Why this poison is interesting

Organophosphate poisoning is the clearest worked example in this library of an antidote that provably hits its target and may not help the patient. Pralidoxime is designed to pull the phosphoryl group off acetylcholinesterase and restore the enzyme, and in a randomised placebo-controlled trial it did exactly that — the authors report substantial and moderate red cell acetylcholinesterase reactivation in patients poisoned by diethyl and dimethyl compounds respectively. Mortality in the pralidoxime arm was 24.8% against 15.8% on placebo, adjusted hazard ratio 1.69 (95% CI 0.88–3.26), and the authors state plainly that the reason for the failure to benefit patients was not apparent.¹

The second reason is chemical. Almost every other poison in this library either acts as it arrives or is converted into something worse. Organophosphates do both, and then do a third thing: the enzyme–poison complex itself changes, irreversibly, after the poisoning is over. That reaction is called aging, and it is the reason the antidote has an expiry time measured from the moment of exposure rather than from the moment of arrival in hospital.

The third is that the syndrome is not one syndrome. Acetylcholine accumulates at muscarinic receptors, at nicotinic receptors on skeletal muscle, and in the central nervous system — three receptor populations, one transmitter, and an antidote that reaches only the first of them. A patient can be fully atropinised, dry and comfortable, and still be unable to breathe.

A poison is a drug whose kinetics have escaped its pharmacology.

The toxic principle

Acetylcholinesterase terminates cholinergic transmission by hydrolysing acetylcholine, and it does so through a serine residue in its active site. The serine's hydroxyl group attacks the acetyl carbon, the enzyme is transiently acetylated, and water removes the acetyl group within microseconds. That last step is what makes the enzyme catalytic rather than consumable.

An organophosphate presents the same serine with a phosphorus atom instead of a carbon. The serine attacks it in the same way, and the enzyme is phosphorylated rather than acetylated. The difference is entirely in the leaving step: a phosphorylated serine is hydrolysed by water so slowly that on any clinical timescale the enzyme is simply gone. The molecule is not a receptor agonist and not a channel blocker. It is a substrate analogue that jams the catalytic step.

The clinically decisive chemistry happens after inhibition. The phosphorylated enzyme still carries alkyl groups on the phosphorus. One of them can be lost — a dealkylation reaction, conventionally called aging — and what remains is a negatively charged phosphoryl group bound to the serine. An oxime works by presenting a better nucleophile than water to that phosphorus; against an aged, charged complex it no longer has anything it can attack. Before aging the lesion is chemically reversible. After aging it is not, and the only route back is synthesis of new enzyme.

Dimethyl and diethyl are not a nomenclature detail

The rate at which the inhibited enzyme ages depends on which alkyl groups the compound carries. Dimethyl compounds — dimethoate, malathion, fenthion — age fast. Diethyl compounds — chlorpyrifos, parathion, diazinon — age slowly. The randomised trial of pralidoxime found substantial red cell acetylcholinesterase reactivation in patients poisoned by diethyl compounds and only moderate reactivation in those poisoned by dimethyl compounds, and incorporating the baseline amount of enzyme already aged into the analysis increased the hazard ratio against pralidoxime rather than rescuing it.¹ A drug whose window is defined by a chemical clock will look ineffective in any trial that cannot recruit inside the window — and it did not become effective in the subgroup where the window was widest.

Toxicokinetics

The kinetics of the parent compound and the kinetics of the lesion have almost nothing to do with one another, and that gap is the reason this poisoning does not follow the shape a clinician expects. The compound can be cleared while the patient deteriorates, because what matters is not how much poison is present but how much enzyme has been taken out of service and how much of that has aged.

