combined (Both Osteo. + Degen. Changes)

No. of pt.

%

No. of pt.

%

No. of pt.

%

No. of pt.

%

Male        No =30

2

6.7

4

13.3

24

80

Female    No =30

3

10

9

30

10

33.3

8

26.7

 

Table-42

X-ray finding

Bone loss found in BMD

No bone loss found in BMD

Positive scan

20

1

Negative scan

31

8

51

9

Discussion:

The present study was under taken in elderly patient’s presenting with low back pain to evaluate the frequency of osteoporotic changes in skeleton and to evaluate the sensitivity of radiology for assessing bone density in medicine units of Rajshahi Medical College Hospital from 12-10-2005 to 16-07-2006. A total 60 cases were studied. Among them 30 patient’s were male & 30 patient’s were female. In this series, the peak incidence of bone mineral losses occurred in 60 & up year’s age group. Next age group was 55-59 years. 50% of patient’s in 60 & up year’s age group and 20% of patient were 55-59 years age group. In male patient’s, highest 60% were in 60 & up years age groups, 2nd highest 20% were in 45-49 years age group, In female patient’s, highest 40% were in 60 & up years age group, second highest 33.3% were in 55-59 years age group. The youngest patient was 45 years and oldest patient was 81 years. On the basis of many epidemiologic clinical and laboratory findings, Riggs and his colleagues have proposed that evolutional osteoporosis is divided in to two major and distinct syndromes, ie, Type- I : post menopausal osteoporosis & Type – II : Age related osteoporosis.168 This study is very much similar to the mentioned categories. 168

Mean height was 163.1cm. Maximum patient’s was in 160-169cm group. Next height number of patient’s was in 150-159 cm group. So 61% patient’s were in 160-169cm height group, & 23% patient’s were in 150-159cm height group. In male patient’s, highest 56.7% were in 160-169 cm height group and next 26.7% of patient’s were in 170 & up cm height group and patient’s in < 150cm height group. In female patient’s, highest 66.7% of patient’s also were in 160-169 cm height group and next 30% of patient’s were in 150-159cm height group and no patient in 170 and up cm height group.

Normal BMD presentation patient’s group, 75% were in 160-169 cm weight group and next 25% were in 150-159cm group. In osteopenic BMD presenting patient, highest 64.7% were in 160-169cm group & next highest 17.6% were in equally in 150-159 cm & 170 and up cm groups. In osteoporotic BMD presenting patient’s, highest 50% were in 160-169 cm group & next 35.7% were in 150-159cm group and 7.1% were equally in < 150 cm & 170 & up cm groups. In combined BMD presenting patient’s, highest 64% patient’s were in 160-169 cm group and next highest 20% were in 150-159cm group. So there is association between the height and bone mineral losses.118, 119

The maximum number patient’s was in < 50kg weight group. Next maximum number of patient’s was in 50-59kg weight group. So 53.3% were in <50kg group and 21.7% were in 50-59kg group. In male patient’s 43.3% were in <50kg group & next highest 26.7% were in 50-59kg group. In female patient’s, highest 63.3% were in <50kg group and next 16.7% were in 50-59 kg group. In normal BMD presenting patient’s, 75% were in 60-69kg group and next 25% were in 50-59kg group. In osteopenic BMD presenting patient’s maximum 29.4% were in <50kg group and next 23.5% were equally distributed to the rest of the groups. In osteoporotic BMD presenting patient’s, highest 78.6% were in <50kg group and in combined BMD presenting patient’s, highest64% were in <50kg group. So there is positive relationship between weight & bone mineral density.120, 127, 169.

The maximum of patient’s BMI were in < 18.5kg /m2 group & next highest number of patient’s were in 18.5 –24.9kg/m2 group. 45% were in < 18.5kg/m2 group and next highest 43.3% were in 18.5-24.9 kg /m2. In male patient’s, 43.3% group were in 18.5-24.9kg/m2 and next highest 40% were in <18.5 kg /m2 group. In Female patient’s, highest 50% were in <18.5kg/m2 group and next highest 43% were in 18.5-24.9 kg/m2 group. In normal BMD presenting patient’s, 50% equally in 18.5-24.9 kg/m2 and 25-29.9 kg/m2 groups. In osteopenic BMD presenting patient’s, maximum 58.8% were in 18.5-24.9 kg/m2 group and next highest 17.6% were in <18.5 kg/m2. In osteoporotic BMD presenting patient’s, maximum 78.6% were in < 18.5% kg/m2 group and next 21.4% were in 18.5-24.9 kg/m2 group. In combined BMD presenting patient’s, highest 52% were in <18.5 kg/m2 group & next highest 44% were in 18.5-24.9 kg/m2 group. So body mass index (BMI) has positive correlation with bone mineral density which is consistent with the study by C.A.F. Zerbini et all from Brazil (2000).170

Highest number of patient 44 (73.3%) from rural, and 16 (26.7%) from urban. In male patient 25(83.3%) from rural and in female patient’s 19(63.3%) from rural. In normal BMD presenting patient’s, 50% equally from urban & rural. In osteopenic BMD presenting patient’s, 76.5% from rural, & 23.5% from urban. In osteoporotic BMD presenting patient’s, 78.6% from rural & 21.4% from urban. In combined BMD presenting patient’s, 72% from rural & 28% from urban. So in rural population, bone mineral losses higher than urban population.

Highest number 33 (55%) patient’s are poor, and then 25(41.7%) patient’s are in middle class. In male patient’s, 56.7% patient’s are poor and then 40% patient’s are in middle class. In female patient’s, 53.3% patient’s are in poor & then 43.3% patient’s are in middle class. In normal BMD presenting patient’s, 75% patient’s are in middle class and 25% patient’s are in poor. In osteopenic BMD presenting patient’s, 58.8% are in poor and 35.3% patient’s are in middle class. In osteoporotic BMD presenting patient’s, highest 75.2% patient’s are poor and than 35.7% patient’s are in middle class. In combined BMD presenting patient’s, 56% are poor & then 44% patient’s are in middle class. So in poor socioeconomic condition, bone mineral losses is high, which in consistent with the study by May-Choowang, et all from USA (2006).171

All female patient’s occupation were housewife. But in male patient’s, others (like land lord) occupation were 63.3% & 16.7% patient’s occupation were business & 10% patient’s occupation equally were labor & service. In normal BMD presenting male patient’s, 66.7% patient’s occupation were others & 33.3% patient’s occupation were service. In osteopenic BMD presenting patient’s, 80% patient’s occupation were others and 10% patient’s occupation equally were business and labor. In osteoporotic BMD presenting male patient’s, 50% patient’s occupation were others and 50% patient occupation were business. In combined BMD presenting male patient’s, 53.8% patient’s occupation were other’s and 15.4% patient’s occupation equally were labor, service and business. So BMD losses marked in other’s occupation patient’s, in which occupation physical labor is minimal.32 So BMD has positive correlation with physical activity which is consistent with the study by Alex A. Florindo, et al from Brazil (2002)172

None of the male patient’s have family history positive. Among female patient’s, only 26.7% patient’s have family history of nontraumatic fractures of bones. In osteopenic BMD presenting patient’s, only 28.6% female patient’s family history positive. In osteoporotic BMD presenting female patient’s, only 10% patient’s have family history positive. In combined BMD patient’s 41.7% patient’s have family history positive. So, those who are family history positive, much of them in combined BMD that is either osteoporosis of lumber vertebra and osteopenia of femoral neck or osteoporosis femoral neck and osteopenia of lumber vertebra. This study consistent with the study by Eric S. Orwoll, et all in 1996.173

Among male patient’s, only 3.3% of patient’s have D.M. & among female patient’s, only 3.3% patient, have D.M. In normal BMD presenting patient’s, 25% patient’s have D.M. and in combined BMD presenting patient’s, only 4% patient’s have D.M. So there is no association between BMD & D.M. This study is consistent with the study by M. Sert, et all in 2003.174

Among the male patient’s, 76.7% patient’s are smokers and only among female patient’s, only 3.3% patient’s are smokers. In normal BMD presenting patient’s, 50% patient’s are smokers. In osteopenic BMD presenting patient’s, 47% patient’s are smokers. In osteoporotic BMD presenting patient’s, only 28.6% patient’s are smokers. In combined BMD presenting patient’s, 40% patient’s are smokers. So there is no significant relation between smoking and BMD. In 1994, H May, el al in U.K. also shown that there is no significant relation between smoking and BMD.175

Among female patient’s, 43.3% patient’s menopausal duration are 5-10 years group. Next highest 36.7% female patient’s menopausal duration are 10 and up years group. In normal BMD presenting patient’s, 100% are in 5-10 years group. In osteopenic BMD presenting patient’s, highest 57.1% patient’s are in <5years menopausal duration group and next 28.6% patient’s are in 5-10 years menopausal duration group. In osteoporotic BMD presenting patient’s, maximum 70% patient’s are in 10and up years menopausal duration group and next 30% patient’s are in 5-10 years menopausal duration group. In combined BMD presenting patient’s, 58.3% patient’s are in 5-10 years menopausal duration group and next maximum 25% patient’s are in 10 and up years menopausal duration group. So there is negative association beteen BMD and menopausal duration. S. Chowdhury, et al (2001) from Dhaka also got negative association between BMD and menopausal duration.169

45% patient’s back pain duration <1years group & 55% patient’s back pain duration> 1 year. In male patient’s, 63.3% patient’s back pain duration > 1years group and only 36.7% patient’s back pain duration <1year.  In female patient’s, 53.3% patient’s back pain duration < 1years group and 46.7% patient’s back pain duration are in > 1year group. In normal BMD presenting patient’s, 50% patient’s are equally distributed in both groups. In osteopenic BMD presenting patient’s, 52.9% patient’s are in <1year back pain group. In osteoporotic BMD presenting patient’s, 57.2% patient’s are in >1year back pain group. In combined BMD presenting patient’s, 60% patient’s are in > 1year back pain duration group. So there is an positive association between BMD and back pain duration. Takashi Manabe in 2003 have shown that there is positive relation between BMD and back pain.176

In normal BMD presenting patient’s, 25% patient’s have systolic B.P. <140mm of Hg and 75% patient’s have systolic B.P. 140-160 mm of Hg. group. In osteopenic BMD presenting patient’s, 52.9% patient’s have systolic B.P. < 140 mm of Hg and 47.1% patient’s have systolic B.P. in 140-160mm of Hg. In osteoporotic BMD presenting patient’s, 57.1% patient’s have systolic B.P. < 140mm of Hg group and 42.9% patient’s have systolic B.P. 140 –160 mm of Hg. In combined BMD presenting patient’s, 48% patient’s systolic equally in <140mm of Hg and 140-160mm of Hg. group and 40% patient’s have systolic B.P. in >160 mm of Hg. group. So there is no association between systolic B.P. and BMD.

In normal BMD presenting patient’s, 25% patient’s have diastolic B.P. <90mm of Hg and 75% patient’s have diastolic B.P. in 90-100 mm of Hg. group. In osteopenic BMD presenting patient’s, 82.4% patient’s have diastolic B.P. < 90 mm of Hg and 17.6% patient’s have diastolic B.P. in 90-100mm of Hg. In osteoporotic BMD presenting patient’s, 48% have diastolic B.P. equally distributed in < 90mm of Hg and 90-100 mm of Hg groups and 4% patient’s have diastolic B.P. >160 mm of Hg groups. So there is no association between diastolic B.P. and BMD.  But E. A. Jan Kowska, et al in 2002 have shown that there is no relationship between BMD and systolic B.P., but inverse relationship between BMD and diastolic B.P.177

In the present study BMD at the lumbar spine and femoral neck level was higher for men than for women in all age groups. BMD at the femoral neck level deceased for both sexes with age but reduction was lesser and later for men. BMD is higher in lumber vertebra then for femoral neck, this is because of osteophytes. This study is consistent with the study by C. A. F. Zerbini, et all from Brazil (2002).170 Radiology is of limited value unless there is severe bone loss or compression fracture occur. Radiology is the least sensitive method for assessing for bone density. This study is consistent with the study by selim M Ansari, et all from Bangladesh (2002).178


Summary and Conclusion: 

A series of 60 cases were studied which included 30 male & 30 female elderly patient’s presenting with low back pain in medicine units of Rajshahi Medical College Hospital, Rajshahi. The mean age of the patient was 58 years. Maximum number of patient’s height is 160-169cm group. Maximum number of patient’s weight were <50kg (male>female) in weight. 50%female & 40% male patient’s BMI were <18.5kg /m2. About 73.3% patient’s were from rural origin. Maximum patient’s were poor. About 76.7% male patient’s were smoker. Females were housewives and most male patient’s occupation were different. Only 26.7% female patient’s had family history of nontraumatic fracture of bones of their mothers. Most of the female patient’s menopausal duration was >5 years.  Maximum female patient’s back pain duration was <1year and maximum male patient’s back pain duration was >1year. Maximum male patient’s presented as either osteopenic of combined BMD and maximum female patient’s either osteoporotic or combined (osteoporosis of the lumber vertebra and osteopenia of the femoral neck or osteoporosis of the femoral neck and osteopenia of the lumber vertebra). There was an inverse relationship between BMD and the age. There was an positive relationship between weight and BMD. Body mass index (BMI) had positive relation with the BMD. Bone mineral losses were high in poor socioeconomic condition. In male patient’s BMD losses marked in other’s type occupation, in which physical labor was minimal. Bone mineral losses were higher in rural population than urban population. Those who had family history that is history of nontraumatic fracture of bones of their mothers, many of them had combined reduction of BMD (either osteoporosis of the lumber vertebra and osteopenia and femoral neck or osteopenia of the lumber vertebra and osteoporosis of the femoral neck) and also reduced BMD. There was no significant relation between smoking and BMD. There was also no relationship between D.M. and BMD. There was negative relationship between menopausal duration and BMD. Blood pressure (Systolic and diastolic) had no relationship with BMD. 80% male patient’s X-ray L-S spines finding was degenerative changes. But in female patient’s, X-ray finding nearly equally distributed in osteoporotic changes or degenerative changes or combined (Both osteoporotic + Degenerative changes) changes. BMD at the lumber spine and femoral neck level was higher for men than for women in all age groups. BMD at femoral neck level decreased for both sexes with age but reduction was lesser and later for men. BMD was higher in lumber vertebra than for femoral neck, this was because of osteophytes. Radiology was of limited value unless there was severe bone loss and compression fractures occurred. Radiology was the least sensitive method for assessing bone density.

We studied only a limited number of patient’s in an urban hospital setting lacking inadequate epidemiological date & works. So this study revealed many features which were not similar to real clinical situations in our country. On the other hand, western standard and styles are also different. On that ground, it may partially meet up the requirements to fill up the gap or better to say to add something to the bottomless ocean of knowledge.

Case No. 01

Md. Abul Kasem, 65 years, from Mohadebpur, Noagan, retired service man of bellow average body build and body weight, ex-smoker, non-diabetic, normotensive admitted on 26-02-2006 bed no P/3, RMCH, Rajshahi with low back pain and pain in the Rt. Knee. His loss of height was absent and morning stiffness for at least 1 hour was absent. He complained weight loss for 1 year. Heat intolerance was absent. His appetite was normal. Bowel habit was normal. His back pain had no radiation; duration was 21/2 months. Pain in the Right Knee joint was sudden onset and joint was swelled up and increase hotness over the joint. He was non alcoholic, His dietary habit was average. His past history was insignificant. He did not give any family history of non traumatic fracture on bones of his parent.

On examination: he was ill looking, below average body build, with anaemia, but had no jaundice, cyanosis, clubbing & oedema. His pulse rate was 76/min, rhythm was regular, character and volume was normal. His BP was 120/65 mm of Hg.

Straight leg raising (SLR) test was negative. Examination of the Rt. Knee joint revealed that temperature was increased, tenderness present, and massage test was positive. Others systemic examination was normal.

On investigation, X-ray L-S spines showed degenerative changes in the lumber spines. BMD study done by DEXA scan, showed osteoporosis in the both hips and osteopenia of the lumbar spines. This is showed in the figure A, B, C. Blood examination showed Hb%-45%, ESR-60 mm in 1st hour. Total count was normal & there was neutrophilia. C-RP was high. Serum calcium was 8.2mg /dl. RBS with CUS and serum creatinine were normal, S. uric acid was 8.5mg/dl. Features of the blood film and bone marrow can not be ruled out storage disease. No punch out lesion was seen on X-ray skull (lateral view). Urinary benze jones protein was negative.

The diagnosis was lumber spondylosis with osteoporosis of the both hips and osteopenia of the lumber spines and acute gout.

Case No: 02

Mrs. Lokjhan 70 years, housewife, from Durgapur, Rajshahi, poor socioeconomic condition, non-diabetic, normotensive, admitted in RMCH, Rajshahi, with the complaints of back pain. There was no radiation of pain, dull in nature, persistent in character, not aggravated by coughing, sneezing.    There was no history of morning stiffness for at least 1 hour. Loss of height, weight loss, and heat intolerance was absent. Appetite was normal. Alteration of bowel habit was absent. She was a non-alcoholic, non-smoker. Her dietary habit was average. She had no significant past illness. She had no family history of non-traumatic fracture of bones of her parent.

On examination, she was ill looking, below average body build with no anaemia, jaundice, cyanosis, clubbing, oedima. Her pulse rate was 70/min, rhythm was regular, character and volume was normal. Her BP was 110/65 mm of Hg.

Straight leg raising (SLR) test was negative. Examination of the other systems was also normal.

