AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

The ED physician may encounter organophosphorous compound (OPC) and carbamate poisoning in a variety of clinical scenarios. Pesticide poisoning is the most common cause of OPC and carbamate poisoning because the vast majority of pesticides still contain OPCs and carbamates. OPC nerve agents may be used in the military setting or in terrorist attacks. An example was sarin used in the Tokyo subway attacks of 1995. Carbamates, such as physostigmine and neostigmine, are commonly used to treat diseases such as glaucoma and myasthenia gravis.

Although OPC and carbamates are structurally distinct, they have similar clinical manifestations and generally the same management. Although most patients with OPC and carbamate poisoning have a good prognosis, severe poisoning is potentially lethal. Early diagnosis and initiation of treatment are important. The ED physician has access to a number of therapeutic options that can decrease morbidity and mortality.

Pathophysiology

OPCs and carbamates bind to 1 of the active sites of acetylcholinesterase (AChE) and inhibit the functionality of this enzyme by means of steric inhibition. The main purpose of AChE is to hydrolyze acetylcholine (ACh) to choline and acetic acid. Therefore, the inhibition of AChE causes an excess of ACh in synapses and neuromuscular junctions, resulting in muscarinic and nicotinic symptoms and signs.

Excess ACh in the synapse can lead to 3 sets of symptoms and signs.

First, accumulation of ACh at postganglionic muscarinic synapses leads to parasympathetic activity of smooth muscle in the lungs, GI tract, heart, eyes, bladder, and secretory glands and increased activity in postganglionic sympathetic receptors for sweat glands. This results in the symptoms and signs that can be remembered with the mnemonic SLUDGE/BBB (see Physical below). Second, excessive ACh at nicotinic motor end plates causes persistent depolarization of skeletal muscle (analogous to that of succinylcholine), resulting in fasciculations, progressive weakness, and hypotonicity. Third, as OPs cross the blood-brain barrier, they may cause seizures, respiratory depression, and CNS depression for reasons not completely understood.

OPCs and carbamates also bind to erythrocyte cholinesterase (also known as RBC cholinesterase) on RBCs and plasma cholinesterase (also known as pseudocholinesterase, serum cholinesterase, or butyrylcholinesterase) in the serum. This binding seems to have only minimal clinical effects but is useful in confirmatory diagnostic studies.

The main difference in the mechanisms of action between OPCs and carbamates is that carbamates spontaneously hydrolyze from the AChE site within 24 hours, whereas OPCs undergo aging. Aging occurs when the phosphorylated AChE nonenzymatically loses an alkyl side chain, becoming irreversibly inactivated. Carbamates, however, reversibly bind to the active site and do not undergo aging.

Frequency

United States

In the United States, more than 18,000 products are licensed for use, and each year more than 2 billion pounds of pesticides are applied to crops, homes, schools, parks, and forests.¹ Occupational exposure is known to result in an annual incidence of 18 cases of pesticide-related illness reported for every 100,000 workers in the United States.² In 2003, approximately 7500 cases of OPC and 3700 cases of carbamate exposure were reported to Poison Control Centers in the United States. Sixteen OPC-related deaths and 2 carbamate-related deaths were reported that year.³

International

Because of the increased use and availability of pesticides (especially in developing countries), the incidence of OPC and carbamate poisoning is high. In China alone, pesticide poisoning, mainly with OPCs, cause an estimated 170,000 deaths per year. Virtually all of these are the result of deliberate self-poisoning by ingestion.⁴

Mortality/Morbidity

Many OPC and carbamate exposures are mild, and symptoms resolve rapidly. The severity of poisoning is largely due to a number of factors, including the type of agent, the amount and route of exposure, and the time to initial treatment. The most common cause of mortality in OPC and carbamate poisoning is respiratory failure; however, death is rare, occurring in 0.04-1% of typical pesticide poisonings.⁵

Race

No racial predilection exists.

Sex

Men have an increased incidence because of increased work-related exposure and increased suicidal attempts with OP and carbamate compounds.

