Pediatric Organophosphates Toxicity
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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).
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]
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.
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]
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.
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.
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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.
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.
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.
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.
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.
Pediatric Organophosphates Toxicity
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