Differential Diagnoses

CBRNE - Chemical Warfare Agents
CBRNE - Nerve Agents, Binary - GB2, VX2
CBRNE - Nerve Agents, G-series - Tabun, Sarin, Soman
Organic Phosphorous Compound and Carbamate Toxicity
Organophosphate Toxicity

Workup

Barakat NH, Zheng X, Gilley CB, MacDonald M, Okolotowicz K, Cashman JR, et al. Chemical synthesis of two series of nerve agent model compounds and their stereoselective interaction with human acetylcholinesterase and human butyrylcholinesterase. Chem Res Toxicol. 2009 Oct. 22(10):1669-79. [QxMD MEDLINE Link]. [Full Text].
Wiercinski A. Nerve Agents. Jackson JP. StatPearls. March 7, 2018. Treasure Island (FL): StatPearls Publishing; 2018 Jan. [Full Text].
Bae SY, Myslinski JM, McMahon LR, Height JJ, Bigley AN, Raushel FM, et al. An OPAA enzyme mutant with increased catalytic efficiency on the nerve agents sarin, soman, and GP. Enzyme Microb Technol. 2018 May. 112:65-71. [QxMD MEDLINE Link].
Khan MA, Ganguly B. Assessing the reactivation efficacy of hydroxylamine anion towards VX-inhibited AChE: a computational study. J Mol Model. 2012 May. 18(5):1801-8. [QxMD MEDLINE Link].
CMA Public Affairs. Last VX nerve agent eliminated from Army stockpile. www.army.mil. Available at http://www.army.mil/article/15572/last-vx-nerve-agent-eliminated-from-army-stockpile/. Accessed: February 5, 2015.
Centers for Disease Control and Prevention. Facts About VX. CDC. Available at http://www.bt.cdc.gov/agent/vx/basics/facts.asp. Accessed: February 5, 2015.
Nakagawa T, Tu AT. Murders with VX: Aum Shinrikyo in Japan and the assassination of Kim Jong-Nam in Malaysia. Forensic Toxicology. July 2018. 36;2:542-544. [Full Text].
Shah bin Mahmood M. Post-mortem examination report for the case of Kim Chol. Malaysia. Kuala Lumpur Hospital. February 15, 2017.
Worek F, Wille T, Koller M, Thiermann H. Toxicology of organophosphorus compounds in view of an increasing terrorist threat. Arch Toxicol. 2016 Sep. 90 (9):2131-45. [QxMD MEDLINE Link].
Marrs TC, Maynard RL, Sidell FR. Chemical Warfare Agents: Toxicology and Treatment. England: John Wiley and Sons; 1996.
Benjamin Kentish. "Poison used on Sergei and Yulia Skripal in Salisbury attack was novichok nerve agent, confirms chemical weapons watchdog". The Independent. April 12, 2018. Available at https://www.independent.co.uk/news/uk/politics/sergei-and-yulia-skripal-in-salisbury-attack-was-a-novichok-nerve-agent-confirms-chemical-weapons-a8301121.html.
Schulze ND, Hamelin EI, Winkeljohn WR, Shaner RL, Basden BJ, deCastro BR, et al. Evaluation of Multiple Blood Matrices for Assessment of Human Exposure to Nerve Agents. J Anal Toxicol. 2016 Apr. 40 (3):229-35. [QxMD MEDLINE Link].
Wolf JC, Schaer M, Siegenthaler P, Zenobi R. Direct Quantification of Chemical Warfare Agents and Related Compounds at Low ppt Levels: Comparing Active Capillary Dielectric Barrier Discharge Plasma Ionization and Secondary Electrospray Ionization Mass Spectrometry. Anal Chem. 2014 Dec 10. [QxMD MEDLINE Link].
Hakonen A, Rindzevicius T, Schmidt MS, Andersson PO, Juhlin L, Svedendahl M, et al. Detection of nerve gases using surface-enhanced Raman scattering substrates with high droplet adhesion. Nanoscale. 2016 Jan 21. 8 (3):1305-8. [QxMD MEDLINE Link].
Pantazides BG, Watson CM, Carter MD, Crow BS, Perez JW, Blake TA, et al. An enhanced butyrylcholinesterase method to measure organophosphorus nerve agent exposure in humans. Anal Bioanal Chem. 2014 Aug. 406(21):5187-94. [QxMD MEDLINE Link].
