- taken directly from a web site which is no longer active
Saved on 27th September 1998.
(Opfaq02 at community care.)


There are more than a hundred organophosphate compounds used regularly.
(Obtaining even clinically relevant data such as the lipid solubility, the half life, the conversion to active metabolites, binding to antidotes and whether they are associated with delayed neuropathy or neuropsychiatric effects is difficult or impossible for many of these compounds).


Organophosphates are extremely toxic chemicals which present with a myriad of clinical problems all of which may lead to difficulties in determining management. Much of what is written in textbooks relates to dermal or occupational exposure to organophosphates. Oral ingestion of organophosphate concentrates may involve doses 100-1000 fold greater and requires an entirely different approach to management.

The organophosphate insecticides are an extremely toxic group of compounds which are rapidly absorbed by the dermal, oral and pulmonary routes.
Following significant exposure symptoms of toxicity generally occur within 4 hours.

The exception to this is extremely lipid soluble organophosphate (eg fenthion and dichlofenthion) which are rapidly taken into fat stores and subsequently slowly and intermittently released and metabolised to more active compounds. In this situation the symptoms of toxicity may not occur for up to 48 hours and may continue for weeks.


The organophosphate compounds phosphorylate and inactivate acetylcholinesterases. This causes an increase in acetylcholine with stimulation of autonomic receptors and depolarising block of neuromuscular junction receptors. This gives rise to a large number of clinical effects in the central nervous system, autonomic nervous system and leads to paralysis.

After the initial organophosphate acetylcholinesterase bonds are formed a conformational change in the molecular structure of the organophosphate occurs which increases the binding and subsequently makes the organophosphate acetylcholinesterase complex irreversibly bound.
This process is called aging & occurs between 12-36 hours after binding.

In addition to the inactivation of acetylcholinesterase and subsequent acetylcholine accumulation there is also central nervous system antagonism of GABA and Dopaminergic neurons.


All organophosphates are rapidly absorbed from the small intestine or dermal exposure. Peak levels may occur within a few hours.


This is a diverse group of compounds with a wide range of lipid/water solubility characteristics and variable but usually large volumes of distribution.

Metabolism & Elimination:

Some organophosphates (-thions) are metabolised in the liver to much more active metabolites (-oxons). These poisons (eg parathion, fenthion, chlorpyrifos) are also usually highly lipid soluble. Thus the slow conversion of these substances, which are widely distributed into fat, may lead to delayed and/or prolonged cholinesterase inhibition and toxic effects. (This also may explain the intermediate syndrome which has only been observed with -thion organophosphates).

The major route of elimination is paraoxonase. This is an enzyme which is present in serum bound to lipoproteins (HDL).


Three clinical syndromes have been described:
* acute cholinergic symptoms and paralysis (most common)
* subacute proximal weakness (Intermediate Syndrome)
* late axonal degeneration

In addition there are long term neuropsychological sequelae that may result from both acute & chronic exposure.

(see also Clinical Grading of Toxicity)


The clinical effects and symptomatology in acute poisoning results from muscarinic, nicotinic and central nervous system effects. (see diagram)

MUSCARINIC effects are those mediated by stimulation of the parasympathetic nervous system. This results in -
* contraction of intestinal & bronchial smooth muscles
* decreased pupil size
* increased secretions from all secretory glands
* decreased sinus node activity (bradycardia), AV conduction defects and occasionally ventricular arrhythmias.

The mnemonic DUMBELS describes most of the significant muscarinic features.

* Diarrhoea
* Urination
* Miosis
* Bronchospasm
* Emesis
* Lacrimation
* Salivation.

NICOTINIC effects are due to the accumulation of acetylcholine both at the neuro-muscular junction and at the preganglionic synapses of the autonomic nervous system.

The accumulation of acetylcholine at the neuro-muscular junction causes initial stimulation followed by depolarisation and paralysis.

Stimulation of the sympathetic nervous system may produce sweating, hypertension and tachycardia.


These include initial cerebral stimulation followed by increasing central nervous system depression leading to coma and occasional seizure activity.


Severe organophosphate poisoning is often complicated by hypotension and tachycardia. In addition, ischaemic sequelae may develop in patients with pre-existing vascular disease.

The vascular effects of the excess ACh are mediated mainly through muscarinic receptors of the endothelium evoking release of nitric oxide and vasodilatation. ACh also acts on nicotinic receptors in the sympathetic ganglia, muscarinic receptors in the muscle layer of medium size arteries to cause vasoconstriction and on CNS muscarinic receptors which have less predictable effects on blood vessels.

Thus the hypotension and tachycardia that occur are usually due to a low total peripheral resistance with a partially compensating high cardiac output. In this case the hypotension and vasodilatation are reversed by atropine (Buckley et al 1993).

Ischaemic complications may be due to unopposed vasoconstriction by acetylcholine at sites of endothelial injury (Buckley et al 1993).

Symptomatology varies between individuals and within the same individual at different points of time. This relates to a varying balance of muscarinic and nicotinic effects.

In addition to the neurologically related complications the patients may also develop non cardiogenic pulmonary oedema, pancreatitis and the adult respiratory distress syndrome.