Organophosphates — where the parent compound and the injury come apart
Parameter	Therapeutic	In overdose	Why it changes
Absorption	Rapid across gut, skin and lung — dermal absorption is the occupational route	Same routes; ingestion of a concentrated liquid formulation gives the largest exposures	All three routes matter and skin is the one that is missed. The hydrocarbon solvent in a liquid formulation is a toxicological problem in its own right, and it is also what makes gastric decontamination hazardous.
Bioactivation	Hepatic P450 desulfuration converts thion to oxon	Continues for as long as parent compound is being released from stores	This row is why the poisoning can worsen after admission. The toxic species is manufactured downstream of absorption, so a falling parent concentration does not mean a falling oxon exposure at the synapse.
Distribution	Varies enormously by compound; the lipophilic ones (fenthion) partition into fat	Fat becomes a reservoir that releases compound over days	A latent phase caused by redistribution, not by manufacture. The library's other redistribution story is digoxin, where the drug moves into the target and the blood level misleads early. Here it moves out of a store and the patient relapses late.
Red cell acetylcholinesterase	—	Inhibited, and it is the enzyme the disease is made of	Red cell acetylcholinesterase is the same enzyme as the synaptic one and is the pharmacodynamic marker used in the randomised trial to prove the antidote reached its target.¹ It recovers with erythrocyte turnover, which is why recovery is slow even after the poison has gone.
Plasma butyrylcholinesterase	—	Inhibited earlier and more readily; not the enzyme causing the illness	The commonly available assay measures the enzyme that is not the target. It is a sensitive marker of exposure and an unreliable marker of severity — a distinction that matters when a number is used to decide whether someone is getting better. Pralidoxime reactivates it variably and unsustainedly, and not at all after the dimethyl compounds dimethoate or fenthion — the authors conclude that butyrylcholinesterase is "unlikely to be clinically useful" for monitoring oxime treatment.⁷
Aging	—	Irreversible dealkylation of the inhibited enzyme; fast for dimethyl compounds, slow for diethyl¹	The only clock in this poisoning that cannot be restarted. It runs from the moment of inhibition, not from the moment of presentation, and it is the reason an antidote can be given correctly and still arrive too late.
Elimination of the parent	Hepatic metabolism and urinary excretion of dialkyl phosphate metabolites	Prolonged where fat stores are loaded	Clearing the compound does not restore the enzyme. Two independent processes have to complete before the patient is well: the poison must go, and the enzyme pool must be rebuilt.
Dialysability	—	Never assessed. EXTRIP has published no recommendation covering organophosphates⁶	This is an absence worth reading carefully rather than dismissing. The compounds vary hugely in protein binding and volume of distribution, so a single class-wide answer would be wrong in either direction — and the lesion is a covalently modified enzyme, which no dialyser can reach whatever it does to the parent compound.

Metabolism and the metabolites

There are two metabolic routes and they compete. One makes the poison and one destroys it, and both run in the liver on the same substrate.

Thion to oxon — a poison the body manufactures on purpose

Thion organophosphate (P=S)The compound in the container. A weak inhibitor of acetylcholinesterase as supplied
P450 oxidative desulfurationOxon (P=O)The species that phosphorylates the enzyme. Bioactivation, not detoxification
Hydrolysis by A-esterases and carboxylesterasesDialkyl phosphates and inactive fragmentsThe detoxifying arm. Excreted in urine, and the basis of exposure biomonitoring
Phosphorylated acetylcholinesteraseCatalytically dead but chemically rescuable — this is the state an oxime can act on
Aged, charged enzyme–phosphoryl complexIrreversible. No oxime reactivates it. Fast for dimethyl compounds, slow for diethyl¹
Acetylcholine accumulates at every cholinergic synapseMuscarinic, nicotinic and central at once — one transmitter, three clinical syndromes

One consequence deserves stating because it inverts a familiar rule. In most poisonings, the presence of a metabolising liver is protective. Here the liver is part of the problem for as long as parent compound remains, and the most relevant thing about the timing of the illness is that manufacture of the toxic species continues after absorption is complete.

Elimination and accumulation

Two things accumulate and they are not the same thing. Compound accumulates in fat, in the lipophilic members of the class, and is released over days. Inhibited enzyme accumulates everywhere, and is not released at all — it is replaced, slowly, by synthesis and by erythrocyte turnover.

