Amrita Journal of Medicine

: 2020  |  Volume : 16  |  Issue : 3  |  Page : 101--104

Killer secretions: Organophosphorus poisoning: Practice eessentials and protocols

KP Amrithachandra1, TP Sreekrishnan2, KP Gireesh Kumar2,  
1 Amrita School of Medicine, AIMS, Kochi Kerala, India
2 Department of Emergency Medicine, AIMS, Kochi Kerala, India

Correspondence Address:
Dr. T P Sreekrishnan
Department of Emergency Medicine, AIMS, Kochi, Kerala


Organophosphorus pesticide self-poisoning is an important clinical problem in rural regions of the developing world and kills an estimated 200,000 people every year. Unintentional poisoning kills far fewer people but is a problem in places where highly toxic organophosphorus pesticides are available. Medical management is difficult, with case fatality generally more than 15%. However, consensus suggests that early resuscitation with atropine, oxygen, respiratory support, and fluids is needed to improve oxygen delivery to tissues. The role of oximes is not completely clear.

How to cite this article:
Amrithachandra K P, Sreekrishnan T P, Gireesh Kumar K P. Killer secretions: Organophosphorus poisoning: Practice eessentials and protocols.Amrita J Med 2020;16:101-104

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Amrithachandra K P, Sreekrishnan T P, Gireesh Kumar K P. Killer secretions: Organophosphorus poisoning: Practice eessentials and protocols. Amrita J Med [serial online] 2020 [cited 2021 Jun 12 ];16:101-104
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Organophosphorus poisoning is one of the leading cause of death in rural region of developing countries.


Pesticide is a chemical or biological substance which kills a pest.

Pesticides are chemicals or chemical compounds used to kill various types of pests such as insects, rodents, fungi, and weeds. Pesticides also used to kill various diseases spreading vectors, mosquitos, etc.By their nature, pesticides are potentially dangerous to other living beings, including humans, and need to be used with proper safety measures.

 Pesticide General Classification


Insecticides are chemical or biological substances that can control or kill insects. Control will result from killing the insect or preventing the insect from engaging in behaviors deemed destructive.

Organophosphates (OPs)CarbamatesOrganochloridesPyrethroidsNeonicotinoidsRyanoids [Table 1].{Table 1}

OPs can be absorbed through the skin, ingested, inhaled, or injected.

Worldwide, mortality varies from 3% to 25% due to OP poisoning. The compounds most commonly involved are malathion, dichlorvos, trichlorfon, and fenitrothion/malathion.

Mechanism of action: OP inhibits acetylcholinesterase (AChE) in the neuromuscular junction. The action of AChE enzyme is the degradation of the neurotransmitter acetylcholine (ACh) into choline and acetic acid.[1],[2]

When AChE is inactivated, ACh gets accumulated in the nerve ending/neuromuscular junction of the nervous system; it leads to overstimulation of muscarinic and nicotinic receptors.

AChE is an enzyme that cleaves ACh. AchE is inhibited by OP through phosphorylation. Inhibited AChE reactivates spontaneously at very slow rates; oximes can speed up this reaction. However, phosphorylated AChE may lose an alkyl side chain nonenzymatically, leaving a hydroxyl group in its place (“aging”). Regeneration is no longer possible after this. The half-life of aging is very fast (8 min) with the nerve gas soman but as slow (33 h) for diethyl pesticides such as chlorpyrifos.

Clinical features of OP poisoning are manifested due to overstimulation of the muscarinic receptors of the nervous systems and at nicotinic receptors on skeletal muscle. Clinical features of OP poisoning can be divided into three major categories: (1) muscarinic effects, (2) nicotinic effects, and (3) central nervous system (CNS) effects.

 Stages of Toxicity Depending on Time Duration

Acute cholinergic phaseIntermediate syndromeDelayed polyneuropathy [Table 2].{Table 2}

 Acute Cholinergic Phase

Starts in minutes, usually within 1 h after ingestionIt lasts up to 48–72 hOPs can produce acute muscarinic, nicotinic, and CNS effects.