On investigation, X-ray L-S spines showed osteoporotic changes. Bone menial density (BMD) study done by DEXA scan showed osteoporosis of the both hips and lumber spines. This was shown in Fig. D, E, F. Blood Examination showed Hb%, ESR, TC, DC, normal & CPBF showed non-specific findings. Random blood sugar was normal.

The diagnosis was osteoporosis of the lumber spines and the both hips.

Corrosive Poisoning


Corrosive Poisoning

 

 

Edited By :

Dr.Salim Al Mamun

MBBS(Raj);CCD(BIRDEM);

CMU(DU);DMUD(Course)

 

 

 

Introduction:

Any chemical when ingested causing tissue injury to the gastrointestinal mucosa may termed as caustics- which are also known as corrosive poisons-i-e. strong acids locally produce corrosion and tissue necrosis, when they come in contact. They coagulate tissue proteins; fix the tissue, extract tissue fluid, and if the person survives for a reasonable period, then there is ulcer formation, sloughing of the necrosed tissue and scar formation with contracture.

Mineral acids and alkalies (corrosive agents) have direct local action, but may have indirect action, when ingested and absorbed in the system viz, circulatory and respiratory systems. Organic corrosive agents cause direct local and remote action as they are absorbed and reache to the different systems.

Classification:

According to chemical action, corrosive agents may classify as:

Corrosive Poison

 

 

Mode of Action:

When ingested, moderately strong acids produce coagulation necrosis of the gut mucosa, and formation of Escher limits the damage up to the superficial layers, while alkalies cause liquifactive nercosis of the mucosa with saponification and continued deeper penetration into the underlying tissues causing extensive damage.

In both strong acids and alkalies, tissues immediately become corroded, soft and some times dissolved, disintegrated and perforated and thus the whole or part of it, or part of the intestine turns into a small soft pulpy mass.

Acids:

Domestic Use: Many of acids are used in various household products like toilet. Bowl cleaner. Metal cleaner, antirust compound, battery fluid and pool sanitizer. Industrial use of acids includes electroplating, photography, calico printing, rayon manufacturing and in different chemical laboratory.

A)   Sulphuric acid: It is a colourless, heavy, oily, odourless hygroscopic liquid. It causes brittle chalky white teeth, ulceration of the mouth, oesophagus and stomach, where there may be perforation followed by generalized peritonitis.

Vitriolage: Throwing of the corrosive substance specially sulphuric acid ( Oil of vitriole) on any person usually on the face for disfiguration due to enemity or rivality is called vitriolage, which is a grievous hurt and a punishable offence.

B)   Nitric acid: Pure nitric acid is a clear, colourless, pungent choking odour liquid and emits white fumes when exposed in open air. Locally it is corrosive agent causing yellow colouration of the teeth and produce respiratory distress.

C)   Hydrochloric acid: Pure hydrochloric acid is a volatile colourless, odourless (Liquid) having burning sour taste. Shock usually occur due to severe pain. There may be no significant change in the teeth.

D)   Oxalic acid: It is a colourless transparent prismatic crystals and sour in taste. It is used in calico printings, manufacturing of straw hats, removing ink from the paper and cloths, removing rust stains from the metallic and wooden articles and preparation of various pickles and chanachurs. Its common clinical features are feeble pulse, cold and clammy skin, low blood pressure and shallow respiration. Coma and death due to asphyxia followed by respiratory failure.

E)   Acetic acid: It is a colourless liquid with sour taste and pungent smell. In concentrated form it is corrosive, but in diluted form it is irritant. Vinegar contains 4-5% acetic acid.

F)   Picric acid: Locally it produces corrosion with tissue necrosis. When ingested, it causes muscular cramping, drowsiness, stupor, decomposes red blood cells, meth-haemoglobinaemia and irritate CNS following convulsion coma and death. In low dose it causes cramping pain in the stomach, yellow vomiting, diarrhea of yellow liquid stool, yellow colouration of the skin and conjunctiva, dilatation of pupil with marked dehydration. Urine first becomes dark yellow, then turns into ruby red colouration with dysuria, even anuria.

G)   Formic acid: When ingested it produces cramping pain in the stomach, petechieal haemorrhage, intravascular haemolysis, disseminated intravascular coagulalation, severe acidosis, renal failure etc.

H)   Carbolic acid: It is a dark magenta coloured liquid with a typical phenol odour. Carbolic acid poisoning (Carbolism) includes- hot burning pain extending from the mouth to the stomach. Skin- becomes cold and clammy with subnormal temperature. Pupil constricted, feeble thready pulse, hypotension, slow laboured stertorous respiration with convulsion and lock jaw.  Oliguria or anuria may be present. Urine contains albumin, blood casts and metabolic products i.e. hydroquinone and pyrocatechol- colouring the urine Olivo green-known as carboluria.


Summary feature of acid poisoning:

Skin contact with acid causes pain, blistering, ulceration and lacerating necrosis, with severe scarring after weeks.

Ingestion by mouth causes immediate pain with pharyngeal edema and burns. Pain and mucosal edema causes difficulty in swallowing. Features of pharyngeal involvement includes hoarseness, stridor, respiratory distress and laryngeal and/or epiglottic edema. Perforation of the esophagus and/or stomach may occur, which can lead to chemical peritonitis. Abdominal pain, vomiting, diarrhea and haematmesis occur in more severe cases. Systemic effect includes circulatory collapse, metabolic acidosis, hypoxia, respiratory failure, intravascular coagulation and hemolysis. Renal failure occurs as the end result of ATN. Later effect of acid ingestion includes pyloric stenosis, stricture formation and achlorohydria.

 

Grading system for corrosive burns of the alimentary tract with endoscopy:

Grade             Features

v  1                Erythema and oedema only

v  2a              Localized,superficial friability,blistes or ulceration

v  2b              Features as for grade 2a,but with circumferential ulceration

v  3                Multiple deep ulcers,area of necrosis

Diagnosis is based on the history of exposure

Management and treatment:

1.            Emesis should not be induced.It is contraindicated.

2.            Attempt at gastric lavage is contraindicated due to danger of perforation.

3.            Dilution and /or neutralization is also contraindicated

4.            Steroids confer no benefit & may mask abdominal sign of perforation

5.            Early endoscopy as soon as possible.

6.            Inj Morphine / Diclofenac sodium for pain

7.            Soluable calcium tablet for hydrofluric acid ingestion if patient able to swallow followed by I.V. Inj. of 10% calcium gluconate 10ml with I.V. infusion of dextrose in normal saline.

8.            Oxygen inhalation and artificial respiration if necessary.

9.            For external burn and eye injury  wash immediately with water or saline for 10 to 30 minutes. Then use oint silver sulphadiazine for skin, and chloramphenicol eye point for eye.

10.         For oedema of the glottis- tracheostomy should be done.

11.         Surgery: For esopheseal stricture and gastric outlet obstruction. Usually done after 4-6 weeks of ingestion.

12.         Management of complications (e.g. peritonitis) if any.

 

Alkalis:

Sodium Hydroxide (Caustic soda) is a constituent of oven and drain cleaners and dishwashers.

Sodium carbonate (washing soda) having strong alkaline taste is less toxic than potassium carbonate.

Potassium hydroxide (caustic Potash) is a soapy viscid in touch, used in hearing aid batteries.

Potassium carbonate is a white crystalline powder having a caustic and alkaline taste used as a cleaning and washing agent.

Bleach: Common house hold bleach has 3-6% of sodium hypochlorite. Its PH is about 11, more of which cause oesophagial ulceration.

Detergents: Most of the detergents contain sodium tripolyphosphate and sodium carbonate which are weakly alkaline and usually do not produce significant toxicity.

Ammonium hydroxide- contains 32.5% of ammonia and is used at home for removing paint, oil and dirt usually from the clothing.

 

Clinical Features:

  • Alkali damage to the oesophagus may produce diffused blurred oesophageal mucosul ulceration, sloughing, with petechial haemorrhagic spottings throughout the whole mucosa and its underlying tissues. Perforation of gastric or intestinal wall is less common. Oesophageal perforation can develop and as its sequel medistinitis pneumonitis, cardiac injury and tracheo oesophageal & aortico-enteric fistula may ensue.
  • Metabolic acidosis may develop in patients with severe gastrointestinal bleeding.
  • Renal failure is a rare complication, may be accompanied by Gl bleeding and shock.
  • Inhalation of alkaline vapour may cause hoarseness,stridor,upper airway oedema, wheezing, pneumonitis and respiratory failure.
  • Ocular exposure may produce severe conjunctival irritation, chemosis, corneal epithelial defects, limbal ischemia and permanent visual loss may occur in severe cases.
  • Dermal contact with alkaline corrosives may produce redness, irritation, pain and sometimes-full thickness burns of the skin.

Diagnosis: Is based on history of the exposure and PH of the collected gastric lavage.

Management/ Treatment:

  1. Dilution or neutralization, induce emesis, gastric aspiration and lavage are contraindicated.
  2. Irrigate exposed eyes with sterile cold water or saline at least for 20 minutes and continue until the PH returns to normal.
  3. Emulcents- egg white, olive oil, butter, cold milk should be avoided.
  4. Clear air way and support with O2 inhalation and artificial respiration, if necessary intensive care unit support including ventilator.
  5. I.V. fluid for maintaining nutrition and electrolyte balance.
  6. As there is no specific antidote for alkaline corrosives, symptomatic treatments are to be done. Neutralisation with alkali now-a-days is not done.
  7. Surgical treatment must be considered for any patient with grade II or III esophageal injury.
  8. Analgesia including Narcotics,or NSAID (Inj. Diclofenac)  may be given to relieve pain
  9. Diagnostic endoscopy should be performed within 12-24 hrs of alkali ingesion.
  10. Corticosteroids have no role in the management of a case and complication. It is rather harmful.

Medico legal importance:

  1. Usually accidental poisoning due to over dose
  2. Suicidal poisoning very rare
  3. Homicidal Poisoning not adopted

Benzodiazepine Poisoning


Benzodiazepine Poisoning:

 

Edited By :

Dr.Salim Al Mamun

MBBS(Raj);CCD(BIRDEM);

CMU(DU);DMUD(Course)

 

 

 

Benzodiazepines (BZD) are commonly used for a variety of situations that include seizure control, anxiety, alcohol withdrawal, insomnia, control of drug-associated agitation, as muscle relaxants, and as pre-anesthetic agents. Because of their widespread popularity, these drugs are commonly abused. In addition, BZDs frequently are used in overdose, either alone or in association with other substances especially in suicidal attempt and transport related poisoning.

The rate of onset of action is determined by rate of benzodiazepine absorption from the GI tract. Benzodiazepine absorption is especially rapid when ethanol is present and the stomach is empty. Peak blood concentrations of most agents occur within 1-3 hours. Benzodiazepines are metabolized predominantly in the liver by oxidation and/or conjugation. Most benzodiazepines are broken down into pharmacologically active metabolites, which may have longer half-lives than the parent compounds.

Mortality/Morbidity:

Benzodiazepines are generally thought to be safe and death is rare. Mortality from a pure benzodiazepine overdose is rare; it usually occurs in conjunction with concomitant alcohol ingestion or use of other sedative-hypnotics. Intravenous administration or overdose of ultrashort-acting benzodiazepines (eg, triazolam) is more likely to result in apnea and death. Elderly individuals and very young persons are more susceptible to the CNS depressant effects of benzodiazepines than people in other age groups. Intravenous administration is associated with greater degrees of hypotension than other routes of administration and occasional cardiac and respiratory arrest.

History: History should include the time, dose, and intent of the overdose. Determine if co-ingestants are present and the duration of benzodiazepine use. Symptoms include – Dizziness, Confusion, Drowsiness, Blurred vision, Unresponsiveness, Anxiety and Agitation.

Physical: The physical examination should focus on the patient’s vital signs and cardiorespiratory and neurologic function. The frequently found physical signs are- Nystagmus, Hallucinations, Slurred speech, Ataxia, Coma, Hypotonia, Weakness, Altered mental status, impairment of cognition, Amnesia, Paradoxical agitation, Respiratory depression and Hypotension

Workup: Qualitative screening of urine or blood may be performed but rarely influences treatment decisions. Obtain an arterial blood gas if respiratory depression is present. Following an intentional overdose, measure serum electrolytes, glucose, BUN, creatine clearance, and acetaminophen concentration. Obtain a pregnancy test in women of childbearing age. Obtain a chest x-ray if respiratory compromise is present. Evaluate for aspiration. Evaluate for acute respiratory distress syndrome (ARDS). Obtain an electrocardiogram (ECG) to evaluate for co-ingestants, particularly cyclic antidepressants.

Treatment:

Prehospital Care: 

  • Supplemental oxygen
  • Intravenous access
  • Rapid blood sugar
  • Naloxone, if the diagnosis is unclear or an opiate co-ingestion is suspected

Emergency Department Care:

  • Continue supportive care and monitoring (e.g., cardiac monitoring, IV, oximetry, vital signs).
  • Decontamination

o   Gastric lavage is not recommended but may be considered if the presence of a lethal co-ingestant is suspected and the patient presents within 1 hour of ingestion.

o   Single-dose activated charcoal is recommended for GI decontamination in patients who present within 1 hours of ingestion or in symptomatic patients when the time of ingestion is unknown.

  • Respiratory depression may be treated with assisted ventilation.

Medications:

Antidote:

Flumazenil is a selective competitive antagonist of the GABA receptor and the only available specific antidote for benzodiazepines; it will reverse effects of benzodiazepines but must be used with caution. In overdose situations, flumazenil may be used for patients with pure benzodiazepine overdose who are verbally unresponsive and have no history of long-term benzodiazepine use or seizure disorder. ECG should be performed before use to confirm the absence of cardiac conduction disturbances (which would suggest the presence of cyclic antidepressants). Use as a diagnostic and therapeutic agent for unsubstantiated drug-associated coma is controversial. A positive response to small titratable doses may obviate the need for endotracheal (ET) intubation and the search for other causes of coma.

The absence of clinical response to 2 mg of flumazenil within 5 to 10 minutes indicates that benzodiazepines poisoning may not be major cause of CNS depression or coma.

The patient regains consciousness within 15 to 30 seconds after injection of flumazenil, but since it is metabolised more rapidly than the benzodiazepines, recurrence of toxicity and CNS depression can occur and the patient should be carefully monitored after initial response to flumazenil therapy.

If the patient becomes unconscious again, flumazenil can be given by IV infusion 100‑400 micrograms/hour rate being adjusted according to level of arousal.

Adult Dose: 0.1-0.2 mg IV q1min to a total dose of 1 mg at one time or 3 mg in 1 h; infusion rates of 0.1 mg/min decrease disconcerting rapid arousal.

Pediatric Dose: 0.002-0.02 mg/kg IV q1min.

 

Contraindications:

Documented hypersensitivity; serious cyclic-antidepressant over dosage; patients using benzodiazepines to control a potentially life-threatening condition (eg, intracranial pressure, status epilepticus); chronic benzodiazepine use.

Pregnancy: category-C Safety for use during pregnancy has not been established.

Precautions:

Patients on benzodiazepines for prolonged periods may experience seizures; monitor for resedation and unmasking of seizures

Abusive Substance Poisoning

People abuse substances such as drugs, alcohol, and tobacco for varied and complicated reasons, but it is clear that our society pays a significant cost. Abused substances produce some form of intoxication that alters judgment, perception, attention, or physical control. Withdrawal of many of these can range from mild anxiety to seizures and hallucinations. Drug overdose may also cause death.

 

Few abusive substances, their toxic symptoms and management are enumerated below (alcoholic intoxication described elsewhere)–

Opiates: codeine, dihydrocodeine, morphine

Toxicity is enhanced if other CNS depressants such as alcohol are ingested as well.

Toxic dose: A toxic dose of opiate is difficult to assess as individual tolerances vary greatly. Therefore, the following doses are to be interpreted with care: Codeine: 350 mg. Dihydrocodeine: 420mg., Morphine: 30 mg (patients may be on higher doses in therapy; the clinical effects may occur if established dose is exceeded). Overdoses may present with nausea and vomiting. Some opioids may cause a rash, itching, flushing, drowsiness and pinpoint pupils. Fensidyl, commonly used recreational medicine in Bangladesh, contains high amount of codeine and dihydrocodeine.

In severe poisoning:

  • Unconsciousness, convulsions, hypotension.
  • Respiratory depression with cyanosis and respiratory arrest. Hypoxia due to respiratory depression is the most frequent cause of death from opioid poisoning. Serious complications include Non-cardiogenic pulmonary oedema, cardiovascular collapse, and renal failure.

 

Management:

  • Activated charcoal can be given within 1 hour of ingestion to reduce absorption unless the patient is drowsy, fitting or vomiting.
  • Naloxone can be given to reverse the signs of severe poisoning (coma, respiratory depression or convulsions) within a few minutes but it has a short life and the patient may relapse.
  • All patients who have taken an overdose of opioid analgesics should be transferred to hospital and observed for at least 6 hours. Patients who require naloxone should be observed for 24 hours. ECG monitoring and ventilation may be needed.

Marijuana (also known as ganja, grass, pot, weed, herb):

Marijuana comes from the plant Cannabis sativa. The plant produces delta-9-tetrahydrocannabinol (THC), the active ingredient associated with intoxication. Marijuana resin, called hashish, contains an even higher concentration of THC. The drug is usually smoked, but it can also be eaten. Common effects of marijuana use include pleasure, relaxation, and impaired coordination and memory. Often, the first illegal drug people use, marijuana is associated with increased risk of progressing to more powerful and dangerous drugs such as cocaine and heroin. It is virtually impossible to overdose from marijuana, which sets it apart from most drugs.