Why a patient can deteriorate after apparently recovering

There are two entirely separate late deteriorations and they are frequently confused. Redistribution relapse is a return of the cholinergic syndrome as compound leaves fat, and it responds to the same treatment as the first episode. The intermediate syndrome is not a cholinergic relapse at all — Senanayake and Karalliedde described 10 patients with paralysis of the proximal limb muscles, neck flexors, motor cranial nerves and respiratory muscles 24 to 96 hours after poisoning, after a well-defined cholinergic phase, with electromyography showing fade on tetanic stimulation, absence of fade on low-frequency stimulation and absence of post-tetanic facilitation, findings they read as a postsynaptic neuromuscular defect.³ Four of their patients urgently required ventilation and the paralysis lasted up to 18 days.³

Jayawardane and colleagues then showed the intermediate syndrome is a spectrum rather than an event. In 78 symptomatic patients assessed prospectively with daily repetitive nerve stimulation, ten met a priori clinical criteria and five of those developed respiratory failure — but a further thirty developed a forme fruste syndrome with less severe weakness that never progressed to respiratory failure.⁴ Characteristic decrement–increment changes on repetitive nerve stimulation appeared before the clinical signs, and severe decrement preceded respiratory failure in four patients.⁴ The electrophysiology declares the syndrome before the patient does.

Where this latent phase sits among the others

Organophosphate insecticides — a fat store emptying — and, separately, a second and unexplained lesion declaring itself at a neuromuscular junction the first phase had already left

The other 26 kinds of latent phase in this library

Amphetamines and MDMA — a hormone acting normally on a kidney behaving normally, while the patient supplies the water
Antipsychotics — a physical object in the stomach — extended-release quetiapine forming a pharmacobezoar
Arsenic — a tissue declaring on its own timetable rather than the poison's — the arsenic is excreted within days, but the nail that was growing while it circulated does not show its white transverse line for several weeks
Arsine and stibine — a red cell mass haemolysing faster than a kidney can cope with — the exposure is over, the haemolysis is silent until the urine changes colour, and the renal failure that follows is the cause of death
Beta-blockers — a repolarisation lesion waiting for an ectopic beat to fall inside it — sotalol prolongs the QT and then, for hours, nothing happens
Calcium-channel blockers — a tablet that has not yet dissolved
Carbon monoxide — an inflammatory process continuing after the poison itself has gone
Chlorine and ammonia — paraquat's cause at its shortest — the time an injured alveolar epithelium takes to leak
Cocaine — a package that has not yet failed — the calcium-channel blocker's cause moved outside the tablet, where wrapping integrity cannot be measured
Digoxin — distribution of the drug to its target — which that page argues is not a latent phase in the paracetamol sense at all
Ethylene glycol — paracetamol's cause with a different enzyme — glycolate accumulating behind glycolate oxidase while the patient looks merely drunk
GHB and GBL — not the poisoning but its withdrawal — a half-life under an hour means admission for any reason interrupts round-the-clock redosing
Hydrofluoric acid — an ion diffusing far enough to reach a nerve ending — and the thinner the solution, the further it travels before anybody feels it
Iron — a true remission — the corrosive injury settling while absorbed iron moves into the cells it will poison, so the patient improves on their way to the dangerous phase
Ketamine — nitrous oxide's cause on a longer clock — urothelial damage accumulating over months to years of repeated exposure
Lead — bone giving lead back — a store with a half-life of 10 to 30 years releasing its contents when pregnancy, lactation, menopause or osteoporosis resorbs it, so the blood concentration rises after the exposure has ended
Lithium — transport across cell membranes
Mercury — distribution on two clocks — tissue concentrations peaking within 24 hours everywhere except the brain, which is not reached until 2 to 3 days, and which then cannot let the poison out again
Methaemoglobin inducers — paracetamol's cause at its shortest — one to four hours manufacturing the toxic species
Methanol — paracetamol's cause again — formate accumulating behind a folate-dependent disposal step that primates perform poorly
Nitrous oxide — damage accumulating to a threshold
Opioids — an antidote wearing off before the poison does — renarcotisation, the only gap in this set that treatment creates rather than reveals
Paracetamol — time spent manufacturing a toxic metabolite
Paraquat — the body responding to an injury that is already complete
Sodium-channel blockade — a gap that cannot be shortened
Thallium — hair on its own clock rather than the poison's — sensory symptoms come first and the alopecia that makes the diagnosis obvious follows them, well after the interval in which treatment is recommended