 Acute Phase: Muscarinic Effects

Salivation, lacrimation, urination, diarrhea, gastrointestinal upset, emesis (SLUDGE) and diaphoresis and diarrhea; urination; miosis; bradycardia, bronchospasm, and bronchorrhea; emesis; lacrimation increased; and salivation (DUMBELS)[3] increased.

Cardiovascular system – bradycardia and hypotensionRespiratory system – rhinorrhea, bronchorrhea, bronchospasm, cough, and severe respiratory distress (adult respiratory distress syndrome)Gastrointestinal (GI) system – increased salivation, nausea and vomiting, abdominal pain, and diarrhea.Urinary system – incontinenceEyes – blurred vision, miosis (constricted pupil), and increased lacrimationSweat glands – diaphoresis.

 Nicotinic Effects

Nicotinic findings seen in OP poisoning include muscle fasciculations, muscle cramping, muscle weakness, and diaphragmatic failure. Autonomic nicotinic features are hypertension, tachycardia, mydriasis, and pallor.

CNS nicotinic effects are the following:

Fear and emotional labilityRestlessness, confusion, and comaAtaxia, tremorsSeizures (generalized tonic-clonic seizure)Apnea respiratory arrest.

Cardiac nicotinic effects

Cardiac arrhythmias, such as heart block and QTc prolongation, are rarely seen in OP poisoning.[4]

Respiratory nicotinic effects

Respiratory arrest may be seen due to respiratory failure by a combination of depression of the CNS respiratory center, neuromuscular respiratory muscle and diaphragmatic weakness, excessive respiratory secretions, and bronchoconstriction.

 Intermediate Syndrome

An intermediate syndrome is a delayed onset of muscle weakness and paralysis after OP poisoning. It normally presents after 48 h of OP poisoning (in 20% cases); it may be delayed up to 72–96 h after resolution of the acute cholinergic toxidromeRisk factors for the intermediate syndrome are mainly due to exposure to a highly fat-soluble organophosphorus agent due to recirculation of lipid-soluble poison and may be related to inadequate doses of oximes. The intermediate syndrome is not seen in carbamates or nerve gas poisoningMuscles involved in intermediate syndrome – ocular muscles (cranial nerves III–VII and X), neck flexor muscles (inability to flex neck), proximal limb muscles with loss of deep tendon reflexes, and respiratory musclesPatients also have anxiety, sweating, and cyanosis and may develop a comaIf muscarinic findings are present, they may respond to an increase in atropine dose.[5],[6],[7]

 Organophosphate Induced Delayed Polyneuropathy

This occurs after 1–3 weeks of exposure due to degeneration of myelinated nerve fibersClinical featuresSymmetrical, flaccid, distal muscle weakness, and foot dropAbsent deep tendon reflexesSensory loss – all starts in distal parts of the lower limb, then the upper limb also.[8],[9]

 Organophosphate Poisoning Diagnosis

Pungent garlic-like smellToxicology analysis for OPs in blood, gastric secretions, and urineSerum (or pseudo) cholinesterase levels reducedHigh lactate, low lactate clearance, and low blood pH are poor prognostic factors.