Heroin (also known as smack, horse): Effects of heroin intoxication include drowsiness, pleasure, and slowed breathing. Withdrawal can be intense and can include vomiting, abdominal cramps, diarrhea, confusion, aches, and sweating. Overdose may result in death from decreased breathing.

 

May present with:

  • Onset of effects within 30 minutes of ingestion or within seconds to minutes after IV injection. The peak effects last for about 10–30 minutes and continue in milder form for 2–4 hours.
  • Nausea, vomiting.
  • Dry mouth, constricted pupils, drowsiness, confusion, euphoria, a sense of calmness, flushing, sweating and a feeling of warmth.

In severe cases:

  • Hypotension, coma, bradycardia, respiratory depression with associated hypoxaemia and pulmonary oedema, cardiac arrhythmias. The pupils may be dilated if hypoxic cerebral damage has occurred.

 

Management:

  • Activated charcoal can be given within 1 hour of ingestion to reduce absorption unless the patient is drowsy, fitting or vomiting.
  • Naloxone can be given to reverse the signs of severe poisoning (coma, respiratory depression or convulsions) within a few minutes, but it has a short life and the patient may relapse.
  • All patients who have taken an overdose of opioid analgesics should be transferred to A&E and observed for at least 6 hours. Patients who require naloxone should be observed for 24 hours. ECG monitoring and ventilation may be needed.
  • Adult dose 0.4mg, can be repeated at intervals of 2-3 minutes to a maximum of 10mg.  (Naloxon ampoule, 0.4mg/ml).

 

Tricyclic antidepressants:

Includes: amitriptyline, amoxapine, clomipramine, dothiepin, doxepin, imipramine, lofepramine, nortriptyline, protriptyline and trimipramine.

Although the individual TCAs have differences in side-effects and kinetics, most behave similarly in an acute overdose. Peak plasma levels normally occur within 2–8 hours of a therapeutic dose because of delayed gastric emptying. After an overdose, peak levels may occur even later. Life-threatening signs usually develop within 6 hours of ingestion or not at all. The complications most often associated with a fatal outcome are severe hypotension and cardiac arrhythmias.

Toxic dose:

  • Hospital observation is recommended for ingestion > 5 mg/kg.
  • 10-20 mg/kg can be life threatening.
  • Anticholinergic effects, sedation and hallucinations can occur at doses
    < 5 mg/kg.

May present with:

  • Dry mouth, dilated pupils, urine retention, hallucinations, jerky movements, drowsiness.
  • Metabolic acidosis and hypokalaemia.

In severe poisoning:

  • Coma, hypotension, hypothermia, convulsions, respiratory depression, pulmonary oedema, cardiac arrhythmias, cardiac arrest. Arrhythmias may not respond to therapy.
  • Lofepramine is less likely to cause cardiac effects.
  • Amoxapine is more likely to cause arrhythmias and convulsions.

Management:

  • Activated charcoal can be given within 1 hour of ingestion to reduce absorption unless the patient is drowsy, fitting or vomiting.
  • Diazepam can be given to control fits if they are prolonged.
  • Because of the potential for serious toxicity, all patients should be transferred to A&E for observation and to monitor their ECG, pH and electrolytes for at least 6 hours post-ingestion.
  • In serious poisoning, ventilation and intensive care will be necessary.

Cocaine (also known as crack, coke, snow, rock):

Derived from the coca plant of South America, cocaine can be smoked, injected, snorted, or swallowed. Desired effects include pleasure and increased alertness. Short-term effects also include paranoia, constriction of blood vessels leading to heart damage or stroke, irregular heartbeat, and death. Severe depression and reduced energy often accompany withdrawal. Both short- and long-term use of cocaine has been associated with damage to the heart, the brain, the lung, and the kidneys.

The fatal dose of cocaine has been approximated 1.2 g, although severe toxic effects have been reported from doses as low as 20 mg.

Symptoms:

The symptoms of cocaine poisoning are referable to the CNS, namely the patient becomes excited, restless, garrulous, anxious and confused. Enhanced reflexes, headache, rapid pulse, irregular respiration, chills, rise in b.p, temperature, mydriasis, exophthalmos, nausea, vomiting, and abdominal pain are noticed in severe overdoses, delirium, Cheyne-Stokes respiration, convulsions, unconsciousness and death from respiratory arrest result. Acute poisoning by cocaine is rapid in developing.

Treatment:

The specific treatment of acute cocaine poisoning is the intravenous administration of a short-acting barbiturate or diazepam. Artificial respiration may be necessary. It is important to limit absorption of the drug. If entrance of the drug into circulation can be checked, and respiratory exchange maintained, the progress is favorable since cocaine is eliminated fairly rapidly.

Amphetamine and MDMA (ecstasy)

MDMA is an amphetamine derivative. It is taken as a tablet or powder enclosed in a capsule. Adverse effects more commonly occur after ‘recreational’ doses rather than with an overdose.

May present with:

  • Onset of symptoms from amphetamine according to the route of exposure.
  • Transient nausea, increased muscle tone, muscle pain, trismus (jaw-clenching), dilated pupils, blurred vision, sweating, dry mouth, agitation, anxiety, palpitations, vomiting, abdominal pain and diarrhoea.
  • Hypertonia, hyper-reflexia, hyperpyrexia, tachycardia, initial hypertension then hypotension, tachypnoea, and visual hallucinations.
  • Effects may be prolonged if a patient has alkaline urine.

In severe poisoning:

  • Delirium, coma, convulsions and cardiac dysrrhythmias that may be fatal.
  • A hyperthermic syndrome may develop with rigidity, hyper-reflexia and hyperpyrexia (>39°C) leading to hypotension, rhabdomyolysis, metabolic acidosis, acute renal failure, disseminated intravascular coagulation, hepatocellular necrosis, adult respiratory distress syndrome and cardiovascular collapse.
  • Death from intracerebral haemorrhage has also been reported in hyperthermic patients.
  • MDMA is also associated with hyponatraemia and cerebral oedema. This can occur in patients who have consumed excessive amounts of water (owing to drug-induced repetitive behaviour). These patients present with mild hypothermia and confusion; they may be unresponsive and staring.

‘Yaba’ is acombination of methamphetamine and caffeine. Yaba, which means crazy medicine in Thai, is produced is Southeast and East Asia. Yaba is produced as tablets. These tablets are generally no larger than a pencil eraser. They are brightly colored, usually reddish-orange or green.

Yaba has recently emerged as a drug of abuse among the young int affluent societies in  Bangladesh. Individuals who use Yaba face the same risks as users of other forms of methamphetamine: rapid heart rate, increased blood pressure, and damage to the small blood vessels in the brain that can lead to stroke. Chronic use of the drug can result in death. Individuals who use Yaba also may have episodes of violent behavior, paranoia, anxiety, confusion, and insomnia.

 

Management:

  • Activated charcoal can be given within 1 hour of ingestion to reduce absorption unless the patient is drowsy, fitting or vomiting.
  • All patients should be transferred to hospital and observed for at least 6 hours with electrocardiogram (ECG) monitoring and the monitoring of electrolytes balance
  • Give diazepam for convulsions.
  • If the rectal temperature > 39°C, instigate cooling measures (fan, sponging, ice packs, cool IV fluids). If this is unsuccessful, the patient will need to be paralysed and ventilated.

 

Follow-up:

Further Inpatient Care: Admit patients with hemodynamic instability, coma, or respiratory depression to the ICU. Watch for signs of withdrawal in patients who have been taking BZDs chronically before overdose.

Further Outpatient Care: Patients may be discharged if they remain asymptomatic 4-6 hours postingestion. Those with mild toxicity may be observed in the emergency department until they recover.

Transfer: Transfer patients who may require more advanced care than is available in inpatient setting.

 

Other Complications of abusive drugs:

  • Aspiration pneumonia
  • Rhabdomyolysis
  • Fatality (rare)

Treatment of Complications:

CNS stimulation may require sedation, usually with a benzodiazepine or a barbiturate. In pure amphetamine poisoning, chlorpromazine or a benzodiazepine may be used. To terminate seizures or prevent their recurrence, a benzodiazepine (eg, diazepam 5 to 10 mg for adults; 0.1 to 0.2 mg/kg for children) is given slowly IV, or Phenobarbital (100 to 200 mg IV or IM for adults; 4 to 7 mg/kg for children) is given. Ideally, phenytoin is avoided. O2 saturation should be closely monitored. Refractory seizures very rarely, if ever, require general anesthesia.

Severe CNS depression requires circulatory and ventilatory support.  Endotracheal intubation and, rarely, tracheostomy may be necessary. In suspected or known narcotic poisoning, naloxone should be used in repeated doses. Stimulants are ineffective and are generally contraindicated.

Cerebral edema is common in poisoning due to sedatives, carbon monoxide, lead, and other CNS depressants. A 20% mannitol solution (5 to 10 mL/kg) is given slowly IV over 30 to 60 min. Corticosteroids are also used (dexamethasone 1 mg/m2 of BSA q 6 h by IV drip). Intracranial monitoring with hyperventilation to try to alter the degree of cerebral edema is used less frequently.

Renal failure, if present, may require dialysis.

Hepatic failure may warrant transplantation.

Medical/Legal Pitfalls:

a.    Unmasking an underlying disorder, specifically seizures, with indiscriminate use of flumazenil

b.    Failure to anticipate withdrawal in a patient with chronic BZD use

c.    Failure to consider the possibility of co-ingestant use or secondary causes of treatable altered mental status (eg, hypoglycemia, meningitis).

 

 

 

 

 

 

Organophosphorus Compound Poisoning


Organophosphorus Compound Poisoning

 

Edited By :

Dr.Salim Al Mamun

MBBS(Raj);CCD(BIRDEM);

CMU(DU);DMUD(Course)

 

 

Introduction:

Organophosphorus compounds are widely used as insecticide in agricultural sector by the farming community in Bangladesh used for the control of insect vectors. Since it is easy and widely available, pesticide become a popular method of self harm. OP poisoning is one of the most common cause of impulsive deliberate self – poisoning that the clinician frequently encounter at different level of Hospital in Bangladesh.

The basic mechanism of toxic effects of organophosphates results from inhibition of cholinesterase action at the nerve ending resulting in accumulation of excess acetylcholine. So, a major role in management is played by combating the action of excess acetylcholine by rational use of atropine and oximes. However, the most suitable oximes for reactivation of cholinesterase have still not been established with certainty, although pralidoxime is widely recommended.

There is no universe consensus regarding diagnosis, grading of severity and management of this serious life-threatening poisoning. Different individualized spectrum of management is available around the world. The supportive and the specific antidotes are given and tuned according to individual patient.

SUBSTANCES INCLUDED IN THIS CATEGORY:

There are more than a hundred organophosphate compounds used regularly.

Some available in Bangladesh include-

Chlorpyrifos                                            Diazinon

Dichlorvos                                              Dimethoat

Fenthion                                                 Malathion

Parathion

Clinical Features: Pesticide poisoning can be acute, sub-acute or chronic.

Acute poisoning: is from substantial intake of the toxicant in a single occasion which occurs because of suicide attempts or accidental ingestion.

Sub-acute poisoning: is due to repeated smaller doses through penetration into the system over a short period of time.

Chronic poisoning: refers to cumulative effect occurring from repeated exposure to small amount of pesticides over a long period of time.

Acute, sub-acute or chronic poisoning may result from ingestion, absorption inhalation.  Fastest absorption takes place through eyes, scalp, back of the neck, forehead and scrotal region. Inhalation of vaporized pesticides commonly takes place during mixing, handling or spraying.

Pathogenesis:

Pathogenesis of Acute Cholinergic Crisis:

Organophosphates inhibit acetyl cholinesterase, an enzyme which itself inactivates the neurotransmitter acetylcholine; the net effect being increased levels of active acetylcholine at its various sites in the nervous system.

These locations include:

– The neuroeffector junctions of the parasympathetic nervous system (and the sympathetic nervous system in the case of the sweat glands)

– The (autonomic) ganglia of both parasympathetic nervous system and sympathetic nervous system

– The neuromuscular junctions

– Some synapses in the central nervous system

The increased neurotransmitter levels can result in increased target organ functional response, or with sustained levels; a decreased response. The various effects have been classified as Muscarinic, Nicotinic and Central effects.

OPC are known primarily as inhibitors of esterases. Phosphorylations of acetylcholinesterase inhibits its catalytic function. The consequent accumulation of unhydrolysed  acetylcholine (Ach) at muscarinic, nicotinic and central sites of nervous system forms the pharmacological basis of Acute Cholinergic Crisis (ACC). It may be mentioned that reactivation of inhibited enzymes may occur spontaneously, the rate depends upon species and tissue, in addition to the chemical group attached to the enzyme. This reactivation process may be induced by some oxime agents but the response declines with time due to ageing of the inhibited enzymes.

Fig: Nicotinic, muscarinic and central syndrome (courtesy- SACTRC, Srilanka)

 

Signs and symptoms of OPC poisoning:

Four clinical syndromes have been described

  • acute cholinergic symptoms and paralysis (most common)
  • subacute proximal weakness (Intermediate syndrome)
  • organophosphate induced delayed neuropathy (OPIDN)
  • chronic organophosphate induced neuropsychiatric disorder (COPIND)

Signs and symptoms of OPC poisoning:

Acute cholinergic crisis (ACC):

Muscarinic

§  Gastrointestinal

  • Respiratory
  • Cardiovascular
  • Pupils
  • Urinary
  • Other
Nausea, vomiting, abdominal cramps, diarrhoea, faecal incontinence
Pulmonary oedema, hypotension
Bradycardia, hypotension
Blurring of vision, miosis
Frequency, incontinence
Increased sweating, salivation and lacrimation
Nicotinic

  • Skeletal muscle
  • Sympathetic ganglion
Muscle twitching, fasciculation, cramps, weakness including respiratory muscles
Pallor tachycardia, hypertension
CNS Giddiness, tension, anxiety, restlessness, difficulty in concentration, confusion, slurred speech, insomnia, headache, tremor, apathy, withdrawal and depression, drowsiness, nightmares, ataxia, generalized weakness, coma, cheyne-stokes respiration, convulsion, depression of respiratory and circulatory centres.

Note: The mnemonic DUMBELS describes most of the significant muscarinic features

Diarrhoea                              Urination

Miosis                              Bronchospasm

Emesis                              Lachrymation

Salivation

Intermediate Syndrome (IMS):

IMS develop about 24-96 hours after OPI intoxication following ACC treated conventionally or while on therapy in certain percentage of patients. Respiratory insufficiency may herald the onset of IMS. The patient is usually conscious. Muscles innervated by cranial nerves show varying degree of weakness. The external ocular muscles are most commonly affected, producing ptosis and defects of ocular movements of mild to moderate severity. These may be accompanied by weakness of muscles of mastication, face and soft palate. Weakness is bilateral and symmetrical, therefore mild abnormalities may easily by overlooked. Weakness of neck flexion often such that the patient cannot raise the head from bed is a constant feature. The muscle tone in the limbs is usually normal but may be decreased. Shoulder abduction and hip flexion show symmetrical weakness of varying severity. Normal power in the distal muscles may give a false impression that the limbs are spared. Tendon reflexes are normal or decreased. There is no sensory impairment.

Respiratory insufficiency develops over approximately 6 hours and initially the accessory muscles of respiration are used. There is increased in respiratory rate, sweating, restlessness and later cyanosis. If untreated the patient may soon become unconscious and die The paralytic signs are 2 types. Type 1 (present on admission) and Type 2 (appearing subsequently and not responding to atropine) the time of onset and the distribution of type 2 signs fit the features of IMS.

Management – in the line of respiratory failure.

Delayed Polyneuropathy:

Organophosphorus induced delayed polyneuropathy (OPIDP) which occurs in a small percentage of patients, manifests following a latent period of 2-4 weeks  after exposure by any route. It generally follows exposures sufficient to cause acute cholinergic symptoms ACC. The cardinal symptoms are distal weakness and in some cases paraesthesia in the distal parts of the limbs, foot drops, wrist drop and claw hands are inevitable consequences, Pyramidal signs may appear after a few weeks or few months. Recovery is variable and the condition may be permanent. Severe cases progress to complete paralysis, impaired respiration and death.

Suggested diagnostic criteria include:

  • Symptoms and signs of polyneuropathy
  • Sometimes later pyramidal tract signs
  • Denervation changes (shown by electromyography)
  • Reasonable exclusion of other causes

Extra pyramidal manifestations

Atypical ocular bobbing, opsoclonus, cerebellar, choreo athetosis, chorea with psychiatric changes and parkinsonism following OP intoxication had been documented mostly as single case reports.

Investigations: Not routinely needed. But can be done if needed.

     a)    Routine Laboratory Test:

Blood count  —    Leucocytosis

Blood Sugar–    Hypoglycemia

LFT             —     Increased PT

S. electrolytes–  Hypokalaemia

Urine              —  Proteinuria

S. Amylase     — Raised

ECG              —  Arrythmia

CXR               —  Pulmonary oedema

Special test: If possible these tests can be done in OP poisoning.

b)    Direct measurement of OPC

c)    Indirect estimation of plasma & red cell Cholinesterases

d)    Estimation of NTE (Neuropathic transferase enzyme)

e)    Electrophysiological study

f)     Neurobehavioral test

g)    Histopathological test

h)   PEFR (Peak expiratory flow rate – Bed side)

i)     Spirometry

Sample of used offending pesticide or preferably container of pesticide as measure of identification is very important in clinical setting. All patients and their attendants should be repeatedly encouraged to bring the sample to the health facility for diagnosis and management.

