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Pediatric
Organophosphates
Toxicity
Updated: Apr 15, 2018
Author: William Freudenthal, MD; Chief Editor: Stephen L Thornton, MD

Overview

Practice Essentials
Organophosphates and carbamates are the most frequently used insecticides
worldwide. These compounds cause 80% of the reported toxic exposures to
insecticides. Organophosphates produce a clinical syndrome that can be
effectively treated if recognized early. The typically described muscarinic clinical
syndrome in adults often does not occur in young children, who instead are more
likely to present with altered levels of consciousness (see Presentation).[1, 2, 3, 4]
Severe exposures require expeditious anticholinergic therapy (see Treatment and
Medication).

Background
Organophosphates were first discovered more than 150 years ago; however, their
widespread use began in Germany in the 1920s, when these compounds were
first synthesized as insecticides and chemical warfare agents. Interest in the
effects of these compounds on humans has increased in recent years due to their
potential use as weapons of mass destruction.[5]

Pathophysiology
Organophosphates form an initially reversible bond with the enzyme
cholinesterase. The organophosphate-cholinesterase bond can spontaneously
degrade, reactivating the enzyme, or can undergo a process called aging. The
process of aging results in irreversible enzyme inactivation.

Cholinesterase is found in two forms: an RBC form, which is known as true

cholinesterase, and a plasma form, which is known as pseudocholinesterase.
Cholinesterases rapidly hydrolyze the neurotransmitter acetylcholine into inactive
fragments. Acetylcholine is found in sympathetic and parasympathetic ganglia and
in the terminal nerve endings of postganglionic parasympathetic nerves at the
motor endplates of nerves in the skeletal muscle. Inactivation of the enzyme
allows acetylcholine to accumulate at the synapse, leading to overstimulation and
disruption of nerve impulses. Skeletal-muscle depolarization and fasciculations
occur secondary to nicotinic stimulation at the motor endplate.

Muscarinic effects occur at the postganglionic parasympathetic synapses, causing

smooth-muscle contractions in various organs including the GI tract, bladder, and
secretory glands. Conduction can be delayed in the sinus and atrioventricular (AV)
nodes. Dysrhythmias are frequently reported; these typically include bradycardia,
though tachycardia can also occur.

Acetylcholine receptors are widely dispersed throughout the CNS. The activation
of these receptors causes a wide range of effects, including CNS stimulation,
seizures, confusion, ataxia, coma, and respiratory or cardiovascular depression.

Organophosphates are generally highly lipid soluble and are well absorbed from
the skin, mucous membranes, conjunctiva, GI system, and respiratory system.

Epidemiology
Frequency

United States

The American Association of Poison Control Centers' (AAPCC's) National Poison

Data System reported 1994 single exposures to organophosphate insecticides
alone in 2016; 582 of those were in children younger than 6 years, 91 in children 6
to 12 years, and 61 in teenagers. These resulted in 17 major outcomes and one
death. In addition, the AAPCC reported 537 single exposures to organophosphate
insecticides in combination with other insecticides (mostly non-carbamate), none
of which were fatal. Of the exposures to combined insecticides, 109 occurred in
children younger than 6 years and 73 in older pediatric patients.[6] Many more
exposures probably occur, but patients with minor symptoms often do not seek
medical care.

International

Worldwide, pesticide poisonings cause an estimated 20,000 deaths and more

than one million serious poisonings annually.[7]

Mortality/Morbidity
Most morbidity and mortality results from anoxic injury due to respiratory failure.
Clinical effects range from mild flulike symptoms with low-level exposures to life-
threatening respiratory failure with larger exposures.

Race-, Sex-, and Age-related Demographics

No known racial differences in mortality or morbidity are reported. No differences

in clinical effects between the sexes are known.

Children are at a significantly increased risk worldwide, particularly in Africa and

other developing regions, where the widespread availability and use of
organophosphates and the lack of regulation and safety packaging are high risk
factors for exposure. Childhood deaths and reported poisonings in the United
States have declined over the last few decades, partly because of educational
efforts and improved regulation and packaging.

Presentation

History
Considerations when taking the history include the following:

Most symptoms appear within 12-24 hours of exposure.

Exposure can occur by means of ingestion, dermal exposure, or inhalation.

Children often ingest home pesticides they find in unmarked or poorly

stored containers.