Age

Children have an increased incidence of unintentional exposure at home. One retrospective study revealed a difference in clinical presentation in children with OPC and carbamate poisoning compared with adults. Pediatric patients had predominately CNS depression and severe hypotonia, whereas muscarinic symptoms were infrequent.⁶

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Patients usually have a history of OPCs or carbamates exposure, either suicidal or unintentional. Pesticides can rapidly be absorbed through the skin, lungs, GI tract, and mucous membranes. The rate of absorption depends on the route of absorption and the type of OP or carbamate. Symptoms usually occur within a few hours after GI ingestion and appear almost immediately after inhalational exposure.

Physical

In the Tokyo sarin attack, miosis was the most common (>90%) indicator of OP poisoning.⁷ Bradycardia is not a reliable finding, and patients may be tachycardic, for 2 reasons: First, hypoxia due to bronchorrhea and bronchospasm can lead to sympathetic outflow, which overrides parasympathetic vagal stimulation of the heart and which causes tachycardia. Second, nicotinic ACh receptors are present in both sympathetic and parasympathetic ganglia. These ganglionic effects in the sympathetic system may contribute to tachycardia.

Patients often present with evidence of a cholinergic toxic syndrome, or toxidrome. It is useful to remember the toxidrome in terms of the 3 clinical effects on nerve endings: nicotinic effects at neuromuscular junctions and autonomic ganglia, CNS effects, and muscarinic effects. Nicotinic signs and symptoms include weakness, fasciculations, and paralysis, whereas CNS effects may lead to seizures and CNS depression. Two common mnemonics to remember the muscarinic signs and symptoms of the cholinergic toxidrome are SLUDGE/BBB and DUMBELS, as follows:

• SLUDGE/BBB mnemonic
• • S = Salivation
  • L = Lacrimation
  • U = Urination
  • D = Defecation
  • G = GI symptoms
  • E = Emesis
  • B = Bronchorrhea
  • B = Bronchospasm
  • B = Bradycardia
• DUMBELS mnemonic
• • D = Diarrhea and diaphoresis
  • U = Urination
  • M = Miosis
  • B = Bronchorrhea, bronchospasm, and bradycardia
  • E = Emesis
  • L = Lacrimation
  • S = Salivation

Causes

Agricultural exposure is the most common cause of OPC and carbamate poisoning. The World Health Organization (WHO) classifies these poisonings as class I (extremely toxic) to class III (slightly hazardous). The WHO advocates banning or strong restrictions on the use of class I pesticides and a reduction in the use of pesticides to a minimal number of compounds that are less hazardous than others.⁸

OPCs may also be encountered in the military setting or as the result of a terrorist attack with nerve agents such as sarin, VX, or soman.

In addition to their use as insecticides, carbamates are used to treat certain medical diseases, such as glaucoma and myasthenia gravis (neostigmine, physostigmine). Some case reports describe clinical illness from foodborne outbreaks due to contamination with OPC-containing pesticides.⁹

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• The most common tests to determine OP and carbamate poisoning are measurements of serum cholinesterase and RBC AChE activity, which are used to estimate neuronal AChE activity.
• Although the RBC AChE test may not be as readily available as the other, it provides a better indicator of neuronal AChE activity than serum AChE.¹⁰
• In many places, neither of these tests are immediately available and therefore are of no assistance in the acute setting or in guiding therapy.
• Moreover, normal levels of enzyme activity vary widely in populations and in individuals.¹¹ Butyryl-cholinesterase activity may vary after exposure to cocaine, succinylcholine, morphine, and codeine.
• These tests are most useful for confirming the diagnosis.
• In the ideal case, the diagnosis is confirmed with a decrease in enzyme activity from baseline (50% for RBC cholinesterase activity), though a baseline, preexposure enzyme level is not available for most patients.

Other Tests

• ECG may be considered.
• Many retrospective studies have shown that a prolonged QTc interval is the most common ECG abnormality.¹²
• Elevation of the ST segment, sinus tachycardia, sinus bradycardia, and complete heart block (rare) may also occur. (Sinus tachycardia occurs just as commonly as sinus bradycardia.)

