Recent Developments in the Clinical Management of Weaponized Nerve Agent Toxicity

  • Alexander F. BarbutoEmail author
  • Peter R. Chai


Human exposure to weaponized organophosphates (e.g. nerve agents) occurs in the context of military and terrorist attacks, assassinations, laboratory accidents, and suicide attempts. Increasing global tensions have led to renewed scrutiny of nerve agents and their deliberate use to poison political enemies. Poisoning from these highly potent agents present several challenges. Toxicitiy from these agents may persist untreated if clinicians do not recognize the resultant cholinergic toxidrome. Despite clinicians lack of familiarity with nerve agent toxicity, large scale exposures due to chemical munitions may significantly stress healthcare systems and deplete antidote availability. Finally, recent history suggests that environmental persistence of some nerve agents may pose additional threat due to delayed exposure and injury to innocent bystanders. This chapter reviews important advances in the clinical management of individuals exposed to nerve agents. It discusses contingency management and alternate antidotes in the setting of mass depletion of existing antidote stock.


  1. ACMT. 2017. American college of medical toxicology. Position statement: Guidance for the use of intravenous lipid emulsion. Journal of Medical Toxicology 13 (1): 124–125.CrossRefGoogle Scholar
  2. Ali-Melkkila, T.M., T. Kaila, J. Kanto, and E. IIsalo. 1990. Pharmacokinetics of I.M. glycopyrronium. British Journal of Anaesthesia 64: 667–669.CrossRefGoogle Scholar
  3. Allon, N., L. Raveh, E. Gilat, E. Cohen, J. Grunwald, and Y. Ashani. 1998. Prophylaxis against soman inhalation toxicity in guinea pigs by pretreatment alone with human serum butyrylcholinesterase. Toxicology Science 43 (2): 121–128.Google Scholar
  4. Anderson, D.R., L.W. Harris, S.L. Bowersox, W.J. Lennox, and J.C. Anders. 1994. Efficacy of injectable anticholinergic drugs against soman-induced convulsive/subconvulsive activity. Drug and Chemical Toxicology 17 (2): 139–148.CrossRefGoogle Scholar
  5. Arendse, R., and E. Irusen. 2009. An atropine and glycopyrrolate combination reduces mortality in organophosphate poisoning. Human & Experimental Toxicology 28: 715–720.CrossRefGoogle Scholar
  6. Baker, M.D. 2007. Antidotes for nerve agent Poisoning: Should we differentiate children from adults? Current Opinion in Pediatrics 19: 211–215.CrossRefGoogle Scholar
  7. Balali-Mood, M., and K. Balali-Mood. 2008. Neurotoxic disorders of organophosphorus compounds and their managements. Archives of Iranian Medicine 11: 65–89.Google Scholar
  8. Bao, H.X., P.J. Tong, C.X. Li, J. Du, B.Y. Chen, Z.H. Huang, and Y. Wang. 2017. Efficacy of fresh packed red blood transfusion in organophosphate poisoning. Medicine 96 (11).CrossRefGoogle Scholar
  9. Baraka, A., M. Saab, M.R. Salem, and A.P. Winnie. 1977. Control of gastric acidity by glycopyrrolate premedication in the parturient. Anesthesia and Analgesia 56 (5): 642–645.CrossRefGoogle Scholar
  10. Barbier, L., et al. 2015. Beneficial effects of a ketamine/atropine combination in soman-poisoned rats under a neutral thermal environment. Neurotoxicology 50: 10–19.CrossRefGoogle Scholar
  11. Bardin, P., and S. VanEeden. 1990. Organophosphate poisoning: grading the severity and comparing treatment between atropine and glycopyrrolate. Critical Care Medicine 18 (9): 956–960.CrossRefGoogle Scholar
  12. Basarslan, S.K., H. Alp, S. Senol, O. Evliyaoglu, and U. Ozkan. 2014. Is intralipid fat emulsion a promising therapeutic strategy on neurotoxicity induced by malathion in rats? European Review for Medical and Pharmacological Sciences 18 (4): 471–476.Google Scholar
