Approach Considerations

Although no laboratory test exists to directly measure nerve agent levels in serum or urine, the acute effects of nerve agents can be estimated by measuring the percent reduction in the activity of red blood cell (RBC) cholinesterase.

Respiratory impairment in nerve agent intoxication produces expected derangement in arterial blood gas values, including a reduction in partial pressure of arterial oxygen (PaO₂).

Hypokalemia has been reported in GB intoxication, although the mechanism is unclear.

Chest x-ray may be helpful in treating patients with significant pulmonary symptoms.

A number of electrocardiographic changes have been reported in nerve agent intoxication, including bradycardia and varying degrees of atrioventricular block (first through third degree) from the direct muscarinic effect on the heart and tachycardia and ventricular dysrhythmias from hypoxia. Nerve agent toxicity has been associated with PR interval prolongation, QT prolongation, and torsade de pointes.

Bedside electroencephalographic monitoring is recommended for patients paralyzed from nerve agent exposure, because paralysis from nicotinic effects of these agents may mask seizures from CNS effects.

Red Blood Cell Cholinesterase

RBC cholinesterase and plasma cholinesterase (pseudocholinesterase) appear to have a physiologic role as buffers for the tissue acetylcholinesterases found in the nervous system. These two enzymes are clinically important, because their activities can be assayed directly in blood, whereas the tissue cholinesterases cannot. Activity of RBC cholinesterase is considered a more sensitive indicator of nerve agent toxicity than that of plasma cholinesterase.

Despite the clinical use of RBC cholinesterase, keep certain limitations in mind when using the activity of RBC cholinesterase to interpret nerve agent effects. Activity of RBC cholinesterase is subject to some individual variation. Without establishing the baseline value of RBC cholinesterase in individuals, measuring the percent reduction in enzyme activity is difficult.

Poor correlation exists between clinical effects of nerve agents and the percent reduction of RBC cholinesterase activity at low-dose exposures. Accordingly, RBC cholinesterase activity always must be correlated with the patient's clinical status and never should determine patient disposition alone.

A good guideline is that severe clinical effects tend to correlate with a 20-25% reduction in RBC cholinesterase activity. A rising RBC cholinesterase level indicates that no further nerve agent absorption is occurring and that the enzyme is regenerating. RBC cholinesterase is replaced fully every 120 days at the natural regeneration rate of RBCs (approximately 1%/d). Draw blood for RBC cholinesterase activity level prior to administering oxime antidotes.