Cibulsky SM, Kirk MA, Ignacio JS, Leary AD, Schwartz MD. Patient Decontamination in a Mass Chemical Exposure Incident:National Planning Guidance for Communities. Department of Homeland Security, Department of Health and Human Services. December 2014. Available at http://www.dhs.gov/sites/default/files/publications/Patient%20Decon%20National%20Planning%20Guidance_Final_December%202014.pdf.
Josse D, Wartelle J, Cruz C. Showering effectiveness for human hair decontamination of the nerve agent VX. Chem Biol Interact. 2015 May 5. 232:94-100. [QxMD MEDLINE Link].
Abou-Donia MB. Organophosphorus ester-induced chronic neurotoxicity. Arch Environ Health. 2003 Aug. 58(8):484-97. [QxMD MEDLINE Link].
Bajgar J, Kuca K, Fusek J, Karasova J, Kassa J, Cabal J. Inhibition of blood cholinesterases following intoxication with VX and its derivatives. J Appl Toxicol. 2007 Sep-Oct. 27(5):458-63. [QxMD MEDLINE Link].
Baker MD. Antidotes for nerve agent poisoning: should we differentiate children from adults?. Curr Opin Pediatr. 2007 Apr. 19(2):211-5. [QxMD MEDLINE Link].
Bowers MB Jr, Goodman E, Sim VM. Some behavioral changes in man following anticholinesterase administration. J Nerv Ment Dis. 1964 Apr. 138:383-9. [QxMD MEDLINE Link].
Chilcott RP, Dalton CH, Hill I. In vivo skin absorption and distribution of the nerve agent VX (O-ethyl-S-[2(diisopropylamino)ethyl]methylphosphonothioate) in the domestic white pig. Hum Exp Toxicol. 2005 Jul. 24(7):347-52. [QxMD MEDLINE Link].
Corvino TF, Nahata MC, Angelos MG, Tschampel MM, Morosco RS, Zerkle J. Availability, stability, and sterility of pralidoxime for mass casualty use. Ann Emerg Med. 2006 Mar. 47(3):272-7. [QxMD MEDLINE Link].
Cresthull P, Konn WS, Musselman NP. Percutaneous exposure of the arm or the forearm of a man to VX vapor. CRDLR 3176. 1963.
Dunn MA, Sidell FR. Progress in medical defense against nerve agents. JAMA. 1989 Aug 4. 262(5):649-52. [QxMD MEDLINE Link].
Foltin G, Tunik M, Curran J, Marshall L, Bove J, van Amerongen R. Pediatric nerve agent poisoning: medical and operational considerations for emergency medical services in a large American city. Pediatr Emerg Care. 2006 Apr. 22(4):239-44. [QxMD MEDLINE Link].
Freeman G, Ludamann H, Cornblath M. Cardiovascular and respiratory effects of an acute parathion poisoning in dogs with particular regard to ventricular fibrillation. Medical Laboratory Research Report 303. AD042287. 1954.
Hamilton MG, Hill I, Conley J. Clinical aspects of percutaneous poisoning by the chemical warfare agent VX:effects of application site and decontamination. Mil Med. 2004 Nov. 169(11):856-62. [QxMD MEDLINE Link].
Harris LW, Stitcher DL. Reactivation of VX-inhibited cholinesterase by 2-PAM and HS-6 in rats. Drug Chem Toxicol. 1983. 6(3):235-40. [QxMD MEDLINE Link].
Henderson JD, Higgins RJ, Dacre JC, Wilson BW. Neurotoxicity of acute and repeated treatments of tabun, paraoxon, diisopropyl fluorophosphate and isofenphos to the hen. Toxicology. 1992. 72(2):117-29. [QxMD MEDLINE Link].
Kales SN, Christiani DC. Acute chemical emergencies. N Engl J Med. 2004 Feb 19. 350(8):800-8. [QxMD MEDLINE Link].
Keyes DC, Burstein JL, Schwartz RC, Swienton R. Medical Response to Terrorism: Preparedness and Clinical Practice. 2004. 449.
Kimura KK, McNamara BP, Sim VM. Intravenous administration of VX in man. CRDLR 3017. 1960.
Kuca K, Jun D, Bajgar J. Currently used cholinesterase reactivators against nerve agent intoxication: comparison of their effectivity in vitro. Drug Chem Toxicol. 2007. 30(1):31-40. [QxMD MEDLINE Link].
Kunkel AM, O'Leary JF, Jones AH. Atropine-induced ventricular fibrillation during cyanosis caused by organophosphorus poisoning. AD758441. Edgewood Arsenal Technical Report 4711. 1973.
LeBlanc FN, Benson BE, Gilg AD. A severe organophosphate poisoning requiring the use of an atropine drip. J Toxicol Clin Toxicol. 1986. 24(1):69-76. [QxMD MEDLINE Link].