Children can also be exposed when playing in areas recently treated with
organophosphate compounds.

A history of possible exposure combined with physical signs and symptoms

consistent with exposure often lead to diagnosis.

Many organophosphates can irritate the skin and mucous membranes.

Some have a characteristic odor, such as a garliclike smell.

Physical
Physical findings vary according to the route of exposure, the age of patient, and
the specific chemical. In general, the signs and symptoms of organophosphate
poisoning fall into the following three broad categories:

Muscarinic
Nicotinic
Central nervous system (CNS)

Muscarinic findings may include the following[8] :

Diaphoresis and diarrhea, urination, miosis, bradycardia, bronchorrhea,

bronchospasm, emesis, lacrimation and salivation (DUMBELS)
Wheezing and/or bronchoconstriction
Pulmonary edema
Increased pulmonary and oropharyngeal secretions
Sweating
Bradycardia
Abdominal cramping and intestinal hypermotility
Miosis

Nicotinic findings may include the following:

Muscle fasciculations (twitching)

Fatigue
Paralysis
Respiratory muscle weakness
Diminished respiratory effort
Tachycardia
Hypertensio

CNS findings may include the following:

Anxiety
Restlessness
Confusion
Headache
Slurred speech
Ataxia
Seizures
Coma
Central respiratory paralysis
Altered level of consciousness and/or hypotonia

Children, particularly young children, are more likely to present with altered levels
of consciousness than with the classic DUMBELS signs that are most commonly
observed in adults. Studies of pediatric organophosphate poisoning have yielded
the following results:

Lifshitz et al (1999) retrospectively examined 36 children aged 2-8 years

who were exposed to organophosphates or carbamates in Israel.[9] The
authors observed a decreased level of consciousness, including coma,
stupor, and hypotonicity in all children.

Zwiener and Ginsburg (1988) retrospectively examined 37 patients aged 1

month to 11 years who had been exposed to insecticides.[10] The most
common signs were miosis, excessive salivation, muscle weakness, and
lethargy. Approximately 49% of these children presented with tachycardia.

Lima and Reis (1995) reported carbamate poisoning in Rio de Janeiro.[11]

Symptoms included salivation, lacrimation, urination, defecation, GI
distress, and emesis (SLUDGE) and were more commonly observed in
adults than in children.

Sofer et al (1989) retrospectively examined 25 patients aged 3 months to 7

years with carbamate or organophosphate poisoning in Israel.[12] The
most common presenting symptoms were CNS depression, stupor, coma,
and flaccidity. The classic SLUDGE symptoms were more likely to be
absent in these children.

DDx

Diagnostic Considerations
Other diagnostic considerations in children with possible organophosphate toxicity
include toxicity due to various poisons, such as carbamates, phosgene, paraquat,
[13] and nerve agents, can cause symptoms similar to those of
organophosphates.

Differential Diagnoses
Animal Bites to the Head and Neck

Workup

Workup

Approach Considerations
the workup for suspected organophosphate toxicity in a pediatric patient includes
the following:

Obtain a complete blood cell count (CBC) to rule out infectious causes.

Chemistry tests may be useful in ruling out electrolyte disturbances.

Red blood cell (RBC) cholinesterase tests may reveal decreased activity,
which confirms the diagnosis

Chest radiography may be performed to evaluate pulmonary edema.

Nonenhanced head computed tomography (CT) scanning may be required

to assess structural lesions if the patient has an altered mental status.

Perform an electrocardiogram (ECG) to evaluate for cardiac arrhythmias.

Treatment

Medical Care
Prehospital care

Prehospital care includes the following:

Ensure airway support and ventilation and perform endotracheal intubation,

if necessary, in patients with respiratory failure.

Circulatory support with intravenous (IV) access, fluids, and cardiac and
pulse oximetry monitoring can facilitate safe transport.

Decontamination is of the utmost importance in minimizing continued

exposure and to protect providers and other patients from contamination.
Decontamination involves removing all of the patient's clothing and
washing him or her with water and soap.

By describing the scene, prevalent odors, or other casualties, prehospital

providers may provide important clues to the presence of exposure.

Emergency department care

Assess the patient's airway, breathing, and circulation (ABCs). Secure the airway
and perform cardiovascular resuscitation if needed. Endotracheal intubation may
be necessary for airway protection and ventilatory support.

