The main goal of treatment is to reduce the high mortality rate and severity of serious complications by using atropine and/or pralidoxime plus supportive care and decontamination of the patient. Management of these patients should involve early expert help and critical care input. The American Heart Association recommends early endotracheal intubation for life-threatening organophosphate poisoning.[14]Lavonas EJ, Akpunonu PD, Arens AM, et al. 2023 American Heart Association focused update on the management of patients with cardiac arrest or life-threatening toxicity due to poisoning: an update to the American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2023 Oct 17;148(16):e149-84.
https://www.ahajournals.org/doi/full/10.1161/CIR.0000000000001161
http://www.ncbi.nlm.nih.gov/pubmed/37721023?tool=bestpractice.com
Suspected poisoning
All patients with suspected significant exposure should be treated presumptively, as treatment needs to be started before test results are returned. The initial approach is focused on cardiorespiratory resuscitation and supportive care.[12]Eddleston M, Buckley NA, Eyer P, et al. Management of acute organophosphorus pesticide poisoning. Lancet. 2008 Feb 16;371(9612):597-607.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17706760
http://www.ncbi.nlm.nih.gov/pubmed/17706760?tool=bestpractice.com
This involves very early use of rapidly escalating doses of atropine until secretions are controlled and the chest is clear, as well as intravenous fluids, airway maintenance, and ventilation.[12]Eddleston M, Buckley NA, Eyer P, et al. Management of acute organophosphorus pesticide poisoning. Lancet. 2008 Feb 16;371(9612):597-607.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17706760
http://www.ncbi.nlm.nih.gov/pubmed/17706760?tool=bestpractice.com
[14]Lavonas EJ, Akpunonu PD, Arens AM, et al. 2023 American Heart Association focused update on the management of patients with cardiac arrest or life-threatening toxicity due to poisoning: an update to the American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2023 Oct 17;148(16):e149-84.
https://www.ahajournals.org/doi/full/10.1161/CIR.0000000000001161
http://www.ncbi.nlm.nih.gov/pubmed/37721023?tool=bestpractice.com
[15]Abedin MJ, Sayeed AA, Basher A, et al. Open-label randomized clinical trial of atropine bolus injection versus incremental boluses plus infusion for organophosphate poisoning in Bangladesh. J Med Toxicol. 2012 Jun;8(2):108-17.
http://www.ncbi.nlm.nih.gov/pubmed/22351300?tool=bestpractice.com
After the patient is stabilised, the next step is decontamination.[12]Eddleston M, Buckley NA, Eyer P, et al. Management of acute organophosphorus pesticide poisoning. Lancet. 2008 Feb 16;371(9612):597-607.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17706760
http://www.ncbi.nlm.nih.gov/pubmed/17706760?tool=bestpractice.com
[14]Lavonas EJ, Akpunonu PD, Arens AM, et al. 2023 American Heart Association focused update on the management of patients with cardiac arrest or life-threatening toxicity due to poisoning: an update to the American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2023 Oct 17;148(16):e149-84.
https://www.ahajournals.org/doi/full/10.1161/CIR.0000000000001161
http://www.ncbi.nlm.nih.gov/pubmed/37721023?tool=bestpractice.com
This involves washing the patient, having first removed their contaminated clothes, and aspiration of stomach contents if the airway is protected. Appropriate personal protective equipment is recommended when caring for patients with organophosphate poisoning which will depend on the circumstances of the organophosphate exposure and potency of the involved organophosphate.[14]Lavonas EJ, Akpunonu PD, Arens AM, et al. 2023 American Heart Association focused update on the management of patients with cardiac arrest or life-threatening toxicity due to poisoning: an update to the American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2023 Oct 17;148(16):e149-84.
https://www.ahajournals.org/doi/full/10.1161/CIR.0000000000001161
http://www.ncbi.nlm.nih.gov/pubmed/37721023?tool=bestpractice.com
Occupational or accidental poisoning
Symptoms are usually mild to moderate in these patients, who may report dermal or respiratory exposure to a particular agent. Supportive care and decontamination procedures are recommended. Gastric aspiration or lavage may be performed if the airway is protected. However, organophosphates are rapidly absorbed, and there is no evidence to support the effectiveness of gastric aspiration or lavage.[16]Li Y, Tse ML, Gawarammana I, et al. Systematic review of controlled clinical trials of gastric lavage in acute organophosphorus pesticide poisoning. Clin Toxicol (Phila). 2009 Mar;47(3):179-92.
