Comment submitted by B. Sachau

public comment on federal register of 8/2/06 vol 71 #148 pg 43740 docket 2006 0618 frl 8082-5 organophosphate i do not approve of any use of this product at all ever. i think it is time epa stopped using the american public and mother earth as sites for poisoning. i think their allowance of far too pervasive toxics is clear far too often. this use should be banned. we simply cannot risk the use of this product in my opinion. You are in: eMedicine Specialties > Medicine, Ob/Gyn, Psychiatry, and Surgery > Critical Care Toxicity, Organophosphate Last Updated: August 7, 2004 Rate this Article Email to a Colleague Get CME/CE for article Synonyms and related keywords: organophosphate poisoning, OP compounds, insecticides, malathion, parathion, diazinon, fenthion, dichlorvos, chlorpyrifos, nerve gases, soman, sarin, tabun, VX, ophthalmic agents, echothiophate, isoflurophate, trichlorfon, herbicides, industrial chemicals AUTHOR INFORMATION Section 1 of 11 Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography Author: Marina C Furtado, MD, Staff Physician, Department of Emergency Medicine, University Medical Center, University of Arizona Coauthor(s): Lisa Chan, MD, Associate Program Director, Department of Emergency Medicine, University of Arizona Marina C Furtado, MD, is a member of the following medical societies: American College of Emergency Physicians Editor(s): Lisa Kirkland, MD, Senior Associate Consultant, Department of Internal Medicine, Division of Area Internal Medicine, Mayo Clinic, Rochester; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Om Prakash Sharma, MD, Professor, Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Southern California; Timothy D Rice, MD, Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, Saint Louis University School of Medicine; and Michael R Pinsky, MD, Professor of Critical Care Medicine, Bioengineering, Anesthesiology, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center Disclosure INTRODUCTION Section 2 of 11 Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography Background: Organophosphate (OP) compounds are a diverse group of chemicals used in both domestic and industrial settings. Examples of OPs include insecticides (malathion, parathion, diazinon, fenthion, dichlorvos, chlorpyrifos), nerve gases (soman, sarin, tabun, VX), ophthalmic agents (echothiophate, isoflurophate), and antihelmintics (trichlorfon). Herbicides (tribufos [DEF], merphos) are tricresyl phosphate?containing industrial chemicals. OP compounds were first synthesized in the early 1800s when Lassaigne reacted alcohol with phosphoric acid. Shortly thereafter in 1854, Philip de Clermount described the synthesis of tetraethyl pyrophosphate at a meeting of the French Academy of Sciences. Eighty years later, Lange, in Berlin, and, Schrader, a chemist at Bayer AG, Germany, investigated the use of OPs as insecticides. However, the German military prevented the use of OPs as insecticides and instead developed an arsenal of chemical warfare agents (ie, tabun, sarin, soman). A fourth agent, VX, was synthesized in England a decade later. During World War II, in 1941, OPs were reintroduced worldwide for pesticide use, as originally intended. Massive OP intoxication from suicidal and accidental events, such as the Jamaican ginger palsy incident in 1930, led to discovery of the mechanism of action of OPs. In 1995, a religious sect, Aum Shinrikyo, used sarin to poison people on a Tokyo subway. Pathophysiology: The primary mechanism of action of OP pesticides is inhibition of acetylcholinesterase (AChE). AChE is a neurotransmitter found in the CNS and the peripheral nervous system, and its normal physiologic action is to break down acetylcholine (ACh). OPs inactivate AChE by phosphorylating the serine hydroxyl group located at the active site of AChE. The phosphorylation occurs by loss of an OP leaving group and establishment of a covalent bond with AChE. Once AChE has been inactivated, ACh accumulates throughout the autonomic nervous system, the somatic nervous system, and the brain, resulting