  13. BBC. 2018. Russian spy: What happened to Sergei and Yulia Skripal. BBC News. 27 Sep 2018. Accessed 1 Feb 2019.
  14. Benschop, H.P., and L.P.A. DeJong. 1988. Nerve agent stereoisomers: Analysis, isolation and toxicology. Accounts of Chemical Research 21 (10): 368–374.CrossRefGoogle Scholar
  15. Black, R.M. 2010. History and perspectives of bioanalytical methods for chemical warfare agent detection. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences 878 (17-18): 1207–1215.CrossRefGoogle Scholar
  16. Buchanan J, Sumpter K, Abercrombie P, Tevault D. 2009. Vapor pressure of GB. ECBC-TR-686. Edgewood Chemical Biological Center, US Army Research, Development and Engineering Command, April, 2009.Google Scholar
  17. Carpentier, P., A. Foquin, G. Rondouin, M. Lerner Natoli, De Groot DMG, and G. Lallement. 2000. Effects of atropine sulphate on seizure activity and brain damage produced by soman in guinea-pigs: ECoG correlates of neuropathology. Neurotoxicology 2: 521–540.Google Scholar
  18. Cave, G., and M. Harvey. 2009. Intravenous lipid emulsion as antidote beyond local anesthetic toxicity: A systematic review. Academic Emergency Medicine 16: 815–824.CrossRefGoogle Scholar
  19. CDC. 2014. Toxic substances portal – Nerve agents (GA, GB, GD, VX). Last updated 21 Oct 2014. Accessed 17 Jan 2018.
  20. ———. 2018. Strategic National Stockpile. Last updated 12 Dec 2018. Accessed 27 Dec 2018.
  21. Chai, P.R., B.D. Hayes, T.B. Erickson, and E.W. Boyer. 2018. Novichok agents: A historical, current, and toxicological perspective. Toxicology Communication 2 (1): 45–48. Epub 2018 Jun 29.CrossRefGoogle Scholar
  22. CHEMM website. 2019. Nerve Agents –Emergency Department/Hospital management. Last updated 23 Jan 2019. Accessed 1 Feb 2019.
  23. Dillman, J.F., III, C.S. Phillips, D.M. Kniffin, C.P. Tompkins, T.A. Hamilton, and R.K. Kan. 2009. Gene expression profile of rat hippocampus following exposure to the acetylcholinesterase inhibitor soman. Chemical Research in Toxicology 22: 633–638.CrossRefGoogle Scholar
  24. Dunn, C., S.B. Bird, and R. Gaspari. 2012. Intralipid fat emulsion decreases respiratory failure in a rat model of parathion exposure. Academic Emergency Medicine 19 (5): 504–509.CrossRefGoogle Scholar
  25. Eddleston, M., and F.R. Chowdhury. 2016. Pharmacological treatment of organophosphorus insecticide poisoning: The old and the (possible) new. British Journal of Clinical Pharmacology 81: 462–470.CrossRefGoogle Scholar
  26. Eisenkraft, A., and A. Falk. 2016. The possible role of intravenous lipid emulsion in the treatment of chemical warfare agent poisoning. Toxicology Reports 3: 202–210.CrossRefGoogle Scholar
  27. Elbe, S., A. Roemer-Mahler, and C. Long. 2015. Medical countermeasures for national security: A new government role in the pharmaceuticalization of society. Social Science & Medicine 131: 263–271.CrossRefGoogle Scholar
  28. Ellison, D.H. 2008. Handbook of chemical and biological warfare agents. 2nd ed. Boca Raton, FL: Taylor and Francis Group.Google Scholar
  29. El-Naggar, Ael-R, M.S. Abdalla, A.S. El-Sebaey, and S.M. Badawy. 2009. Clinical findings and cholinesterase levels in children of organophosphates and carbamates poisoning. European Journal of Pediatrics 168 (8): 951–956.CrossRefGoogle Scholar
  30. Erdmann, W.D., and H. Engelhard. 1964. Pharmacological-toxicological investigations with the dichloride of the bis- [4-hydroxyiminomethyl-pyridinium (1) -methyl] -ether, a new esterase-reactivator. Drug Discovery 14: 5–11.Google Scholar
  31. Eyer, P., I. Hagedorn, and B. Ladstetter. 1988. Study on the stability of the oxime HI 6 in aqueous solution. Archives of Toxicology 62 (2-3): 224–226.CrossRefGoogle Scholar
