This copyrighted information is available online from:
emedicine: EMERGENCY MEDICINE An on-line Medical Reference
Toxicity, Organophosphate and Carbamate
Authored by Debra Slapper, M.D., Instructor, Department of Cardiology, University of Miami
Edited by Dana A. Stearns, M.D., Assistant Director, Undergraduate Education, Instructor, Department of Emergency Medicine, Massachusetts General Hospital; John T. VanDeVoort, Pharm.D., ABAT, Clinical Assistant Professor, Pharmacy Manager, Regions Hospital Pharmacy, University of Minnesota College of Pharmacy; Fred Harchelroad, M.D., Department of Emergency Medicine, Allegheny General Hospital; John Halamka, M.D., Executive Director, Center for Quality and Value, Instructor, Division of Emergency Medicine, Beth Israel Deaconess Medical Center; and Raymond J. Roberge, M.D., M.P.H., Vice-Chair, Clinical Associate Professor, Department of Emergency Medicine, Western Pennsylvania Hospital
Topic Last Updated: 12/29/1999 00:05:48
Background: Over 25,000 brands of pesticides are readily available in the U.S. for a variety of home and agricultural uses. Most are either organophosphate or carbamate compounds and account for over 80% of the pesticide poisonings in the U.S. Many of the toxic "nerve agents" used by the military are similar organophosphate compounds. Exposure to organophosphates and carbamates produces a characteristic, treatable syndrome in humans. Its recognition and timely intervention is of great importance to emergency physicians and their patients.
Pathophysiology: Organophosphates irreversibly bind to cholinesterase causing the phosphorylation and deactivation of acetylchoinesterase. The subsequent accumulation of acetylcholine at the neural synapse causes an initial overstimulation followed by eventual exhaustion and disruption of neural transmission in the central and peripheral nervous systems (CNS and PNS).
If the organophosphate/cholinesterse bond is not broken by pharmacologic intervention within 24 hours, large amounts of cholinesterase are destroyed causing long-term morbidity or death.
Carbamate poisoning exhibits a similar clinical picture to organophosphates. However, it temporarily binds cholinesterase for approximately six hours with no permanent damage. Carbamates have poor CNS penetration and cause minimal CNS symptoms.
The nicotinic effects from accumulation of acetylcholine at motor end-plate cause persistant depolarization of skeletal muscles, resulting in fasciculations, as well as muscle weakness, hypertension and tachycardia.
Muscarinic effects from potentiation of postganglionic parasympathetic activity of smooth muscles may cause smooth muscle contractions in all organs (e.g., lung, gastrointestinal [GI], eye, bladder and secretory glands), as well as reduction of sinus node and AV conduction, causing bradyarrhythmias or resultant ventricular dysrhythmias.
Central nervous system effects may cause excessive stimulation (possible seizure), then depression and coma.
Actual signs and symptoms depend on the balance between muscarinic and nicotinic receptors.
In the U.S.: There are reported approximately 20,000
organophosphate exposures per year, although it is estimated that as few
as 1% of field worker illness from pesticide exposure is reported. According
to the 1998 annual report of the American Association of Poison Control Centers,
there were 4332 exposures to carbamates, with one reported death, and 16,392
exposures to organophosphates, with 11 reported deaths in the United States.
Internationally: Exact numbers are not known but organophosphate poisoning occurs in virtually every country in the world. Third world countries have less legislation regarding safe agricultural use of pesticides and a much higher incidence of poisoning and among field workers and the public buying produce from these fields.
Mortality/Morbidity: Mild flu-like symptoms from minimal exposures frequently go unreported or untreated and may be considered a viral illness rather than recognized as poisoning.
*Epidemics of flu among field workers have been found to be caused by
chronic, low-level exposure to organophosphates.
*Common presenting symptoms include headache, diffuse muscle cramping,
weakness, excessive secretions, nausea, vomiting and diarrhea.