in overstimulation of the muscarinic and nicotinic receptors. The preganglionic and postganglionic neurons in the parasympathetic nervous system release ACh. Postganglionic ACh acts on muscarinic receptors on the heart, eyes, glands, GI tract, and respiratory system. Somatic motor axons emerge from the spinal cord and directly innervate muscle cells at the neuromuscular junction, releasing ACh on nicotinic receptors. The brain and spinal cord both contain muscarinic and nicotinic receptors. The brain is richer in muscarinic receptors, whereas the spinal cord has relatively more nicotinic receptors. Cholinergic pathways in the brain are associated with various behaviors and functions, including hunger, thirst, thermoregulation, respiration, aggression, and cognition. Once an OP binds to AChE, the enzyme can undergo 3 processes, including (1) endogenous hydrolysis of the phosphorylated enzyme by esterases or paraoxonases, (2) reactivation by a strong nucleophile such as pralidoxime (2- PAM), and (3) biological changes that render the phosphorylated enzyme inactive (aged). OPs can be absorbed cutaneously, or they can be ingested or inhaled. Although most patients become symptomatic 12 hours after exposure, onset and duration of action depend on the nature and type of compound, the degree and route of exposure, the mode of action of the compound, lipid solubility, and rate of metabolic degradation. Frequency: In the US: The American Association of Poison Control Centers' National Incidence Report indicates that pesticide injuries number 70,000-80,000 annually. Nationwide, 3.9% of poisonings are due to insecticides. Internationally: Pesticide poisonings are the most common mode of suicide in some developing countries (eg, Sri Lanka). Mortality/Morbidity: Worldwide mortality studies report mortality rates from 3-25%. The compounds involved most frequently are malathion, dichlorvos, trichlorfon, and fenitrothion/malathion. Mortality rates depend on the type of compound used, amount ingested, general health of the patient, delay in discovery and transport, insufficient respiratory management, delay in intubation, and failure in weaning off ventilatory support. Complications include respiratory distress, seizures, and aspiration pneumonia. Respiratory failure is the most common cause of death. Age: A study by Emerson et al found that men aged 30-50 years were more likely to attempt suicide with OPs. In the study, 68 of the 69 patients were men. Agarwal found that most OP poisonings occur in patients aged 21-30 years. The male-to-female ratio in the study was 2.1:1. Both Emerson and Agarwal found that accidental poisoning was more likely in children than in adults. CLINICAL Section 3 of 11 Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography History: Signs and symptoms of OP poisoning can be divided into 3 broad categories, including (1) muscarinic effects, (2) nicotinic effects, and (3) CNS effects. Muscarinic effects by organ systems include the following: Cardiovascular - Bradycardia, hypotension Respiratory - Rhinorrhea, bronchospasm, bronchorrhea, cough Gastrointestinal - Increased salivation, nausea and vomiting, abdominal pain, diarrhea, and fecal incontinence Genitourinary - Urinary incontinence Ocular - Blurred vision, miosis Glands - Increased lacrimation, increased sweating Mnemonic devices used to remember the muscarinic effects of OPs are SLUDGE (salivation, lacrimation, urination, diarrhea, GI upset, emesis) and DUMBELS (diaphoresis and diarrhea; urination; miosis; bradycardia, bronchospasm, bronchorrhea; emesis; lacrimation excess; salivation excess). Nicotinic signs and symptoms include muscle fasciculations, cramping, weakness, and diaphragmatic failure. Autonomic nicotinic effects include hypertension, tachycardia, pupillary dilation, and pallor. CNS effects include anxiety, restlessness, confusion, ataxia, seizures, insomnia, dysarthria, tremors, and coma. Physical: Vital signs Depressed respiratory rate, bradycardia, and hypotension are common. Hypothermia also can be observed. Paralysis Type I - Acute paralysis