Lubash GD, Clark BJ. Some metabolic studies in humans following percutaneous exposure to VX. CRDLR 3033. 1960.
Marrs TC, Rice P, Vale JA. The role of oximes in the treatment of nerve agent poisoning in civilian casualties. Toxicol Rev. 2006. 25(4):297-323. [QxMD MEDLINE Link].
McDonough JH, McLeod CG, Nipwoda MT. Direct microinjection of soman or VX into the amygdala produces repetitive limbic convulsions and neuropathology. Brain Res. 1987 Dec 1. 435(1-2):123-37. [QxMD MEDLINE Link].
Newmark J. The birth of nerve agent warfare: lessons from Syed Abbas Foroutan. Neurology. 2004 May 11. 62(9):1590-6. [QxMD MEDLINE Link].
Newmark J. Therapy for nerve agent poisoning. Arch Neurol. 2004 May. 61(5):649-52. [QxMD MEDLINE Link].
Newmark J, Hurst CG. Acute chemical emergencies. N Engl J Med. 2004 May 13. 350(20):2102-4; author reply 2102-4. [QxMD MEDLINE Link].
Nozaki H, Aikawa N, Fujishima S, et al. A case of VX poisoning and the difference from sarin. Lancet. 1995 Sep 9. 346(8976):698-9. [QxMD MEDLINE Link].
Oberst FW, Ross RS, Christensen MK. Resuscitation of dogs poisoned by inhalation of the nerve gas GB. Mil Med. 1956. 119:377-386.
Okudera H. Clinical features on nerve gas terrorism in Matsumoto. J Clin Neurosci. 2002 Jan. 9(1):17-21. [QxMD MEDLINE Link].
Okumura T, Suzuki K, Fukuda A, et al. The Tokyo subway sarin attack: disaster management, Part 1: Community emergency response. Acad Emerg Med. 1998 Jun. 5(6):613-7. [QxMD MEDLINE Link].
Parker RM, Crowell JA, Bucci TJ. Negative delayed neuropathy study in chickens after treatment with isopropyl methylphosphonofluoridate (sarin, type 1). Toxicologist. 1988. 8:248.
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].
Robineau P, Guittin P. Effects of an organophosphorous compound on cardiac rhythm and haemodynamics in anaesthetized and conscious beagle dogs. Toxicol Lett. 1987 Jun. 37(1):95-102. [QxMD MEDLINE Link].
Schier JG, Ravikumar PR, Nelson LS, Heller MB, Howland MA, Hoffman RS. Preparing for chemical terrorism: stability of injectable atropine sulfate. Acad Emerg Med. 2004 Apr. 11(4):329-34. [QxMD MEDLINE Link].
Shih TM, Rowland TC, McDonough JH. Anticonvulsants for nerve agent-induced seizures: The influence of the therapeutic dose of atropine. J Pharmacol Exp Ther. 2007 Jan. 320(1):154-61. [QxMD MEDLINE Link].
Sidell FR. Clinical considerations in nerve agent intoxication. Somani SM, ed. Chemical Warfare Agents. San Diego: Harcourt Brace Jovanovich; 1992.
Sidell FR. Human responses to intravenous VX. EATR 4082. 1967.
Sidell FR. Soman and sarin: clinical manifestations and treatment of accidental poisoning by organophosphates. Clin Toxicol. 1974. 7(1):1-17. [QxMD MEDLINE Link].
Sidell FR, Groff WA. The reactivatibility of cholinesterase inhibited by VX and sarin in man. Toxicol Appl Pharmacol. 1974 Feb. 27(2):241-52. [QxMD MEDLINE Link].
Sim VM. Variability of different intact human skin sites to the penetration of VX. CRDLR 3122. AD271163. 1962.
Sim VM, Stubbs JL. VX percutaneous studies in man. CRDLR 3015. AD318533. 1960.
Tokuda Y, Kikuchi M, Takahashi O, Stein GH. 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].
Volans GN, Karalliedde L. Long-term effects of chemical weapons. Lancet. 2002 Dec. 360 Suppl:s35-6. [QxMD MEDLINE Link].
Wills JH, DeArmon IA. A statistical study of the Ademek report. Medical Laboratory Special Report 54. AD045106.
Wright PG. An analysis of the central and peripheral components of respiratory failure produced by anticholinesterase poisoning in the rabbit. J Physiol. 1954 Oct 28. 126(1):52-70. [QxMD MEDLINE Link].