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Prehospital Care

Identification of the type of chemical is important in determining the patient's clinical course and prognosis. Emergency Medical Service (EMS) personnel should attempt to bring in the labels or the names of chemicals the patient was exposed to because different OPCs have different aging and reactivation times, which may help in guiding treatment. As a general rule, dimethyl OPCs undergo rapid aging, which makes early initiation of oximes critical. In comparison, diethyl compounds may cause delayed toxicity, and oxime therapy may need to be prolonged.¹³

Emergency Department Care

• Airway, breathing, and circulation (ABCs): Care of the ABCs should be initiated first because intubation may be necessary in cases of severe poisoning. 
• • Because succinylcholine is metabolized by means of plasma cholinesterase, OPC or carbamate poisoning may cause prolonged paralysis. Increased doses of nondepolarizing agents, such as pancuronium or vecuronium, may be required to achieve paralysis because of the excess ACh at the receptor.¹⁰
  • Providers with appropriate personal protective equipment (PPE) can address the ABCs before decontamination.
• Decontamination: Decontamination is an important part of the initial care. In general, the importance of decontamination depends on the route of poisoning. Patients with dermal and inhalation exposures, as expected in a terrorist attack, are more likely to cause nosocomial poisoning than patients with GI exposure. Patients with GI exposure should also be decontaminated, but ED staff should not delay urgent treatment with excessive decontamination, given that nosocomial poisoning from GI exposure is rare and controversial. Patients with dermal and inhalation poisonings must be decontaminated before being brought into the ED if it was not done in the prehospital setting.
• • Case reports have described nosocomial poisoning in staff members treating patients who have been exposed to OPCs and carbamates^{4, 14, 15}; one describes OPC toxicity from mouth-to-mouth resuscitation¹⁶. Only one case discusses serious poisoning in which a staff member required treatment and eventual intubation.¹⁷ However, none of these cases were confirmed with diagnostic studies.
  • In addition, nosocomial OPC poisoning has not been reported in developing countries with a high incidence of severe OPC poisoning.
  • Moreover, the odors often smelled when one cares for a patient poisoned from pesticide are commonly due to the hydrocarbon solvent, which may cause symptoms independent of the OPC agent.¹⁸
  • The patient's clothes must be removed and isolated, and his or her body washed with soap and water.
• GI decontamination: Oral administration of activated charcoal is a reasonable intervention after GI poisoning. However, as with any poisoned patient, the risks and benefits must be weighed.
• Atropine: Atropine is a pure muscarinic antagonist that competes with ACh at the muscarinic receptor.
• • Atropine is most commonly given in intravenous (IV) form at the recommended dose of 2-5 mg for adults and 0.05 mg/kg for kids with a minimum dose of 0.1 mg to prevent reflex bradycardia. Atropine may be redosed every 5-10 minutes. Severe OP poisonings often require hundreds of milligrams of atropine.
  • In one case report, a patient required frequent doses of atropine and was eventually converted to an atropine infusion to a total of 30 g over 5 days.¹⁹
  • Most sources recommend starting atropine on patients with anything more than ocular effects and then observing the drying of secretions as an endpoint in titrating to the appropriate dose.
  • From the Tokyo sarin experience, patients poisoned by nerve agents had modest atropine requirements, with none requiring more than 10 mg.
• Oximes: The only oxime available in the United States is pralidoxime (2-PAM).