secondary to persistent depolarization at the neuromuscular junction Type II (intermediate syndrome) - Intermediate syndrome was described in 1974, with an incidence from 8-49%. It develops 24-96 hours after resolution of acute cholinergic poisoning symptoms and manifests commonly as paralysis and respiratory distress. This syndrome involves proximal muscle groups, with relative sparing of distal muscle groups. Various degrees of cranial nerve palsies also are observed. Neuromuscular transmission defect and toxin-induced muscular instability play a role in intermediate syndrome. Intermediate syndrome persists for 4-18 days, can require intubation, and can be complicated by infections or cardiac arrhythmias. Type III - Organophosphate-induced delayed polyneuropathy (OPIDP) occurs 2-3 weeks after exposure to large doses of certain OPs. Distal muscle weakness with relative sparing of the neck muscles, cranial nerves, and proximal muscle groups characterize OPIDP. Recovery can take up to 12 months. Neuropsychiatric effects - Impaired memory, confusion, irritability, lethargy, psychosis, and chronic OP-induced neuropsychiatric disorder Extrapyramidal effects - Dystonia, cogwheel rigidity Other neurological and/or psychological effects - Guillain-Barr?like syndrome, isolated bilateral recurrent laryngeal nerve palsy Ophthalmic effects - Optic neuropathy, retinal degeneration, defective vertical smooth pursuit, myopia, and miosis (due to direct ocular exposure to OPs) Ears - Ototoxicity Respiratory effects - Muscarinic, nicotinic, and central effects contribute to respiratory distress in acute and delayed OP toxicity. Muscarinic effects, such as bronchospasm and laryngeal spasm, can lead to airway obstruction. Nicotinic effects lead to weakness and paralysis of respiratory oropharyngeal muscles. Central effects can lead to cessation of respiration. Rhythm abnormalities - Sinus tachycardia, sinus bradycardia, extrasystoles, atrial fibrillation, ventricular tachycardia, and ventricular fibrillation Other cardiovascular effects - Hypotension, hypertension, and noncardiogenic pulmonary edema GI manifestations such as nausea, vomiting, diarrhea, and abdominal pain are the first to occur after OP exposure. Genitourinary and/or endocrine effects - Urinary incontinence, hypoglycemia or hyperglycemia Causes: In a study of OP poisoning in India, Agarwal found that 67.4% of patients had suicidal intentions, 16.8% of the poisonings were caused by occupational exposures, and 15.8% of patients were poisoned accidentally. An Australian study of OP poisoning performed by Emerson found that only 36% of patients had suicidal intentions compared to 65-75% in developing countries. Job exposure matrices (JEMs) are used widely in occupation epidemiology when biological and environmental monitoring data are scant. DIFFERENTIALS Section 4 of 11 Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography Gastroenteritis, Viral Toxicity, Mushroom Other Problems to be Considered: Carbamate Nicotine Carbachol Methacholine Arecoline Bethanechol Pilocarpine Mushroom poisoning Myasthenia gravis Eaton-Lambert syndrome Guillain-Barr? syndrome Quick Find Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography Laboratory diagnosis of OP poisoning is based on the measurement of cholinesterase activity. Both erythrocyte and plasma cholinesterase levels can be used. Urinary paranitrophenol can be measured in parathion poisoning. Depressed cholinesterase levels only confirm the diagnosis of OP poisoning retrospectively because testing requires approximately 4-7 weeks. Draw blood for measurement of RBC count and plasma cholinesterase levels prior to treatment with 2-PAM. Erythrocyte AChE represents the AChE found in CNS gray matter, RBCs, and peripheral nerve, tissue, muscle, and brain. Plasma cholinesterase is a liver acute phase protein that circulates in the blood plasma. It is found in CNS white matter, the pancreas, and the heart. Erythrocyte cholinesterase is the more accurate of the 2 measurements, but plasma cholinesterase is easier to assay and is more widely