eMedicine Specialties > Neurology > Neurotoxicology
Organophosphates: Treatment & Medication
Updated: Oct 12, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
The patient exposed to organophosphates often arrives at the hospital with cutaneous contamination. The clothing should be removed and discarded. All traces of residue must be removed by careful washing with alkaline soap or bleach solution.
- Laboratory studies should be drawn and a baseline ECG done.
- Patients who have had a high level of exposure and are obtunded should be intubated; those having seizures or severe spasms should be given diazepam.
- Volume depletion may be a problem if the patient is having diarrhea. Intravenous infusion with 5% dextrose in water should be started.
Surgical Care
Surgical care such as tracheotomy and ventilatory assistance generally is not needed unless toxic effects are severe. In late-onset neuropathy, phrenic nerve function may be compromised and the patient may need ventilatory assistance.
Consultations
Consultation should be sought from pulmonary medicine, neurology, and if possible, psychiatry. An agitated patient requiring intubation in the acute phase of treatment can be difficult to control because sedatives may worsen the condition.
Diet
- Feeding the patient should be avoided until the patient's condition is stabilized.
- During acute intoxication, vomiting, diarrhea, and involuntary urination may occur.
- The patient should be hydrated intravenously.
Activity
- Patients in the acute phase of organophosphate toxicity may be agitated and should be kept in a quiet environment. As weakness and respiratory difficulties resolve, normal physical activity can resume.
- The patient should be monitored closely during the first 24-48 hours.
- The patient may respond initially to therapy and then become confused or agitated, requiring repeat doses of medication.
Medication
Atropine was used as the sole treatment until oximes were developed; it is still used as the sole treatment in developing countries where oximes are not available. In the United States, oximes are used in mild cases; in more severe cases oximes are augmented by the use of atropine.
In cases of oral ingestion, activated charcoal in suspension may be used if the patient is seen within 30 minutes of ingestion.
Antidotes
These agents reactivate cholinesterases inactivated by phosphorylation due to exposure to organophosphates.
Pralidoxime chloride (Protopam, 2-PAM chloride)
Strong nucleophilic agent that reactivates cholinesterase by reversing phosphorylation of serine hydroxyl group at active site of receptor membrane. Should be used within first 12-24 h and may need to be repeated over 2- to 3-week period. One patient in India, who ingested OPs in suicide attempt, required 92 g of pralidoxime over 23-d period.20 Effective against OP that is not irreversibly bound. Metabolized in liver and excreted in kidney. Early treatment most effective. Half-life 74-77 min. Not effective against carbamates. Should be used in severe OP toxicity.
Adult
When given with atropine, atropine is given first
Atropine sulfate: 1-5 mg IV after cholinesterase levels measured; may repeat q10-30min until patient fully atropinized (ie, experiencing dry mouth, tachycardia, clearing of tracheobronchial secretions, dilated pupils)
Pralidoxime: 1 g IV over 15-30 min when patient has fasciculations, muscle weakness, or respiratory depression on examination; may be repeated q8-12h for up to 3 doses
Pediatric
25-50 mg/kg IV given as 5% solution in isotonic saline; repeat in 12 h if symptoms persist or recur
Potentiates action of barbiturates; 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)
Documented hypersensitivity
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
Rapid injection can cause tachycardia, laryngospasm, muscle rigidity, pain at 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 normal volunteers; decrease in renal function increases drug levels in blood because 2-PAM excreted in urine; can produce transient elevation in CPK; 1 of 6 patients have elevation in SGOT and/or SGPT
Anticholinergic agents
These agents are used to reduce the clinical manifestations of organophosphate toxicity.
Atropine (AtroPen)
Antagonizes ACh at muscarinic receptor, leaving nicotinic receptors unaffected. Continue administration until excess muscarinic symptoms improve, which can be gauged by increased ease of breathing in conscious patient or improvement in ease of ventilation of intubated patient.
Adult
1-2 mg/dose IV q10-20 min to effect, then q1-4h for 24 h; not to exceed 50 mg in first 24 h (or 2 g over several days if intoxication severe)
Pediatric
0.02-0.05 mg/kg IV q10-20 min to effect, then q1-4h for at least 24 h
Other anticholinergics have additive effects; may increase pharmacologic effects of atenolol and digoxin; may decrease antipsychotic effects of phenothiazines; TCAs with anticholinergic activity may increase effects
Documented hypersensitivity; thyrotoxicosis; narrow-angle glaucoma; tachycardia
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
Caution in Down syndrome and/or children with brain damage to prevent hyperreactive response; caution also in coronary heart disease, tachycardia, congestive heart failure, cardiac arrhythmias, hypertension, peritonitis, ulcerative colitis, hepatic disease, and hiatal hernia with reflux esophagitis; in prostatic hypertrophy or prostatism, patients can have dysuria and may require catheterization
More on Organophosphates |
| Overview: Organophosphates |
| Differential Diagnoses & Workup: Organophosphates |
 Treatment & Medication: Organophosphates |
| Follow-up: Organophosphates |
| Multimedia: Organophosphates |
| References |
| « Previous Page | Next Page » |
References
Lotti M, Becker CE, Aminoff MJ. Organophosphate polyneuropathy: pathogenesis and prevention. Neurology. May 1984;34(5):658-62. [Medline].
Sung JJ, Kim SJ, Lee HB, et al. Anticholinesterase induces nicotinic receptor modulation. Muscle Nerve. Sep 1998;21(9):1135-44. [Medline].