Grading of severity of poisoning:

a) Clinical grading

b) Biochemical Grading

The following table has been suggested as a guide to determining severity by South Asian Cilinical Toxicology Research Collaboration . However if a patient has any CNS signs or paralysis or has ingested a concentrated preparation, the poisoning is likely to be severe irrespective of other initial signs.

Management of Organophosphorus Insecticide (OPC) Poisoning

A patient of organophosphate poisoning should be hospitalized and the subsequent management consists of:

  1. Initial stabilization of patient by maintaining respiration and other vital signs.
  2. Reduction of exposure.
  3. Administration of specific antidote.
  4. Supportive treatment.

Initial Stabilization of the patient:

The initial objective should be the establishment of a clear airway and adequate ventilation because the patient with acute organophosphate poisoning (ACC) commonly presents with respiratory distress secondary to excessive oropharyngeal secretion, bronchospasm, respiratory muscle paralyis and rarely, acute respiratory distress syndrome and pulmonary oedema. It is essential to improve tissue oxegenation as much as possible prior to administration of atropine. In case of moderate to severe poisoning patients should be managed in ICU if facilities are available.

Exposure reduction:

Thoroughly wash exposed areas, including axillae, groin, umbilicus, other skin folds, ears, eyes, hair and under the nails; with soap and tepid water. Consider lavage only if a patient has taken a highly toxic pesticide and arrives at hospital within 1–2 hours. There is currently no evidence that either single or multiple dose regimens of activated charcoal result in clinical benefit

 

There are two antidotes in the treatment of OPC poisoning

Atropine– Is the antidote of choice which reverses the muscarinic features.

Oxime-    Which reactivate cholinesterases inhibited by organophosphates and reverses the nicotinic features.

Atropine:

Atropine acts as physiological antidote in all anti-cholinesterase intoxication. Atropine antagonises the effects of acetylcholine reversing the excessive para- sympathetic stimulation by competing for identical binding sites at muscarinic receptors.

Dosage regimens of Atropine:

Patients poisoned by organophosphorus esters are tolerant to the pharmacological effects of atropine and consequently very large doses are usually required. Repeated doses of atropine should be administered until signs of atropinisation appear.

Signs of Atropinisation

  • Mydriasis
  • Tachycardia.
  • Flushing
  • Dry mouth & nose
  • Anhydrosis
  • Bronchodilation

Dosage regimens are usually designed according to the severity of poisoning and to the signs of atropinisation

v  1 ampoule contains 0.6 mg atropine sulphate.

v  Interval of atropine sulphate dose -every 5 min

Test dose of Atropine:

It is preferable to initiate the antidote therapy with a ‘test dose’ of parenteral atropine-sulphate (1.2 mg in adults and 0.01 mg/kg in children, by the intravenous route). This therapeutic test provides a measure of severity of organophosphate poisoning. If the signs of atropinisation occur rapidly, it is unlikely that the poisoning is severe or it may not be OP poisoning. However, these mildly poisoned patients who received a single dose of atropine should be observed for at least 24 hours to detect further recurrence of toxicity after the effects of atropine have subsided.

 

There are alternative therapy with atropine than current practice which have shown excellent outcome as treatment and practiced in different south east Asian country like Srilanka, Thailand etc. This practice is evidence based and strongly recommended to follow for managing the organophosphate poisoning. The therapy is described below:

Loading with atropine and IV fluids:

 

Dose of atropine

For an unconscious patient, give atropine 1.8–3 mg (three to five 0.6 mg vials) rapidly IV into a fast-flowing IV drip. Although it is preferable that oxygen is given early to all ill patients, do not delay giving atropine if oxygen is unavailable. Because atropine dries secretions and reduces bronchospasm, its administration will improve patient oxygenation. There is no good evidence that giving atropine to a cyanosed patient causes harm. Atropine takes only a few minutes to work. During the 5 min after atropine administration, record three other signs of cholinergic poisoning against which atropine dosing will be titrated (Table 1): (1) air entry into lungs; (2) blood pressure; (3) heart rate.

There is no need to do this before atropine is given, because pinpoint pupils and sweating in a region where these pesticides are common are sufficient to indicate OP/ carbamate poisoning and trigger the decision to give atropine. If the clinical presentation is not clear, administer atropine 0.6–1 mg. A marked increase in heart rate (more than 20–25 beats/min) and flushing of the skin suggest that the patient does not have significant cholinergic poisoning and further atropine is not required.

 

 

 

 

Table 1

An observation chart recording the initial atropinisation of an organophosphorus-poisoned patient

Initials

XX

Study

number

Axxxx

Date of

arrival

xx/xx/xx

 

 

 

 

 

 

 

 

Time

Heart

rate

>80

Clear

lungs

Pupil

size

Dry

axilla

Syst.

BP>80

mmHg

Bowel

sounds

(ND/Nil)

Confused

Fever

(>37.5CC)

Atropine

infusion

Bolus

given?

 

22.30

52

Creps+

Pinpoint

No

90/60

I

No

No

2.4 mg

22.35

60

Creps+

Pinpoint

No

90/60

I

No

No

4.8 mg

22.40

82

+/-

Pinpoint

Yes

110/60

N

No

No

4mg

22.50

100

Wheeze

2 mm

Yes

D

No

No

2mg

23.00

105

Clear

3 mm

Yes

D

No

No

2 mg/h

Infusion

23.15

105

Clear

3-4mm

Yes

D

No

No

2 mg/h

Infusion

23.32

102

Clear

3-4 mm

Yes

D

No

No

2 mg/h

Infusion

00.30

98

Clear

3-4mm

Yes

110/60

D

No

No

2 mg/h

Infusion

01.30

85

Clear

3-4 mm

Yes

D

No

No

2 mg/h

Infusion

02.30

72

Wheeze

3-4 mm

Yes

N/D

No

No

2 mg

02.35

96

Clear

3-4 mm

Yes

D

No

No

2.4 mg/h

Infusion

02.45

98

Clear

3-4 mm

Yes

D

No

No

2.4 mg/h

Infusion

04.00

102

Clear

3-4 mm

Yes

D

No

No

2.4 mg/h

Infusion

{Atropinisation was reached at 23.00, 30 mm after the first atropine dose was given; a total of 13.4 mg of atropine was required. After 10 mm, doubling doses were no longer used because there was a clear response to therapy with the pulse climbing above 80 beats/mm and the chest sounding better. After a further 1.5 hours, the pulse rate started to drop but it was not until it had dropped below 80 beats/mm and wheeze had become audible in the chest that another 2 mg bolus was given to atropinise the patient again. The atropine infusion rate was also increased and the patient remained stable for the next few hours. AID/N/I, absent/decreased/normal/increased; creps,crepitations; syst. BP, systolic blood pressure. Clinical features in bold type indicate that atropine is required. Dashes indicate that no BP reading was taken.}

Giving fluids

While waiting for the atropine to have effect, ensure that the two IV drips have been set up (one for fluid and drugs, the other for atropine). Give 500–1000 ml (10–20 ml/kg) of normal saline over 10–20 min.

Table 2:

Target end-points for atropine therapy

1. Clear chest on auscultation with no wheeze

2. Heart rate >80 beats/min

3. Pupils no longer pinpoint

4. Dry axillae

5. Systolic blood pressure >80 mmHg

Notes:

1.   The aim of atropine therapy is to clear the chest and reach the end-points for all five parameters (Table-2).

2.   There is no need to aim for a heart rate of 120–140 beats/min. This suggests atropine toxicity rather than simple reversal of cholinergic poisoning. Such high heart rates will cause particularly severe complications in older patients with pre-existing cardiac disease – myocardial infarctions may result. However, tachycardia are also caused by hypoxia, agitation, alcohol withdrawal, pneumonia, hypovolaemia, and fast oxime administration. Tachycardia is not a contraindication for atropine if other features suggest under atropinisation.

3.   Aspiration will commonly result in focal crepitations. Attempt to distinguish such crepitations from the more general crepitations of bronchorrhoea.

4.   Splashes of organophosphorus into the eye will produce intense miosis that may not respond to atropine therapy. However, symmetrical miosis is likely to be due to systemic effects of the ingested pesticide.

Assess whether enough atropine has been given – is the patient atropinised?

Three to five minutes after giving atropine, check the five markers of cholinergic poisoning (Table 2). Mark them on an OP/ carbamate observation sheet (Table 1). A uniform improvement in most of the five parameters is required, not improvements in just one. However, the most important parameters are air entry on chest auscultation, heart rate, and blood pressure.

Pupil dilatation is sometimes delayed. and the other parameters may improve more rapidly, it is reasonable to  observe air entry on chest auscultation, heart rate, and blood pressure as the main parameters for adequate atropinisation.. When all the parameters are satisfactory, the patient has received enough atropine and is ‘atropinised’.

 

Continuation of bolus atropine loading to reach atropinisation

If after 3–5 min a consistent improvement across the five parameters has not occurred, then more atropine is required. Double the dose, and continue to double each time that there is no response (Table 1). Do not simply repeat the initial dose of atropine. Some patients need tens or hundreds of mg of atropine, so repeating 3 mg doses will mean that it may take hours to give sufficient atropine .Severely ill patients will be dead by this point – atropinise the patient as quickly as possible. Beware of pupils that do not dilate because pesticide has been splashed into them directly, and lung crepitations that are due to aspiration of the pesticide rather than the systemic effects of the pesticide. Generalised wheeze may be a better sign of under-atropinization in a patient who has aspirated pesticide.

Atropine treatment after atropinization

Once atropinised (with clear lungs, adequate heart rate [more than 80 beats/min] and blood pressure [more than 80 mmHg systolic with good urine output], dry skin, and pupils no longer pinpoint), set up an infusion using one of the two IV cannulae. This should keep the blood atropine concentration in the therapeutic range, reducing fluctuation compared with repeated bolus doses.

In the infusion, try giving 10–20% of the total amount of atropine that was required to load the patient every hour. If very large doses (more than 30 mg) were initially required, then less can be used. Larger doses may be required if oximes are not available. It is rare that an infusion rate greater than 3–5 mg/ hour is necessary. Such high rates require frequent review and reduction as necessary.

Observation of the patient

Review the patient and assess the five parameters every 15 min or so to see whether the atropine infusion rate is adequate. As atropinisation is lost, with for example recurrence of bronchospasm or bradycardia, give further boluses of atropine until they disappear, and increase the infusion rate (Table 1). Once the parameters have settled, see the patient at least hourly for the first 6 hours to check that the atropine infusion rate is sufficient and that there are no signs of atropine toxicity. As the required dose of atropine falls, observation for recurrence of cholinergic features can be done less often (every 2–3 hours). However, regular observation is still required to spot patients at risk of, and going into, respiratory failure.

Atropine toxicity

Excess atropine causes agitation, confusion, urinary retention, hyperthermia, bowel  ileus and tachycardia. During regular observation for signs of over treatment, check for the features given in Table 2. The presence of all three suggests that too much atropine is being given. Stop the atropine infusion. Check again after 30 min to see whether the features of toxicity have settled. If not, continue to review every 30 min or so. When they do settle, restart at 70–80% of the previous rate. The patient should then be seen frequently to ensure that the new infusion rate has reduced the signs of atropine toxicity without permitting the reappearance of cholinergic signs. Do not follow heart rate and pupil size because they can be fast or slow, and big or small, respectively, depending on the balance of nicotinic and muscarinic features. Tachycardia also occurs with rapid administration of oximes and with pneumonia, hypovolaemia, hypoxia, and alcohol withdrawal, and is not a contraindication to giving atropine. Catheterize unconscious patients soon after resuscitation is completed. Look for urinary retention in an agitated confused patient; agitation may settle after insertion of the catheter.

          Table 3: Clinical features of Atropine toxicity

a) Peripheral effect

–      Dry mouth

–      Mydriasis

–      blurred vision

–      hot dry skin

–      tachycardia

b) Central effect

–      hyperpyrexia

–      restlessness

–      anxiety

–      excitement

–      hallucination

–      delirium

–      mania

–      cerebral depression

–      coma

There is a American verbal felicity to describe a patient of atropine poisoning.

–      as hot as a hare

–      as blind as a bat

–      as dry as a bone

–      as red as a beet

–      as mad as a hen.

Special circumstances with atropine therapy

(a)        As atropine can induce ventricular tachycardia & ventricular fibrillation in a severely hypoxic patient, hypoxia should be corrected before administration of atropine. This is accomplished by artificial respiration & oxygen therapy.

(b)        As severely poisoning patients exhibit marked atropine resistance, they may require up to 2-3 times the standard dose of atropine.

Oximes:

Although atropine is the excellent ‘initiator antidote’ in reversing the muscarinic effects of OPC poisoning, it can not ameliorate the nicotinic action & CNS effects and also cannot reactivate the inhibited cholinesterase. For this reason, oximes are used in the pharmacological management of OPC poisoning to ameliorate the nicotinic, muscarinic & C.N.S. effects and to reactivate the inhibited cholinesterase.

Mechanism of Action of Oximes:

Oximes are the specific biochemical antidote for OPI intoxication.

They reactivate the inhibited cholinesterase by cleavage of phosphorylated active sites. Oximes are effective only when the phsophorylated AchE has not undergone ‘ageing’.

Pralidoxime (2-pyridine aldoxime or 2- PAM) is currently the most commonly used in humans. Among the four salts of pralidoxime, (chloride, iodide, mesylate, methylsulphate) pralidoxime chloride is the best because it has less side effects and chloride ion is more physiological. Currently obidoxime has been introduced. It crosses blood brain barrier more than pralidoxime.

Praliodoxime is used in conjunction with atropine in moderate and severe poisoning. It has a strong synergistic effect with atropine and provides a dose sparing effect on the amount of atropine. Pralidoxime is not equally effective against all organophosphates.

Dosage regimen of pralidoxime:

It is generally accepted that it should be given as early as possible but should not be preceded by administration of atropine. The clinical benefit of oximes for OP pesticide poisoning is not clear, being limited by the type of OP, poison load, time to start of therapy, and dose of oxime.

Current WHO recommend giving a 30 mg/kg loading dose of pralidoxime over 10–20 min, followed by a continuous infusion of 8–10 mg/kg per hour until clinical recovery (for example 12–24 hours after atropine is no longer required or the patient is extubated) or 7 days, whichever is later. Where obidoxime is available, a loading dose of 250 mg is followed by an infusion giving 750 mg every 24 hours.

Treatment with pralidoxime should be continued, in conjunction with atropine, until there is symptomatic improvement. The intramuscular route is acceptable if venous access is difficult, particularly in convulsing patient.

Oximes are not recommended for carbamate poisoning.

Side effect of pralidoxime:

No significant side effects other than mild biochemical signs of liver toxicity, have been observed in normal doses of pralidoxime using 1-2gm. intravenously but mild nausea and vomiting have been reported in case of oral administration. Too rapid administration will result in vomiting, tachycardia and hypertension (especially diastolic hypertension).

Administration of oximes may require reduction in the doses of atropine to avoid atropine toxicity.

Pralidoxime Toxicity:

Very few cases of pralidoxime toxicity have been reported. Dizziness, blurred vision, diplopia, headache, nausea and tachycardia have been reported if the rate of administration exceeds 0.5 gm. per minute. However, very few of these features occur concurrently and pralidoxime may be safely used, in the recommended doses, in cases of moderate to severe poisoning.

Supportive Treatment of OPC Poisoning:

Administration of specific antidote or some emergency medicine doses not complete the total management of OPC poisoning. A complementary and sometimes obligatory supportive treatment constitutes the model of total management, which includes the following:

  • Management of respiratory insufficiency.
  • Maintenance of circulation.
  • Treatment of convulsion and other complications.
  • Fluid and electrolyte balance.
  • Control of infections (aspiration pneumonia).
  • Maintenance of nutrition.
  • Control of body temperature.

Artificial Respiration:

As the clinical picture of OPC poisoning is dominated by respiratory insufficiency, management of respiratory failure represents the corner stone of treatment. Artificial ventilation should be started at the first sign of respiratory failure. For pulmonary oedema, high concentration 02 therapy and diuretic should be used. Morphine and aminophlline should be avoided. Broad spectrum antibiotic is used as prophylactic measure, especially when there are chances of aspiration pneumonia, which sometimes complicates severe OPC poisoning.

Diazepam:

  • Counteract CNS effects
  • Relieves anxiety
  • Antagonize convulsions
  • Improve morbidity and mortality

Dose of Diazepam: Adult:   10-20 mg. intravenously or subcutaneously

& also may be repeated as required

                               Children:    0.25-0.4mg./kg

Follow up of the patient:

  • Vital signs
  • Signs of Atropinisation
  • Effect of oxime
  • Toxicity of atropine and oxime
  • RBC and plasma AChE level
  • Recurrence of symptoms on withdrawal of antidote.
  • Restart the treatment promptly if recurrence occurs.
  • Patient’s general condition.

Cause of Death in OPC poisoning:

1.  Immediate death:

–     Seizures.

–     Complex ventricular arrhythmias.

2.  Death within 24 hours:

Attributable to the effect of organophosphate in acute cholinergic crisis in untreated severe case

  • Respiratory failure.