available. Mild poisoning is defined as depression in cholinesterase activity to 20-50% of normal. Moderate poisoning occurs when activity is 10-20% of normal. Severe poisoning occurs at less than 10% of cholinesterase enzyme activity. Small short- term exposures can depress cholinesterase activity to very low levels with minimal symptoms. Levels do not always correlate with clinical illness. The level of cholinesterase activity is relative and is based on population estimates. Neonates and infants have baseline levels that are lower than those in adults. Because most patients do not know their baseline level, the diagnosis can be confirmed by observing a progressive increase in the cholinesterase value until the values plateau over time. Falsely depressed levels of RBC cholinesterase can be found in cases of pernicious anemia, hemoglobinopathies (eg, sickle cell anemia, thalassemia), use of antimalarial drugs, and use of oxalate blood tubes. Falsely depressed levels of plasma cholinesterase are observed in cases of liver dysfunction (eg, cirrhosis), low protein conditions (eg, malnutrition), neoplasia, and infectious hypersensitivity reactions. In addition, the use of drugs such as succinylcholine, codeine, and morphine renders falsely depressed plasma cholinesterase levels. The first and second trimesters of pregnancy and genetic deficiency of plasma cholinesterase are other causes. Other laboratory findings include leukocytosis with a normal differential consistent with a stress reaction, increased hematocrit from hemoconcentration due to fluid losses, anion gap acidosis due to poor tissue perfusion and hyperglycemia with hypokalemia, and hypomagnesemia due to catecholamine excess. Hydration status determines blood urea nitrogen, creatinine, and urine specific gravity. Other Tests: ECG findings - Prolonged QTc interval (most common, up to 67%), elevated ST segments, inverted T waves, prolonged PR interval TREATMENT Section 6 of 11 Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography Medical Care: Secure the patient's airway. Intubation might be necessary in cases of respiratory distress from laryngospasm, bronchospasm, or severe bronchorrhea. Monitor neck muscle weakness, respiratory rate, arterial blood gas, and mental status regularly to assess progression or decompensation. The tidal volume initiated by the patient can be used as a measure of disease severity in patients who are intubated. Withhold administration of atropine until a cardiac monitor and a defibrillator are in place and until the patient's airway is secured. Atropine can precipitate ventricular fibrillation in hypoxic patients. Continuous cardiac monitoring and an ECG are necessary. Electrical pacing is the treatment of choice for ventricular tachycardia associated with a prolonged QTc. Atropine can reverse some cardiac manifestations. Electrolyte abnormalities might cause dysrhythmias. Strip and gently cleanse patients with suspected OP exposure with soap and water because OPs are hydrolyzed readily in aqueous solutions with a high pH. Consider clothing hazardous waste and discard accordingly. Ethyl alcohol has been used to wash intact skin to prevent further absorption of the OP compound through the skin. Healthcare providers must avoid contaminating themselves while handling patients. Use personal protective equipment, such as neoprene or nitrile gloves and gowns, when decontaminating patients because hydrocarbons can penetrate nonpolar substances such as latex and vinyl. Use charcoal cartridge masks for respiratory protection when decontaminating patients. Irrigate the eyes of patients with ocular exposures using isotonic sodium chloride solution or lactated Ringer's solution. Morgan lenses can be used for eye irrigation. Activated charcoal (0.5-1 g q4h) is used for gastric decontamination. Sorbitol can be used; however, many patients have increased GI motility following OP poisoning. MEDICATION Section 7 of 11 Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography The mainstay of medical therapy in OP poisoning is atropine or glycopyrrolate, 2- PAM, and