  32. FDA. n.d. U.S. Food & Drug Administration, “Emergency use authorization” Accessed 27 Dec 2018.
  33. Ghanem, E., and F.M. Raushe. 2005. Detoxification of organophosphate nerve agents by bacterial phosphotriesterase. Toxicology and Applied Pharmacology 207: S459–S470.CrossRefGoogle Scholar
  34. Gorecki L, Soukup O, Kucera T, Malinak D, Jun D, Kuca K, Musilek K, Korabecny J. (2018): Oxime K203: a drug candidate for the treatment of tabun intoxication, Arch Toxicol. Dec 18.Google Scholar
  35. Guard, B.C., and S.J. Wiltshire. 1996. The effect of glycopyrrolate on postoperative pain and analgesic requirements following laparoscopic sterilization. Anaesthesia 51 (12): 1173–1175.CrossRefGoogle Scholar
  36. Hague, J., and J. Derr. 2004. Military implications of atropine hypersensitivity. Military Medicine 169 (5): 389–391.CrossRefGoogle Scholar
  37. Harris, L., B. Talbot, W. Lennox, D. Anderson, and R. Solana. 1991. Physostigmine (alone and together with adjunct) pretreatment against soman, sarin, tabun and VX intoxication. Drug and Chemical Toxicology 14 (3): 265–281.CrossRefGoogle Scholar
  38. Higgins, G.M., J.F. Muniz, and L.A. McCauley. 2001. Monitoring acetylcholinesterase levels in migrant agricultural workers and their children using a portable test kit. Journal of Agricultural Safety and Health 7 (1): 35–49.CrossRefGoogle Scholar
  39. Hirbec, H., M. Gaviria, and Vignon J. Gacyclidine. 2001. A new neuroprotective agent acting at the N-methyl-D-aspartate receptor. CNS Drug Reviews 7 (2): 172–198.CrossRefGoogle Scholar
  40. Hoegberg, L.C.G., T.C. Bania, V. Lavergne, et al. 2016. Systematic review of the effect of intravenous lipid emulsion therapy for local anesthetic toxicity. Clinical Toxicology 54: 167–193.CrossRefGoogle Scholar
  41. Institute of Medicine. 2010. Medical countermeasures dispensing: Emergency use authorization and the postal model, workshop summary. Institute of Medicine (US). Forum on Medical and Public Health Preparedness for Catastrophic Events. Washington, DC. National Academies Press. 2010. Available at Accessed 27 Dec 2018.
  42. Jamshidi, F., A. Yazdanbakhsh, M. Jamalian, et al. 2018. Therapeutic effect of adding magnesium sulfate in treatment of organophosphorus poisoning. Open Access Macedonia Journal of Medical Science 6 (11): 2051–2056.CrossRefGoogle Scholar
  43. Jortani, S., J. Snyder, and R. Valdes. 2000. The role of the clinical laboratory in managing chemical or biological terrorism. Clinical Chemistry 12: 11.Google Scholar
  44. Josse, D., J. Wartelle, and C. Cruz. 2015. Showering effectiveness for human hair decontamination of the nerve agent VX. Chemico-Biological Interactions 232: 94–100.CrossRefGoogle Scholar
  45. Kassa, J., D. Jun, K. Kuca, and J. Bajgar. 2007. Comparison of reactivating and therapeutic efficacy of two salts of the oxime HI-6 against tabun, soman and cyclosarin in rats. Basic & Clinical Pharmacology & Toxicology 101 (5): 328–332.CrossRefGoogle Scholar
  46. Katalan, S., S. Lazar, R. Brandeis, I. Rabinovitz, I. Egoz, E. Grauer, E. Bloch-Shilderman, and L. Raveh. 2013. Magnesium sulfate treatment against sarin poisoning: dissociation between overt convulsions and recorded cortical seizure activity. Archives of Toxicology 87 (2): 347–360.CrossRefGoogle Scholar
  47. Knechtges P. (2008): An evaluation of blood cholinesterase testing: methods for military health surveillance, USACEHR Technical Report 0801. May, 2008. United States Army Center for Environmental Health Research. Fort Detrick.Google Scholar
  48. Kozer, E., A. Mordel, S. Bar Haim, M. Bulkowstein, M. Berkovitch, and Bentur Y. Pediatric. 2005. Poisoning from trimedoxime (TMB4) and atropine automatic injectors. The Journal of Pediatrics 146: 41–44.CrossRefGoogle Scholar