3.  Death within 10 days of poisoning:

Respiratory failure in treated case due to respiratory muscle paralysis in intermediate syndrome

4.  Late death:

Late death due to organophosphate poisoning has been described and is believed to be secondary to ventricular arrhythmias, including Torsades de Pointes, which may occur up to 15 days after acute intoxication.

Prognosis of Organophosphorus Insecticide Poisoning

Deaths from severe organophosphate poisoning usually occur within the first 24 hours in untreated cases and within 10 days in treatment failure cases. If there has been no anoxic brain damage, recovery will usually occur within 10 days, although there may be residual sequelae, which has been discussed before.

Snake Bite


Snake  Bite

 

Edited By :

Dr.Salim Al Mamun

MBBS(Raj);CCD(BIRDEM);

CMU(DU);DMUD(Course)

 

About snake

There are about 2500 species of snake in the world, among them 250 are poisonous. In Bangladesh among the 82 species of snake 28 are venomous, 12 species of them are sea snake.1 Venomous snakes of the world belong to the families Viperidae (sub family Viperinae: Old world vipers; sub family Crotalinae: new world and Asian pit vipers), Elapidae (including cobras, kraits, coral snakes and all Australian venomous snakes), Hydrophiidae (sea snakes), Atractaspididae (burrowing asps), and Colubridae (a large family, of which most species are non venomous and only a few are dangerously toxic to humans).2 There are 5 medically important groups of snake in our country, these are- cobra, krait, russel viper, green pit viper and sea snake. Among this majority of venomous bites in our country are cobras and kraits. They are mainly neurotoxic, and respiratory failure is the main cause of death following envenomation1. Snakes are docile in nature3. They bite defensively or when agitated. All the snake bites do not produce symptoms, only the bites by poisonous snake produces specific sign symptoms. Even 50% of the bite inflicted by poisonous snake does not produce any sign of envenomation. Bites rates are highest in temperate and tropical regions where the population subsists by manual agriculture. Estimates indicate >5 million bites annually by venomous snakes worldwide, with > 12,5000 deaths2. A World Health Organisation-funded study estimated about 8,000 cases of snakebite with over 20% mortality in BangladeshBangladesh are recorded between May and October (rainy season) with highest number in June. Lower and upper limbs are most common sites of snakebite, but it may happen in other sites as well. Delayed presentation to the hospital, lack of availability of antisnake venom and modern management facility are the main causes of death4.

Habitat of Snake

1. Paddy field

2. Lake

3. Hill

4. Root of tree

5. River

6. Ponds3

Foods and Feeding

Types of prey: all snakes are carnivorous3.

Snake venom

Snake venom is modified digestive juice. Main

function is digestion, to kill the prey. Composition:

complex-protein and non protein mixture5.

Venom injected by snake

• Cobra injects ~ 60 mg venom / bite (average)

•  Only 12mg is fatal.

The venom is 15-40 times more potent than Tubocurarine.

50% of the venomous snake bite does not

produce sign of envenomation

Venom action

 Venom action                  Clinical effect
 Vasodilators               Hypotension
 Coagulopathic           Consumption coagulopathy
 Hyalurodinase               Spread of venom
 Haemmolysin           Bleeding from fangs site
 Haemorrahagin               Bleeding from fangs site
 Myotoxin           Local tissue necrosis
Neurotoxin      Muscle paralysis, respiratory failure
Cardiotoxin        Coronary vasoconstriction, AV block5

Epidemiology of snake bite

  • World wide 3-5 million victims/ year
  • 50000 death annually
  • 400000 amputation/ year
  • Epidemiology of snake bite in Bangladesh
  • Incidence : about 8,000 per year
  • Mortality : 22%
  • Age: 11 – 20 years
  • Most of the incidents occur during May to October (Rainy season).
  • Because snakes are flushed out of their natural environment4.

Symptoms following  Snake bite

    Non specific symptoms– Headache, Vomiting, loss of

consciousness

    Neurological symptoms–  Muscle paralysis, Ptosis,

dysphagia

    Haematological symptoms– Sponteneous bleeding

e.g. gum bleeding, Haematuria

    Other symptoms– severe muscle pain, dark urine,

Progressive local swelling5

Laboratory investigation
(Depending C/F)

FBC

 Urea & Creatinine

 Urine analysis & naked eye exam. Of    urine

 CPK

 ECG

 ELISA

Blood grouping & Rh typing

20 min whole blood coagulation test

20 min whole blood coagulation test is a

Simple bed side test to detect venom induced

consumption coagulopathy.

 

 

References:

  1. Faiz MA, Hossain M, Amin R, Ghose A, Basher A, National guideline of management of snake bite, second edition, DGHS, 2008; 1-32.
  2. Paul S.Auerbach, Robert L. Norris, Disorders Caused by Reptile Bites and Marine Animal Exposure. In Fauci AS, Braunwald E, Kasper DL, et al. 17th edition. Harrison’s Principles of Internal Medicine. New York: The McGraw- Hill Companies, 2008:2741- 2748.
  3. Apobo nandy, animal irritants, Principle of Forensic Medicine, second edition. New central book agency, 2004: 506-516.
  4. http://www.banglapedia.org/httpdocs/HT/S_0439.HTM
  5. Thomas S.H.L, . White J, Poisoning  In:  Colledge NR,  Walker B R, Ralstone S H Davidson’s Principles & Practice of Medicine, 21th edition, Churchill Livingstone Elsevier, 2010; 203-207

Spittimg cobra

Medically important snakes of Bangladesh

1.Group I: Cobra

2.Group II: Krait

3.Group III: Russel viper

4.Group IV: Green pit Viper

5.Group V: Sea snake

Group I: Cobra

Monocellete cobra/ghokra

Distributed all administrative divisions in Bangladesh

Binocellate cobra

More co        Common in west of Jamuna.

King cobra

King cobra, Raj ghokra, Sankochur

Distributed in Shylet, Chittagong and Barisal

out krait

Group II: Krait

Bungarus caeruleus, common krait, kal kewtey, Malcha alad

Distributed all administrative divisions in Bangladesh.

Bangarus faciatus, Banded krait, Mama-bhagna

More in Chittagong and rare  in Rajshahi

Copy right Dr. Ratindra Nath Mondal

Bungarus niger (black krait), Bungarus wall

Recently found in  Chittagong and other

 Parts of the country

Group III Russel viper

Daboia (Daboia russeli, Russel viper

Distributed in Rajshahi & Khulna, may be found in Chittagong.

Group IV Green pit Viper

Ovophis Green snake, bash-bora, sabuj-bora

Distributed in Shylet, Chittagong, Barisal & Khulna

Group V Sea snake

Enhydrina schistosa, Hooknosed sea snake, Samudrik shap

Distributed in sea and coastal saline water of Bangladesh.

Copy right:Dr.Ratindra Nath Mondal

Fig: Non-poisonous snake

First aid in snake bite

Why the snake bite???

Snake are docile in nature

Snakes do not attack man.

They bite defensively or when agitated

!? What to do if you see a snake!?

  1. Don’t hello the snake
  2. Do not be afraid
  3. Do not get close to them
  4. Allow the snake to go away
  5. Do not kill the snake unnecessarily

What to do in case of snakebite ?

  1. If you are the victim: Do not panic
  2. Sit down, be calm, seek help
  3. Wipe the site of bite
  4. Cover it with dressing
  5. Assurance: Reassure the victim who may be very anxious.
  6. If the bite is in upper limb: do not move the limb.
  7. Ideal is – to provide pressure immobilization (cobra and krait bite).
  8.  Figure….
  9. This should not be used for viper bite & Green snake bite. Fig: Procedure of immobilization as first aid
  10. Fig: Ideal procedure of immobilization
  11. Immobilize the bitten limb with a splint or sling as practiced in fracture of long bone.
  12. If the bite is in lower limb: do not walk.
  13. If the snake is killed, bring the snake with the patient to hospital for identification
  14. Get the victim to the closest hospital or medical facility as soon as possible 

First Aid Methods – Not Recommended

1.       Multiple ligature with application of herbal medicines

2.       Incisions at the site of snake bite or any other place. 

3.       Local suction either by mouth or by application of chick. 

4.       Application of ice at the biting area

  1. Application of herbal medicines, stones, seeds, saliva, potassium permanganate solution. 
  2. Actively attempt to locate a venomous snake
  3. Unnecessary delayingn to take the pt. to hospital.

 

Fig: Tight arterial ligature not recommended

Fig: Suction at the bite mark not recommended

Fig: Incision around the bite mark not recommended

Fig: Wrong first aid by faith healers not recommended

Why these traditional methods are not practised?

Effect of  “Traditional tight tourniquets

Fig: Effect of tight ligature

Management of snake bite in Health care facility

20 min whole blood coagulation test

Simple bed side test to detect venom induced consumption coagulopathy.

Steps of 20 minutes whole blood coagulation test

Fig: Blood is drawn(3-5 ml), kept in test tube in vertical position & waite for 20 minutes

Fig: After 20 minutes look whether the blood in the test tube is cogulated or not.

The test is positive if blood is not cogulated after 20 minutes.

In perspective of Bangladesh, incoagulable blood is diagnostic

of Viper bite and rules out Elapid bite (Krait & Cobra).

Treatment in Health Facility

1.     Airway  -Rapid assessment and resuscitation

2.     Breathing

3.     Circulation

4.     Antibiotic

5.     Tetanus prophylaxis

6.     Polyvalent Antisnake venom

Poly valent Antivenom:

1.      Each vial 10 mg of antivenom. Work against Cobr, krait, Russel’s viper & saw scaled viper.

2.     Not used in bites by Green snake, Sea snakes and identified nonvenomous snake.

3.     One vial of polyvalent ASV neutralize 6 mg of the cobra venom.

4.     Neurotoxicity usually improves -30 minutes.

5.      Response is best within 4 hrs of bites.

Dose of Antivenom

Fig: Polyvallent antivenom

Each dose require 10 vial of antivenom. 10 such vials

(100 ml) are further diluted or mixed with 100 ml of

fluid (Dextrose water or saline).

Then it is administered with intravenous infusion

within 40-60 min (60-70 drops/min).

Children must therefore be given exactly the same

dose of antivenom as adult.

Criteria: using Polyvalent  ASV

1.     Neurotoxic signs

2.     Rapid extension of local swelling

3.     Acute renal failure

4.     Cardiovascular abnormalities

5.     Bleeding abnormalities

6.     Haemoglobinuria / myoglobinuria

Contraindication to antivenom

There is no absolute contraindication to antivenom treatment.

Additional treatment

1. If neurotoxicity

– inj. Neostigmine & Atropine (Inj. Atropine 15

µg/kg IV followed by Inj. Neostigmine50-100 µg/kg S/C

4 hourly until neurotoxic features improves)

2. If Haematological abnormalities

– Fresh frozen plasma/

– Fresh Blood transfusion

Criteria for repeating the initial dose of antivenom:

• If no improvement or deterioration after 1-2 hours

• Persistence or recurrence of blood incoagulability after 6 hours

Conservative treatment when no antivenom is available

1. Assisted ventilation in respiratory paralysis.

2. If Neurotoxicity

– Neostigmine &

– Atropine

3. In case of haemostatic abnormalities

– Strict bed rest

– Avoid I/M injection.

– Fresh blood transfusion.

– Avoid NSAID or Aspirin for pain

How we can avoid snake bite??

  • Avoid places where snakes may live.
  • Watch where you step and where you sit when outdoors.
  • When moving through tall grass or weeds, poke at the ground in front of you with a long stick to care away snakes

• Wear loose, long pants, thick leather or rubber boots.

• Shine a flashlight on your path when walking outside at night.

  • Look care fully before going to bed, wearing shirt
  • Switch on the light when entering room

Never handle a snake, even if you think it is dead. Recently killed snakes may still bite by reflex.

 

 

 

Introduction of poisoning management

 

What is a poison?

A poison is any substance that causes harm if it gets into the body.
Harm can be mild(for example, headache or nausea) or severefor example,
fits or very high fever),and severely poisoned people may die.

The amount of a chemical substance that gets into the body at one
time is called the dose. A dose that causes poisoning is a poisonous
dose or toxic dose. The smallest amount that causes harm is the threshold
dose. If the amount of a chemical substance that gets into the body is
less than the threshold dose, the chemical will not cause poisoning and
may even have good effects. For example, medicines have good effects
if people take the right doses, but some can be poisonous if people
take too much.

Exposure to a poison

When people are in contact with a poison they are said to be exposed
to it. The effect of exposure depends partly on how long the contact
lasts and how much poison gets into the body, and partly on how much
poison the body canget rid of during this time. Exposure may happen
only once or many times. Acute exposure is a single contact that
lasts for seconds, minutes or hours, or several exposures over about
a day or less.

Chronic exposure is contact that lasts for many days, months or years.
It may be continuous or broken by periods when there is no contact.
Exposure that happens only at work, for example, is not continuous.

Chronic exposure to small amounts of poison may not cause any signs
or symptoms of  poisoning at first. It may be many days or months
before there is enough chemical inside the body to cause poisoning.
For example, a person may use pesticide every day. Each day the person
is exposed to only a small amount of pesticide, but the amount of
pesticide in the body gradually builds up, until eventually, after many
days, it adds up to a poisonous dose. Only then does the person
begin to feel unwell.

How poison gets into the body:

The way poison gets into the body is called the route of exposure or
the route of a bsorption. The amount of poison that gets into the
blood during a given time depends on the route.

1) Through the mouth by swallowing (ingestion)

Most poisoning happens this way. Small children often swallow poison
accidentally, and adults who want to poison themselves may swallow
poison. If people eat, drink or smoke after they have been handling
poisons, without first washing their hands, they may accidentally
swallow some of the poison. This is a common cause of pesticide
poisoning.

When poisons are swallowed they go to the stomach. Some poisons can
pass through the gut walls and into the blood vessels. The longer
a poison stays in the gut the more will get into the blood and the
worse the poisoning will be.

If a person vomits soon after swallowing a poison, it may be expelled
from the body before a poisonous dose gets into the blood. So, if
the person does not vomit straight away, it is sometimes useful to
make the person vomit. There are two other ways to stop poisons
passing from the gut into the blood: (1) give activated charcoal
because this binds some poisons so that they cannot pass through
the gut walls; or (2) give laxatives to make the poison move through
the gut and out of the body more quickly. Poisons that do not pass
through the gut walls do not get into the blood and so cannot affect
other parts of the body. They move along the gut and leave the body
in the faeces.

2) Through the lungs by breathing into the mouth or nose  (inhalation)

Poisons in the form of gas, vapour, dust, fumes, smoke or fine spray droplets may be
breathed into the mouth and nose and go down the air passages into the lungs. Only
particles that are too small to be seen can pass into the lungs. Larger particles are
trapped in the mouth, throat and nose and may be swallowed. A person may breathe in
poison when working with a poisonous substance inside a building without fresh air,
or when spraying pesticide without wearing adequate protection. Oil or gas heaters,
cookers, and fires give off poisonous fumes which may reach dangerous concentrations
if the smoke cannot get outside or if the room does not have a good supply of fresh
air. Poison that gets into the lungs passes into the blood vessels very quickly
because the air passages in the lungs have thin walls and a good blood supply.

3) Through the skin by contact with liquids, sprays or mists

People working with chemicals such as pesticides may be poisoned

if the chemical is sprayed or splashed onto the skin, or if they wear clothes soaked
with chemical. The skin is a barrier that protects the body from poisons. However,
some poisons can pass through the skin. They pass through warm, wet, sweaty skin more
quickly than through cold, dry    skin, and they pass through skin damaged by
scratches or burns more quickly than through undamaged skin. A poison that damages
the skin will pass through more quickly than one that does not damage the skin. It
may be possible to wash poison off the skin before a poisonous dose gets into the
body.

4) By injection through the skin

Poisons can be injected through the skin from a syringe, or a pressure gun, or during
tattooing, or by the bite or sting of a poisonous animal, insect, fish or snake. The
injection may go directly into the blood vessels or under the skin into muscle or fatty
tissues. Poison injected into the blood has a very quick effect. Poison injected
under the skin or into muscle has to pass through several layers of tissue before
reaching the blood vessels, so it acts more slowly.

How poison is carried round the body

Once a poison gets into the blood it is carried to the whole body as the blood is
pumped round the body by the heart.

How poison is broken down by the body

Some poisons are changed by the body into other chemicals. These are called metabolites,
and may be less poisonous or more poisonous than the original substance. The
metabolites are more easily passed out of the body than the original chemicals. These
changes take place mostly in the liver.

How poison leaves the body

Unchanged poisons or their metabolites usually leave the body in the urine, faeces or
sweat, or in the air that a person breathes out. The movement of poison from the blood
into urine takes place in the kidneys, and the movement of poison from blood into
breathed-out air takes place in the lungs. Poison in the faeces may have passed down
the gut without being absorbed into the blood or it may have been absorbed into the
blood and then passed out into the gut again. Some poisons, like DDT, pass into body
tissues and organs where they may stay for a long time.

Effects of poison

The effects of a chemical substance on the body may be described as either local or
systemic.

A local effect is limited to the part of the body in contact with the chemical: the
skin, the eyes, the air passages or the gut. Examples of local effects are skin rashes,
skin burns, watery eyes, and irritation of the throat causing coughing. Many poisons
cause local effects, but there are also many poisons that do not.

A systemic effect is a more general effect that occurs when a poison is absorbed into
the body.

Some poisons cause both local effects and systemic effects. If someone has local
effects from exposure to a chemical it is important to check whether they also have
signs or symptoms of systemic poisoning.