Target organs — and why those

Acetylcholine is used everywhere, so the question why this organ has an unusual answer here: the selectivity is not anatomical, it is by receptor type, and the receptor types differ in what the antidote can reach.

Airway and bronchial mucosa

TargetMuscarinic receptors on glands and bronchial smooth muscle

Why hereMuscarinic receptor overstimulation produces secretion and bronchoconstriction simultaneously, and the two combine into an airway that is both narrowed and flooded. This is the one target atropine genuinely treats, which is why atropine is titrated against the chest rather than against the heart rate. Established

At the bedsideBronchorrhoea, wheeze, and the classic muscarinic set — salivation, lacrimation, urination, defecation, vomiting, miosis. The end point of atropine treatment is a dry chest, not a dry mouth.

Neuromuscular junction and diaphragm

TargetNicotinic receptors on skeletal muscle

Why hereAccumulated acetylcholine first fasciculates and then depolarising-blocks the junction, and this receptor population is pharmacologically invisible to atropine. The intermediate syndrome adds a second, later insult at the same site, with electrophysiology suggesting a postsynaptic defect³ whose cause remains unexplained. Inferred

At the bedsideFasciculation, then weakness, then paralysis of the neck flexors, proximal limbs and diaphragm. A fully atropinised patient can still need intubation, and this card is why.

Central nervous system

TargetCentral cholinergic synapses

Why hereCentral acetylcholine accumulation depresses consciousness and lowers seizure threshold. Atropine crosses the blood–brain barrier and glycopyrronium does not, which is the mechanistic argument for preferring atropine over other antimuscarinics here. Inferred

At the bedsideAgitation, confusion, coma, seizures, and centrally mediated respiratory depression. Together with the diaphragm and the secretions, this is the third independent route to respiratory failure.

Heart

TargetMuscarinic receptors at the sinoatrial and atrioventricular nodes

Why hereVagal overactivity slows the node. The direction is not reliable, though: nicotinic ganglionic stimulation can drive tachycardia at the same time, and hypoxia drives it further. A normal or fast heart rate does not exclude the diagnosis, and treating to a heart rate rather than to the chest is the commonest way atropine is under-given. Established

At the bedsideBradycardia, atrioventricular block, and QT prolongation described with some compounds. Tachycardia in an organophosphate-poisoned patient usually means hypoxia, hypovolaemia or under-atropinisation rather than an absence of poisoning.

Peripheral nerve — the late lesion

TargetNeuropathy target esterase, an enzyme unrelated to acetylcholinesterase

Why hereOrganophosphate-induced delayed polyneuropathy is a separate lesion at a separate enzyme, appearing two to three weeks after exposure³ and only with some compounds. Senanayake and Karalliedde explicitly positioned the intermediate syndrome between the acute cholinergic crisis and the expected onset of this delayed neuropathy³, and one of their ten patients went on to develop it.³ Three distinct neurological syndromes from one exposure, on three different timescales. Established

At the bedsideDistal sensorimotor polyneuropathy with a glove-and-stocking distribution, appearing after the patient has left hospital, and recovering slowly or incompletely.