• • OPCs and carbamates bind and phosphorylate one of the active sites of AChE and inhibit the functionality of this enzyme. Oximes bind to the OP or carbamate, causing the compound to break its bond with AChE. Most of the effects are on the peripheral nervous system because entry into the CNS is limited.
  • Atropine does not bind to nicotinic receptors; therefore, it is ineffective in treating neuromuscular toxicity (particularly weakness of respiratory muscles).
  • The main therapeutic effect of pralidoxime is predicted to be recovery of neuromuscular transmission at nicotinic synapses. However, oximes also enhance cholinesterase activity at muscarinic sites, decreasing the requirement for atropine. In vitro experiments have shown that oximes are effective reactivators of human AChE inhibited by OP compounds.²⁰
  • In some situations, reactivation of inhibited AChE by oximes is likely to be absent or limited when affinity for the particular OP-AChE complex is poor, the dose or duration of treatment is insufficient, the OP persists in the patient and therefore rapid reinhibition of the newly reactivated enzyme occurs, and the inhibited AChE ages.
  • The degree of reactivation depends on the specific identities and concentrations of the oxime and the OP.^{21, 22, 23, 20} Because diethyl-OP–inhibited AChEs reactivate and age notably slower than the dimethyl analogs, they generally require prolonged oxime treatment.²⁴ The half-lives of aging of dimethyl phosphorylated or diethyl phosphorylated AChE, as determined in isolated human RBCs in vitro, are 3.7 or 33 hours, respectively, and the therapeutic windows (4 times the half-life) are a maximum of 13 or 132 hours, respectively.^{25, 26}
  • Although animal data²⁶ and observational clinical data^{23, 25, 27} suggest regeneration of AChE and improved outcome, only a few randomized controlled studies have been done.
  • • One study by Johnson et al was a comparison of pralidoxime 1 g as a bolus, with pralidoxime 12 g as an infusion (no bolus) over 4 days. Mortality rates, need for ventilation, and rates of intermediate syndrome were higher with the infusion group than with the bolus group.²⁸
    • Another study by Cherian et al was a comparison of pralidoxime 12 g given over 3 days with placebo. Results were similar in both groups, with increased rates of mortality, ventilatory support, and intermediate syndrome.²⁹
    • A more recent randomized study by Pawar et al in patients with moderately severe anticholinesterase pesticide poisoning (all patients received initial 2 g bolus dosing of pralidoxime over 30 min) compared continuous pralidoxime infusion of 1 g/h versus pralidoxime 1 g every 4 hours. Patients with the continuous pralidoxime infusion were found to have decreased atropine requirements and decreased need for intubation.³⁰ 
  • Both the 1-g bolus dose and the 12-g infusion dose fall short of WHO-recommended dosing for adults, which is a bolus of at least 30 mg/kg followed by an infusion of at least 8 mg/kg/h. Pediatric dosing is a 25-50 mg/kg bolus given over 30 minutes then an infusion of 10-20 mg/kg/h. This WHO recommendation is based on the doses known to achieve serum pralidoxime concentration of greater than 4 mg/L, the minimum effective concentration reported in an early study.³¹ Randomized controlled studies with oxime therapy at the WHO-recommended doses are needed to further delineate its effectiveness.
  • The WHO protocol for oxime therapy is recommended for any patient with clinically significant poisoning.
• Benzodiazepines: Seizures are an uncommon complication of OP poisoning. When they occur, they represent severe toxicity. As with most seizures of toxicologic etiology, benzodiazepines are the preferred medication.
• Other treatments: Prospective studies of both magnesium and fresh-frozen plasma as adjunctive therapy in OP poisoning have shown improved mortality rates with both treatments.^{32, 33} However, both must be evaluated further. Nebulized ipratropium bromide may also have therapeutic effects as an adjunct agent.