The condition may progress to seizure, coma, paralysis, respiratory failure
More often, one will see eventual resolution of the acute symptoms, though
with residual neurologic symptoms if not treated acutely.
*Organophosphate and carbamate exposures that are rapidly and adequately
treated have a short course of illness with no residual symptoms.
or inadequate treatment of organophosphate poisoning
can lead to
prolonged (months) or permanent neurotoxic symptoms.
*Death is rare, from 0.04-1% in normal pesticide poisonings.
Respiratory failure is the most common etiology.
used as nerve gas for warfare are particularily
potent. They more rapidly and more frequently cause death.
Race: There is no known racial differences in morbidity or mortality.
Sex: Poisoning is often related to agricultural workers, thus, males are more frequent victims. There is no sex difference in morbidity and mortality given the same exposure.
Age: Due to the high incidence of occupational exposure, significant poisoning is more common in males 15-45 years of age.
A significant incidence of severe poisoning exists in young children as a smaller
dose is required to cause symptoms.
Children have become ill after accidental ingestion in the home as well as playing in fields that have been sprayed recently.
*Pesticides can be rapidly absorbed from lungs, skin, GI tract, and mucous membranes.
*Symptoms typically appear within a few hours after exposure.
*However, large doses can produce immediate symptoms.
*Some of the highly lipid-soluble organophosphates may cause only mild initial
symptoms and not produce cholinergic crisis for 24-96 hours.
Occasionally, approximately 24 - 96 hours
after appropriate treatment of
acute organophosphate cholinergic toxicity, respiratory paresis, muscular
weakness (extraocular, nuchal, facial, palatal, and proximal limb muscles)
and depressed tendon reflexes occur, an entity termed the Intermediate Syndrome.
*The patient often knows he or she was exposed and is able to tell you the
*When the exposure is not known by the patient, the emergency physician must
rely on the physical assessment of classical cholinergic symptoms and high
index of suspicion to try to identify a possible exposure.
Physical: Examination findings are dependent upon the specific poison which
can cause a predominance of muscarinic or nicotinic effects.
Hypertension, tachycardia, muscle cramps and fasciculations may be seen
when nicotinic effects predominate.
Hypotension, bradycardia and excessive secretions occur if muscarinic
receptors are dominant.
Miosis, muscle fasciculations and increased secretions are the most
Altered mental status, pulmonary edema and cyanosis can be seen.
Several mnemonics have been developed to describe symptoms
of cholinergic excess.
DUMBELS refers to diarrhea, urination, miosis, bronchospasm,
emesis, lacrimation and salivation.
One study showed 92% of victims had muscarinic symptoms,
44% nicotinic, 40% CNS and 17% combined symptoms.
*Agricultural exposure is the most common cause of organophosphate
poisoning and can affect any worker in the industry.
*This might include field workers,
truckers who transport pesticides
or produce, crop dusters and manufacturers of pesticides.
*Other occupational exposures include dog groomers who have suffered
from overexposure to flea dip, pest control workers and various domestic
and custodial workers who use these compounds.
*Accidental exposure to the unsuspecting public near sprayed fields
secondary to winds has been reported.
*Accidental ingestion usually occurs by children or pets who find home pesticides.
*There is a relatively high incidence of intentional ingestion as a means of suicide.
*Mass public contamination from food has been reported in many countries
but not in the U.S.
*Military use of nerve gas can cause mass fatalities in warfare and accidental
poisoning to military personnel handling these weapons.
Abdominal Trauma, Blunt
Chemical Warfare Agents
Congestive Heart Failure and Pulmonary Edema
[Plant Poisoning, Mushroom - Disulfuram-like Toxins]
Plant Poisoning, Mushroom - Gyromitra Toxin
Other Problems to be Considered:
Several other poisons can mimic some symptoms of organophosphate poisoning,
including the muscarine-type mushrooms, paraquat, and inhalational agents
causing non-cardiogenic pulmonary edema. Delayed neuropathies as part
of either of two recognized syndromes (Intermediate Syndrome; Organophosphate-
Induced Delayed Neurotoxicity) should be considered in the differential with
other peripheral neuropathies.