  49. Lallement, G., D. Baubichon, D. Clarençon, M. Galonnier, M. Peoc’h, and P. Carpentier. 1999a. Review of the value of gacyclidine (GK-11) as adjuvant medication to conventional treatments of organophosphate poisoning: primate experiments mimicking various scenarios of military or terrorist attack by soman. Neurotoxicology 20 (4): 675–684.Google Scholar
  50. Lallement, G., D. Clarençon, M. Galonnier, D. Baubichon, M.F. Burckhart, and M. Peoc’h. 1999b. Acute soman poisoning in primates neither pretreated nor receiving immediate therapy: Value of gacyclidine (GK-11) in delayed medical support. Archives of Toxicology 73 (2): 115–122.CrossRefGoogle Scholar
  51. Leal, J.K., M.J. Adjobo-Hermans, R. Brock, and G.J. Bosman. 2017. Acetylcholinesterase provides new insights into red blood cell ageing in vivo and in vitro. Blood Transfusion 15 (3): 232.Google Scholar
  52. Lennox, W.J., L.W. Harris, D.R. Anderson, R.P. Solana, M.L. Murrow, and J.V. Wade. 1992. Successful pretreatment/therapy of soman, sarin and VX intoxication. Drug and Chemical Toxicology 15 (4): 271–283.CrossRefGoogle Scholar
  53. Lessenger, J.E., and B.E. Reese. 1999. Rational use of cholinesterase activity testing in pesticide poisoning. The Journal of the American Board of Family Practice 12 (4): 307–314.CrossRefGoogle Scholar
  54. Lifshitz, M., M. Rotenberg, S. Sofer, T. Tamiri, E. Shahak, and S. Almog. 1994. Carbamate poisoning and oxime treatment in children: A clinical and laboratory study. Pediatrics 93 (4): 652–655.Google Scholar
  55. Lundy, P.M., A.S. Hansen, B.T. Hand, and C.A. Boulet. 1992. Comparison of several oximes against poisoning by soman, tabun and GF. Toxicology 72: 99–105.CrossRefGoogle Scholar
  56. Lundy, P., M. Hamilton, T. Sawyer, and J. Mikler. 2011. Comparative protective effects of HI-6 and MMB-4 against organophosphorous nerve agent poisoning. Toxicology 285 (3): 90–96.CrossRefGoogle Scholar
  57. Madsen, JM. (n.d.): USAMRICD special publication 98-01, pyridostigmine. United States Army Medical Research Institute of Chemical Defense. Accessed 23 Jan 2018.
  58. McDonough JH. 2002. Midazolam: An improved anticonvulsant treatment for nerve agent-induced seizures, Army Medical Research Inst of Chemical Defense. Aberdeen Proving Ground, MD. 2002.Google Scholar
  59. McDonough, J.H., and T.M. Shin. 1993. Pharmacological modulation of soman-induced seizures. Neuroscience and Biobehavioral Reviews 17 (2): 203–215.CrossRefGoogle Scholar
  60. McDonough, J., J. McMonagle, T. Copeland, L.D. Zoeffel, and T.M. Shih. 1999. Comparative evaluation of benzodiazepines for control of soman-induced seizures. Archives of Toxicology 73 (8-9): 473–478.CrossRefGoogle Scholar
  61. McDonough, J., L.D. Zoeffel, J. McMonagle, T. Copeland, C.D. Smith, and T.M. Shih. 2000. Anticonvulsant treatment of nerve agent seizures: Anticholinergics versus diazepam in soman-intoxicated guinea pigs. Epilepsy Research 38: 1–14.CrossRefGoogle Scholar
  62. McEvoy, G.K., ed. 2012. Drug information 2012. Vol. 1299-1303, 2903–2904. Bethesda: American Society of Health-System Pharmacists.Google Scholar
  63. Meaney, C.J., H. Sareh, B.D. Hayes, and J.P. Gonzales. 2013. Intravenous lipid emulsion in the management of amlodipine overdose. Hospital Pharmacy 48: 848–854.CrossRefGoogle Scholar
  64. Medical Countermeasures Database. 2017. HI-6, last updated 10 Nov 2017.Google Scholar
  65. Menes K, Tintinalli J, Plaster L. 2017. How one Las Vegas ED saved hundreds of lives after the worst mass shooting in U.S. history. 3 Nov 2017. Accessed 12 Jan 2018.