SUBACUTE (Intermediate Syndrome)

A subacute syndrome has been described in which patients develop proximal muscle weakness and cranial nerve lesions after recovery from cholinergic effects. This has been thought to be due to primary motor end plate degeneration due to prolonged inhibition of acetylcholinesterase. It has not been reported where high doses of pralidoxime have been used.


Late neurological sequelae include a peripheral neuropathy which is due to axonal degeneration. This may be due to the inhibition of the enzyme neurotoxic esterase (reported in occupational exposures). It is much more common with (though not limited to) certain compounds with a higher affinity for this enzyme.

Long term neuropsychiatric sequelae have been described for all degrees of exposure. Formal neuropsychological testing and regular follow up should be performed.



Is a sensitive marker of exposure but on its own gives little idea of severity of exposure. The normal range is 3000-7000 U/L. Its utility can be improved in a number of novel ways in the following situations.


The test can be done sequentially to confirm exposure in patients whose results fall within the low part of the normal range. Repeating the test a few weeks later will show whether the levels rebound to a higher level.


PChE is measured in the patients plasma and in a normal plasma sample and in a 50-50 mixture of the two samples. If there is no free organophosphate in the patients plasma (ie adequate doses of pralidoxime are being given to neutralise the organophosphate) then the mixed sample will have a PChE value equal to the mean of the other two measures. Lower values indicate insufficient pralidoxime has been given.


If the patient appears to be clinically well on a pralidoxime infusion (after atropine has been ceased) it is difficult to judge when to cease the infusion. In this scenario, the PChE is measured in the patients plasma, the pralidoxime is ceased and the PChE is measured 4-8 hours later. Pralidoxime may be recommenced while awaiting results. If there is no residual organophosphate in the patient then the second sample will be similar to the first. If the second PChE value has fallen this indicates continuing exposure to organophosphates (probably due to lipid soluble organophosphates stored in the patients fat)


This correlates well with severity and prognosis. It is a better indicator of tissue acetylcholinesterase inhibition and is much less sensitive than plasma cholinesterase. (This is not available at many centres - send away 10 mls of blood in a Heparinised tube).


Should be done in moderate to severe poisonings as brady and tachyarrhythmias may occur.

CXR & Blood Gases

These are indicated in all severe poisonings as aspiration pnuemonia (contributed to by hydrocarbon diluents) is not uncommon

Plasma organophosphate levels:

These are unhelpful in aiding management.


Difficulties in diagnosis usually arise when an unconscious or delirious patient is known to have ingested an unknown chemical from the garden shed (see Differential diagnosis of garden shed poisoning).

The absence of miosis does not exclude significant organophosphate poisoning. The presence of muscle fasciculations and associated weakness strongly supports the diagnosis. Organophosphates often have an odour similar to garlic though this may be masked by hydrocarbon diluents.
Significant (ie not mild) poisoning will almost invariably be associated with a low plasma cholinesterase. Similar but usually milder clinical features may occur with poisoning with carbamate insecticides.


Often, organophosphates are listed according to their lethal dose in animals as being low, moderate or high toxicity. As the compounds are usually prepared in concentrations that account for their relative potency, these lists do not give any indication of the likelihood of developing clinical consequences from an exposure.

In deliberate ingestions of concentrates, these poisons vary from being very poisonous to extremely poisonous. The major differences are that a number of these poisons require metabolic activation and thus may have a delayed or prolonged course.


The following table has been suggested as a guide to determining severity by . 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.

  • Walks & Talks
  • Headache & Dizzy
  • Nausea & Vomiting
  • Abdominal Pain
  • Sweating
  • Dyspnoea
  • S. Cholinesterase
  • <10% of normal
  • Can't Walk
  • Soft Voice
  • Muscle Fasciculations
  • Small Pupils
  • Increased bronchial secretions
  • Crackles or wheeze
  • S. Cholinesterase
  • 20%-50% of normal
  • Unconscious
  • No pupillary reflex
  • Muscle Fasciculations
  • Flaccid Paralysis
  • Salivating
  • Respiratory Failure
  • S. Cholinesterase
  • 10%-20% of normal


    Maintenance of airway, ventilation, IV access and fluids are an early priority as patients may deteriorate rapidly.

    Staff should also
    * Wear gown and gloves
    * Remove (and destroy) patients clothes
    * Wash the patient a number of times (soap, alcohol and soap)


    Patients with moderate or severe poisoning should be transferred to an Intensive Care facility. Asymptomatic patients who have ingested organophosphate concentrate should also be managed in ICU.


    Activated Charcoal:

    Oral activated charcoal should be given to all patients ingesting organophosphates. Patients with any history, signs or investigation indicating severe poisoning should have elective intubation, gastric lavage and activated charcoal and the specific treatment outlined below.

    In addition some organophosphates & their active metabolites have entero-hepatic circulation and therefore repeated doses of activated charcoal should be given if not contraindicated.

    Elimination enhancement is not useful.