Local effects

1) On the skin

Chemicals that damage the skin cause reddening or a rash, pain, swelling, blisters or
serious burns. The burns are like the burns caused by fire.

An irritant chemical causes itching, a burning feeling, or pain when it first touches
the skin, but does not cause burns if washed off straight away. However, if it is in
contact with the skin for a long time, for example when people wear contaminated
clothes for several hours, it might cause burns.

Some irritant chemicals have no effect the first few times they touch the skin, but
with continued contact they cause reddening or a rash. This might happen with repeated
use of a household cleaner.

Sometimes people become sensitive to a chemical after they have used it many times.
They may have no effects at first but after a few weeks or months they get a rash every time they use it.

A corrosive or caustic chemical very quickly causes painful burns and destroys the
skin. There may be blisters and the skin may turn grey-white or brown.

2) On the eyes

Irritant or corrosive chemicals can cause severe pain if they get into the eyes.
They may very quickly burn the surface of the eye and cause scars or even blindness.
The eyes will look red and watery. The person may not want to open the eyes and bright
light will hurt.

3) Inside the gut

Irritant or corrosive chemicals may damage the mouth and throat or the inside of the
gut. The person will have belly pain, vomiting and diarrhoea, and the vomit and faeces
may contain blood. If the throat is burnt it may swell very quickly, so that the person
cannot breathe.

4) Inside the air passages and lungs

Some gases and vapours can irritate the nose, throat and upper air passages and cause
coughing and choking. Some gases and vapours damage the lungs in a way that causes
them to fill with water. This may happen very soon after a person breathe in the
substance, or it may happen up to 48 hours afterwards. A person with water in the
lungs cannot breathe properly and may drown. He or she must be taken to a hospital as
quickly as possible. Water in the lungs is called
lung oedema. Some of the gases that cause lung oedema also irritate the nose, throat
and upper air passages, and make people cough and choke.

Some poisonous gases, such as carbon monoxide, have no effect on the nose and throat.
Poisonous gases that do not cause coughing and choking are very dangerous because
people may not know they are breathing poison.  Petroleum distillate liquids, such as
kerosene, may cause lung oedema when swallowed.

5) At injection sites

Irritant poisons that are injected into the skin, such as poisons from insect stings
and snake bites, may cause pain and swelling where they are injected. People who
accidentally inject themselves with veterinary products, when giving injections to
animals or birds, may get local effects.

6) Systemic effects

There are many ways in which poisons can cause harm:

*    By damaging organs such as the brain, nerves, heart, liver,

lungs, kidneys, or skin. Most poisons have a greater effect on

one or two organs than on other parts of the body. The organs

that are most affected are called the target organs.

*    By blocking messages between nerves.

*    By stopping the body working properly, for example, by blocking

energy supply or oxygen supply.

Effects on unborn babies

Some poisons can harm a baby inside the womb. This is most likely during the first
three months of pregnancy when the nervous system and all the major organs begin to
form. The parts of the baby usually affected are the bones, eyes, ears, mouth and
brain. If the damage is very bad the baby will stop growing and die. Some poisonous
chemicals may harm a baby in the womb without harming the mother. This is serious
because there is nothing to warn the mother that her baby is in danger. If a mother
drinks alcohol or smokes during pregnancy it may harm her baby. Medicines may also
harm a baby in the womb. Pregnant women should never take medicines unless they are
prescribed by a doctor.

When systemic effects happen

Systemic effects only happen when the amount of poison in the body is greater than
the amount the body can get rid of, and the poison builds up and reaches the threshold
level.

Some poisonings happen by accident but some happen when people try deliberately to
harm themselves (self-poisoning) or others. There are other circumstances that may
result in poisoning:

–       eating food containing poison;

–       taking, or being given, the wrong kind of medicine or the wrong dose;

–       taking drugs because they change mood or behaviour, or using

–       plants or chemical products for this purpose.

Accidental poisoning

Accidental poisoning may happen when:

–       young children or old people handle poisons not knowing what they are;

–       people mistake poison for food or drink because it is not in its original
container;

–       people misuse chemical products or medicines;

–       people use or misuse pesticides;

–       people work with chemicals;

–       people are exposed to carbon monoxide, usually at home.

Poisoning in childhood

Many poisoning accidents in the home happen to small children aged between 1 and 4
years. At this age children want to explore. They like to put things in their mouths
but they are not old enough to understand that some things might be harmful.

The chemical products most often swallowed by children are:

–       household cleaners such as bleach, detergent and disinfectant;

–       paraffin and kerosene used as household fuels;

–       cosmetics;

–       medicines;

–       paint and products for household repairs;

–       household pesticides.

Poisoning in old age

Old people may poison themselves accidentally. If they cannot see very well, they may
pick up the wrong bottle and swallow a household cleaner, for example, instead of a
drink or a medicine.

Taking products out of their own containers

Accidents can happen when someone takes a chemical product out of its container and
puts it in another one. The new container does not have the right label so nobody
else will know what is inside. Even the person who did it may forget.

Pesticide poisoning

Most pesticides are also poisonous or harmful to humans if they get on the skin, or
if they are breathed into the lungs in the form of gases, fumes, dust or fine spray
droplets, or if they are swallowed.

Poisoning at work

Many chemicals that are made, used, or stored in workplaces are poisonous. People who
work with these chemicals need to know how to handle them safely to avoid being
poisoned. Sometimes workers may not know that they are handling a poisonous chemical,
or they may know that the chemical is poisonous but not have been told or shown how
to handle it safely. They may not have read the label or the safety information.
Sometimes they may know the dangers but be too lazy or careless to use safe methods.         Accidents, fires or explosions at work may result in chemicals spilling or leaking out of their containers onto roads or into rivers, or vapours and gases being released into the air. Sometimes chemicals spread over a large area and poison many people. Chemical waste and empty chemical containers may be serious safety hazards if they are not dealt with in the right way.

Self-poisoning

People may try to harm themselves by deliberately taking poison -this is called
self-poisoning. In some countries people take medicines to poison themselves, but
people living in rural communities are more likely to take pesticides. People
suffering from depression, serious illness, or alcohol dependence may try to kill
themselves by taking poison. They may swallow large amounts of medicine, pesticide
or other poisons. If they recover they might try to poison themselves again unless
they receive appropriate treatment.

Poison in food or drink

Food or drink can be contaminated by poison from microscopic organisms such as
bacteria, viruses, or mould, or by chemical poisons. Some plants, mushrooms, animals
or sea-creatures contain poisonous chemicals. Poisons made by plants, animals or
microorganisms are called toxins.

Chemical poisons

There are many ways chemical poisons can get into food and drink, for example:

–       when people working with chemicals eat in the workplace or do not wash
their hands before eating;

–       when chemicals spill onto food as it is being moved from place to place,
or when it is in a storeroom;

–       when food or drink is stored or cooked in containers that are contaminated
with chemicals;

–       when people make flour from grain that has been treated with pesticide
because it was meant to be used for seed or bait, not for food;

–       when people brew their own alcoholic drinks and produce poisonous alcohols,
such as methanol;

–       when water supplies are polluted by accidental spills of chemicals, or by
chemical waste from factories or waste dumps near watercourses.

Medical poisoning

Sometimes people are poisoned by medicines given to them by a doctor or another health
care worker. They may be given the wrong medicine or be given the wrong dose of the
right medicine.

Abuse of drugs, chemicals or plants

People may take drugs to change their mood or behaviour, to feel relaxed, or to get
more energy. This is called drug abuse because it is not a medical use of the drug.
Some people abuse drugs such as heroin, cocaine or barbiturates. Drinking too much
alcohol is an important kind of drug abuse.

Common Poisoning Symptoms and signs                                                                                                                                 

Poisons

Symptoms and signs

Atropine, Amitriptyline, Antihistamines, Datura stramonium Atropa belladonna, some kinds of  Mushrooms dry, hot skin, fever, thirst, dry mouth, large pupils, fast pulse, difficulty in passing urine, hallucinations, fits, shallow breathing unconsciousness
Organophosphorus and  Carbamate insecticides, some kinds of Mushrooms small pupils, wet mouth, sweating, wet eyes vomiting, slow pulse, diarrhoea, fits, unconsciousness
Opiates small pupils, slow breathing, unconsciousness,  weak pulse                                    low temperature, , vomiting
Amfetamines, cocaine, Theophylline large pupils, fever, fast pulse, hallucinations, fits, anxiety, sweating, flushed skin, over-                                              activity, confusion
Barbiturates, Diazepam and similar drugs, Meprobamate,  Drug withdrawal, barbiturates, diazepam and similar  medicines, opiates

              

unconsciousness, low blood pressure, shallow breathing, low temperature

diarrhoea, gooseflesh, fast pulse, watering eyes, yawning, cramps, hallucinations, restlessness, shaking

Dr. Ratin’s Personal Site

Principle of poisoning management

Assessment: Airway, Breathing, Circulation and Consciousness, should be assessed in all patients with poisoning.

Level of consciousness:

  • The Glasgow Coma Scale (GCS) is commonly used though it is not validated. A GCS score of less than 8 (not obeying commands, not speaking, not eye opening) is unarousable unconsciousness.
  • Are laryngeal (gag) reflexes present? If it is lost, prompt assessment of respiration is essential.

Airway:

Most common factor contributing to death from poisoning and drug overdose is loss of airway protective reflex.

  • Assessment:

o      Patient who are awake and talking- Likely to have intact airway, but should be monitored closely.

o      In lethargic and obtunded patient- Check gag reflex. If lost: Airway reflex is likely to be lost.

Breathing:

Along with the airway problem, breathing difficulties are the major cause of morbidity and mortality in poisoning. These are: ventilatory failure, hypoxia and bronchospasm.

Assessment:

Be done by observing efforts of ventilation, respiratory rate, cyanosis, use of accessory muscle of respiration and SP02 by pulse oximetry. Ineffective respiration and cyanosis are two important clinical parameters for assessing the ventilation. If these parameters are present, the patient may need ventilator support.

Pulse oximetry to measure oxygen saturation (Displayed reading is inaccurate if 02 saturation is below 70%, poor perfusion, presence of carboxyhaemoglobin and methaemoglobin).

  • SP02 <90% demands immediate 02 inhalation.
  • SP02 91-95% states 02 inhalation necessary.
  • SP02 >95% is normal.

Circulation:

Maintenance of adequate circulation is a must for every case of poisoning and drug overdose.

Assessment:

Check BP, pulse rate and rhythm, capillary refill time (CRT).

If SBP <90mm Hg and pulse >100/min; patient is in shock.

In Children: SBP <80mm Hg.

In shock CRT >2sec

ECG monitoring may be needed in case of TCA, yellow oleander, Digitalis glycoside and beta blocker poisoning.

History taking:

Medical, psychiatric, toxicological and socioeconomic history should be taken in every case of poisoning.

In Adult: 80% of patients who arrived at the hospital are conscious and diagnosis of self poisoning is made from history. In the rests who are unconscious, history from relatives, friends or attendants is helpful and diagnosis is often inferred from brought specimen (e.g. tablet bottles or a suicide note) or made by exclusion of other causes.

It is pertinent to try to establish the nature of the substance taken, the amount involved, the route and the time of exposure to anticipate the clinical course and to assess risks. In children (<13 yrs) history is very unreliable in regard to amount.

Assessment of psychiatric problems:

1     Events that preceded the act

2.     Degree of suicidal intent

3.     Current problems faced by the patient

4.     H/O psychiatric disorder

5.     Personality traits and disorder

6.     Family and personal history

7.     H/O previous self injury

8.     Risk of further overdose and subsequent suicide

Circumstantial evidences:

  • Suicide note is a reliable indicator of drug overdose in absence of evidence of physical violence as a cause of coma.
  • Circumstances in which the patient was found: Children may be found eating potential toxins or with tab around clothing, or having smell of the ingested substances from body and oral cavity. Similar thing may be seen in unconscious adults or may be with empty drug containers, tablets or capsules nearby.

Physical examination:

Initial assessment of vital signs and managed accordingly.

Subsequent examination depends upon type, amount, nature and time of poisoning. Some common clustering features may point towards a particular poisoning, and are described below.

 

 

 

 

 

 

Common clusters of features that may be diagnostic:

Feature cluster

Likely Poison

Coma, hypotonia, hypo-reflexia, plantar responses: flexor or non-elicitable, hypotension.

hypotension.

Barbiturates, benzodiazepines and alcohol combinations, severe TCA poisoning

TCA poisoning.

Smell of OPC, bronchorrhea, incontinence of urine & stool, miosis and hyper salivation Organophosphorus and carbamate insecticides, nerve agents
Coma, miosis, reduced respiratory rate Opioids.
Nausea, vomiting, tinnitus, deafness, sweating, hyperventilation, vasodilatation, metabolic acidosis. Salicylates
Restlessness, agitation, mydriasis, anxiety, tremor, tachycardia, convulsion, arrhythmias

arrhythmias.

Sympathomimetic drugs (Bronchodilator, theophylline)
Blindness (usually with other features) Quinine, methanol
Smell of OPC, bronchorrhea, incontinence of urine & stool, miosis and hyper salivation Organophosphorus and carbamate insecticides, nerve agents

NB: All the features of a particular poison may not be present in a particular case.

Diagnostic trial of antidotes:

Administration of I.V naloxone and flumazenil has been used to make rapid clinical diagnoses of opioid and benzodiazepine poisoning respectively; this approach depends on noticeable improvement in the patient’s clinical condition within 1-2 minutes.

 

Toxicological investigations:

Toxicological screening of blood or urine can be used to establish a diagnosis of poisoning. The concentration is measured in the plasma or serum rather than whole blood except Carboxyhaemoglobin.

Emergency measurement of plasma concentration of known toxins is necessary for the following toxins:

  • Carboxyhaemoglobin
  • Ethanol
  • Ethylene glycol
  • Iron
  • Lithium
  • Methanol
  • Paracetamol
  • Salicylate
  • Theophylline
  • Benzodiazepine

Screening for unknown toxins:

In multiple drug overdoses benzodiazepine and paracetamol measured routinely. Laboratory screening for poisons in an unconscious patient usuaIly concentration are requested when the cause of coma is unknown.

Urine (20ml) is usually a more appropriate fluid for detecting unknown poison. Once identified their concentration in blood or plasma can be determined by specific method if necessary.

Non-toxicological investigations:

Inspection of brought specimen – Generic name, amount left in bottle smell color etc.

Inspection of blood:

  • Chocolate-coloured blood indicates methaemoglobin caused by drugs e.g. Dapsone, nitrites or nitrates.
  • Pink plasma suggests hemolytic poisons e.g. sodium chlorate
  • Brown plasma suggests the presence of circulating myoglobin secondary to rhabdomyolysis

Inspection of urine:

  • Brown discolouration of the urine by the presence of heamoglobin (intravascular haemolysis), myoglobin secondary to rhabdomyolysis or metabolites of paracetamol.
  • Crystals in primidone overdose or ethylene glycol.

Haematology:

Is of little value except prolongation of prothrombin time in anticoagulants or paracetamol overdoses and also in snake bite.

Biochemical indicator of various poisoning:

  • Serum sodium: e.g. hyponatraemia in Ecstasy poisoning.
    • Serum potassium: e.g. hypokalaemia in theophylline, hyperkalaemia in digoxin poisoning, rhabdomyolysis and haemolysis.
    • Plasma creatinine e.g. renal failure in ethylene glycol poisoning.
    • Blood sugar e.g. hypo or hyperglycaemia in salicylate poisoning.
    • Serum calcium e.g. hypocalcaemia in ethylene glycol poisoning.
    • Serum ALT/AST e.g. increased in paracetamol poisoning.
    • Serum phosphate e.g. hypophosphataemia in severe paracetamol induced renal tubular damage
    • RBC cholinesterase activity e.g. organophosphorus and nerve agents poisoning.
    • Whole blood methaemoglobin concentration e.g. in nitrite poisoning.

Radiology and ECG are of little value but sometimes important for complication of poisoning. Radiology can be used to confirm ingestion of metallic objects (coins, button, batteries or ingestion of globules of metallic mercury) and iron tablet.

In ECG sinus tachycardia with prolongation of PR & QRS interval should prompt consideration of tricyclic antidepressant poisoning. ECG is also important in yellow oleander poisoning and phenothiazines overdose.

 

 

Clinical Features and Complications of Poisoning:

The toxicity of a substance and therefore the features of poisoning can generally be predicted from:

  • Its physiochemical properties
  • Its pharmacological / toxicological actions
  • Its route of exposure
  • Its dose

These features are classified as either direct or systemic

Principles of Management of Poisoned Patient:

Most patients with self-poisoning require only general care and support of the vital systems. However, for a few drugs additional therapy is required. The challenge for clinicians managing poisoned patients is to identify at an early stage, those who are at risk of developing serious complications and who might potentially benefit from an antidote or treatment to increase elimination of the poison.

 

Strategy:

  • Provide immediate supportive treatment (ABC).
  • Is the use of an antidote appropriate?
  • Is it appropriate to attempt to reduce poison absorption?
  • Is it appropriate to perform toxicological investigations?
  • Will non-toxicological investigations assist?
  • Should urine alkalinization, multiple-dose activated charcoal, and haemodialysis be employed to increase poison elimination?

 Airway, Breathing and Circulation (ABC) (See Chapter-17)

Respiratory support:

Food, vomit, secretion and dentures should be removed from the patient’s mouth and the pharynx and the tongue prevented from falling back. The patient should be nursed in left lateral position to minimise the risk of aspiration of gastric contents into the lungs.