Consultations

Consult a regional poison control center or toxicologist for further recommendations for patient care. Consult a psychiatrist in any intentional or suspected intentional ingestions.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Control of clinically significant cholinergic excess is the key to management. Anticholinergic agents can be used to substantially reduce or eliminate the secretory effects of muscarinic excess. Endpoints for therapy include elimination of bronchorrhea (atropine) and improved muscle strength (oximes). Reaching these endpoints may require more medication than commonly prescribed.

Drug Category: GI decontaminant

This drug is used to bind recently ingested agents, thereby limiting systemic absorption. It is not useful for noningestion exposures.

Drug Category: Antidotes

Anticholinergics, such as atropine, cause pharmacologic antagonism of excess anticholinesterase activity at muscarinic receptors. Oximes reverse the inhibition of AChE and nicotinic effects, including muscle paralysis.

Drug Name	Pralidoxime (2-PAM, Protopam)
Description	Indications include muscle weakness (especially respiratory) in known or suspected OP poisoning. Rarely needed in carbamate poisonings. Muscle strength should increase in 30 min. Must be used early in poisoning, before OP-AChE bond has aged, to be effective. May help prevent intermediate and delayed neuromuscular and neuropsychiatric OP syndromes.
Adult Dose	At least 30 mg/kg IV over 15 min initially; then 8 mg/kg/h IV until muscle strength improves
Pediatric Dose	25-50 mg/kg IV over 30 min initially; then 10-20 mg/kg/h IV until muscle strength improves
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions	Relatively nontoxic compounds; not effective for OP poisonings caused by without anticholinesterase activity

Drug Category: Benzodiazepine

This drug is used to control seizures.

Drug Name	Lorazepam (Ativan)
Description	DOC for treatment of status epilepticus because persists in CNS longer than diazepam. Rate of injection not to exceed 2 mg/min. May be administered IM if IV access not available.
Adult Dose	0.044 mg/kg (range, 2-4 mg) IV, titrate to effect Status epilepticus: 4 mg IV over 2-5 min; may repeat in 10-15 min if needed; not to exceed 8 mg
Pediatric Dose	Children: 0.05 mg/kg IV (range, 0.02-0.1 mg/kg) Adolescents: Administer as in adults Status epilepticus: Neonates: 0.05 mg/kg IV over 2-5 min; may repeat in 10-15 min if needed Infants and children: 0.1 mg/kg IV over 2-5 min; not to exceed 4 mg; second dose 0.05 mg/kg IV at 10-15 min, if needed Adolescents: 0.7 mg/kg IV slowly over 2-5 min; not to exceed 4 mg; may repeat in 10-15 min, if needed
Contraindications	Documented hypersensitivity; preexisting CNS depression; hypotension; narrow-angle glaucoma
Interactions	Alcohol, phenothiazines, barbiturates, and MAOIs increase CNS toxicity
Pregnancy	D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions	Monitor for respiratory depression with high or repeated doses; contains benzyl alcohol, which may be toxic to infants in high doses; caution in renal or hepatic impairment, myasthenia gravis, organic brain syndrome, Parkinson disease, or inhibited benzodiazepine metabolism and clearance (eg, in use of nicotine or cimetidine)

Drug Name	Midazolam (Versed)
Description	Alternative to terminate refractory status epilepticus. Because water soluble, takes approximately 3 times longer than diazepam to peak EEG effects. Wait 2-3 min to fully evaluate sedative effects before starting procedure or repeating dose. Has twice the affinity for benzodiazepine receptors than diazepam. May be administered IM if vascular access unavailable.
Adult Dose	0.01-0.05 mg/kg IV slowly over several min; usually 0.5-4 mg, not to exceed 10 mg; may repeat q10-15min until adequate response achieved
Pediatric Dose	<32 weeks: 0.5 mcg/kg/min IV infusion >32 weeks: 1 mcg/kg/min IV infusion Children: 0.05-0.2 mg/kg IV over 2-3 min, followed by 1-2 mcg/kg/min continuous infusion Status epilepticus (refractory to standard therapy), >2 months and children: 0.15 mg/kg then continuous infusion 1 mcg/kg/min; titrate upward q5min until seizures controlled
Contraindications	Documented hypersensitivity; preexisting hypotension; narrow-angle glaucoma; sensitivity to propylene glycol (diluent)
Interactions	Theophyllines may antagonize sedative effects; narcotics, cimetidine, ethanol, and erythromycin may accentuate sedative effects because of decreased clearance; reduce dose of thiopental by 15% when used together
Pregnancy	D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions	Caution in congestive heart failure, pulmonary disease, renal impairment, hepatic failure, neuromuscular disease, hypotension, and patients >60 y; monitor for respiratory depression with high or repeated doses; consider reduced doses in organic brain syndrome and inhibited benzodiazepine metabolism and clearance (eg, in use of nicotine or cimetidine)