Timeline of effects

Organophosphates — a crisis, a recovery, and then a second and different paralysis

Time

What you seeWhat is happening

Minutes–hoursCholinergic crisis
What you seeMiosis, bronchorrhoea, wheeze, vomiting, incontinence, sweating, fasciculation, bradycardia, agitation or coma, seizures.
What is happeningAcetylcholinesterase inhibited at muscarinic, nicotinic and central synapses. The oxon is being manufactured throughout, so the peak may lag the ingestion.
HoursAging proceeds
What you seeNothing visible changes. The patient looks the same whether or not the chemistry has crossed this line.
What is happeningDealkylation converts a reactivatable complex into a permanent one. Fast for dimethyl compounds, slow for diethyl.¹ This is the phase in which an oxime either has a target or does not, and there is no bedside test that says which.
Hours–daysRedistribution relapse
What you seeApparent improvement, then a return of the cholinergic syndrome — most characteristically with lipophilic compounds such as fenthion.
What is happeningCompound stored in fat re-enters the circulation and is bioactivated again. The poison did not run out; it was parked.
24–96 hIntermediate syndrome
What you seeWeakness of neck flexors, proximal limbs, motor cranial nerves and respiratory muscles, after a well-defined cholinergic phase has resolved.³ Paralysis lasted up to 18 days in the original series.³
What is happeningA postsynaptic neuromuscular defect on electrophysiology³, preceded by characteristic decrement–increment changes on repetitive nerve stimulation.⁴ Atropine does not treat it and oximes have not been shown to prevent it.
Days–weeksEnzyme pool rebuilt
What you seeSlow recovery of strength and of secretions; prolonged ventilation is common in those who need it at all.
What is happeningAged enzyme is not repaired, it is replaced. Red cell acetylcholinesterase recovers with erythrocyte turnover, which sets a floor under how fast anyone can get better.
2–3 weeksDelayed polyneuropathy
What you seeDistal sensorimotor neuropathy in a minority, with some compounds, often after discharge.
What is happeningA different enzyme — neuropathy target esterase — and a different lesion, so there is no reason to expect it to track the severity of the cholinergic phase. Inferred

What the mechanism predicts at the bedside

Titrate atropine against the chest, not the heart rate. The receptors that produce bronchorrhoea are the ones atropine can reach; a tachycardia usually means hypoxia or under-treatment rather than enough atropine.
A comfortable, dry, atropinised patient can still stop breathing. The neuromuscular junction is a nicotinic synapse and atropine has no action there.
Ask which compound, and whether it is dimethyl or diethyl. It is the single piece of history that changes what an oxime could plausibly do, because it sets the aging rate.¹
Ask whether the compound is lipophilic. Fenthion and its relatives relapse from fat over days, and a patient who improves early is not necessarily finished.
Protect yourself and decontaminate. Dermal absorption is a real occupational route, and the solvent in a liquid formulation is its own hazard.
The plasma cholinesterase that is easy to measure is not the enzyme that is making the patient ill. Butyrylcholinesterase is a marker of exposure; red cell acetylcholinesterase is the disease.
Watch for the intermediate syndrome after the cholinergic phase resolves, specifically at the neck flexors — inability to lift the head off the pillow is the sign that arrives before the diaphragm fails.³
A forme fruste intermediate syndrome is commoner than the full one — thirty of 78 patients in the prospective cohort, versus ten meeting full criteria.⁴ Mild weakness after recovery is not reassurance.
Extracorporeal removal has never been assessed and cannot reach the lesion⁶ — a covalently modified enzyme is not dialysable whatever happens to the parent compound.
Recovery is limited by protein synthesis and cell turnover, not by clearance. That is why the illness outlasts the poison by so far.

The antidote, from the poison's side

This poisoning has two antidotes with completely different logics. Atropine treats the consequence: it competes with accumulated acetylcholine at muscarinic receptors and does nothing to the enzyme. An oxime treats the cause: it attacks the phosphorylated enzyme and attempts to restore catalytic function. The one that treats the consequence is the one that is established.