http://www.ncbi.nlm.nih.gov/pubmed/18988062?tool=bestpractice.com
Evidence suggests that activated charcoal is ineffective in reducing clinical effects.[17]Eddleston M, Juszczak E, Buckley NA, et al; Ox-Col Poisoning Study collaborators. Multiple-dose activated charcoal in acute self-poisoning: a randomised controlled trial. Lancet. 2008 Feb 16;371(9612):579-87.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430417
http://www.ncbi.nlm.nih.gov/pubmed/18280328?tool=bestpractice.com
Atropine is recommended to control secretions.[12]Eddleston M, Buckley NA, Eyer P, et al. Management of acute organophosphorus pesticide poisoning. Lancet. 2008 Feb 16;371(9612):597-607.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17706760
http://www.ncbi.nlm.nih.gov/pubmed/17706760?tool=bestpractice.com
[14]Lavonas EJ, Akpunonu PD, Arens AM, et al. 2023 American Heart Association focused update on the management of patients with cardiac arrest or life-threatening toxicity due to poisoning: an update to the American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2023 Oct 17;148(16):e149-84.
https://www.ahajournals.org/doi/full/10.1161/CIR.0000000000001161
http://www.ncbi.nlm.nih.gov/pubmed/37721023?tool=bestpractice.com
Deliberate ingestion or terrorism/warfare with nerve agent
Symptoms are usually severe in these patients, who may be confused or semi-conscious. Supportive care and decontamination procedures are recommended.[14]Lavonas EJ, Akpunonu PD, Arens AM, et al. 2023 American Heart Association focused update on the management of patients with cardiac arrest or life-threatening toxicity due to poisoning: an update to the American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2023 Oct 17;148(16):e149-84.
https://www.ahajournals.org/doi/full/10.1161/CIR.0000000000001161
http://www.ncbi.nlm.nih.gov/pubmed/37721023?tool=bestpractice.com
Gastric aspiration or lavage may be performed if the airway is protected. However, organophosphates are rapidly absorbed, and there is no evidence to support the effectiveness of gastric aspiration or lavage.[16]Li Y, Tse ML, Gawarammana I, et al. Systematic review of controlled clinical trials of gastric lavage in acute organophosphorus pesticide poisoning. Clin Toxicol (Phila). 2009 Mar;47(3):179-92.
http://www.ncbi.nlm.nih.gov/pubmed/18988062?tool=bestpractice.com
Evidence suggests that activated charcoal is ineffective in reducing clinical effects.[17]Eddleston M, Juszczak E, Buckley NA, et al; Ox-Col Poisoning Study collaborators. Multiple-dose activated charcoal in acute self-poisoning: a randomised controlled trial. Lancet. 2008 Feb 16;371(9612):579-87.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2430417
http://www.ncbi.nlm.nih.gov/pubmed/18280328?tool=bestpractice.com
Atropine is used to control secretions.
Pralidoxime (an oxime) can also be given to reactivate inhibited acetylcholinesterase.[14]Lavonas EJ, Akpunonu PD, Arens AM, et al. 2023 American Heart Association focused update on the management of patients with cardiac arrest or life-threatening toxicity due to poisoning: an update to the American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2023 Oct 17;148(16):e149-84.
https://www.ahajournals.org/doi/full/10.1161/CIR.0000000000001161
http://www.ncbi.nlm.nih.gov/pubmed/37721023?tool=bestpractice.com
However, it only reactivates 'non-aged' acetylcholinesterase-organophosphate complexes. 'Ageing' is the process whereby phosphorylated acetylcholinesterase loses an alkyl side chain non-enzymatically, leaving a hydroxyl group in its place, with the result that regeneration is no longer possible. Pralidoxime is, therefore, of limited or no effectiveness against organophosphates that form rapidly aging acetylcholinesterase complexes. Pralidoxime is often given in severe poisoning cases, but evidence is conflicting and generally negative.[18]Banerjee I, Tripathi SK, Roy AS. A study on comparative evaluation of add-on pralidoxime therapy over atropine in the management of organophosphorus poisoning in a tertiary care hospital. JK Science. 2011 Apr-Jun;13(2):65-9.
http://www.jkscience.org/archive/volume132/A%20Study%20on%20Comparative%20Evaluation%20of%20Add-on%20Pralidoxime%20Therapy%20over%20Atropine%20in%20the%20Management%20of%20Organophosphorus%20Poisoning%20in%20a%20Tertiary%20Care%20Hospital.pdf
[19]Banerjee I, Tripathi SK, Roy AS. Efficacy of pralidoxime in organophosphorus poisoning: revisiting the controversy in Indian setting. J Postgrad Med. 2014 Jan-Mar;60(1):27-30.
http://www.jpgmonline.com/article.asp?issn=0022-3859;year=2014;volume=60;issue=1;spage=27;epage=30;aulast=Banerjee
http://www.ncbi.nlm.nih.gov/pubmed/24625936?tool=bestpractice.com
[20]Buckley NA, Eddleston M, Li Y, et al. Oximes for acute organophosphate pesticide poisoning. Cochrane Database Syst Rev. 2011 Feb 16;(2):CD005085.