If respiratory depression is present, as determined by clinical features and pulse oximetry or preferably by arterial blood gas analysis. Supplemental oxygen should be administered in needed. Pulse oximetry alone will detect hypoxia but not hypercapnia.

Loss of the cough or gag reflex is the prime indication for intubation. The gag reflex can be assessed by positioning the patient on one side and making him or her gag using a suction tube. In many severely poisoned patients the reflexes are depressed sufficiently to allow intubation without the use of sedatives or relaxants.

If ventilation remains inadequate after intubation, as shown by hypoxaemia and hypercapnia, intermittent positive-pressure ventilation (IPPV) should be instituted.

Cardiovascular support:

Although hypotension (systolic blood pressure below 90 mmHg) is a recognized feature of acute poisoning, the classic features of shock – tachycardia and pale cold skin – are observed only rarely. As a first step the patient should be placed head down position (the foot end should be elevated by 15 cm). If there is no improvement, infusion of crystalloid solution should be started. In patients with marked hypotension, volume expansion with gelatins or etherified starches (e.g. heta- starch, hexa-starch) should be used, guided by monitoring of central venous pressure (CVP). Urine output (aiming for 35-50 mL/h) is also a useful guide to the adequacy of the circulation.

If a patient fails to respond to the above measures, more intensive therapy is required. Dobutamine 2.5-10 microgram/kg/min or epinephrine 0.5-2 microgram/kg/min is indicated in such case. Dopamine 10-20 microgram/kg/min is an alternative (see flow chart).

Arrhythmias are observed occasionally in poisoned patients, for example after the ingestion of a tricyclic antidepressant or theophylline. All patients with shock should have ECG monitoring. Known arrhythmogenic factors such as hypoxia, acidosis and hypokalaemia should be corrected.

Care of unconscious patient:

In all cases the patient should be nursed in the lateral position with the lower leg straight and the upper leg flexed; in this position the risk of aspiration is reduced (see fig. chapter 17). A clear airway passage should be ensured by removal of any obstructing object, vomit or dentures, and by backward pressure on the mandible. Nursing care of the mouth and pressure areas should be instituted.

Immediate catheterization of the bladder in unconscious patients is usually unnecessary as it can be emptied by gentle suprapubic pressure.

Insertion of a venous cannula is usual, but administration of intravenous fluids is unnecessary unless the patient has been unconscious for more than 12 hours or is hypotensive.

On admission, or at an appropriate time post-overdose, a timed blood sample should be taken. The determination of the concentrations of the drugs will be valuable in management. Drug screens on blood and urine are occasionally indicated in severely poisoned patients in whom the cause of coma is unknown.

Some routine investigations are of value in the differential diagnosis of coma or the detection of poison-induced hypo or hyperkalaemia, hypo or hyperglycaemia, hepatic and renal failure or of acid-base disturbances. Measurement of carboxyhaemoglobin, methaemoglobin and cholinesterase activities are of assistance in the diagnosis and management of cases of poisoning due to carbon monoxide, methaernoglobin-inducing agents such as nitrites, and organophosphorus insecticides respectively.

 

Other Problems:

Body temperature:

Hypothermia -a rectal temperature below 35°C is a recognized complication of poisoning, especially in older patients or those who are comatose. The patient should be covered with a ‘space blanket’ and, if necessary, given intravenous and intragastric fluids at normal body temperature. Inspired gases should also be warmed to 37°C.

Hyperthermia may develop with CNS stimulant ingestion. Removal of clothing and sponging with tepid water will promote evaporation.

Rhabdomyolysis:

Rhabdomyolysis can occur from pressure necrosis in drug-induced coma, or as a complication of sea snake bite or MDMA (Ecstasy) abuse in the absence of coma. Patients with rhabdomyolysis are at risk of developing firstly, renal failure from myoglobinaemia, particularly if they are hypovolaemic and have an acidosis, and. secondly, wrist or ankle drop from the development of a compartment syndrome.


Convulsions:

These may occur in poisoning due to tricyclic antidepressants, mefenamic acid or opioids. Usually the fits are short-lived but, if they are prolonged, diazepam 10-20 mg i.v. should be administered. Persistent fits must be controlled rapidly to prevent severe hypoxia, brain damage and laryngeal trauma. If diazepam in repeated doses is ineffective, the patient should also receive a loading dose of phenytoin (15 mg/kg) administered intravenously at a rate of not more than 50 mg per minute, with blood pressure and ECG monitoring.

Stress ulceration and bleeding:

Medication to prevent stress ulceration of the stomach should be started on admission in all patients who are unconscious and require intensive care. An H2-receptor antagonist or a proton pump inhibitor should be administered intravenously.

Specific Management: Antidotes:

Specific antidotes are available for only a small number of poisons.

Poison

Antidote

Aluminium Desferrioxmine
Arsenic Dimercaprol (BAL), DMSA
Benzodiazepines Flumazenil
ß-adrenoceptor blocking drugs Atropine, glucagon
Copper Dimercaprol, D-penicillamine, DMPS
Cyanide Oxygen,dicobaltedetate,hydroxocobalamin, Sodium thiosulphate
Digoxin and digitoxin Digoxin-specific antibody fragments
Ethylene glycol Fomepizole, Ethanol
Iron salts Desferrioxamine
Lead (inorganic) Sodium calcium edetate, DMSA
Methaemoglobinaemia Methylthioninium chloride (Methylene blue)
Methanol Fomepizole, Ethanol
Mercury (inorganic) DMPS
Opioids Naloxone
Organophosphorus compounds Atropine, pralidoxime
Paracetamol N-acetylcysteine,Methionine
Thallium Prussian (Berlin) blue
Warfarin and other anticoagulants Vitamin K1

Dose of antidotes—annexure 3

Antidotes may exert a beneficial effect by:

  • Forming an inert complex with the poison (e.g. desferrioxamine, dicobalt edetate, dimercaprol, DMSA, DMPS, digoxin-specific antibody fragments, hydroxocobalamin, penicillamine, pralidoxime, protamine, Berlin (Prussian) blue, sodium calcium edetate)
  • Accelerating the detoxification of the poison (e.g. methionine, N-acetylcysteine, sodium thiosulphate)
  • Reducing the rate of conversion of the poison to a more toxic compound (e.g. ethanol, fomepizole)
  • Competing with toxic substances for essential receptor sites (e.g. oxygen, naloxone, vitamin K1)
  • Blocking essential receptors through which the toxic effects are mediated (e.g. atropine)
  • Bypassing the effect of the poison (e.g. oxygen).

Reduction of Poison Absorption:

Inhaled:

To reduce poison absorption through the lungs, the casualty should be removed from the toxic atmosphere, without the rescuers themselves being put at risk.

 

Skin:

If clothing is contaminated this should be removed to reduce dermal absorption. In addition, contaminated skin should be washed thoroughly with soap and water.

 

Gut decontamination:

The efficacy of current methods to remove unabsorbed drug from the gastrointestinal tract remains unproven. The two major international societies of clinical toxicology (American Academy of Clinical Toxicology (AACT) and the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT)) have produced Position Statements on each method and are quoted below.

 

Gastric lavage:

Gastric lavage involves the insertion of a large-bore orogastric tube into the stomach. Small amounts (200-300 mL in an adult) of warm (38°C) fluid (water or 0.9% saline) are introduced and removed by suction. Lavage is continued until the recovered solution is clear of particulate matter. Gastric lavage should not be employed routinely in the management of poisoned patients. The amount of marker removed by gastric lavage is highly variable and diminishes with time. There is no certain evidence that its use improves clinical outcome and it may cause significant morbidity. Gastric lavage should only be considered, therefore, if a patient has ingested a potentially life-threatening amount of a poison and the procedure can be undertaken within 1 hour of ingestion.

Gastric lavage can be given upto 4 hours in poisoning with salicylates, anticholinergic and iron. Gastric lavage is contraindicated if airway-protective reflexes are lost (unless the patient is intubated) and also if a hydrocarbon with high aspiration potential (e.g. Kerosine) or a corrosive substance has been ingested.

 

Syrup ipecacuanha:

Syrup of ipecacuanha contains two alkaloids, emetine and cephaeline, which induce vomiting by a central action and by a local action (emetine). Syrup of ipecacuanha should not be administered in the management of poisoned patients. There is no evidence that it improves the clinical outcome and therefore its administration, even in children, should be abandoned.

 

Single dose activated charcoal:

Activated charcoal has a highly developed internal pore structure which is able to adsorb a wide variety of compounds and drugs, e.g. aspirin, carbamazepine, aminophylline, digoxin, barbiturates, phenytoin, paracetamol. It does not absorb strong acids and alkalis, ethanol, ethylene glycol, iron, lithium, mercury and methanol.

Single-dose activated charcoal should not be administered routinely in the management of poisoned patients. Based on volunteer studies, the effectiveness of activated charcoal decreases with time; the greatest benefit is within 1 hour of ingestion. The administration of activated charcoal should only be considered if a patient (with an intact or protected airway) has ingested a potentially toxic amount of a poison (which is known to be adsorbed to charcoal) up to 1 hour previously. Again, there is no evidence that this improves the clinical outcome.

Cathartics:

Whole bowel irrigation (WBI) requires the insertion of a nasogastric tube into the stomach and the introduction of polyethylene glycol electrolyte solution 1500-2000 mL/h in an adult. WBI is continued until the rectal effluent is clear.

WBI should not be used routinely in the management of the poisoned patient. Although some volunteer studies have shown substantial decreases in the bioavailability of ingested drugs, no controlled clinical trials have been performed and there is no conclusive evidence that WBI improves the outcome of the poisoned patient.

Based on volunteer studies, WBI should be considered for potentially toxic ingestions of sustained-release or enteric-coated drugs. There are insufficient data to support or exclude the use of WBI for potentially toxic ingestions of iron, lead, zinc, or packets of illicit drugs; WBI remains a theoretical option for these ingestions.

WBI is contraindicated in patients with bowel obstruction, perforation, ileus, and in patients with haemodynamic instability or compromised unprotected airways. WBI should be used cautiously in debilitated patients or in patients with medical conditions that may be further compromised by its use.

 

Increasing Poison Elimination:

Treatments that might speed poison elimination are forced diuresis, urine alkalinization, acid diuresis, multiple-dose activated charcoal, dialysis and haemoperfusion.

Forced diuresis:

The efficacy of forced diuresis depends on the poison being excreted unchanged by the kidney or as an active metabolite. Most drugs are either degraded by the liver to non-toxic metabolites or have such large volumes of distribution that there is insufficient active drug elimination in urine for forced diuresis to be of any clinical value. The amount removed in this way is insignificant compared to that removed by hepatic metabolism and forced diuresis should not be used.

 

Urine alkalinization:

Most drugs, particularly unionized, lipid-soluble molecules, are largely reabsorbed by the renal tubules. Increasing the concentration of ionized drug in the urine should reduce reabsorption and further enhance elimination. This is achieved by manipulating urine pH which enhances ionization and hence elimination of weakly acidic compounds such as salicylates, phenobarbital, and chlorophenoxy herbicides. In practice, urine alkalinization is only employed commonly in salicylate intoxication.

 


Urine acidification:

Although, theoretically, induction of urine acidification increases the elimination of basic drugs such as amphetamines, there is no evidence that it is of clinical value in cases of poisoning.

 

Multiple dose activated charcoal:

Multiple doses of activated charcoal aid the elimination of some drugs from the circulation by interrupting their enterohepatic circulation and also by adsorbing the drug that has diffused into the intestinal juices. The rate of transfer of the latter is dependent upon the blood supply to the gut, the area of mucosa available for transfer, and the concentration gradient of the drug across the mucosa. The adsorptive capacity of charcoal is such that as zero concentrations of free drug are present in luminal fluid, the diffusion gradient still remains as high as possible. The process has been termed ‘gut dialysis’ since, in effect, the intestinal mucosa is being used as a semipermeable membrane.

Although many studies have demonstrated that multiple-dose activated charcoal increases drug elimination significantly, this therapy has not yet been shown to reduce morbidity and mortality. Multiple-dose activated charcoal should be considered only if a patient has ingested a life-threatening amount of carbamazepine, dapsone, phenobarbital, quinine or theophylline. In all of these cases there are data to confirm enhanced elimination, though no controlled studies have demonstrated clinical benefit. Adults should receive 50-100 g initially, followed by 50 g 4-hourly or 25 g 2-hourly until charcoal appears in the faeces or recovery occurs.

 

Dialysis:

Haemodialysis in acute poisoning is most commonly indicated for the treatment of acute renal failure and only infrequently to increase the elimination of poisons. The rate of elimination across the dialysis membrane depends upon a number of variables including the molecular weight of the poison, the extent to which it is protein-bound, the concentration gradient, and pH of blood and dialysate. Haemodialysis is of little value in patients who ingest poisons with large volumes of distribution, e.g. tricyclic antidepressants, because the plasma contains only a small proportion of the total amount of drug in the body. Haemodialysis is indicated in patients with severe clinical features and high plasma concentrations of ethanol, ethylene glycol, isopropanol, lithium, methanol or salicylate.

Peritoneal dialysis increases the elimination of poisons such as ethylene glycol and methanol but is much less efficient than haemodialysis.

 

Haemoperfusion:

This technique is not available routinely. It involves the passage of blood through an adsorbent material, e.g. activated charcoal, but is no better than oral multidose activated charcoal for the removal of phenobarbital, carbamazepine and theophylline. Other barbiturate and non-barbiturate hypnotics can be removed effectively but are now only rarely prescribed.


 

Research works  

Types of snake and pattern of envenomation in Rangpur

  Dr. Ratindra Nath Mondal1, Dr. Moni Rani2, Dr. Md. Sarawarul Islam3,  Dr. Md. Ashraful Haque4, Dr.  Md. Zakir   Hossain5, Dr. Amaresh Chandra Saha6,  Dr. M.A. Faiz7.

1,2Honarary Medical officer, 3MD thesis part student, 4Assistant Professor, 5, 6 Professor of Medicine, RpMC , 7Professor of Medicine, SSMC.

Abstract:

Background: Snakebite is the second leading cause of unnatural death in Bangladesh. Incidence of snake bite is common in rural areas. Objectives: To see the types of snake, incidence of envenomation and mortality rate of snake bite in Rangpur, a northern district of Bangladesh. Methods: It was a cross sectional study carried out in department of Medicine, Rangpur Medical College Hospital, Rangpur from 01/06/2010 – 28/02/11. A total number of 111 snake bite patient with age ranged from 18 years to above of both sexes were studied. Patient admitted in inpatient department with history of snake bite were enrolled. Result: A total 111 patient, 18 years of age and above were admitted. Among them male were 69 (62.16%) and female were 42 (37.84%). Among the study population most were farmer 35 (31.53%) and house wife 35 (31.53%), and least are snake charmer 01 (0.90%). The study showed that most of the snake bite did not show signs of envenomation 90.09% ( n=100) and envenomation occurred in 9.91% ( n=11) and most of the venomous bite were by krait (77.78%%) and cobra (22.23 %). Among the study population mortality were found 5.71%. Conclusion: In our study envenomation occurred in 9.91%, most of the venomous bite was by krait (77.78%) and mortality rate among envenomated patient was 54.55%.

Introduction:

There are about 2500 species of snake in the world, among them 250 are poisonous. In Bangladesh among the 82 species of snake 28 are venomous, 12 species of them are sea snake.1 Venomous snakes of the world belong to the families Viperidae(sub family Viperinae: Old world vipers; sub family Crotalinae: new world and Asian pit vipers), Elapidae (including cobras, kraits, coral snakes and all Australian venomous snakes), Hydrophiidae (sea snakes), Atractaspididae (burrowing asps), and Colubridae (a large family, of which most species are non venomous and only a few are dangerously toxic to humans).2 There are 5 medically important groups of snake in our country, these are- cobra, krait, russel viper, green pit viper and sea snake. Among this majority of venomous bites in our country are cobras and kraits. They are mainly neurotoxic, and respiratory failure is the main cause of death following envenomation1. Snake usually lives in the paddy field, river, hills, roots of the tree, rat hole etc. Snakes are docile in nature, they are carnivorous they eat frog, rats etc3. They bite defensively or when agitated. All the snake bites do not produce sign, symptoms, only the bites by poisonous snake produces specific sign symptoms. Even 50% of the bite inflicted by poisonous snake does not produce any sign of envenomation. Bites rates are highest in temperate and tropical regions where the population subsists by manual agriculture. Estimates indicate >5 million bites annually by venomous snakes worldwide, with > 12,5000 deaths2 A World Health Organisation-funded study estimated about 8,000 cases of snakebite with over 20% mortality in Bangladesh annually. Incidence of snakebite is usually recorded in young people (11-20 years) engaged in active physical work in rural areas. Most bites in Bangladesh are recorded between May and October (rainy season) with highest number in June. Lower and upper limbs are most common sites of snakebite, but it may happen in other sites as well. Delayed presentation to the hospital, lack of availability of antisnake venom and modern management facility are the main causes of death4.

Methods:

It was a cross sectional study carried out in department of Medicine, Rangpur Medical College Hospital, Rangpur from 01/06/2010 – 28/02/11. A total number of 111 snake bite patient with age ranged from 18 years to above of both sexes was studied. Patient admitted in inpatient department of medicine with history of snake bite were enrolled. The statistical analysis was done by using windows SPSS version 12.