    ,b>Specific Antidotes:


    Atropine is used to block muscarinic effects due to excessive acetylcholine. Initial treatment is to give a test dose of 1-2 mg of Atropine over 10 minutes (in adults). If the patient exhibits signs of atropinisation after this test dose it is likely that they have mild poisoning. In other patients this dose should be repeated at 10 minute intervals until the patient is atropinised.

    The end point of atropinisation is traditionally the absence of oro-pharyngeal secretions. Pupil size can only be used as an end point if miosis is present on admission. Patients will often require an atropine infusion to maintain atropinisation and infusions of 10-20 mgs/hr are commonly required with severe poisonings.

    In severe poisonings, measurement of peripheral vascular resistance may be a better method of measuring adequate atropinisation as, in some circumstances, cholinergic features may be surprisingly minimal (perhaps due to a depolarising block of the muscarinic receptors) and hypotension/tachycardia due to circulating acetylcholine are dominant clinical features.


    Pralidoxime binds to organophosphates and removes them from acetylcholinesterase if ageing has not occurred. The pralidoxime-organophosphate complex is water soluble and rapidly excreted by the kidneys.

    Patients with mild to moderate poisoning should receive Pralidoxime with an initial dose of 2 gms intravenously over 30 minutes followed by 1 gm 8th hourly for a minimum of 48 hours. Severe poisonings or oral exposures should have an infusion of 500 mgs/hour after the initial dose. The success of pralidoxime binding to available organophosphate may be determined by the mixed plasma cholinesterase test and the infusion adjusted accordingly.

    For the majority of organophosphate poisonings this treatment is only of use in the first 36 hours but pralidoxime should be utilized in severe poisonings regardless of the time of exposure.

    For poisonings with highly lipid soluble organophosphates this treatment may be commenced later and may need to be continued for up to 2-3 weeks. The dose of Pralidoxime in children is 25-50 mg/kg. Pralidoxime undergoes renal excretion, in patients with renal failure the dose may need to be reduced.

    Treatment of specific complications


    Initially, diazepam 10-20 mg IV followed by phenobarbitone 15 mg/kg IV and elective intubation and ventilation (without paralysis).


    Patients who become hypotensive often have extremely low peripheral vascular resistance which can respond to very large doses of atropine. These patients should have a Swan-ganz catheter inserted to monitor the effects of therapy. These patients may seem to be adequately atropinised using the normal clinical criteria.

    Paradoxical vasoconstriction can occur at atheromatous sites due to endothelial dysfunction at these sites and unopposed action of acetylcholine receptors in the arterial smooth muscle. In theory this vasoconstriction should respond to atropine and be exacerbated by adrenaline and dopamine. Also, most patients have high rather than low cardiac output. Thus atropine, rather than inotropic drugs, should be used for the treatment of hypotension. See hypertext article


    Magnesium, isoprenaline or overdrive pacing (rate 120-140) are indicated for torsade de pointes and should be considered for all tachyarrhythmias

    Magnesium is normally the drug of choice for treating torsade de pointes but its calcium channel blocking activity may aggravate the hypotension and heart block that can also complicate organophosphate poisoning.


    Late neurological sequelae include a peripheral neuropathy which is due to axonal degeneration. This may be due to the inhibition of the enzyme neurotoxic esterase (reported in occupational exposures).
    It is much morecommon with (though not limited to) certain compounds with a higher affinity for this enzyme.

    Long term neuropsychiatric sequelae have been described for all degrees of exposure.
    Formal neuropsychological testing and regular follow up should be performed.

    Additional information

    (From a recognised laboratory in 2004)

    Normal detection limits in mg / kg

    Acephate (epa; cornell)   0.02
    Azinphos   0.05
    Azinphos methyl   0.05
    Bromophos ethyl    0.05
    Bromophos    0.05
    Cadusafos    0.05
    Carbophenothion (see products containing)   0.05
    Chlorfenvinphos (and FAO data sheet)   0.05
    Chlorpyrifos   0.05
    Chlorpyrifos methyl   0.05
    Demeton-S-methyl    0.05
    Diazinon   0.02
    Dichlorvos    0.05
    Dimethoate   0.05
    Ethion    0.05
    Ethoprophos    0.05
    Etrimfos    0.05
    Fenchlorphos   0.01
    Fenitrothion    0.05
    Fensulfothion    0.05
    Fenthion    0.05
    Fonophos   0.05
    Heptenophos    0.05
    Iodofenphos    0.05
    Malathion    0.05
    Methacrifos   0.05
    Methamidophos    0.01
    Methidathion    0.02
    Mevinphos   0.05
    Monocrotophos   0.05
    Omethoate   0.05
    Parathion   0.05
    Parathion methyl   0.05
    Phosalone   0.05
    Phosmet   0.05
    Phosphamidon   0.05
    Pirimiphos methyl   0.05
    Quinalphos    0.05
    Sulfotep   0.05
    Terbufos    0.05
    Tolclofos methyl   0.05
    Triazophos    0.02

    Note that no details are provided for glyphosate or for any toxic breakdown products.
    It was stated that only the manufacturers had access to the tests.

    Dated 27/9/1998    Updated 8/03/2016

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