New vistas in neuromuscular blockers

Abstract

The medication drawer of a modern anesthesiology workstation may contain up to five neuromuscular-blocking drugs (NMBs): succinylcholine, vecuronium, rocuronium, and possibly pancuronium and cisatracurium. With such an extensive armamentarium for providing muscle relaxation, why would an anesthesiologist require additional compounds? Although the depolarizing neuromuscular-blocking compound succinylcholine has been at anesthesiologists’ disposal since 1952 and remains the sole short-acting neuromuscular-blocking agent capable of providing adequate conditions for rapid tracheal intubation, succinylcholine nevertheless possesses an adverse effect profile well known to all practicing anesthesiologists: muscle fasciculations, hyperkalemia, cardiac arrest, and increased intraocular and intracranial pressures. Vecuronium, rocuronium, and pancuronium all possess a much more favorable adverse effect profile, but all three exhibit altered pharmacokinetics in the setting of end-organ perturbations. Cisatracurium is currently the only clinically available nondepolarizing neuromuscular-blocking compound with organ-independent metabolism and thus a lack of cumulative effects; however, this compound has an intermediate duration of action, a high potency, and therefore a relatively slow onset of action insufficient for rapidly securing a patient's airway. Clearly, additions to the current armamentarium of neuromuscular-blocking compounds would prove useful in clinical practice, and the search for new molecules to fill the clinical voids has been ongoing since the 1970s.