Organophosphate Toxicity Medication

  • Author: Kenneth D Katz, MD, FAAEM, ABMT; Chief Editor: Michael R Pinsky, MD, CM, FCCP, FCCM   more...
 
Updated: Jan 23, 2012
 

Medication Summary

The mainstays of medical therapy in organophosphate (OP) poisoning include atropine, pralidoxime (2-PAM), and benzodiazepines (eg, diazepam). A novel route of administration of intraosseous (bone injection gun, BIG) midazolam demonstrated rapid peak concentrations in swine compared with intravenous and intramuscular routes; the authors concluded this may play a role in quickly terminating seizures, especially in the prehospital arena.[13] Initial management must focus on adequate use of atropine. Optimizing oxygenation prior to the use of atropine is recommended to minimize the potential for dysrhythmias.

de Silva et al studied the treatment of organophosphate poisoning with atropine and 2-PAM and, later the same year, with atropine alone.[14] They found that atropine seemed to be as effective as atropine plus 2-PAM in the treatment of acute organophosphate 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. Improved survival has been shown in moderately severe OP poisoned patients who received early, continuous 2-PAM infusion compared with those who received intermittent boluses.[15]

A meta-analysis and review of the literature performed by Peter et al emphasized optimal supportive care along with discriminate use of 2-PAM, especially early in the course of treatment of moderately to severely OP poisoned patients, are the hallmarks of treatment.[16] More prospective data are required.

Because large amounts of atropine may be required for patients with organophosphate poisoning, reconstitution of powdered atropine is a viable option, especially in mass-casualty settings.[17] Recently, Rajpal et al demonstrated the clinical safety and efficacy of sublingual atropine to healthy volunteers. This may offer another route of administration for the OP poisoned patient, especially in a mass-casualty scenario.[18]

Intravenous glycopyrrolate or diphenhydramine may provide an alternative centrally acting anticholinergic agent used to treat muscarinic toxicity if atropine is unavailable or in limited supply. Additionally, Yavuz et al demonstrated reduced myocardial injury and troponin leak in fenthion-poisoned rats treated with diphenhydramine.[19]

In a single-center, randomized, single-blind study by Pajoumand et al found a benefit to magnesium therapy in addition to standard oxime and atropine therapy in reducing hospitalization days and mortality rate in patients with organophosphate poisoning.[20] The mechanisms appear to be inhibition of acetylcholine (ACh) and organophosphate antagonism. Larger randomized studies are needed to demonstrate magnesium efficacy in organophosphate (OP) poisoning.

Possible future interventions include neuroprotective agents used to prevent nerve damage and bioscavengers aimed to prevent AChE inhibition by nerve agents or organophosphate. Investigations into adjunctive and alternative therapies have mostly used animal models and have resulted in variable conclusions.[21, 22]

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Anticholinergic agents

Class Summary

These agents act as competitive antagonists at the muscarinic cholinergic receptors in both the central and the peripheral nervous system. These agents do not affect nicotinic effects.

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Atropine IV/IM (Isopto, Atropair)

 

Initiated in patients with OP toxicity who present with muscarinic symptoms.

Competitive inhibitor at autonomic postganglionic cholinergic receptors, including receptors found in GI and pulmonary smooth muscle, exocrine glands, heart, and eye.

The endpoint for atropinization is dried pulmonary secretions and adequate oxygenation. Tachycardia and mydriasis must not be used to limit or to stop subsequent doses of atropine. The main concern with OP toxicity is respiratory failure from excessive airway secretions.

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Glycopyrrolate (Robinul)

 

Indicated for use as an antimuscarinic agent to reduce salivary, tracheobronchial, and pharyngeal secretions. Does not cross the blood-brain barrier. Can be considered in patients at risk for recurrent symptoms (after initial atropinization) but who are developing central anticholinergic delirium or agitation.

Since glycopyrrolate does not cross BBB, it is not expected to control central cholinergic toxicity. Bird et al suggested that atropine (rather than glycopyrrolate) was associated with lower, early OP-induced mortality

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Antidotes, OP poisoning

Class Summary

These agents prevent aging of AChE and reverse muscle paralysis with OP poisoning.

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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 (aged). Current recommendation is administration within 48 h of OP poisoning. Because it does not significantly relieve depression of respiratory center or decrease muscarinic effects of AChE poisoning, administer atropine concomitantly to block these effects of OP poisoning.

Signs of atropinization might occur earlier with addition of 2-PAM to treatment regimen. 2-PAM administration is not indicated for carbamate exposure since no aging occurs.

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Benzodiazepines

Class Summary

These agents potentiate effects of gamma-aminobutyrate (GABA) and facilitate inhibitory GABA neurotransmission.

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Diazepam (Valium, Diastat, Diazemuls)

 

For treatment of seizures. Depresses all levels of CNS (eg, limbic and reticular formation) by increasing activity of GABA.

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Contributor Information and Disclosures
Author

Kenneth D Katz, MD, FAAEM, ABMT  Assistant Professor, Division of Medical Toxicology, Department of Emergency Medicine, University of Pittsburgh Medical Center; Medical Director, Pittsburgh Poison Center

Kenneth D Katz, MD, FAAEM, ABMT is a member of the following medical societies: American Academy of Emergency Medicine and American College of Medical Toxicology

Disclosure: Nothing to disclose.

Coauthor(s)

Daniel E Brooks, MD  Co-Medical Director, Banner Good Samaritan Poison and Drug Information Center, Department of Medical Toxicology, Banner Good Samaritan Medical Center

Daniel E Brooks, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Emergency Physicians, and American College of Medical Toxicology

Disclosure: Nothing to disclose.

Specialty Editor Board

Lisa Kirkland, MD, FACP, CNSP, MSHA  Assistant Professor, Department of Internal Medicine, Division of Hospital Medicine, Mayo Clinic; ANW Intensivists, Abbott Northwestern Hospital

Lisa Kirkland, MD, FACP, CNSP, MSHA is a member of the following medical societies: American College of Physicians, Society of Critical Care Medicine, and Society of Hospital Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Om Prakash Sharma, MD, FRCP, FCCP, DTM&H  Professor, Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Southern California Keck School of Medicine

Om Prakash Sharma, MD, FRCP, FCCP, DTM&H is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Osler Society, American Thoracic Society, New York Academy of Medicine, and Royal Society of Medicine

Disclosure: Nothing to disclose.

Timothy D Rice, MD  Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, St Louis University School of Medicine

Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians

Disclosure: Nothing to disclose.

Chief Editor

Michael R Pinsky, MD, CM, FCCP, FCCM  Professor of Critical Care Medicine, Bioengineering, Cardiovascular Disease and Anesthesiology, Vice-Chair of Academic Affairs, Department of Critical Care Medicine, University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine

Michael R Pinsky, MD, CM, FCCP, FCCM is a member of the following medical societies: American College of Chest Physicians, American College of Critical Care Medicine, American Heart Association, American Thoracic Society, Association of University Anesthetists, European Society of Intensive Care Medicine, Shock Society, and Society of Critical Care Medicine

Disclosure: LiDCO Ltd Honoraria Consulting; iNTELOMED Intellectual property rights Board membership; Edwards Lifesciences Honoraria Consulting; Applied Physiology, Ltd Honoraria Consulting; Cheetah Medical Consulting fee Consulting

Additional Contributors

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors Marina C Furtado, MD, and Lisa Chan, MD, FACEP, to the development and writing of this article.

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