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Most patients who require therapy for OPC poisoning warrant admission to the hospital for continued monitoring and treatment. Patients who require continuous monitoring or treatment should be admitted to the ICU.
• Patients with clinically significant poisoning should be evaluated frequently to monitor their airway and respiratory secretions. In addition, frequent neurologic examination should be performed to evaluate for neuromuscular blockade.
• Therapy is largely titrated to the physical findings. Atropinization is based on the drying of respiratory secretions, and oxime therapy is based on an improvement in neuromuscular signs.
• A toxicologist may be of help in determining specific aging and reactivation times of the particular OPC or carbamate agent.

Further Outpatient Care

• Patients without any symptoms and with questionable or minimal exposure to OPs or carbamates may be considered for discharge after 6-12 hours of observation.
• Patients with residual neurologic symptoms should be given a follow-up appointment with a neurologist.
• Follow-up with a psychiatrist should be arranged as indicated.

Complications

• Intermediate syndrome
• • Intermediate syndrome was first described in 1987 as a sudden respiratory paresis, with weakness in cranial nerves and proximal-limb and neck flexor muscles.³⁴
  • These clinical features appear 24-96 hours after exposure and are distinct from the previously described delayed neurotoxicity (see below).
  • Although intermediate syndrome is incompletely understood, more recent reports suggest that this is due to presynaptic and postsynaptic dysfunction of neuromuscular transmission and that it may result from insufficient oxime treatment.^{35, 36}
• OPC-induced delayed neurotoxicity  
• • OPC-induced delayed neurotoxicity (OPCIDN) is a sensorimotor polyneuropathy that typically occurs 9-14 days after OP exposure.
  • The patient initially presents with distal motor weakness and sensory paresthesias in the lower extremities, which may progress proximally and eventually affect the upper extremities.
  • Most sources suggest that the mechanism involves inhibition of neuropathy target esterase (NTE), an enzyme that metabolizes esters in nerve cells.
  • Some patients may recover over 12-15 months, but permanent losses with spasticity and persistent upper motor neuron findings have been reported.¹⁰
• Pancreatitis
• • Pancreatitis has been reported as a rare complication.
  • One case series reported that 12.76% of OP poisonings were associated with acute pancreatitis, although this has not been the experience in other series.^{37, 38}

Prognosis

• In severe poisoning, death usually occurs within the first 24 hours if it is untreated.
• With nerve-agent poisoning, death may occur within minutes if untreated.
• • Even with adequate respiratory support, intensive care, and specific treatment with atropine and oximes, the mortality rate is still high in severe poisonings.³⁹
  • A delay in treatment can also lead to late and permanent neurologic sequelae.
  • Most patients with minimal symptoms fully recover.

Patient Education

• Advise patients to destroy the clothes they were wearing at the time of exposure because of the risk of repeat contamination.
• For excellent patient education resources, visit eMedicine's Poisoning Center and Poisoning - First Aid and Emergency Center. Also, see eMedicine's patient education articles Poisoning, Chemical Warfare, Activated Charcoal, and Poison Proofing Your Home.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to recognize cholinergic symptoms and a delay in intervention may increase morbidity and mortality.
• Failure to adequately decontaminate the exposed patient may result in secondary contamination of others.
• Failure to consider the possibility of an intermediate syndrome or OP-induced delayed neurotoxicity is a pitfall.
• Failure to administer an adequate dose of atropine to control secretions (sometimes in the range of 1000 mg over 24 h)

Special Concerns

• Pregnant women should receive the same treatment as that given to other adults.
• Both atropine and pralidoxime are pregnancy class C drugs.
• In the Tokyo subway attacks, 5 pregnant women were mildly poisoned, and all had normal babies without complications.⁷

