Medical Aspects of Chemical Warfare (2008) - The Black Vault

Incapacitating Agentsthis chapter.During the Cold War (1945–1991), a great deal ofresearch was directed to chemicals that were not necessarilylethal but would incapacitate enemy personnel.The United States and the former Soviet Union, inparticular, investigated a wide number of pharmacologicalagents for their potential as incapacitants, suchas depressants, hallucinogens, belladonna drugs, andopiate derivatives. 62 The relatively recent developmentof several highly potent opioids is potentially significantfor military use. Fentanyl, the first of these newopioids, is many times more potent than morphine. Super-potentderivatives of fentanyl have since appearedand might be used to produce incapacitation.Since 1996 a number of different analogs of fentanylhave been introduced for use in anesthesia; the bestknown are carfentanil, sufentanil, and remifentanil.Their pharmacological activity is similar to that ofother opiates; consequently, they produce all of theeffects of heroin, including analgesia, euphoria, miosis,and respiratory depression. Because of their high lipidsolubility, regardless of the route of administration, thefentanyls reach the brain very quickly, thus providing avery fast onset of action. This quality led to their popularityas illicit drugs; they were initially unregulated ascontrolled substances, but this loophole has since beenclosed by the US Drug Enforcement Agency. 63Among the multiple opioid receptors, 64 μ-receptorsmediate analgesia, euphoria, physical dependence, anddepression of ventilation, whereas κ-receptors mediatesedation and diuresis. Drugs may act at more thanone opiate receptor, with varying effects. Traditionally,narcotic antagonists such as naloxone and naltrexonehave been used to reverse opioid agonists’ effects. 65Also, when used clinically, longer acting opioids suchas fentanyl may produce renarcotization because ofdifferences in the pharmacokinetics of agonists andantagonists.Because fentanyl is not listed in any of the schedulesof the 1993 Chemical Weapons Convention (CWC), andis traditionally characterized by the rapid onset andshort duration of 15 to 30 minutes of analgesia, somepeople are arguing for it to be legally considered ariot control agent according to the definition set forthin the CWC. 62 On October 23, 2002, at least 129 of thealmost 800 hostages held by Chechen terrorists in theMoscow Dubrovka Theatre Center died when Russianauthorities pumped what many believe was fentanylinto the building. 66–68 Although the Russian authoritiesinsisted that emergency personnel were preparedwith 1,000 doses of antidote in anticipation of the raid,controversy continues over whether local hospitals andphysicians were adequately informed about the gasprior to its use in the rescue operation. 69 According tosome reports, a few Russian officials suggested that amixture of fentanyl and halothane, as well as massivedoses of carfentanil, were used to produce a fully incapacitatingconcentration inside the theater. 70Carfentanil, an even more potent opioid, is oftenused to rapidly immobilize large wild animals, aswell as horses and goats. 71 This drug produces rapidcatatonic immobilization, characterized by limb andneck hyperextension. Adverse effects include musclerigidity, bradypnea, and oxygen desaturation.Recycling and renarcotization have been reported aspossible causes of death when low doses of antagonistare used. This occurs when the antagonist has a shorterduration than the opioid it reverses. To avoid this, thetreating physician must ensure close observation andmay need to administer additional doses of antagonist.Recent research suggests that selective stimulation ofthe 5-HT 4aserotonin receptor might be a way to reverseor prevent μ-receptor–induced respiratory depression.72,73 This is because the 5-HT 4areceptor affects theintracellular concentration of cyclic adenosine monophosphatein respiration-regulating brainstem neuronsin a manner opposite to the μ-receptor. 72 Numerousinvestigators are currently pursuing this promisingline of research, hoping to separate the anesthetic fromthe respiratory effects of μ-agonists.Following antagonist treatment, residual opioidmay still be present at lethal levels, even when it haspartially cleared the body. Although there were naloxonesyringes found in the Dubrovka theater, it isalso possible that the doses given were insufficient toreverse the respiratory depression.Dissociative AnestheticsPCP (Sernyl, Parke Davis and Co, Detroit, Mich),introduced as an anesthetic in the 1950s, has a uniquecombination of pharmacological properties never seenpreviously. 74 Without causing loss of consciousnessor respiratory depression, it prevents awareness ofsurgical pain. For a time it was touted as an anestheticbreakthrough, but as subsequent reports of unnaturalagitation and disruptive behavior began to accumulate,its use in adults was halted. Because it prevented respiratoryproblems, it continued to be used in childrenfor short procedures, but it also produces delirium andfrequently caused management problems.PCP was subsequently designated for use only inveterinary surgery, where its subjective effects areevidently less of a problem. In its place, ketamine(Ketalar, Parke Davis and Co, Detroit, Mich), a shortactingchemical relative of PCP, proved more manageableclinically and became an acceptable anestheticfor certain surgical procedures in both humans and419