The diagnosis of cholinergic excess is largely clinical. It requires recognition
of the syndrome in the appropriate clinical setting.
Supportive laboratory test (e.g., arterial blood gas [ABG], electrolytes and
serum glucose) should be ordered as indicated by the patients symptoms.
Markedly decreased red blood cell (RBC) cholinesterase levels are diagnostic
but usually not available in a timely fashion to guide treatment of the patient.
They should be ordered to facilitate correct diagnosis and long-term treatment,
should the patient have a complicated recovery.
RBC cholinesterase levels regenerate slowly (0.5% to 1% per day).
There is a wide distribution in the range of normal levels, and patients with a
"high normal" RBC cholinesterase level may be symptomatic with a level still
n the low normal range.
Ideally, the diagnosis is based on a decrease of 50% from baseline activity.
Unfortunately, only occupational workers frequently exposed to organophosphates
will have baseline levels.
Plasma cholinesterase levels are available on a more widespread basis
but are not considered the diagnostic test of choice.
It is a hepatic acute phase protein, and many other conditions (e.g.,cirrhosis,
neoplasia, morphine, cocaine, and pregnancy) will decrease its level.
Mild poisoning is defined as a decrease in the RBC cholinesterase activity
to 20% to 50% of baseline.
Moderate poisoning occurs when activity is 10% to 20% of baseline.
Severe poisoning is defined as a decrease in the RBC cholinesterase level
to less than 10% of the baseline activity.
In the case of a chronic exposure associated with peripheral neuropathy , or
increasing peripheral neuropathy following a significant exposure, a blood
speciman should be sent for neuron specific enolase.
A chest x-ray is useful in evaluating pulmonary edema (rare).
Cranial CT scanning may be useful in evaluating the patient with altered mental status.
An electrocardiogram (ECG) may be useful for evaluating the rare dysrhythmias
(e.g., atrial fibrillation, ventricular tachycardia and Torsades de points) or the
more common QT prolongation.
Rarely secretions become so profuse as to require intubation to protect the airway.
In such cases it will be difficult to ventilate the patient as well.
Paramount to the management of the organophosphate or carbamate-poisoned
patient is decontamination.
This should begin before or during the initial medical management.
Care is required to prevent secondary casualties, as the compounds are well
absorbed through the skin and lungs.
Appropriate barrier protection and ventilation must be maintained.
Supportive care, including airway control, oxygenation, ventilation and seizure
management, is most important in managing the organophosphate or carbamate-
Placement of an IV line, use of a pulse oximeter and cardiac monitoring are indicated.
In identified, or strongly suspected, cases of cholinergic excess, anticholinergic
agents should be used to enhance supportive care.
Prehospital personnel are often key to the identification of the organophosphate
or carbamate-poisoned patient. The presence of agricultural spray equipment,
bottles of insecticides, odors (garlic-like) and other clues to the diagnosis are
often unavailable to other health care personnel. Failure to note these clues
and initiate prevention of secondary casualties may jeopardize the safety of
the patient and numerous other medical personnel.
Emergency Department Care:
Again, decontamination and prevention of secondary casualties must be a high
priority for the organophosphate or carbamate-poisoned patient.
Patients should be thoroughly decontaminated with clothing removal and a soap
and water (or hypochlorite) bath or shower before entering the ED.
If this is impossible, contaminated areas should be isolated and thoroughly
cleaned before used for other patients or by non-contaminated personnel.
Atropine, to control secretions and bronchospasm, may be more helpful than
intubation for the patient in respiratory distress.
Anticholinergic agents should be used to antagonize signs and symptoms (e.g., bronchoconstriction, bronchorrhea and excessive secretions).
