Organophosphate and Carbamate Toxicosis BASIC INFORMATION DEFINITION Organophosphates and carbamates are cholinesterase-inhibiting chemicals. Organophosphates include dichlorvos, ronnel, diazinon, chlorpyrifos, and phosmet, and carbamates include carbaryl, aldicarb, methomyl, and carbofuran. Many other organophosphates and carbamates exist.
SYNONYM(S) Organophosphates have been called organic phosphates, phosphorus insecticides, and nerve gas relatives.
EPIDEMIOLOGY SPECIES, AGE, SEX Organophosphates and carbamates inhibit the enzyme cholinesterase, which is used by the nervous system of all mammals. All animals are affected, so there is no species, age, or sex predilection. RISK FACTORS Farm animals are at a higher risk because of the common use of these chemicals in a farm setting. GEOGRAPHY AND SEASONALITY The organophosphates and carbamates are used as insecticides, so more of the compounds are used in the warmer months, but exposure can occur year round. Rural areas can be more at risk than urban environments.
CLINICAL PRESENTATION DISEASE FORMS/SUBTYPES There is great variation in the types of clinical signs observed from an excessive dose of either of these groups of compounds.
Many times these compounds are so potent that animals will be found dead with no previous signs of illness. HISTORY, CHIEF COMPLAINT Acute death may be the chief complaint. The history often indicates exposure to these two classes of chemicals because insecticides were being used or animals gained access to these chemicals inadvertently. PHYSICAL EXAM FINDINGS • The clinical signs observed are associated with muscarinic, nicotinic, and central nervous system (CNS) stimulation. • Muscarinic receptor–associated effects include salivation, lacrimation, urination, diarrhea, miosis (pinpoint pupils), and lung edema. • Bradycardia, bronchoconstriction, and bronchorrhea may also be observed. • Nicotinic receptor–associated effects are related to the stimulation of autonomic ganglia and skeletal muscles. The clinical signs of nicotinic stimulation include muscle twitching, tremors, and seizures. • CNS stimulation can cause depression, hyperactivity, and seizures. ETIOLOGY AND PATHOPHYSIOLOGY • Organophosphates and carbamates inhibit the enzyme acetylcholinesterase, which is within nerve tissue and at neuromuscular junctions. Acetylcholinesterase destroys the neurotransmitter acetylcholine. • When the acetylcholine concentrations increase in nerve tissue or at the neuromuscular junction, the acetylcholine receptors become overstimulated.
• The cholinergic system is widely distributed within the CNS and peripheral nervous system. There is a wide range in clinical signs when the cholinergic system is upregulated.
DIAGNOSIS DIFFERENTIAL DIAGNOSIS Differential diagnosis includes exposure to stimulants and compounds with mixed effects on the CNS such as: • Lead • Mercury • Carbon disulfide • Ivermectin • Ionophores • Plant toxins such as fumonisins, yellow star thistle poisoning, marijuana, and sleepy grass, as well as others
INITIAL DATABASE • A history of exposure to an organophosphate or carbamate insecticide within 24 hours before the onset of clinical signs is usually enough to begin treatment with atropine. • Usually there is not enough time to measure acetylcholinesterase values in whole blood before initiation of treatment. Response to treatment with atropine helps confirm an excess exposure to an organophosphate or carbamate. • Many times an animal will exhibit clinical signs compatible with an organophosphate or carbamate toxicosis but the history is not complete, and there is no time to evaluate acetylcholinesterase activity. In these
Organophosphate and Carbamate Toxicosis cases, a test dose of atropine can be used to rule in or rule out organophosphate or carbamate toxicosis. After a low dose of atropine (0.02 mg/kg IV), if an organophosphate or carbamate toxicosis has not occurred, the pupils will dilate, salivation will stop within 15 minutes, and the heart rate will increase dramatically. If none of the clinical signs decrease in severity, this indicates a probable organophosphate or carbamate toxicosis, and a therapeutic dose of atropine can be used.