  66. Meridian Medical Technologies. 2008. Product label: Pralidoxime Chloride injection [Meridian Medical Technologies, Inc.] Last revised: June 2008.
  67. Miller V. 2004. The health effects of project shad chemical agent: VX nerve agent. The National Academies. Silver Spring. Contract No. IOM-2794-04-00.Google Scholar
  68. Miller, M., M. Marty, A. Arcus, J. Brown, D. Morry, and M. Sandy. 2016. Differences between children and adults: Implications for risk Assessment at California EPA. International Journal of Toxicology 21: 403–418.CrossRefGoogle Scholar
  69. Mion, G., J.P. Tourtier, F. Petitjeans, F. Dorandeu, G. Lallement, et al. 2003. Neuroprotective and antiepileptic activities of ketamine in nerve agent poisoning. Anesthesiology 98 (6): 1517.CrossRefGoogle Scholar
  70. Mir, S.A., and R. Rasool. 2014. Reversal of cardiovascular toxicity in severe organophosphate poisoning with 20% Intralipid emulsion therapy: Case report and review of literature. Asia Pacific Journal of Medical Toxicology 3: 169–172.Google Scholar
  71. Moeller B, Espelien B, Weber W, Kuehl P, Doyle-Eisele M, Garner CE et al. (2018): The pharmacokinetics of ketamine following intramuscular injection to F344 rats, Drug Testing and Analysis. 2018 Jan 1.Google Scholar
  72. Moshiri, M., E. Darchini-Maragheh, and M. Balali-Mood. 2012. Advances in toxicology and medical treatment of chemical warfare nerve agents. DARU Journal of Pharmaceutical Sciences 20 (1): 81. Scholar
  73. Ohbu, S., et al. 1997. Sarin poisoning on Tokyo subway. Southern Medical Journal 90 (6): 587–593.CrossRefGoogle Scholar
  74. Okayama, H., T. Aikawa, M. Okayama, H. Sasaki, S. Mue, and T. Takishima. 1987. Bronchodilating effect of intravenous magnesium sulfate in bronchial asthma. JAMA 257: 1076–1078.CrossRefGoogle Scholar
  75. Okumura, S., T. Okumura, S. Ishimatsu, K. Miura, H. Maekawa, and T. Naito. 2005. Clinical review: Tokyo - protecting the health care worker during a chemical mass casualty event: An important issue of continuing relevance. Critical Care 9 (4): 397–400.CrossRefGoogle Scholar
  76. OPCW. 2001. The sarin gas Attack in Japan and the related forensic investigation. OPCW News. 1 June 2001. Accessed 13 Dec 2018.
  77. ———. 2018. Issues report on technical assistance requested by the United Kingdom. 12 Apr 2018. Accessed 1 Feb 2019.
  78. Ozcan, M.S., and G. Weinberg. 2014. Intravenous lipid emulsion for the treatment of drug toxicity. Journal of Intensive Care Medicine 29: 59–70.CrossRefGoogle Scholar
  79. Pajoumand, A., S. Shadnia, A. Rezaie, M. Abdi, and M. Abdollahi. 2004. Benefits of magnesium sulfate in the management of acute human poisoning by organophosphorus insecticides. Human & Experimental Toxicology 23 (12): 565–569.CrossRefGoogle Scholar
  80. Peronne, J., F. Henretig, M. Sims, M. Beers, and M.A. Grippi. 2003. A role for ipratropium in chemical terrorism preparedness. Academic Emergency Medicine 10: 290.CrossRefGoogle Scholar
  81. Petroianu, G.A., M.Y. Hasan, S.M. Nurulain, N. Nagelkerke, J. Kassa, and K. Kuča. 2007a. New K-oximes (K-27 and K-48) in comparison with obidoxime (LuH-6), HI-6, trimedoxime (TMB-4), and pralidoxime (2-PAM): Survival in tats exposed IP to the organophosphate paraoxon. Toxicology Mechanisms and Methods 17 (7): 401–408.CrossRefGoogle Scholar
  82. Petroianu, G.A., S.M. Nurulain, N. Nagelkerke, M. Shafiullah, J. Kassa, and K. Kuca. 2007b. Five oximes (K-27, K-48, obidoxime, HI-6 and trimedoxime) in comparison with pralidoxime: Survival in rats exposed to methyl-paraoxon. Journal of Applied Toxicology 27 (5): 453–457.CrossRefGoogle Scholar