diazepam, which can be used for seizure control. In 1991, De Silva studied the treatment of OP poisoning with atropine and 2-PAM and, later the same year, with atropine alone. He found that atropine seemed to be as effective as atropine plus 2-PAM in the treatment of acute OP poisoning. The controversy continued when other authors observed more respiratory complications and higher mortality rates with use of high-dose 2-PAM. Low-dose (1-2 g slow IV) 2-PAM is the current recommendation. Studies are underway to assess the role of low-dose 2-PAM. Drug Category: Anticholinergic agents -- Believed to work centrally by suppressing conduction in the vestibular cerebellar pathways. They may have an inhibitory effect on the parasympathetic nervous system.Drug Name Atropine (Isopto, Atropair) -- Initiated in patients who manifest muscarinic symptoms with OP toxicity. Competitive inhibitor at autonomic postganglionic cholinergic receptors, including receptors found in GI and pulmonary smooth muscle, exocrine glands, heart, and eye. Place the patient on a cardiac monitor, have a defibrillator in the room, and secure patient's airway before administering atropine because it can cause cardiac dysrhythmias. The endpoints for atropinization are heart rate >100 beats/min, midsized pupils, and present bowel sounds. Adult Dose 1-2 mg IV bolus, repeat 2 mg IV q5-15min prn to relieve muscarinic symptoms Atropine drip titrated to the above endpoints can be initiated until patient's condition is stabilized Pediatric Dose 0.05 mg IV, repeat q10-30min prn to relieve muscarinic symptoms; maintenance dose 0.02-0.05 mg/kg Contraindications Documented hypersensitivity; thyrotoxicosis; narrow-angle glaucoma; tachycardia Interactions Coadministration with other anticholinergics has additive effects; pharmacologic effects of atenolol and digoxin might increase; antipsychotic effects of phenothiazines might decrease; tricyclic antidepressants with anticholinergic activity might increase effects of atropine Pregnancy C - Safety for use during pregnancy has not been established. Precautions Avoid in patients with Down syndrome and/or children with brain damage to prevent hyperreactive response; avoid in coronary heart disease, tachycardia, CHF, cardiac arrhythmias, and hypertension; caution in peritonitis, ulcerative colitis, hepatic disease, and hiatal hernia with reflux esophagitis; in prostatic hypertrophy, prostatism can cause dysuria and might require catheterization Drug Name Glycopyrrolate (Robinul) -- Indicated for use as an antimuscarinic agent to reduce salivary, tracheobronchial, and pharyngeal secretions. Acts in smooth muscle, CNS, and secretory glands, where blocks action of ACh at parasympathetic sites. Reduces volume and acidity of gastric secretions. Blocks cardiac vagal inhibitory reflexes. Unlike atropine, does not cross the blood-brain barrier. Adult Dose 0.1 mg IV q3-4h prn to reverse muscarinic effects Pediatric Dose 4-10 mcg/kg IV q3-4h prn to reverse muscarinic effects; not to exceed 0.2 mg/dose or 0.8 mg q24h Contraindications Documented hypersensitivity; narrow-angle glaucoma; tachycardia; ulcerative colitis; paralytic ileus; acute hemorrhage Interactions Levodopa decreases effects; amantadine and cyclopropane increase glycopyrrolate toxicity Pregnancy C - Safety for use during pregnancy has not been established. Precautions Might produce blurred vision, cycloplegia, increased intraocular tension, xerostomia, decreased sweating, palpitations, nausea, vomiting, constipation, bloating, urinary hesitancy and retention, impotence, suppression of lactation, headaches, nervousness, confusion, weakness, drowsiness, insomnia, rash, urticaria, or anaphylaxis; might increase chances of developing megacolon, hyperthyroidism, CHF, CAD, hiatal hernia, and BPH; not recommended for children <12 y or patients with Down syndrome Drug Category: Antidotes, OP poisoning -- Reverse muscle paralysis with toxic exposure to OP poisoning.Drug Name Pralidoxime (2-PAM, Protopam) -- Nucleophilic agent that reactivates the phosphorylated AChE by binding to the OP