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

1. US EPA Office of Pesticide Programs. FY 2002 Annual Report. Washington, DC: US Environmental Protection Agency. Available at http://www.epa.gov/oppfead1/annual/2002/2002annualreport.pdf.
2. Calvert GM, Plate DK, Das R, Rosales R, Shafey O, Thomsen C, et al. Acute occupational pesticide-related illness in the US, 1998-1999: surveillance findings from the SENSOR-pesticides program. Am J Ind Med. Jan 2004;45(1):14-23. [Medline].
3. Watson WA, Litovitz TL, Klein-Schwartz W, Rodgers GC Jr, Youniss J, Reid N, et al. 2003 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 2004;22(5):335-404. [Medline].
4. Eddleston M, Phillips MR. Self poisoning with pesticides. BMJ. Jan 3 2004;328(7430):42-4. [Medline].
5. Tsao TC, Juang YC, Lan RS, Shieh WB, Lee CH. Respiratory failure of acute organophosphate and carbamate poisoning. Chest. Sep 1990;98(3):631-6. [Medline].
6. Lifshitz M, Shahak E, Sofer S. Carbamate and organophosphate poisoning in young children. Pediatr Emerg Care. Apr 1999;15(2):102-3. [Medline].
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8. Eddleston M, Karalliedde L, Buckley N, Fernando R, Hutchinson G, Isbister G, et al. Pesticide poisoning in the developing world--a minimum pesticides list. Lancet. Oct 12 2002;360(9340):1163-7. [Medline].
9. Greenaway C, Orr P. A foodborne outbreak causing a cholinergic syndrome. J Emerg Med. May-Jun 1996;14(3):339-44. [Medline].
10. Aaron C. Ford: Clinical Toxicology. St Louis, MO: MD Consult; 2001:818-28.
11. Worek F, Koller M, Thiermann H, Szinicz L. Diagnostic aspects of organophosphate poisoning. Toxicology. Oct 30 2005;214(3):182-9. [Medline].
12. Kiss Z, Fazekas T. Arrhythmias in organophosphate poisonings. Acta Cardiol. 1979;34(5):323-30. [Medline].
13. Eyer P. The role of oximes in the management of organophosphorus pesticide poisoning. Toxicol Rev. 2003;22(3):165-90. [Medline].
14. Butera R, Locatelli C, Barretta S. Secondary exposure to malathion in emergency department healthcare workers. Clin Toxicol. 2002;40:386.
15. Stacey R, Morfey D, Payne S. Secondary contamination in organophosphate poisoning: analysis of an incident. QJM. Feb 2004;97(2):75-80. [Medline].
16. Koksal N, Buyukbese MA, Guven A, Cetinkaya A, Hasanoglu HC. Organophosphate intoxication as a consequence of mouth-to-mouth breathing from an affected case. Chest. Aug 2002;122(2):740-1. [Medline]. [Full Text].
17. Geller RJ, Singleton KL, Tarantino ML, Drenzek CL, Toomey KE. Nosocomial poisoning associated with emergency department treatment of organophosphate toxicity--Georgia, 2000. J Toxicol Clin Toxicol. 2001;39(1):109-11. [Medline].
18. Little M, Murray L,. Consensus statement: risk of nosocomial organophosphate poisoning in emergency departments. Emerg Med Australas. Oct-Dec 2004;16(5-6):456-8. [Medline].
19. LeBlanc FN, Benson BE, Gilg AD. A severe organophosphate poisoning requiring the use of an atropine drip. J Toxicol Clin Toxicol. 1986;24(1):69-76. [Medline].
20. Worek F, Kirchner T, Backer M, Szinicz L. Reactivation by various oximes of human erythrocyte acetylcholinesterase inhibited by different organophosphorus compounds. Arch Toxicol. 1996;70(8):497-503. [Medline].
21. Buckley NA, Eddleston M, Szinicz L. Oximes for acute organophosphate pesticide poisoning. Cochrane Database Syst Rev. 2005;(1):CD005085. [Medline]. [Full Text].
22. Johnson MK, Jacobsen D, Meredith TJ. Evaluation of antidotes for poisoning in organophorus pesticides. Emerg Med. 2000;12(1):22-37.
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Article Last Updated: Aug 23, 2007