  83. PHE (2018): Stockpile products. Public Health Emergency. Last updated 17 Dec 2018. Accessed 21 Jan 2019.
  84. Prall, Y.G., K.K. Gambhir, and F.R. Ampy. 1998. Acetylcholinesterase: an enzymatic marker of human red blood cell aging. Life Sciences 63: 177–184.CrossRefGoogle Scholar
  85. Proakis, A.G., and G.B. Harris. 1978. Comparative penetration of glycopyrrolate and atropine across the blood-brain and placental barriers in anaesthetised dogs. Anaesthesiology 48: 339–344.CrossRefGoogle Scholar
  86. Raipal, S., G. Mittal, R. Sachdeva, M. Chhillar, R. Ali, S.S. Agrawal, R. Kashyap, and A. Bhatnagar. 2009. Development of atropine sulphate nasal drops and its pharmacokinetic safety evaluation in healthy human volunteers. Environmental Toxicology and Pharmacology 27: 206–211.CrossRefGoogle Scholar
  87. Raipal, S., R. Ali, A. Bhatnagar, S.K. Bhandari, and G. Mittal. 2010, 28. Clinical and bioavailability studies of sublingually administered atropine sulphate. The American Journal of Emergency Medicine: 143–150.Google Scholar
  88. RamaRao, G., and B.K. Bhattacharya. 2012. Multiple signal transduction pathways alterations during nerve agent toxicity. Toxicology Letters 208 (1): 16–22.CrossRefGoogle Scholar
  89. RamaRao, G., P. Afley, J. Acharya, and B. Bhattacharya. 2014. Efficacy of antidotes (midazolam, atropine and HI-6) on nerve agent induced molecular and neuropathological changes. BMC Neuroscience 15 (1): 47. Scholar
  90. Raveh, L., E. Grauer, J. Grunwald, E. Cohen, and Y. Ashani. 1997. The stoichiometry of protection against soman and VX toxicity in monkeys pretreated with human butyrylcholinesterase. Toxicology and Applied Pharmacology 145 (1): 43–53.CrossRefGoogle Scholar
  91. Reddy, S.D., and D.S. Reddy. 2015. Midazolam as an anticonvulsant antidote for organophosphate intoxication--A pharmacotherapeutic appraisal. Epilepsia 56 (6): 813–821.CrossRefGoogle Scholar
  92. Rice, H., T.M. Mann, S.J. Armstrong, M.E. Price, A.C. Green, and J.E.H. Tattersall. 2016. The potential role of bioscavenger in the medical management of nerve-agent poisoned casualties. Chemico-Biological Interactions 259: 175–181.CrossRefGoogle Scholar
  93. Robenshtok, Eyal, Shay Luria, Zeev Tashma, and Ariel Hourvitz. 2002. Adverse reaction to atropine and the treatment of organophosphate intoxication. The Israel Medical Association Journal 4: 535–539.Google Scholar
  94. Rosman, Y., A. Eisenkraft, N. Milk, A. Shiyovich, N. Ophir, S. Shrot, et al. 2014. Lessons learned from the Syrian sarin attack: Evaluation of a clinical syndrome through social media. Annals of Internal Medicine 160: 644–648.CrossRefGoogle Scholar
  95. Rowe, B.H., M.L. Edmonds, C.H. Spooner, and C.A. Camargo. 2001. Evidence-based treatments for acute asthma. Respiratory Care 46 (12): 1380–1390.Google Scholar
  96. Ryniak, S., P. Harbut, W. Gozdzik, J. Sokolowski, P. Paciorek, and J. Halas. 2011. Whole blood transfusion in the treatment of an acute organophosphorus poisoning – A case report. Medical Science Monitor 17 (9): CS109–CS111.CrossRefGoogle Scholar
  97. Sacan, O., P. White, B. Tufanogullari, and Klein K. Sugammadex. 2007. Reversal of rocuronium-induced neuromuscular blockade: A comparison with neostigmine–glycopyrrolate and edrophonium–atropine. Anesthesia & Analgesia 104 (3): 569–574.CrossRefGoogle Scholar