Atropine: A competitive muscarinic antagonist. It does not reactivate anything, does not shorten the poisoning, and does not touch the neuromuscular junction — and it is the intervention with the strongest claim to keep the patient alive, because the airway is the proximate cause of death. Its therapeutic end point is physiological rather than a dose. Established
Pralidoxime and the oximes: Presents a nucleophile to the phosphorylated serine and pulls the phosphoryl group off, restoring the enzyme — provided it has not aged. In a randomised, double-blind, placebo-controlled trial of 235 patients, pralidoxime produced substantial and moderate red cell acetylcholinesterase reactivation in diethyl- and dimethyl-poisoned patients respectively, and mortality was non-significantly higher: 30/121 (24.8%) versus 18/114 (15.8%), adjusted HR 1.69 (95% CI 0.88–3.26), p = 0.12, with no evidence of benefit in confirmed chlorpyrifos or dimethoate poisoning analysed alone.¹ The Cochrane review concludes that current evidence is insufficient to indicate whether oximes are harmful or beneficial and that the WHO-recommended regimen is not supported.² Traditional teaching
Why the reactivation did not translate: The trial's authors state the reason was not apparent.¹ The Cochrane review offers the standing hypotheses: late presentation, dimethyl compounds that have already aged, and a large excess of organophosphate that simply re-inhibits the enzymes the oxime has just reactivated.² Each is mechanistically coherent and none has been shown to be the answer.
Benzodiazepines: For seizures, on the ordinary grounds that a cholinergically driven seizure is still a seizure. This page makes no claim about neuroprotection.
Extracorporeal removal: Never assessed. EXTRIP has published no recommendation covering organophosphates⁶, and the lesion is a covalently modified enzyme rather than a circulating drug.
Fresh frozen plasma and enzyme replacement: The logic of supplying exogenous butyrylcholinesterase as a stoichiometric scavenger is attractive and is not established practice; nothing on this page should be read as supporting it.

Critical appraisal

The pralidoxime badge rests on a citation for the doubt, and on two of them. The randomised trial found reactivation with non-significantly higher mortality and reported that the reason for the failure to benefit was not apparent¹; the Cochrane review states that current evidence is insufficient to say whether oximes are harmful or beneficial and that the WHO regimen is not supported.² That contests the claim rather than merely failing to support it, which is the standard this library requires before a downgrade.
The thion-to-oxon bioactivation claim is badged established on standard organophosphate chemistry with no direct citation on this page. It is flagged here in the same way Band C flagged the synthetic-cannabinoid agonism claim, so that it can be tested rather than discovered. If a primary source is required for the badge, the badge should move to inferred rather than the claim being softened.
The consumable-versus-catalytic argument about esterases is inference, badged as such. It is a reconstruction from enzyme kinetics, it explains the steep dose–response well, and no source on this page demonstrates it in poisoned humans.
The aging rates are described qualitatively — fast for dimethyl, slow for diethyl — badged established on uncontested textbook chemistry, with no half-life quoted and no citation claimed for the rates themselves. The trial supports the direction of the difference through its reactivation data and its aged-enzyme analysis¹; specific aging half-lives were not taken from a source available to this page and are therefore not printed.
Senanayake and Karalliedde's series is ten patients³ and Jayawardane's cohort is 78 with ten meeting criteria.⁴ They establish that the intermediate syndrome exists, that it is a spectrum, and that it is electrophysiologically detectable before it is clinically apparent. They do not establish incidence in a UK population, and nothing here should be read as if they did.
No lethal dose, no minimum lethal dose and no comparative lethality between compounds appears on this page. The dimethyl/diethyl distinction is printed because it changes what an antidote can do, not because it ranks compounds by danger.
The delayed polyneuropathy is described but not sourced beyond the original series' single case³; neuropathy target esterase is named as the target on standard pharmacology, and a reader wanting the primary literature for it will not find it cited here.
EXTRIP's silence is genuinely uninformative here⁶ rather than a gap awaiting an answer, because the lesion is covalent and the class is too heterogeneous for one recommendation.