Inadequate use of atropine is a frequent cause of treatment failure and morbidity. Anticholinergics do not reverse muscle paralysis and, thus, should be used with
2PAM combats muscle weakness and paralysis. It is the definitive antidote
and reverses the phosphorylation of cholinersterase,
if used early.
Arrhythmias may not respond to the usual medications and require pacing.
The patient should be monitored during administration of atropine and 2PAM
until the QT interval is normal.
Diazepam is the drug of choice for seizures, however, 2PAM can be administered concomitantly.
Gastric lavage and charcoal are indicated for acute ingestions.
IV fluids may be needed if the patient has had a prolonged course of vomiting, diarrhea and excessive secretions.
Consultation with the regional poison control center, or your local medical toxicologist (certified through the American Board of Medical Toxicology and/or the American Board
of Emergency Medicine) may provide additional information and patient care recommendations.
Prolonged critical care management is often required for the pulmonary complications in those patients requiring endotracheal intubation.
Control of significant cholinergic excess is the key to management. Anticholinergic agents can be used to significantly reduce or eliminate the significant (gastrointestinal) and life-threatening (pulmonary and neuro-muscular) effects. Endpoints for therapy include elimination of bronchorrhea (atropine) and improved muscle strength (oximes). Reaching these endpoints may require more medication than is commonly prescribed.
Drug Category: Anticholinergics - Pharmacologic antagonism of excess anticholinesterase activity at muscarinic receptors.
Drug Name Atropine - The indications include GI or pulmonary distress
in the setting of known or suspected organophosphate or carbamate poisoning.
Continue therapy until control of bronchoconstriction and bronchorrhea occur.
High doses may be required in the first 24 h of treatment. Treatment may be
required for 48 h in severe cases. Doses required may be reduced by the
concurrent use of oximes.
Adult Dose 1 mg IV (initial or diagnostic)
2-4 mg IV q15min (therapeutic) until drying of pulmonary secretions
There are reports of poisoning requiring 2 mg/kg/h IV drip for several
week to control secretions.
Pediatric Dose 0.015 mg/kg (initial or diagnostic)
0.015 to 0.05 mg/kg q15min (therapeutic) until drying of pulmonary secretions
Contraindications Known atropine sensitivity or existing signs of atropinization
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Watch for atropinization (tachycardia, dilated pupils, dry red skin and dry mucous membranes).
Drug Category: Oximes - Reversal of inhibition of acetylcholinesterase
and nicotinic effects, including muscle paralysis.
Drug Name Pralidoxime (2-PAM) - The indications include muscle weakness
(especially respiratory muscle weakness) in the setting of known or
suspected organophosphate poisoning. Pralidoxime is very rarely needed
in carbamate poisoning. Increased muscle strength should begin in 30 min.
To be effective, they must be used early in the
course of poisoning, before the organophosphate-
acetlycholinesterase bond has aged.
Their use may help prevent intermediate and delayed
neuro-muscular and neuropsychiatric organophosphate
syndromes and decrease the dose of atropine required.
Adult Dose 1-2 g IV over 15 min followed by 500 mg/h IV until improved
muscle strength seen
Pediatric Dose 25 mg/kg IV given over 30 min, followed by 10-20 mg/kg/h IV
until improved muscle strength seen
Contraindications Known pralidoxime sensitivity
Pregnancy C - Safety for use during pregnancy has not been established.
Precautions Oximes are relatively non-toxic compounds.
Drug Category: Benzodiazepines - These are used for control of seizures.
Drug Name Diazepam (Valium)
Adult Dose 5-10 mg IV over 3-5 min
Pediatric Dose 30 days - 5 y: 0.2-0.5 mg IV (slowly) q2-5min
until symptoms resolve or to a maximum dose of 5 mg
5 y or older: 1 mg IV (slowly) q2-5min until symptoms resolve
or to a max dose of 10 mg
Contraindications Known hypersensitivity and acute narrow angle glaucoma
Interactions Effects are potentiated by phenothiazines, narcotics, barbiturates,
MAOIs and other antidepressants
Pregnancy D - Unsafe in pregnancy
Precautions Monitor for respiratory depression with high or repeated doses.