http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005085.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/21328273?tool=bestpractice.com
[21]Blumenberg A, Benabbas R, deSouza IS, et al. Utility of 2-Pyridine Aldoxime Methyl Chloride (2-PAM) for Acute Organophosphate Poisoning: A Systematic Review and Meta-Analysis. J Med Toxicol. 2018 Mar;14(1):91-98.
https://www.doi.org/10.1007/s13181-017-0636-2
http://www.ncbi.nlm.nih.gov/pubmed/29230717?tool=bestpractice.com
One study suggested that routine use of high doses of pralidoxime may cause more harm than benefit in many cases, despite reactivating red blood cell (RBC)-acetylcholinesterase.[22]Eddleston M, Eyer P, Worek F, et al. Pralidoxime in acute organophosphorus insecticide poisoning - a randomised controlled trial. PLoS Med. 2009 Jun 30;6(6):e1000104.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2696321/?tool=pubmed
http://www.ncbi.nlm.nih.gov/pubmed/19564902?tool=bestpractice.com
Adverse effects of pralidoxime may be serious and are more common if high bolus doses of pralidoxime are given rapidly. Further clinical trials are required to determine if certain dosing strategies may be useful in particular groups of patients.
If given outside of trials, pralidoxime dose should be titrated according to patient response as measured by nerve conduction studies or RBC-acetylcholinesterase assays.[23]Thiermann H, Zilker T, Eyer F, et al. Monitoring of neuromuscular transmission in organophosphate pesticide-poisoned patients. Toxicol Lett. 2009 Dec 15;191(2-3):297-304.
http://www.ncbi.nlm.nih.gov/pubmed/19793545?tool=bestpractice.com
Plasma cholinesterase may also be reactivated by pralidoxime but the response is variable, smaller, and not sustained. Therefore, it should not be used to monitor the response to oximes.[24]Konickx LA, Worek F, Jayamanne S, et al. Reactivation of plasma butyrylcholinesterase by pralidoxime chloride in patients poisoned by WHO class II toxicity organophosphorus insecticides. Toxicol Sci. 2013 Dec;136(2):274-83.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858199
http://www.ncbi.nlm.nih.gov/pubmed/24052565?tool=bestpractice.com
Benzodiazepines may be required in some patients to control seizures or to sedate ventilated patients.[12]Eddleston M, Buckley NA, Eyer P, et al. Management of acute organophosphorus pesticide poisoning. Lancet. 2008 Feb 16;371(9612):597-607.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17706760
http://www.ncbi.nlm.nih.gov/pubmed/17706760?tool=bestpractice.com
[14]Lavonas EJ, Akpunonu PD, Arens AM, et al. 2023 American Heart Association focused update on the management of patients with cardiac arrest or life-threatening toxicity due to poisoning: an update to the American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2023 Oct 17;148(16):e149-84.
https://www.ahajournals.org/doi/full/10.1161/CIR.0000000000001161
http://www.ncbi.nlm.nih.gov/pubmed/37721023?tool=bestpractice.com
[25]Roberts DM, Aaron CK. Management of acute organophosphorus pesticide poisoning. BMJ. 2007 Mar 24;334(7594):629-34.
http://www.ncbi.nlm.nih.gov/pubmed/17379909?tool=bestpractice.com
Refractory hypotension and paralysis
Several manifestations of severe organophosphate poisoning are frequently refractory to standard treatment. In particular, severe hypotension is an ominous sign; high doses of atropine and vasopressors may be tried, but success is likely to be limited.
Central nervous system features and paralysis often do not respond well to antidotes, and prolonged intensive supportive care may be required. No treatments have been shown to prevent delayed neuropathy, but this is an uncommon complication.
Intermediate syndrome
About 1 to 5 days post-poisoning, often when other signs are resolving, increasing proximal muscle weakness and cranial nerve palsies can occur. In severe cases of intermediate syndrome, respiratory failure may occur. Treatment is supportive with close monitoring and assisted ventilation, if required. Ventilation for up to 2 to 3 weeks is often needed. Recurrence of respiratory failure the day following extubation requiring re-intubation is also common.[26]Alahakoon C, Dassanayake TL, Gawarammana IB, et al. Prediction of organophosphorus insecticide-induced intermediate syndrome with stimulated concentric needle single fibre electromyography. PLoS One. 2018 Sep 27;13(9):e0203596.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0203596
http://www.ncbi.nlm.nih.gov/pubmed/30261032?tool=bestpractice.com
Organophosphate-induced delayed neuropathy
Delayed neuropathy may occur 1 to 5 weeks after ingestion. It may overlap with intermediate syndrome. This is predominantly a motor neuropathy, but there may also be upper motor neuron problems and cognitive defects. There is no known treatment, but it may resolve slowly over months to years.