Treatment & Management

Holstege CP, Kirk M, Sidell FR. Chemical warfare. Nerve agent poisoning. Crit Care Clin. 1997 Oct. 13(4):923-42. [QxMD MEDLINE Link].
Wright LK, Lee RB, Vincelli NM, Whalley CE, Lumley LA. Comparison of the lethal effects of chemical warfare nerve agents across multiple ages. Toxicol Lett. 2015 Nov 24. [QxMD MEDLINE Link].
Sidell FR, Borak J. Chemical warfare agents: II. Nerve agents. Ann Emerg Med. 1992 Jul. 21(7):865-71. [QxMD MEDLINE Link].
[Guideline] Agency for Toxic Substance & Disease Registry (ATSDR). Medical Management Guidelines for Nerve Agents: Tabun (GA); Sarin (GB); Soman (GD); and VX. ATSDR.cdc.gov. Available at https://wwwn.cdc.gov/TSP/MMG/MMGDetails.aspx?mmgid=523&toxid=93. January 12, 2017; Accessed: September 25, 2021.
Worek F, Herkert NM, Koller M, Thiermann H, Wille T. Application of a dynamic in vitro model with real-time determination of acetylcholinesterase activity for the investigation of tabun analogues and oximes. Toxicol In Vitro. 2015 Sep 11. [QxMD MEDLINE Link].
Sidell FR. Nerve agents. Medical Aspects of Chemical and Biological Warfare. 1987. 129-179.
da Silva Gonçalves A, França TC, Caetano MS, Ramalho TC. Reactivation steps by 2-PAM of tabun-inhibited human acetylcholinesterase: reducing the computational cost in hybrid QM/MM methods. J Biomol Struct Dyn. 2013 Mar 25. [QxMD MEDLINE Link].
Kato T, Hamanaka T. Ocular signs and symptoms caused by exposure to sarin gas. Am J Ophthalmol. 1996 Feb. 121(2):209-10. [QxMD MEDLINE Link].
Nozaki H, Hori S, Shinozawa Y, et al. Relationship between pupil size and acetylcholinesterase activity in patients exposed to sarin vapor. Intensive Care Med. 1997 Sep. 23(9):1005-7. [QxMD MEDLINE Link].
Rickett DL, Glenn JF, Beers ET. Central respiratory effects versus neuromuscular actions of nerve agents. Neurotoxicology. 1986 Spring. 7(1):225-36. [QxMD MEDLINE Link].
Organisation for the Prohibition of Chemical Weapons. OPCW Director-General Shares Incontrovertible Laboratory Results Concluding Exposure to Sarin. OPCW.org. Available at https://www.opcw.org/news/article/opcw-director-general-shares-incontrovertible-laboratory-results-concluding-exposure-to-sarin/. April 19, 2017; Accessed: September 25, 2021.
Droste DJ, Shelley ML, Gearhart JM, Kempisty DM. A systems dynamics approach to the efficacy of oxime therapy for mild exposure to sarin gas. Am J Disaster Med. 2016 Spring. 11 (2):89-118. [QxMD MEDLINE Link].
Nakajima T, Sato S, Morita H, Yanagisawa N. Sarin poisoning of a rescue team in the Matsumoto sarin incident in Japan. Occup Environ Med. 1997 Oct. 54(10):697-701. [QxMD MEDLINE Link].
Okumura T, Takasu N, Ishimatsu S, et al. Report on 640 victims of the Tokyo subway sarin attack. Ann Emerg Med. 1996 Aug. 28(2):129-35. [QxMD MEDLINE Link].
White RF, Steele L, O'Callaghan JP, Sullivan K, Binns JH, Golomb BA, et al. Recent research on Gulf War illness and other health problems in veterans of the 1991 Gulf War: Effects of toxicant exposures during deployment. Cortex. 2015 Sep 25. [QxMD MEDLINE Link].
Department of Homeland Security/Federal Bureau of Investigation. Potential Terrorist Attack Methods. Available at https://nsarchive2.gwu.edu//nukevault/ebb388/docs/EBB015.pdf. April 23, 2008; Accessed: September 25, 2021.
The National Institute for Occupational Safety and Health (NIOSH). SARIN (GB): Nerve Agent. CDC.gov. Available at https://www.cdc.gov/niosh/ershdb/emergencyresponsecard_29750001.html. November 8, 2017; Accessed: September 25, 2021.
de Araujo Furtado M, Rossetti F, Chanda S, Yourick D. Exposure to nerve agents: from status epilepticus to neuroinflammation, brain damage, neurogenesis and epilepsy. Neurotoxicology. 2012 Dec. 33 (6):1476-90. [QxMD MEDLINE Link].
Chao LL, Rothlind JC, Cardenas VA, Meyerhoff DJ, Weiner MW. Effects of low-level exposure to sarin and cyclosarin during the 1991 Gulf War on brain function and brain structure in US veterans. Neurotoxicology. 2010 Sep. 31(5):493-501. [QxMD MEDLINE Link]. [Full Text].
Yokoyama K, Araki S, Murata K, et al. A preliminary study on delayed vestibulo-cerebellar effects of Tokyo Subway Sarin Poisoning in relation to gender difference: frequency analysis of postural sway. J Occup Environ Med. 1998 Jan. 40(1):17-21. [QxMD MEDLINE Link].
Nakajima T, Ohta S, Fukushima Y, Yanagisawa N. Sequelae of sarin toxicity at one and three years after exposure in Matsumoto, Japan. J Epidemiol. 1999 Nov. 9(5):337-43. [QxMD MEDLINE Link].
U.S. Department of Health and Human Services: Chemical Hazards Emergency Medical Management. Nerve Agents: Acute Management Overview. CHEMM.hhs.gov. Available at https://chemm.hhs.gov/na_prehospital_mmg.htm. August 16, 2021; Accessed: September 23, 2021.
Tokuda Y, Kikuchi M, Takahashi O. Prehospital management of sarin nerve gas terrorism in urban settings: 10 years of progress after the Tokyo subway sarin attack. Resuscitation. 2006 Feb. 68(2):193-202. [QxMD MEDLINE Link].
Aroniadou-Anderjaska V, Apland JP, Figueiredo TH, De Araujo Furtado M, Braga MF. Acetylcholinesterase inhibitors (nerve agents) as weapons of mass destruction: History, mechanisms of action, and medical countermeasures. Neuropharmacology. 2020 Dec 15. 181:108298. [QxMD MEDLINE Link].
National Center for Disaster Preparedness. Atropine Use in Children After Nerve Gas Exposure. Pediatric Expert Advisory Panel (PEAP) Info Brief. Spring 2004. 1:[Full Text].
McDonough JH. Midazolam: An Improved Anticonvulsant Treatment for Nerve Agent Induced Seizures. Defense Technical Information Center. JAN 2002. [Full Text].
De Araujo Furtado M, Aroniadou-Anderjaska V, Figueiredo TH, Apland JP, Braga MFM. Electroencephalographic analysis in soman-exposed 21-day-old rats and the effects of midazolam or LY293558 with caramiphen. Ann N Y Acad Sci. 2020 Nov. 1479 (1):122-133. [QxMD MEDLINE Link].
Krishnan JKS, Arun P, Appu AP, Vijayakumar N, Figueiredo TH, Braga MFM, et al. Intranasal delivery of obidoxime to the brain prevents mortality and CNS damage from organophosphate poisoning. Neurotoxicology. 2016 Mar. 53:64-73. [QxMD MEDLINE Link].
Worek F, Koller M, Thiermann H, Wille T. Reactivation of nerve agent-inhibited human acetylcholinesterase by obidoxime, HI-6 and obidoxime+HI-6: Kinetic in vitro study with simulated nerve agent toxicokinetics and oxime pharmacokinetics. Toxicology. 2016 Mar 28. 350-352:25-30. [QxMD MEDLINE Link].
Worek F, Thiermann H, Wille T. Catalytic bioscavengers in nerve agent poisoning: A promising approach?. Toxicol Lett. 2016 Feb 26. 244:143-8. [QxMD MEDLINE Link].
Katz FS, Pecic S, Schneider L, Zhu Z, Hastings A, Luzac M, et al. New therapeutic approaches and novel alternatives for organophosphate toxicity. Toxicol Lett. 2018 Jul. 291:1-10. [QxMD MEDLINE Link].