  98. Saxena, A., N.B. Hastings, W. Sun, P.A. Dabisch, S.W. Hulet, E.M. Jakubowski, R.J. Mioduszewski, and B.P. Doctor. 2015. Prophylaxis with human serum butyrylcholinesterase protects Göttingen minipigs exposed to a lethal high-dose of sarin vapor. Chemico-Biological Interactions 238: 161–169.CrossRefGoogle Scholar
  99. Schlager, J.W., T.W. Dolzine, J.R. Stewart, G.L. Wannarka, and M.L. Shih. 1991. Operational evaluation of three commercial configurations of atropine/HI-6 wet/dry autoinjectors. Pharmaceutical Research 8 (9): 1191–1194.CrossRefGoogle Scholar
  100. Schwartz MD, Sutter ME, Eisnor D, Kirk MA.. 2018. Contingency medical countermeasures for mass nerve-agent exposure: Use of pharmaceutical alternatives to community stockpiled antidotes, Disaster Med Public Health Prep. 2018 Oct 15:1–8.Google Scholar
  101. Solana, R., C. Gennings, D. Anderson, W. Carter, R. Carchman, and L. Harris. 1989. Comparing the response surfaces of two cholinolytics when used in combination with physostigmine as a pretreatment against organophosphate challenge. Drug and Chemical Toxicology 12 (3-4): 197–219.CrossRefGoogle Scholar
  102. Soukup, O., J. Krůšek, M. Kaniaková, U.K. Kumar, M. Oz, D. Jun, J. Fusek, K. Kuča, and G. Tobin. 2011. Oxime reactivators and their in vivo and in vitro effects on nicotinic receptors. Physiological Research 60 (4): 679–686.CrossRefGoogle Scholar
  103. Stolbach, A., V. Bebarta, M. Beuhler, S. Carstairs, L. Nelson, M. Wahl, P. Wax, and C. McKay. 2018. ACMT position statement: Alternative or contingency countermeasures for acetylcholinesterase inhibiting agents. Journal of Medical Toxicology 14 (3): 261–263.CrossRefGoogle Scholar
  104. Sungurtekin, H., E. Gürses, and C. Balci. 2008. Evaluation of several clinical scoring tools in organophosphate poisoned patients. Clinical Toxicology 44: 121–126. Scholar
  105. Tang, S.Y.H., and J.T.S. Chan. 2002. A review article on nerve agents. Hong Kong Journal Emergency Medicine 9: 83–89.CrossRefGoogle Scholar
  106. Thiermann, H., S. Seidl, and P. Eyer. 1996. HI 6 dimethanesulfonate has better dissolution properties than HI 6 dichloride for application in dry/wet autoinjectors. International Journal of Pharmaceutics 137 (2): 167–176.CrossRefGoogle Scholar
  107. Thiermann, H., U. Mast, R. Klimmek, P. Eyer, A. Hibler, R. Pfab, N. Felgenhauer, and T. Zilker. 1997. Cholinesterase status, pharmacokinetics and laboratory findings during obidoxime therapy in organophosphate poisoned patients. Human & Experimental Toxicology 16 (8): 473–480.CrossRefGoogle Scholar
  108. Towne, A.R., J.M. Pellock, D. Ko, and R.J. DeLorenzo. 1994. Determinants of mortality in status epilepticus. Epilepsia 35 (1): 27–34.CrossRefGoogle Scholar
  109. Tracey, J.A., and H. Gallaghar. 1990. Use of glycopyrrolate and atropine in acute organophosphorus poisoning. Human & Experimental Toxicology 9 (2): 99–100.CrossRefGoogle Scholar
  110. UK Government. 2018. Novichok nerve agent use in Salisbury: UK government response, March to April 2018. Last updated 18 Apr 2018. Accessed 1 Feb 2019.