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Table.

Code Name	Chemical Name
VX	O-Ethyl-S-[2(diisopropylamino)ethyl] methylphosphonothioate
VE	O-Ethyl-S-[2-(diethylamino)ethyl] ethylphosphonothioate
VG	O,O-Diethyl-S-[2-(diethylamino)ethyl] phosphorothioate
VM	O-Ethyl-S-[2-(diethylamino)ethyl] methylphosphonothioate
V-gas	Russian equivalent of VX

Table.

Agent	LCt50 (mg ⋅ min/m³)	LD50 (mg)	Aging Half-Life
Tabun (GA)	400	1000	46 h
Sarin (GB)	100	1700	5.2-12 h
Soman (GD)	50	100	40 sec to 10 min
VX	10	10	50-60 h

Table 3. Pharmacologic Effects of Nerve Agents*

Receptor Involved	Clinical Effect
Acetylcholine, GABA, N -methyl-D -aspartate: Central (CNS)	Anxiety, restlessness, seizures, failure to concentrate, depression, coma, apnea
Acetylcholine: Muscarinic Postganglionic parasympathetic	"DUMBELS" (commonly used mnemonic) D - Diarrhea U - Urination M - Miosis B - Bronchorrhea, bronchoconstriction E - Emesis L - Lacrimation S - Salivation Note: The other commonly used mnemonic "SLUDGE" is not used here, as it does not include an important sign and symptom: bronchorrhea and bronchoconstriction.
Acetylcholine: Nicotinic Motor endplate Sympathetic and parasympathetic ganglia	Pallor, tachycardia, hypertension, muscle weakness and/or paralysis, fasciculations Note: Some use the days of the week as an easy mnemonic for these: M - Mydriasis T - Tachycardia W - Weakness tH - Hypertension F - Fasciculations
* Adapted from Marrs, Maynard, and Sidell.^[10]

Table 4. Severity of Toxicity from Liquid and Vapor Exposures

Severity of Exposure	Signs and Symptoms - Liquid	Signs and Symptoms - Vapor
Onset of symptoms	Possibly delayed toxicity	Rapidly manifesting toxicity
Minimal	Localized sweating at site Localized fasciculations at site	Miosis Rhinorrhea Mild dyspnea
Moderate	Fasciculations Diaphoresis Nausea, vomiting, and diarrhea Generalized weakness	Above symptoms and the following: Moderate-to-marked dyspnea (bronchorrhea and/or bronchoconstriction)
Severe	Above symptoms and the following: Loss of consciousness Seizures Generalized fasciculations Flaccid paralysis and apnea	Above symptoms and the following: Loss of consciousness Seizures Generalized fasciculations Flaccid paralysis and apnea