If the patient's condition is stable, decontamination is the next priority. Patients

who are inadequately decontaminated may expose rescue personnel and hospital
staff to the toxin. Prehospital providers may also need decontamination. The
dermal decontamination of exposed individuals is a priority before they enter the
emergency department, where they can contaminate other patients and staff
members. Gastric decontamination with activated charcoal should be performed
in cases of ingestion.

Severe exposures require expeditious anticholinergic therapy. Atropine

antagonizes the central and muscarinic effects by blocking these receptors.
Atropine does not bind to nicotinic receptors; hence, muscular weakness,
including respiratory muscle weakness, is not affected.

Anticholinergic agents should be used in doses large enough to reverse the

cholinergic signs. Some authors recommend giving atropine until signs of
atropinization appears. These signs include warm, dry, flushed skin; dilated pupils;
and an increased heart rate.

Atropine should be used for at least 24 hours to reverse the cholinergic signs
while the organophosphate is metabolized.[14] Atropine is indicated when
evidence of bronchorrhea and other secretions is present.

Pralidoxime (2-PAM) is a cholinesterase reactivator and the antidote for

organophosphate poisoning. Administer 2-PAM to patients with organophosphate
exposure and signs of muscle and respiratory muscle weakness. This drug
primarily affects the nicotinic receptors and does not reverse the CNS effects.
Administer 2-PAM as soon as possible because its effectiveness decreases with
prolonged exposure due to the aging of the organophosphate-cholinesterase
bond.[15] Administer 2-PAM as an IV infusion after a loading dose until signs of
weakness improve.

Treat seizures that do not respond to 2-PAM with benzodiazepines. In

experimental models, midazolam effectively terminates seizures caused by
organophosphates; however, the efficacy of benzodiazepines decreases when
these drugs are given 30 minutes or more after organophosphate exposure or
seizure onset.[16]

In a child with acute, severe organophosphate poisoning that was unresponsive to

standard treatments, Yesilbas and colleagues reported successful treatment with
high-volume continuous venovenous hemodiafiltration and therapeutic plasma
exchange combined with lipid infusion.[17]

Avoid the use of morphine, caffeine, loop diuretics, theophylline, and

succinylcholine in patients with organophosphate poisoning because these drugs
can increase the toxicity of the exposure.

Consultations
See the list below:

Consult a medical toxicologist or poison control center personnel early in

the course of treatment.

Consult a critical care specialist early in severe poisonings for ongoing care
outside the emergency department.

Medication

Medication Summary
Anticholinergic agents are important for controlling the life-threatening effects of
organophosphate exposure. Initiate atropine therapy early to control secretions,
bronchoconstriction, bronchospasm, and gastrointestinal toxicity. Pralidoxime (2-
PAM) is an oxime that reactivates cholinesterase, restoring respiratory and
skeletal muscle strength. 2-PAM does not cross the blood-brain barrier; hence,
the central effects are not reversed.

Anticholinergic agents

Class Summary
These agents are thought to work centrally by suppressing conduction in the
vestibular cerebellar pathways. They may have an inhibitory effect on the
parasympathetic nervous system. Anticholinergic agents also improve conduction
through the AV node by reducing vagal tone by means of muscarinic receptor
blockade.

Atropine IV/IM
Competitive antagonist of acetylcholine and other muscarinic agonists. Competes
for common binding site on muscarinic receptor. Used to treat GI, pulmonary, and
upper airway symptoms after known or suspected organophosphate exposure.
Administer until cholinergic signs reverse. Large doses may be needed.

Cholinesterase reactivators

Class Summary
These medications are used as antidotes to reverse the inhibition of
acetylcholinesterase (AChE). The effectiveness of oxime compounds is attributed
to their 2-formyl-1-methylpyridinium ions.

2-PAM (Protopam)
Nucleophilic agent that reactivates phosphorylated AChE by binding to
organophosphate molecule. Used to treat muscle weakness and respiratory
muscle weakness in known or suspected exposure. Must be administered within
24 h, before organophosphate-cholinesterase bond ages. Earlier administered,
better result. Effects should occur within 20-30 min.

Because it does not substantially relieve respiratory center depression or

decrease muscarinic effects of AChE poisoning, concomitantly administer
atropine to block effects of organophosphate poison on these areas. Signs of
atropinization might occur earlier with addition of 2-PAM.