  111. United States Senate. 1995. Global proliferation of weapons of mass destruction: hearings before the Permanent Subcommittee on Investigations of the Committee on Governmental Affairs, United States Senate, One Hundred Fourth Congress, first session, 24 Chemical Weapons Disarmament in Russia: Problems and Prospects.
  112. US Army. 2005. Potential military chemical/biological agents and compounds. FeM 3-11.9. US Army Training and Doctrine Command, Fort Monroe, VA. January 2005. Ch. 2 Chemical Warfare agents and their properties.Google Scholar
  113. Uysal, M., and S. Karaman. 2018. In vivo effects of intravenous lipid emulsion on lung tissue in an experimental model of acute malathion intoxication. Toxicology and Industrial Health 34 (2): 110–118.CrossRefGoogle Scholar
  114. Van Der Schans, M.J., A. Fidder, D. Van Oeveren, A.G. Hulst, and D. Noort. 2008. Verification of exposure to cholinesterase inhibitors: generic detection of OPCW Schedule 1 nerve agent adducts to human butyrylcholinesterase. Journal of Analytical Toxicology 32 (1): 125–130.CrossRefGoogle Scholar
  115. Vaserhelyi, G., and L. Foldi. 2007. History of Russia’s chemical weapons. AARMS 6 (1): 135–146.Google Scholar
  116. Vijayakumar, H.N., K. Ramya, D.R. Duggappa, K.V. Gowda, K. Sudheesh, S.S. Nethra, and R.R. Rao. 2016. Effect of melatonin on duration of delirium in organophosphorus compound poisoning patients: A double-blind randomised placebo controlled trial. Indian Journal of Anaesthesia 60 (11): 814.CrossRefGoogle Scholar
  117. Vijayakumar, H.N., S. Kannan, C. Tejasvi, D.R. Duggappa, K.M. Veeranna Gowda, and S.S. Nethra. 2017. Study of effect of magnesium sulphate in management of acute organophosphorous pesticide poisoning. Anesthesia, Essays and Researches 11 (1): 192–196.CrossRefGoogle Scholar
  118. Von Bredow, J., K. Corcoran, G. Maitland, A. Kaminskis, N. Adams, and J. Wade. 1991. Efficacy evaluation of physostigmine and anticholinergic adjuncts as a pretreatment for nerve agent intoxication. Fundamental and Applied Toxicology 17 (4): 782–789.CrossRefGoogle Scholar
  119. Whitmore, C., A.R. Cook, T. Mann, M.E. Price, E. Emery, N. Roughley, D. Flint, S. Stubbs, S.J. Armstrong, H. Rice, and J.E.H. Tattersall. 2018. The efficacy of HI-6 DMS in a sustained infusion against percutaneous VX poisoning in the guinea-pig. Toxicology Letters 293: 207–215.CrossRefGoogle Scholar
  120. Worek, F., R. Widmann, O. Knopff, and L. Szinicz. 1998. Reactivating potency of obidoxime, pralidoxime, HI 6 and HLö 7 in human erythrocyte acetylcholinesterase inhibited by highly toxic organophosphorus compounds. Archives of Toxicology 72 (4): 237–243.CrossRefGoogle Scholar
  121. Xue, S.Z., X.J. Ding, and Y. Ding. 1985. Clinical observation and comparison of the effectiveness of several oxime cholinesterase reactivators. Scandinavian Journal of Work, Environment & Health 11 (suppl 4): 46–48.Google Scholar
  122. Zivkovic, A.R., J. Bender, T. Brenner, S. Hofer, and K. Schmidt. 2016. Reduced butyrylcholinesterase activity is an early indicator of trauma-induced acute systemic inflammatory response. Journal of Inflammation Research 9: 221–230.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Harvard Medical Toxicology Program at Boston Children’s HospitalBostonUSA
  2. 2.Harvard Medical School, Division of Medical Toxicology, Department of Emergency MedicineBrigham and Women’s Hospital, Adjunct Faculty, The Fenway InstituteBostonUSA

Personalised recommendations