Table 5. Drugs Used to Treat Nerve Agent–Poisoned Patients*

Drug	Dose	Route	Indications	Contraindications
Atropine	2 mg q5-10min prn Note: the Mark 1 kit contains 2 mg of atropine	IV/IM/ETT	Excessive muscarinic symptoms	Relative - IV route in hypoxia has been associated with ventricular fibrillation
2-PAM Cl (pralidoxime chloride, Protopam)	15-25 mg/kg over 20 min; can be repeated after 1 h Note: The Mark 1 kit contains 600 mg of pralidoxime.	IV/IM	Symptomatic nerve agent poisoning	Rapid infusion may result in hypertension
Diazepam (Valium)	2-5 mg IV or 10 mg IM	IV/IM	Active seizures; administer as prophylaxis if moderate or severe signs of poisoning are present	None
*Adapted from Sidell.

Table 6. Summary of Treatment Modalities According to Severity of Exposure*

Severity/Route of Exposure	Atropine	2-PAM Cl	Diazepam	Other
Suspected	No	No	No	Decontamination and 18-h observation for liquid exposures
Mild	2 mg for severe rhinorrhea or dyspnea; may repeat prn	Administer if patient has nonimproving dyspnea or GI symptoms	No	Decontamination and 18-h observation for liquid exposures; oxygen
Moderate	6 mg; may require repeat doses	Administer with atropine	Administer even in absence of seizures	Decontamination, oxygen
Severe	Start with 6 mg; may need to repeat	Administer with atropine; should repeat once or twice	Administer even in absence of seizures	ABCs, decontamination
*Adapted from Sidell.

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Author

Daniel C Keyes, MD, MPH Associate Chair, Academic Affairs, Department of Emergency Medicine, St Joseph Mercy Hospital; Clinical Faculty, Emergency Medicine Residency, University of Michigan Medical School; Clinical Associate Professor, Department of Surgery, Division of Emergency Medicine and Toxicology, University of Texas Southwestern School of Medicine

Daniel C Keyes, MD, MPH is a member of the following medical societies: American Association of Poison Control Centers, American College of Emergency Physicians, American College of Medical Toxicology, American College of Physician Executives, American College of Physicians

Disclosure: Nothing to disclose.

Coauthor(s)

Fernando L Benitez, MD Assistant Medical Director, Dallas Metropolitan BioTel (EMS) System; Associate Professor in Emergency Medicine, Department of Surgery, Division of Emergency Medicine, University of Texas Southwestern Medical Center and Parkland Health and Hospital

Fernando L Benitez, MD is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, National Association of EMS Physicians

Disclosure: Nothing to disclose.

Larissa I Velez-Daubon, MD Professor, Program Director, Department Emergency Medicine, University of Texas Southwestern Medical School, Parkland Memorial Hospital; Staff Toxicologist, Department of Emergency Medicine, North Texas Poison Center, Parkland Memorial Hospital

Larissa I Velez-Daubon, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Emergency Physicians, American College of Medical Toxicology, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

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

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Duane C Caneva, MD, MSc Senior Medical Advisor to Customs and Border Protection, Department of Homeland Security (DHS) Office of Health Affairs; Federal Co-Chair, Health, Medical, Responder Safety Subgroup, Interagency Board (IAB)

Disclosure: Nothing to disclose.

Additional Contributors

Fred Henretig, MD Director, Section of Clinical Toxicology, Professor, Medical Director, Delaware Valley Regional Poison Control Center, Departments of Emergency Medicine and Pediatrics, University of Pennsylvania School of Medicine, Children's Hospital

Disclosure: Nothing to disclose.

Sections CBRNE - Nerve Agents, V-series - Ve, Vg, Vm, Vx
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CBRNE - Nerve Agents, V-series - Ve, Vg, Vm, Vx Differential Diagnoses

Differential Diagnoses

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