Follow-up

Further Outpatient Care

Patients with minor or no symptoms of toxicity after organophosphate exposure
may be discharged from the emergency department after 6 hours of observation.
Discharged patients usually do not require outpatient medications.

Further Inpatient Care

See the list below:

Admit patients to the hospital if they require therapy with anticholinergenic

agents or 2-PAM. Monitoring, respiratory support, and ventilation may be
needed.

Consult poison control center personnel for information regarding the

specific agent, the length of inpatient treatment, and the duration of likely
toxicity.

Transfer
See the list below:

Transfer pediatric patients with severe life-threatening exposures to a

facility with a pediatric intensivist and intensive care unit.

Patients should be clinically stable before their transfer.

Deterrence/Prevention
Parents sould be educate regarding the following:

Use of safety lids on accessible containers of pesticides

Proper storage of chemicals in the home

On a societal level, legislation regarding the sale and storage of dangerous

chemicals can be effective in reducing organophosphate poisoning.

Complications
Intermediate syndrome can develop 24-96 hours after exposure.[18, 19] A
combination of presynaptic and postsynaptic impairment of neuromuscular
transmission probably causes the syndrome. Features of intermediate syndrome
as as follows:

The syndrome tends to occur in patients with prolonged exposure before

treatment.
The syndrome is characterized by weakness in the motor cranial nerves,
proximal limb muscles, neck flexors, and respiratory muscles.
A delayed peripheral neuropathy may develop days to weeks after the
exposure.

Patients may also have persistent CNS effects, weakness, lethargy,

fatigue, and memory impairment.[20]

Shahar et al reported extrapyramidal parkinsonism as a complication of acute

organophosphate poisoning.[21, 22] Symptoms developed 5 days after exposure
and completely resolved after treatment with amantadine

Prognosis
See the list below:

The prognosis for patients treated early is excellent; most patients fully
recover in 7-10 days.

Patients with toxicity untreated for more than 24 hours may have a
prolonged and severe course with lasting neurologic complications.[23]

Contributor Information and Disclosures

Author

William Freudenthal, MD Staff Physician, Department of Emergency Medicine,

St Vincent Hospital

William Freudenthal, MD is a member of the following medical societies: American

College of Emergency Physicians, Association of Military Surgeons of the US

Disclosure: Nothing to disclose.

Coauthor(s)

Mark E Ralston, MD, MPH Staff Pediatrician, Naval Hospital Oak Harbor;
Assistant Professor of Pediatrics, F Edward Hebert School of Medicine,
Uniformed Services University of the Health Sciences

Mark E Ralston, MD, MPH is a member of the following medical societies:

American Academy of Pediatrics

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska

Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Jeffrey R Tucker, MD Assistant Professor, Department of Pediatrics, Division of

Emergency Medicine, University of Connecticut School of Medicine, Connecticut
Children's Medical Center

Disclosure: Received salary from Merck for employment.

Chief Editor

Stephen L Thornton, MD Associate Clinical Professor, Department of

Emergency Medicine (Medical Toxicology), University of Kansas Hospital; Medical
Director, University of Kansas Hospital Poison Control Center; Staff Medical
Toxicologist, Children’s Mercy Hospital

Stephen L Thornton, MD is a member of the following medical societies: American

Academy of Clinical Toxicology, American College of Emergency Physicians,
American College of Medical Toxicology

Disclosure: Nothing to disclose.

Additional Contributors

Michael E Mullins, MD Assistant Professor, Division of Emergency Medicine,

Washington University in St Louis School of Medicine; Attending Physician,
Emergency Department, Barnes-Jewish Hospital

Michael E Mullins, MD is a member of the following medical societies: American

Academy of Clinical Toxicology, American College of Emergency Physicians

Disclosure: Received stock ownership from Johnson & Johnson for none;
Received stock ownership from Savient Pharmaceuticals for none.

Timothy E Corden, MD Associate Professor of Pediatrics, Co-Director, Policy

Core, Injury Research Center, Medical College of Wisconsin; Associate Director,
PICU, Children's Hospital of Wisconsin

Timothy E Corden, MD is a member of the following medical societies: American

Academy of Pediatrics, Phi Beta Kappa, Society of Critical Care Medicine,
Wisconsin Medical Society

Disclosure: Nothing to disclose.

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