ADVANCED OR CONFIRMATORY TESTING • Measurement of acetylcholinesterase activity in whole blood or the brain will help rule in or out exposure to organophosphates or carbamates. • Stomach content, hair, grain, hay, or suspected baits can be analyzed for the presence of organophosphates or carbamates. • There are no specific micropathologic lesions associated with these compounds because death is rapid.
TREATMENT THERAPEUTIC GOAL(S) Activate acetylcholinesterase in the body, remove the organophosphate or carbamate and provide symptomatic care.
ACUTE GENERAL TREATMENT • Initial treatment for exposure to excessive amounts of organophosphates and carbamates is to administer atropine. The recommended dosage of atropine is somewhat controversial, and no one standard dosage is accepted by all. The dosage of atropine for treatment of organophosphates and carbamates is higher than the dosage used for other conditions because the drug must outcompete acetylcholinesterase that has accumulated at receptor sites. One suggested regimen is to administer atropine at a dosage of 0.2 mg/kg, dosing 25% of the dose IV with the remainder given IM or SC. However, this can potentially result in ileus, causing serious complications in horses.
Another method of administration designed to avoid ileus involves diluting the calculated dosage of atropine in saline and administering the diluted solution slowly IV while ausculting the abdomen. The suggested dose range is 0.02 to 0.2 mg/ kg given to effect with the endpoint of treatment based on improvement of respiratory signs. Administration should be stopped before any decrease in gastrointestinal (GI) motility occurs. Treating until salivation stops can potentially result in atropine toxicity. Also remember that atropine will not reverse nicotinic signs, so muscle tremors will not diminish with atropine treatment. Repeated doses of atropine may be given every few hours if needed to effect. • Oximes such as 2-PAM (protopam chloride or pralidoxime chloride) may be used as ancillary therapy for organophosphate exposure but not carbamate exposure. 2-PAM can be dosed at 20 mg/kg given IV and repeated at 4- to 6-hour intervals. • As soon as the horse is stabilized, activated charcoal should also be used at a dose of 250 g in foals and 750 g in adults. This amount of activated charcoal should be suspended in water to make a slurry. Up to 4 L of water can be used in adults. The water should be warm and the mixture administered with a stomach tube. The mixture should be left in the stomach for 20 to 30 minutes, and then a laxative can be given to move this mixture out of the GI tract. • Gastric lavage can be used but is more problematic. • Dermally exposed animals should be washed with soap and water.
DRUG INTERACTIONS Morphine, physostigmine, phenothiazine tranquilizers, pyridostigmine, neostigmine, and succinyl chloride can interfere with cholinesterase activity and should be avoided.
POSSIBLE COMPLICATIONS Ileus may occur after treatment with atropine.
RECOMMENDED MONITORING The degree of salivation, pupillary size, respiratory signs, intestinal motility, and heart rate can all be monitored to evaluate treatment success.
PROGNOSIS AND OUTCOME Early treatment is effective and the prognosis is good. Some organophosphates and carbamates are so potent that treatment has to be within minutes to hours to be effective. Treatment may be needed for up to 48 hours postexposure with supportive care needed for days.
PEARLS & CONSIDERATIONS COMMENTS Atropine will not reverse the clinical signs associated with nicotinic stimulation.
PREVENTION Use caution when applying insecticides. Keep all chemicals safely stored away from animals and remove chemicals from barns and sheds where animal can gain access.
CLIENT EDUCATION Remind clients that repeated applications of organophosphate or carbamate insecticides for fly control can potentially be problematic.
SUGGESTED READING Blodgett DJ: Organophosphate and carbamate insecticides. In Peterson ME, Talcott PA (eds). Small animal toxicology, St Louis, 2006, Elsevier, pp 941–955. Meerdink GL: Anticholinesterase Insecticides. In Plumlee KH (ed). Clinical veterinary toxicology, St Louis, 2004, Mosby Elsevier, pp 178–180. Plumb DC: Veterinary drug handbook, Ames, IA, 2002, Iowa State University Press. AUTHOR: STEVE ENSLEY EDITOR: CYNTHIA L. GASKILL