69: Neuromuscular Blockers

HISTORY AND EPIDEMIOLOGY

Curare is the generic term for the resinous arrowhead poisons used to paralyze hunted animals.¹⁰⁴ The curare alkaloids are derived from the bark of the Strychnos vine, and the most potent alkaloids, the toxiferines, are derived from Strychnos toxifera. Fortunately for the hunters who used curare, ingestion of their prey did not cause paralysis. Sir Walter Raleigh discovered the use of curare in Guyana in 1595, and he was the first person to bring curare to Europe. Curare played a pivotal role in the discovery of the mechanism of neuromuscular transmission. In 1844, Claude Bernard placed a small piece of dry curare under the skin of a live frog and observed that the frog became limp and died.⁷ He performed an immediate autopsy and discovered that the heart was beating. Because direct muscle stimulation produced contraction but nerve stimulation did not, Bernard concluded that curare paralyzed the motor nerves. He later observed, however, that bathing the isolated nerve did not affect neuromuscular transmission, leading him to conclude: “Curare must act on the terminal plates of motor nerves.”¹⁵ Curare was also used by Nobel Laureate physiologists Charles Sherrington, John Eccles, and Bernard Katz to further elucidate neuromuscular physiology. Its first clinical use was described in 1878 when Hunter used curare to treat patients with tetanus and seizures.¹⁰⁴ In 1932, Raynard West used curare to reduce the muscular rigidity of hemiplegia.¹⁰⁴ The use of curare (d-tubocurarine) in anesthesia spanned almost 60 years until it was replaced by superior agents that caused less histamine release and hypotension.

More recent nonmedical uses of succinylcholine have been less benign.² The anesthesiologist Dr. Carl Coppolino was accused of murdering his wife in 1965 by succinylcholine injection.⁷⁰ In 1983, shortly after Dr. Michael Swango began his internship at Ohio State University Hospital, patients began dying inexplicably, and he was relieved of his duties.⁹⁷ After multiple residencies and jobs over 14 years, extending as far as Mnene Hospital in Zimbabwe, the prosecution secured Swango’s guilty plea for the murder of three victims. The toxicologic analysis of the remains of the 7 year-old victim revealed succinylcholine in the liver and gallbladder and its metabolite succinylmonocholine in multiple organs, which assisted in the Swango conviction.

With the advent of new modalities of drug delivery, toxicologists must be attuned to possible malicious intent. Emergency personnel responding to a 911 call observed the widow removing an insulin pump reservoir from her dead husband’s body with the stated intent to donate the costly equipment.⁴ A natural cause of death was presumed, yet surprisingly, forensic analysis revealed etomidate and laudanosine (a metabolite of atracurium) in the victim’s liver.

Understanding the pharmacokinetics of the depolarizing and nondepolarizing neuromuscular blockers (NMBs) improves care in the emergency department, intensive care unit (ICU), and operating room. Understanding and early recognition of the complications of each NMB limit associated ...