References

1
Eddleston M, Eyer P, Worek F, et al. Pralidoxime in acute organophosphorus insecticide poisoning — a randomised controlled trial. PLoS Medicine 2009 Jun 30;6(6):e1000104. PMID 19564902. (235 patients randomised, 121 pralidoxime and 114 saline placebo; 2 g loading dose over 20 min then 0.5 g/h for up to 7 days. "Pralidoxime produced substantial and moderate red cell acetylcholinesterase reactivation in patients poisoned by diethyl and dimethyl compounds, respectively." Mortality 30/121 (24.8%) versus 18/114 (15.8%), adjusted HR 1.69, 95% CI 0.88–3.26, p = 0.12; intubation 26/121 (21.5%) versus 24/114 (21.1%), adjusted HR 1.27, 95% CI 0.71–2.29. Incorporating baseline aged enzyme and plasma organophosphate concentration increased the hazard ratio. No benefit in confirmed chlorpyrifos or dimethoate poisoning analysed alone. "The reason for this failure to benefit patients was not apparent.")
2
Buckley NA, Eddleston M, Li Y, et al. Oximes for acute organophosphate pesticide poisoning. Cochrane Database of Systematic Reviews 2011 Feb 16;(2):CD005085. PMID 21328273. (Seven pralidoxime randomised trials: three versus placebo, 366 patients; four comparing doses, 479 patients. "Current evidence is insufficient to indicate whether oximes are harmful or beneficial." "The WHO recommended regimen (30 mg/kg pralidoxime chloride bolus followed by 8 mg/kg/hr infusion) is not supported." Notes theoretical reasons oximes may not help, particularly late presentation of dimethyl compounds and a large excess of organophosphate that re-inhibits reactivated enzyme.)
3
Senanayake N, Karalliedde L. Neurotoxic effects of organophosphorus insecticides. An intermediate syndrome. New England Journal of Medicine 1987 Mar 26;316(13):761–3. PMID 3029588. (10 patients with paralysis of proximal limb muscles, neck flexors, motor cranial nerves and respiratory muscles 24 to 96 hours after poisoning, after a well-defined cholinergic phase; compounds fenthion, monocrotophos, dimethoate and methamidophos; four needed urgent ventilation, paralysis lasted up to 18 days, three died, one later developed a delayed polyneuropathy. Electromyography showed fade on tetanic stimulation, absence of fade on low-frequency stimulation and absence of post-tetanic facilitation, suggestive of a postsynaptic defect.)
4
Jayawardane P, Dawson AH, Weerasinghe V, et al. The spectrum of intermediate syndrome following acute organophosphate poisoning: a prospective cohort study from Sri Lanka. PLoS Medicine 2008 Jul 15;5(7):e147. PMID 18630983. (78 symptomatic patients assessed prospectively with daily repetitive nerve stimulation; 10 met a priori criteria for the intermediate syndrome and 5 of those developed respiratory failure; a further 30 developed a forme fruste syndrome that never progressed to respiratory failure. Decrement–increment changes preceded clinical signs; severe decrement preceded respiratory failure in four patients.)
5
Lamb T, Selvarajah LR, Mohamed F, et al. High lethality and minimal variation after acute self-poisoning with carbamate insecticides in Sri Lanka — implications for global suicide prevention. Clinical Toxicology 2016 Sep;54(8):624–31. PMID 27252029. (Cited here for the comparison with carbamates: no patients showed delayed onset of toxicity akin to the intermediate syndrome seen after organophosphate poisoning.)
6
EXTRIP Workgroup — published recommendations index. Extracorporeal Treatments in Poisoning Workgroup. Cited for the absence of any recommendation covering organophosphate insecticides. extrip-workgroup.org/recommendations
7
Konickx LA, Worek F, Jayamanne S, et al. Reactivation of plasma butyrylcholinesterase by pralidoxime chloride in patients poisoned by WHO class II toxicity organophosphorus insecticides. Toxicological Sciences 2013 Dec;136(2):274–83. PMID 24052565. (Cited for the fact that plasma butyrylcholinesterase reactivation by pralidoxime has been measured as a separate quantity from red cell acetylcholinesterase reactivation.)

Organophosphate insecticides

At a glance