Drug Category: GI Decontamination
Drug Name Activated Charcoal +/- Cathartics
Adult Dose 1 g/kg PO (first dose usually with cathartic, although
not necessary if diarrhea, secondary to cholinergic stimulation,
is present); up to 50-100 g
May repeat the dose q4h at 0.5 g/kg (alternate use of cathartic,
monitor for active bowel sounds).
Pediatric Dose 1-2 g/kg PO (Under 2 y: omit cathartic); up to 15-30 g
May repeat the dose q4h at 0.5 g/kg (alternate use of cathartic, if using
and monitor for active bowel sounds.
Contraindications Unprotected airway with absent gag reflex
Interactions Will adsorb most recently ingested substances
Pregnancy A - Safe in pregnancy
Precautions Monitor for presense of active bowel sounds before
readministration to minimize the risk of a charcoal ileus.
Further Inpatient Care:
Most patients requiring therapy for organophosphate poisoning require hospital admission for continued monitoring and therapy. The patient should be observed for 24 hours after the last dose of atropine is given. There have been reports of delayed respiratory arrest following inadequate treatment.
Contact the poison control center, or your local medical toxicologist, for information on the anticipated duration of effect for the particular agent involved.
The use of opioids, phenothiazines and antihistamines should be avoided as they can potentiate effects of organophosphates. Similarily, succinylcholine has been reported to cause several hours of respiratory paralysis following one dose.
Further Outpatient Care:
Patients with non-life-threatening symptoms due to carbamate poisoning or with questionable exposure to organophosphates and no symptoms may be considered for discharge after adequate decontamination and observation for six hours.
Adequately treated patients require no medication when leaving the hospital and should be totally asymptomatic within one week.
Patients with residual neuropathies, neuropsychiatric symptoms, confusion, headaches and malaise may require neurology, medical toxicology, occupational medicine, or psychiatry follow up for extended periods.
Patients discharged after exposure to organophosphates or carbamates should
avoid further exposure to such agents until they are
asymptomatic and their acetycholinesterase activity level can be shown to
have returned to at least 75% of baseline, which may take several months.
Persistent CNS effects
(i.e., irritability, fatigue, impaired memory, depression and psychosis) and
(i.e., weakness, paresthesia, ataxia and chronic pain) have been reported
in survivors of significant organophosphate poisoning, as well as in patients with
multiple small exposures over a long time period.
This can last for weeks, months or years.
In untreated, severely intoxicated patients, death usually occurs within 24 hours.
It may be much more rapid with nerve agents.
Most patients treated quickly and optimally fully recover
within 10 days.
If treatment is delayed 24 hours or is inadequate, recovery may take months,
and neurological complications may be permanent.
Patients should be advised to destroy the clothes that they were wearing at the
time of exposure because of the risk of repeat contamination.
*Failure to recognize the cholinergic symptoms, thereby delaying
or missing treatment.
This will result in increased morbidity, and possible mortality.
*Failure to adequately decontaminate the exposed patient resulting in
secondary contamination of others.
*Failure to consider the possibility of an Intermediate Syndrome
or Organophosphate-Induced Delayed Neurotoxicity.
Pregnancy: Patients have been successfully treated after organophosphate poisoning in the second and third trimesters of pregnancy with atropine and palidoxime with delivery of healthy newborns.
CME Question 1: A comatose patients arrives in your ED. You are told he was found unconscious in his back yard. He is in respiratory distress, has pinpoint pupils, is incontinent of urine and feces, appears to have vomited and has a large amount of secretions in his airway. What is the initial treatment?
D: CT brain
Your Choice: (Answers provided on emedicine website, see below.)