Ethical Consideration

All patients will be given an explanation of the study, and informed consent will be taken. The study will not involve any additional investigation procedures and significant risk as well as economic burden to the patients.

Results:

A total 111 patient were studied, among them male were 69(62.16%)and female were 42 (37.84%), in between 18-80 years of age. 35 (31.53%) were farmer, 35 (31.53%) were house wife, 32 (28.82%) were student, 04 (3.60%) were school teacher, 04 (3.60%) were shoop keeper, 01 (0.90%) was snake charmer. Among the victims (n-111) envenomation occurred in 11 (9.91%) and envenomation did not occur in 100 (90.09%). Among the envenomated patient 9 were bitten by krait & 2 were bitten by cobra (as detected by syndrome approach) and among the studied sample (n-111) day time bite was 64 (57.66%) and night time bite is 47 (42.34%) but in envenomated patient night time bite was 06 (54.55%)& day time was 05 (45.45%). 47 (42.34%)  bite was during working in the field, 43 (38.74%) bite was during house hold activities and 09 (8.10%)  bite was during sleeping, 12 (10.81%) while walking along road. Among the envenomous patient 6 (54.55%) were died & 5 (45.45%) survived completely.

Table I: Distribution of the patient by sex

N= 111

             Male          Female
        69(62.16%)      42 (37.84%)

Table II: Distribution of the patient by residence

N= 111

Rural Urban
89 (80.18)% 22 (19.81%)

Table III: Distribution of the patient by occupation

N= 111

              Occupation   Number/ percentage
           Farmer         35 (31.53%)
           House wife         35 (31.53%)
           Student         32 (28.82%)
           Teacher         04 (3.60%)
           Shop keeper         04 (3.60%)
           Snake charmer         01 (0.90%)

Table IV: Incidence of envenomation

N=111

     Envenomation         11 (9.91%)
     Not envenomation         100 (90.09%)

Table V: Time of biting in all patients

N=111

          Time of biting Number/ percentage
          Day time       64 (57.66%)
          Night time       47 (42.34%)

Table VI: Time of biting in envenomated patient

N=11

          Time of biting Number/ percentage
          Night time       06 (54.55%)
          Day time       05 (45.45%)

Table VII: Distribution of victim’s activities during biting

N=111

Activities during biting Number/ percentage
Working in the field   47 (42.34%)
House hold activities  43 (38.74%)
Sleeping  09 (8.10%)
Walking along road  12 (10.81%)

Table VIII: Distribution of patient by site of bite

N=70

      Site of biting Number/ percentage
      Lower limb            74 (66.67%)
     Upper limb            37 (33.33%)

Table XI: Distribution of first aid taken by victims

N=111

         Form of first aid      Number/ percentage
        Tight ligature            104 (93.69%)
        Both ligature & incision            03 (2.70%)
        Only multiple incision            03 (2.70%)
        None            01 (0.90%)

Table X: Type of snake among envenomous patient

(Detected by seeing snake & syndrome approach)

N=11

Krait  09 (77.78%)
Cobra  02 (22.23%)

Table XI: Mortality rate among envenomous patient

N=11

Survived 5 (45.45%)
Death 6 (54.55%)

Table XII: Distribution of mortality rate

  Mortality rate
        In all patient               6 (5.40%)
    In envenomated patient               6 (54.55%)

Discussion:

In our study venomous snake bite was found 9.91% and in other study 39.59 %5. Majority of the bite in lower limb was 66.67% but 65.95% % in other study6. Ligatures had been applied in 93.69%  but in other study 95% 5. Maximum reported cases from rural areas 80.18% in other study it was 99 %6. Mortality rate among venomous snake bite was 54.55% in other study mortality was 44%7.

Conclusion:

In our study envenomation of snake bites occurred in 9.91%  & majority of the victims were from rural areas. Most of the venomous snake bite was by Krait (77.78%).  Among the envenomous patient mortality rate was 54.55%. Delayed presentation to the hospital, lack of availability of antisnake venom & modern management facility is the main causes of death.

Recommendations:

Snake bite patients should be managed in ICU or well facilitated ward and by trained persons.  Improvement of mass awareness about snake bite in rural people and health workers will improve mortality.

Acknowledgement:

The authors of this study acknowledge to the professors, doctors and stuff of department of Medicine who were heartedly helped to do the study.

References:

  1. Faiz MA, Hossain M, Amin R, Ghose A, Basher A, National guideline of management of snake bite, second edition, DGHS, 2008; 1-32.
  2. Paul S.Auerbach, Robert L. Norris, Disorders Caused by Reptile Bites and Marine Animal Exposure. In Fauci AS, Braunwald E, Kasper DL, et al. 17th edition. Harrison’s Principles of Internal Medicine. New York: The McGraw- Hill Companies, 2008:2741- 2748.
  3. Apobo nandy, animal irritants, Principle of Forensic Medicine, second edition. New central book agency, 2004: 506-516.
  4. http://www.banglapedia.org/httpdocs/HT/S_0439.HTM
  5. John B. H., Md. Abul Faiz, M. Ridwanur Rahmanc, Md. M.A. Jalil, Md. Farid Ahsan, R. David G. Theakston, David A. Warrell, Ulrich Kuch; a study of bitten patients who developed no signs of systemic envenoming, in Chittagong Division, Bangladesh Volume 104Issue 5, Pages 320-327 (May 2010),
  6. Abu Bakar, Nazmul Ahasan, Manwar Ahsan, Snake bite in Bangladesh, Pak Armed Forces Med J Mar 2006;56(1):68-72.
  7. Md Titu Miah, AKM Aminul Hoque, Binoy Krishna Tarafder, Md Kamal Hossain Patwary, Raihan Rotap Khan, Shah Mohd Eftar Jahan Kabir, Epidemiology, Clinical Profile and Outcome of Patients of Snake Bite in Mymensingh Medical College Hospital, Journal of Bangladesh College of Physicians and Surgeons, volume 27, no2 (2009).
Study of incidence of acute poisoning in department of Medicine, Rangpur Medical College Hospital, Rangpur.

Dr.Ratindra Nath Mondal1, Dr.Nurmohammod2, Dr.Md.Zakir Hossain3, Dr.A.C.Shaha 4, Dr. Md. Rakibul Islam5, Dr.Ashraful Haque6, Dr.KamruzzamanSarkar7, Dr.Robed Amin8, Dr. Moni Rani9, Dr.M.A.Faiz10.

 

 1Honarary Medical officer, RpMC; 2Registrar of Medicine,RpMC; 3, 4 Professor of Medicine, RpMC 5 Associate Professor of Medicine,  RpMC; 6,7, Asst. Prof. of Medicine, RpMC;8 Asst. Prof. of Medicine,DMC;9 Honarary Medical officer, RpMC; 10Prof. of Medicine, SSMC.

Abstract:

Background: Acute poisoning is one of the most common reasons for acute admission to a medical ward.Poisoning is a common method of suicide, especially in the developing world. Objectives: To see the incidence, outcome and etiological aspect of different acute poisoning. Methods: It was a descriptive and cross sectional study carried out in department of Medicine, Rangpur Medical College Hospital, Rangpur from 01/12/2010 – 25/02/11. A total number of 188acute poisoning patient with age ranged from 18 years to above of both sexes were studied. Patient admitted in inpatient department with history of acute poisoning were enrolled. Result:  A total 188 patient were studied, majority of them female were 52.66%, maximum  92.55% in the age range  between 18 -40 years, 56.38% were married, farmer were 17.55%, 29.79% were house wife, 36.17% were student, 2.13% were serviceman, and others were 14.36%, 71.27% ingested poison due to familial disharmony, 6.91% Stupefied while travelling, 4.78% due to fail to pass in examination, 3.72% due to economic loss, 3.73% due to psychiatric illness, 1.60% due to chronic illness and accidental poison occurs in 7.44%. 81.92% ingested poison to committed suicide, 6.91% cases accidental exposure to poison occured, during travelling 6.91% stupefied, 3.19% ingested poison due to homicidal motive and recreational drug used by 1.06%. Majority 68.62% took OPC, 11.17% ingested sedative drugs, 11.17% by unknown poison, 5.85% corrosive, 2.12% rodenticide, 1.06% paracetamol, 1.06% TCA, 0.53% and other poison 1.06%. 84.04% patients survived, 7.98% died and abscondened 7.98%.

Conclusion: In our study 68.62% ingested OPC, suicidal motive were in 81.92%, 71.27% ingested poison due to familial disharmony, 6.91% stupefied by robbers during travel. Mortality rate was 7.98%.

 

Introduction:

Acute poisoning is exposure to a poison on one occasion or during a short period of time1. In many hospitals all over the world, acute poisoning is one of the most common reasons for acute admission to a medical ward.2 Acute poisoning accounting for about 10% of hospital admissions in the UK. In developed countries, the most frequent cause is intentional drug overdose in the context of self harm and usually involves prescribed or ‘over the counter’ medicines.3 About 5million poisoning exposures occurs USA every year. Most are acute accidental, involve single agent, occurs in at home, result in minor or no toxicity and involve children less than 6 yrs of age. Pharmaceuticals are involved in 47% of exposure and 84% of serious or fatal poisoning.4

Poisoning is a common method of suicide, especially in the developing world.5  In many Indian reports, the rates of poisoning as suicidal method range from 20.6% (10.3% organophosphorus)6 to 56.3% (43.8% organophosphorus).7,8 Important substances involved in acute poisoning are organophosphorus and carbamate insecticides, snake venoms, anti depressants, sedatives, alcohol, stupefying agents and kerosene etc. In developing countries the frequency of self harm is more difficult to estimate because patient may be reticent in admitting to deliberate poisoning. Household and agricultural products such as pesticide and herbicides are more freely available, are common source of poisoning. In China and South-east Asia pesticides account for about 300 000 suicides each year.3

In adult, self poisoning is commonly a “cry for help.” Those involved are most often females under the age of 35 years who are in good physical health. In those older than 55years of age men predominant and the overdose is usually taken in the course of a depressive illness or because of poor physical health. A third of self poisoning patients state that they are unaware of the toxic effects of the substance involved. 2  Accidental exposures can result from the improper use of chemicals at work or play, product mislabeling, label misreading, mistaken identification of unlabeled chemicals, uninformed self medication and dosing errors by nurses, parents, pharmacist, physician and elderly.

Induced poisoning by robbers during travel and using public transport is an emerging social and public health emergency in Bangladesh, The trends of pattern of induced poisoning from dhutura to unidentified stupefying agent particularly during journey is a major concern of care facility.9

Background: Poisoning is an important health problem in Bangladesh leading around 16000 episodes and 1500 deaths per year (Bangladesh Health Bulletin 1976). Self harm is claimed as commonest mode of poisoning.9 Organophosphorus compounds are used as insecticide in agricultural sector by the farming community in Bangladesh for the control of pest.10 So it is easily available and people usually use it as a suicidal agent.

Aim and Objective:

  1. To see the incidence of different poisoning
  2. To see the outcome of different poisoning
  3. Study of aetiological aspect of acute poisoning

Materials and methods:

Study design: Descriptive and cross sectional study.

Place of study: Rangpur Medical College Hospital, Rangpur

Period of study: 1st December 2010 to 25th February, 2011

Study Population:

Acute poisoning patients admitted in medicine unit of Rangpur Medical College Hospital, Rangpur.

Inclusion Criteria:

Patients admitted with the history of acute poisoning in Medicine ward, Rangpur Medical College Hospital, Rangpur.

Exclusion criteria:

      1. Patient refuses to take part in the study.

      2. Patients below 18 years

Ethical Consideration

All patients will be given an explanation of the study, and informed consent will be taken. The study will not involve any additional investigation procedures and significant risk as well as economic burden to the patients.

   Data collection and sampling method

Data will be collected using a structured research instrument (data collection format) containing the variables of interest. Purposive sampling method will be followed as per inclusion and exclusion criteria. Evaluation of patient will be based on history, physical examinations.

Results:

A total 188 patient were studied, among them male were 47.34% and female were 52.66%, maximum  92.55% in the age range  between 18 -40 years, 56.38% were married and 43.62% are unmarried. 32.98% are from rural area and 67.02% from urban area. Farmer were 17.55%, 29.79% were house wife, 36.17% were student, 2.13% were serviceman, and others were 14.36%, 71.27% ingested poison due to familial disharmony, 6.91% Stupefied while travelling, 4.78% due to fail to pass in examination, 3.72% due to economic loss, 3.73% due to psychiatric illness, 1.60% due to chronic illness and accidental poison occurs in 7.44%. 81.92% ingested poison to committed suicide, 6.91% cases accidental exposure to poison occurs while giving pesticides in the paddy field, during travelling 6.91% stupefied, 3.19% ingested poison due to homicidal motive and recreational drug used by 1.06%. Majority 68.62% took OPC, 11.17% ingested sedative drugs, 11.17% by unknown poison, 5.85% corrosive, 2.12% rodenticide, 1.06% paracetamol, 1.06% TCA, 0.53% and other poison 1.06%. 84.04% patients survived, 7.98% died and abscondened 7.98%. Among the death cases maximum are OPC (66.67%).

Table I: Distribution of the patient by sex

N= 188

Male Female
47.34% 52.66%

Table II: Distribution of the patient by age

N= 188

Age 18-40 years Age 41-60 years Age >60 years
92.55% 5.85% 1.60%

Table III: Distribution of the patient by marital status

N= 188

Married Unmarried
56.38% 43.62%

Table IV: Distribution of the patient by occupation

N= 188

Farmer Student Housewife Service Others
17.55% 36.17% 29.79% 2.13% 14.36%

Table V: Distribution of the patient by residence

N= 188

Rural Urban
32.98% 67.02%

Table VI: Distribution of the patient by cause of poisoning

N= 188

Familial disharmony Failed to pass Economic loss Chronic illness Psychiatric illness Stupefying Accidental
71.27% 4.78% 3.72% 1.60% 3.73% 6.91% 7.44%

Table VII: Distribution of the patient by motive of poisoning

N= 188

Suicidal Homicidal Accidental Stupefying Recreational
81.92% 3.19% 6.91% 6.91% 1.06%

Table VIII: Distribution of the patient by types of poison ingested

N= 188

OPC Sedative Unknown Corrosive Paracetamol Rodenticide Alcohol TCA Other
68.62% 11.17% 8.51% 5.85% 1.06% 2.12% 0.53% 1.06% 1.06%

Table IX: Outcome of patent

N= 188

Survived Death Abscondened
84.04% 7.98% 7.98%

Table X: Sex distribution of death patient

N=15

                     Male               Female
8 (53.53%) 7 (46.67%)

Table XI: Age distribution of death patient

N= 15

18-40 years 41-60 years
10 (66.67%) 5 (33.33%)

Table XII: Types of poison ingested among death patient

N=15

OPC Unknown Herpic Nitric acid Methanol
10 (66.67%) 2 (13.33%) 1 (6.67%) 1 (6.67%) 1 (6.67%)

Conclusion: In our study 68.62% ingested OPC, suicidal motive were in 81.92%, 71.27% ingested poison due to familial disharmony, 6.91% stupefied by robbers during travel and using public transport is an emerging social and public health emergency in Bangladesh. There is an increasing tendency to ingest corrosive (5.85%) like detol, herpic, savlon etc. 84.04% patient survived and mortality rate was 7.98%. Among the death cases maximum are OPC (66.67%). Lack of ICU, well facilitied separate poisoning unit, trained stuff contributed to this high mortality rate.

Recommendations:

Acute poisoning  patients should be managed in ICU or well facilitated ward and by trained persons. Improving awareness, ensuring unavailability of OPC and sedative drugs without prescription of registered physician, will reduce the incidence of acute poisoning and mortality rate.

Acknowledgement:

The authors of this study acknowledge to the professors, doctors and stuff of department of Medicine who were heartedly helped to do the study.

 

References:

1. Complete diving manual by Jack Jackson

2. Rawlins M and Vale JA, Drug therapy and poisoning In:KUMAR P, CLARK M CLINICAL MEDICINE, 6TH EDITION, ELSEVIER SAUNDERS, Reprinted 2008; 1002

3. Thomas S.H.L, . White J, Poisoning

In:  Colledge NR,  Walker B R, Ralstone S H Davidson’s Principles & Practice of Medicine, 21th edition, Churchill Livingstone Elsevier, 2010; 203-207

4. Christopher H. Linden, Michael J. Burns Poisoning and Drug overdosage, In: Kasper, Braunwald, Fauci, Hauser, Longo, Jameson, et al., Harrison’s Principles of Internal Medicine. 16th edition. New York: The McGraw- Hill Companies, 2005:2580- 1562.

5. Vijayakumar L: Suicide prevention: the urgent need in developing countries. World Psychiatry 2004, 3(3):158-159.

6. Ponnudurai R, Heyakar J: Suicide in Madras. Indian Journal of Psychiatry 1980, 22:203-205.

7. Gururaj G, Isaac MK: Epidemiology of suicide in Bangalore. NIMHANS Publication No. 43, Bangalore; 2001.

8. Nandi DN, Mukherjee SP, Banerjee G, Ghosh A, Boral GC, Chowdhury A, Bose J: Is suicide preventable by restricting the availability of lethal agents? A rural survey of West Bengal. Indian Journal of Psychiatry 1979, 21:251-255.

9. Bangladesh Health Bulletin, UMIS, Director General of Health Services.(2001);vol17:121-122(s)

10.Faiz MA, Ahmed S, Amin M R, Ghose A, Hoque MM: Training Manual on Management of Poisoning  Guideline – 2007

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