molecule. Used as an antidote to reverse muscle paralysis resulting from OP AChE pesticide poisoning but is not effective once the OP compound has bound AChE irreversibly. Current recommendation is administration within 48 h of OP poisoning. Because it does not relieve depression of respiratory center significantly or decrease muscarinic effects of AChE poisoning, administer atropine concomitantly to block effects of OP poison on these areas. Signs of atropinization might occur earlier with addition of 2-PAM to treatment regimen. Adult Dose 1-2 g IV in 100 mL isotonic sodium chloride soln/D5W over 15-30 min; repeat in 1 h if muscle weakness is not relieved; then repeat q3-8h if signs of poisoning recur Pediatric Dose 20-40 mg/kg IV in 100 mL isotonic sodium chloride soln/D5W over 15-30 min; repeat in 1-2 h if muscle weakness not relieved; then repeat q10-12h prn to relieve cholinergic symptoms IM/SC can be used if IV is not feasible; can be used with atropine Contraindications Documented hypersensitivity Interactions Use barbiturates with caution because action of barbiturates is potentiated by AChE inhibitors; antagonism with neostigmine, pyridostigmine, and edrophonium; morphine, theophylline, aminophylline, succinylcholine, reserpine, and phenothiazines can worsen condition of patients poisoned by OP insecticides or nerve agents (do not administer) Pregnancy C - Safety for use during pregnancy has not been established. Precautions Rapid injection can cause tachycardia, laryngospasm, muscle rigidity, pain at the injection site, blurred vision, diplopia, impaired accommodation, dizziness, drowsiness, nausea, tachycardia, hypertension, and hyperventilation; can precipitate myasthenia crisis in patients with myasthenia gravis and muscle rigidity in healthy volunteers; decrease in renal function will increase drug levels in the blood because 2-PAM is excreted in the urine; can produce transient elevation in creatine phosphokinase; 1 of 6 patients will have an elevation in SGOT and/or SGPT Drug Category: Benzodiazepines -- By binding to specific receptor sites, these agents appear to potentiate the effects of gamma-aminobutyrate (GABA) and facilitate inhibitory GABA neurotransmission and other inhibitory transmitters.Drug Name Diazepam (Valium, Diastat, Diazemuls) -- For treatment of seizures. Depresses all levels of CNS (eg, limbic and reticular formation) possibly by increasing activity of GABA. Adult Dose 5-15 mg IV q5min, repeat prn; not to exceed 30 mg q8h Pediatric Dose 0.05-0.3 mg/kg/dose IV/IM over 2-3 min q15-30min, repeat in 2-4 h prn; not to exceed 10 mg Contraindications Documented hypersensitivity; narrow-angle glaucoma Interactions Increases toxicity of benzodiazepines in CNS with coadministration of phenothiazines, barbiturates, alcohols, and MAOIs Pregnancy D - Unsafe in pregnancy Precautions Caution with other CNS depressants, low albumin levels, or hepatic disease (might increase toxicity) FOLLOW-UP Section 8 of 11 Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography Further Inpatient Care: Because of risk of development of respiratory depression or intermediate syndrome after resolution of an acute cholinergic crisis, hospitalizing all symptomatic patients for at least 4-6 days following resolution of symptoms is recommended. Some sources suggest that asymptomatic patients can be discharged from the emergency department (ED) after decontamination and 6 hours of observation. Follow-up care must be certain. Following occupational exposure, patients should not be allowed to work with OPs until serum cholinesterase activity returns to 75% of the known baseline level. Deterrence/Prevention: Health care providers must avoid contaminating themselves while handling patients poisoned by OPs. Use personal protective equipment, such as neoprene or nitrile gloves and gowns, when decontaminating patients because hydrocarbons can penetrate nonpolar substances such as latex and vinyl. Use charcoal cartridge masks for respiratory protection when decontaminating patients. Complications: Complications include respiratory