CME Question 2: Which of the following chemicals does NOT permanently bind cholinesterase?
Your Choice: (Answers provided on emedicine website, please see below.)
Pearl Question 1: What is the most common cause of death from organophosphate
poisoning? (Answers provided on emedicine website, please see below.)
Pearl Question 2: What is the definitive antidote for organophosphate poisoning?
(Answers provided on emedicine website, please see below.)
Pearl Question 3: Which drug is used to control the most uncomfortable symptoms
of organophosphate poisoning?
(Answers provided on emedicine website, please see below.)
Pearl Question 4: For how long must a patient who has been treated for
organophosphate avoid exposure again to organophosphate?
(Answers provided on emedicine website, please see below.)
Cable GG, Doherty S: Acute carbamate and organochlorine toxicity
causing convulsions in an agricultural pilot: a case report. Aviat Space
Environ Med 1999 Jan; 70(1): 68-72 [Medline].
Carlock LL, Chen WL, Gordon EB: Regulating and assessing risks of cholinesterase-inhibiting pesticides: divergent approaches and interpretations.
J Toxicol Environ Health B Crit Rev 1999 Apr-Jun; PT - REVIEW, TUTORIAL(2): 105-60[Medline].
DeBeleecker J, Willems J, Van Den Neucker K, et al: Prolonged toxicity with intermediate syndrome after combined parathion and methyl parathion
poisoning. j Toxicol Clin Toxicol 1992; 30: 333-345.
DeBleecker J, Van den Neucker K, Colarydn F: Intermediate syndrome in organophosphate poisoning. Crit Care Med 1993; 21: 1706-1711.
Ellenhorn MJ: Organophosphates. Ellenhorns Medical Toxicology
Farrar HC: Continuous infusion of pralidoxime for treatment of
organophosphate poisoning in children. Pediatrics 90; 116: 658.
Lotti M, Becker CE, Aminoff MJ: Organophosphate polyneuropathy:
pathogenesis and prevention. Neurology 1984; 34: 658-662.
Morgan D: Recognition and management of pesticide poisonings.
US Government printing office 82;.
Tuovinen K, Kaliste-Korhonen E, Raushel FM: Success of pyridostigmine,
physostigmine, eptastigmine and phosphotriesterase treatments in acute
sarin intoxication. Toxicology 1999 Jun 15; 134(2-3): 169-78 [Medline].
Whorton M: Persistence of symptoms after mild to moderate organophosphate
poisoning in 19 farm workers. Journal of Toxicologic and Environmental
Health 83; 11: 347.
The copyrighted text used on this page,
including the answers to the Test Questions, may be accessed at:
We have reformatted, hyperlinked, and highlighted
parts of this material
in order to present this reference information for educational purposes only
and provide emphasis on various portions of the text.
This would not have been possible if we had
merely provided to link to the emedicine site.
We ask for the gracious forbearance of the authors as
our intention is not to infringe in any way on this copyright,
but to educate an entire generation of SBU students who,
without their consent or knowledge, have been unethically or illegally
exposed to potentially harmful organophosphate pesticides.
Please visit the emedicine website.
The Table of Contents and Introduction:
An on-line Medical Reference
NOTE from the emedicine site:
Medicine is a constantly changing science and not all therapies are clearly established. New research changes drug and treatment therapies daily. The authors, editors, and publisher of this textbook have used their best efforts to provide information that is up-to-date and accurate and is generally accepted within medical standards at the time of publication. However, as medical science is constantly changing and human error is always possible, the authors, editors, and publisher or any other party involved with the publication of this text do not warrant the information in this text is accurate or complete, nor are they responsible for omissions or errors in the text or for the results of using this information. The reader should confirm the information in this text from other sources prior to use. In particular, all drug doses, indications, and contraindications should be confirmed in the package insert.
~Updates~ ~~Return to Welcome~~ ~How Can I Help?~