 Organophosphate Poisoning Management

Take care airway, breathing, and circulationCorrection of oxygenation before the use of atropine is recommended to minimize the potential for dysrhythmiasRemove the cloths, clean, and wash skin with soap and water. Health care workers must ensure that washing does not delay from other management priorities and should protect themselves from skin contact to poison and contaminationGastric lavage (consider gastric lavage for oral poisonings if a presentation is within 1 h of ingestion; if massive ingestion, it may be useful even after this time period) – send the sample for a toxicology screenInduction of emesis is contraindicatedActivated charcoal – 50–100 g initially, followed by 50 g four hourly until charcoal appears in the feces or recovery occursAtropine infusion (atropine reverses ACh-induced bronchospasm, bronchorrhea, bradycardia, and hypotension)Atropine competes with ACh at muscarinic receptors present in GI and pulmonary smooth muscle, exocrine glands, heart, and eye, preventing cholinergic activationInitial dose 1 mg IV, if no adverse effects give 2 mg every 15 min till the patient develops atropinization (drying of secretions, tachycardia, dry mouth, and dilated pupil)Injection (Vial) – 1 mL contains: atropine 1 mg, (ampule – 1 ml = 0.6 mg)Atropine also can be used as an infusion (the average patient requires approximately 40 mg/day)Monitor the patient – heart rate, pupil size, fasciculations, secretions, and lung crepitationThe endpoint for atropinization in OP poisoning is dried pulmonary secretions and adequate oxygenation. Tachycardia and pupil changes (mydriasis) must not be used to reduce or to stop subsequent doses of atropineGlycopyrrolate is a medication of the muscarinic anticholinergic group. It does not cross the blood–brain barrier and will not produce CNS effectsThis drug is used as an alternative to atropine injections when atropine produces psychological adverse effectsInjection – each 1 mL contains glycopyrrolate 0.2 mgIf atropine is not available or avoided because of complications, glycopyrrolate or diphenhydramine may be used as an alternative anticholinergic agent for treating muscarinic toxicity; however, glycopyrrolate will not cross the blood–brain barrier and not useful for the treatment of central effects of OP poisoning. Hence, in patients with CNS symptoms with agitation glycopyrollate with small doses atropine combination can be triedIpratropium bromide nebulization can also be used for muscarinic effects in the lungsOximes – they reactivate phosphorylated AChE. These agents may prevent the aging of AChE and can reverse muscle weakness in OP poisoning. However, it is not useful once the OP compound has agedSince atropine does not bind to nicotinic receptors, it may be ineffective in treating neuromuscular dysfunction. Pralidoxime (2-PAM) and other oximes, such as HI-6 and obidoxime, are AChE reactivating agents that are effective in treating both muscarinic and nicotinic symptoms2-PAM should NOT be administered without concurrent atropine to prevent worsening symptoms due to transient oxime-induced AChE inhibition2-PAM 1 g (at least 30 mg/kg in adults and 25 to 50 mg/kg for children in 100 ml normal saline IV over 30 min) eighth hourly for 1st 24–48 h2-PAM should be administered slowly over 30 min, since rapid administration has occasionally been associated with cardiac arrest, and slow administration prevents the muscle weakness that results from the transient inhibition of AChE as 2-PAM can bind to the enzymeAfter the bolus dose, it appears that superior antidotal effects occur with 2-PAM given as a continuous infusion of at least 8 mg/kg/h in adults and 10–20 mg/kg/h for childrenSevere poisonings may result in prolonged redistribution of toxin; therefore, continuous IV therapy should be adjusted based on the patient's clinical response, and several days of therapy may be requiredConvulsions – treat with benzodiazepine and phenytoin, if severe seizures require muscle relaxants, do not use succinylcholine, which may result in prolonged paralysisOP poison-induced seizures should be treated with a benzodiazepine. Prophylactic diazepam injections have been shown to decrease neurocognitive dysfunction after OP poisoningSupport respiratory failure with mechanical ventilationAvoid the use of succinylcholine during rapid sequence intubation in patients with OP poisoning. Succinylcholine is metabolized by AChE (which is inhibited by OP compounds) leading to exaggerated and prolonged neuromuscular blockade in OP poisoned patients. Nondepolarizing neuromuscular blocking agents (e.g. rocuronium) can be used in OP-poisoned patients but may be less effective at standard doses due to competitive inhibition at the neuromuscular junction. Therefore, higher doses will likely be needed.

 Carbamate Poisoning

Carbamates are commonly used as insecticides. Carbamate insecticides are associated with similar toxicities of OP compounds[10]Carbamate compounds: aldicarb, carbofuran, and methomylThey are very short acting (half-life is only 30–40 min): carbamates are rapidly absorbed via all routes of exposure. Unlike OPs, these agents are transient cholinesterase inhibitors, which spontaneously hydrolyze from the cholinesterase enzymatic site within 48 h. OPs, however, can irreversibly bind to cholinesterase. Carbamate toxicity tends to be of shorter duration than that caused by equivalent doses of OPsTheir clinical features are the same as OPs but less severe and short actingThey reversibly inactivate AChEThey can also produce pancreatitisTreatment – atropine infusionUnlike OPs, carbamate intoxications do not irreversibly inhibit cholinesterase, and thus, 2-PAM is not usually required and may worsen symptoms.

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Conflicts of interest

There are no conflicts of interest.


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