distress, seizures, and aspiration pneumonia. Patient Education: For excellent patient education resources, visit eMedicine's Poisoning - First Aid and Emergency Center and Bioterrorism and Warfare Center. Also, see eMedicine's patient education articles Poisoning, Activated Charcoal, Poison Proofing Your Home, Chemical Warfare, and Personal Protective Equipment. MISCELLANEOUS Section 9 of 11 Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography Medical/Legal Pitfalls: Because of the risk of development of respiratory depression or intermediate syndrome after resolution of an acute cholinergic crisis, hospitalizing all symptomatic patients for at least 4-6 days following resolution of symptoms is recommended. Some sources suggest that asymptomatic patients can be discharged from the ED after decontamination and 6 hours of observation. Follow-up care must be certain, and failure to follow up is a potential pitfall. As stated in Differentials, the symptoms of OP poisoning can mimic other toxidromes and diseases. The clinician must keep in mind that misdiagnosis is a potential medical/legal pitfall. PICTURES Section 10 of 11 Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography Caption: Picture 1. Chemical Terrorism Agents and Syndromes. Signs and symptoms. Chart courtesy of North Carolina Statewide Program for Infection Control and Epidemiology (SPICE), copyright University of North Carolina at Chapel Hill, www.unc.edu/depts/spice/chemical.html. Picture Type: Image BIBLIOGRAPHY Section 11 of 11 Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Pictures Bibliography Aaron CK, Howland MA: Insecticides: Organophosphates and carbamates. In: Goldfrank LR, Flomenbaum NE, Lewin NA, Weisman RS, Howland MA, Hoffman RS, eds. Goldfrank's Toxicologic Emergencies. 6th ed. Stamford, Ct: Appleton & Lange; 1429-48. 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Emerson GM, Gray NM, Jelinek GA: Organophosphate poisoning in Perth, Western Australia, 1987-1996. J Emerg Med 1999 Mar-Apr; 17(2): 273-7[Medline]. Johnson S, Peter JV, Thomas K: Evaluation of two treatment regimens of pralidoxime (1 gm single bolus dose vs 12 gm infusion) in the management of organophosphorus poisoning. J Assoc Physicians India 1996 Aug; 44(8): 529-31 [Medline]. Khurana D, Prabhakar S: Organophosphorus intoxication. Arch Neurol 2000 Apr; 57(4): 600-2[Medline]. London L, Myers JE: Use of a crop and job specific exposure matrix for retrospective assessment of long-term exposure in studies of chronic neurotoxic effects of agrichemicals. Occup Environ Med 1998 Mar; 55(3): 194-201[Medline]. Matkevich VA, Simonenkov AP, Ostapenko IuN, et al: [Use of serotonin adipinate in acute oral poisoning]. Anesteziol Reanimatol 1995 May-Jun; (3): 16-20 [Medline]. Mileson BE, Chambers JE, Chen WL: Common mechanism of toxicity: a case study of organophosphorous pesticides. Toxicol Sci 1998 Jan; 41(1): 8-20 [Medline]. Moretto A: Experimental and clinical toxicology of anticholinesterase agents. Toxicol Lett 1998 Dec 28; 102-103: 509-13[Medline]. Peter JV, Cherian AM: Organic insecticides. Anaesth Intensive Care 2000 Feb; 28 (1): 11-21[Medline]. Wagner SL: Diagnosis and treatment of organophosphate and carbamate intoxication. Occup Med 1997 Apr-Jun; 12(2): 239-49[Medline]. Yamashita M, Yamashita M, Tanaka J: Human mortality in organophosphate poisonings. Vet Hum Toxicol 1997 Apr; 39(2): 84-5[Medline]. NOTE: 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 journal 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 article do not warrant the information in this article is accurate or complete, nor are they responsible for omissions or errors in the article or for the results of using this information. The reader should confirm the information in this article from other sources prior to use. In particular, all drug doses, indications, and contraindications should be confirmed in the package insert. FULL DISCLAIMER Toxicity, Organophosphate excerpt it is my opinion that this kind of risk cannot be assumed for the continued use of this product. b. sachau 15 elm st florham park nj 07932