Organophosphorus Compound Poisoning

Organophosphorus Compound Poisoning


Edited By :

Dr.Salim Al Mamun






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.


There are more than a hundred organophosphate compounds used regularly.

Some available in Bangladesh include-

Chlorpyrifos                                            Diazinon

Dichlorvos                                              Dimethoat

Fenthion                                                 Malathion


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 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):


§  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

  • 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


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 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






Date of












































2.4 mg










4.8 mg














2 mm









3 mm





2 mg/h










2 mg/h





3-4 mm





2 mg/h











2 mg/h





3-4 mm





2 mg/h





3-4 mm





2 mg




3-4 mm





2.4 mg/h





3-4 mm





2.4 mg/h





3-4 mm





2.4 mg/h


{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


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.


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.


  • 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.

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