Trojan DA, Collet JP, Shapiro S, et al. A multicenter, randomized, double-blinded trial of pyridostigmine in postpolio syndrome. Neurology. Oct 12 1999;53(6):1225-33. [Medline].
Abou-Donia MB. Organophosphorus ester-induced chronic neurotoxicity. Arch Environ Health. Aug 2003;58(8):484-97. [Medline].
Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet. Feb 16 2008;371(9612):597-607. [Medline].
Compston JE, Vedi S, Stephen AB, et al. Reduced bone formation after exposure to organophosphates. Lancet. Nov 20 1999;354(9192):1791-2. [Medline].
Alavanja MC, Hoppin JA, Kamel F. Health effects of chronic pesticide exposure: cancer and neurotoxicity. Annu Rev Public Health. 2004;25:155-97. [Medline].
Eskenazi B, Maizlish NA. Effects of Occupational Exposure to Chemicals on Neurobehavioral Functioning. In: Tarter RE, Thiel DHV, Edwards KL, eds. Medical Neuropsychology: The Impact of Disease on Behavior. New York, NY: Plenum Press; 1988.
Rosenstock L, Keifer M, Daniell WE, et al. Chronic central nervous system effects of acute organophosphate pesticide intoxication. The Pesticide Health Effects Study Group. Lancet. Jul 27 1991;338(8761):223-7. [Medline].
Menegon A, Board PG, Blackburn AC, Mellick GD, Le Couteur DG. Parkinson's disease, pesticides, and glutathione transferase polymorphisms. Lancet. Oct 24 1998;352(9137):1344-6. [Medline].
Bhatt MH, Elias MA, Mankodi AK. Acute and reversible parkinsonism due to organophosphate pesticide intoxication: five cases. Neurology. Apr 22 1999;52(7):1467-71. [Medline].
Himuro K, Murayama S, Nishiyama K, et al. Distal sensory axonopathy after sarin intoxication. Neurology. Oct 1998;51(4):1195-7. [Medline].
Senanayake N, Jeyaratnam J. Toxic polyneuropathy due to gingili oil contaminated with tri-cresyl phosphate affecting adolescent girls in Sri Lanka. Lancet. Jan 10 1981;1(8211):88-9. [Medline].
Senanayake N, Karalliedde L. Neurotoxic effects of organophosphorus insecticides. An intermediate syndrome. N Engl J Med. Mar 26 1987;316(13):761-3. [Medline].
Morgan JP, Penovich P. Jamaica ginger paralysis. Forty-seven-year follow-up. Arch Neurol. Aug 1978;35(8):530-2. [Medline].
Maselli RA, Soliven BC. Analysis of the organophosphate-induced electromyographic response to repetitive nerve stimulation: paradoxical response to edrophonium and D-tubocurarine. Muscle Nerve. Dec 1991;14(12):1182-8. [Medline].
Rutchik JS, Rutkove SB. Effect of temperature on motor responses in organophosphate intoxication. Muscle Nerve. Jul 1998;21(7):958-60. [Medline].
De Luca CJ, Buccafusco JJ, Roy SH, et al. The electromyographic signal as a presymptomatic indicator of organophosphates in the body. Muscle Nerve. 2006;33(3):369-76. [Medline].
Singh G, Sidhu UP, Mahajan R, et al. Phrenic nerve conduction studies in acute organophosphate poisoning. Muscle Nerve. Apr 2000;23(4):627-32. [Medline].
Pawar KS, Bhoite RR, Pillay CP, Chavan SC, Malshikare DS, Garad SG. Continuous pralidoxime infusion versus repeated bolus injection to treat organophosphorus pesticide poisoning: a randomised controlled trial. Lancet. Dec 16 2006;368(9553):2136-41. [Medline].
Feldman RG. Organophosphates. In: Occupational and Environmental Neurotoxicology. Philadelphia, Pa: Lippincott-Raven; 1998.
Grandjean P, Landrigan PJ. Developmental neurotoxicity of industrial chemicals. Lancet. Dec 16 2006;368(9553):2167-78. [Medline].
Kamel F, Engel LS, Gladen BC, et al. Neurologic symptoms in licensed private pesticide applicators in the agricultural health study. Environ Health Perspect. Jul 2005;113(7):877-82. [Medline].
Ludomirsky A, Klein HO, Sarelli P, et al. Q-T prolongation and polymorphous ("torsade de pointes") ventricular arrhythmias associated with organophosphorus insecticide poisoning. Am J Cardiol. May 1982;49(7):1654-8. [Medline].
Maddy KT, Edmiston S, Richmond D. Illness, injuries, and deaths from pesticide exposures in California 1949-1988. Rev Environ Contam Toxicol. 1990;114:57-123. [Medline].
Savage EP, Keefe TJ, Mounce LM, et al. Chronic neurological sequelae of acute organophosphate pesticide poisoning. Arch Environ Health. Jan-Feb 1988;43(1):38-45. [Medline].
Taylor P. Development of acetylcholinesterase inhibitors in the therapy of Alzheimer's disease. Neurology. Jul 1998;51(1 Suppl 1):S30-5; discussion S65-7. [Medline].
Tune LE, Damlouji NF, Holland A, et al. Association of postoperative delirium with raised serum levels of anticholinergic drugs. Lancet. Sep 26 1981;2(8248):651-3. [Medline].
Further Reading
Keywords
organophosphates, nerve agent, pesticides, organophosphate insecticides, diazinon, disulfoton, azinphos-methyl, fonofos, therapeutic use of organophosphates, toxic nerve agents, sarin, neurotoxicity
