Applied pharmacology of common neuromuscular blocking agents in critical care

Abstract

While all neuromuscular blocking agents (NMBAs) effectively interrupt neuromuscular transmission, it must be emphasized that these drugs are completely devoid of analgesic, sedative, or amnestic properties. The increasing use of NMBAs in the ICU requires familiarity with their basic pharmacologic properties, as well as an appreciation of potential problems associated with chronic (> 24 hrs) neuromuscular blockade. Although NMBAs possess an impressive safety record, the majority of recommendations for neuromuscular blocker use in the ICU are extrapolated from short-term perioperative studies in healthy patients. NMBAs are structurally related to acetylcholine and their main site of action is the postjunctional nicotinic acetylcholine receptor, although prejunctional interaction may be an important component of total activity. These drugs act to either sustain a depolarization at the postjunctional membrane (succinylcholine), or they inhibit neuromuscular transmission by a competitive (non-depolarizing) blocking mechanism. Adverse hemodynamic consequences may result from concurrent stimulation of muscarinic receptors, autonomic ganglia, histamine, or catecholamine release associated with some agents. The metabolism and excretion of NMBAs may be altered in ICU patients with end-organ dysfunction, concurrent medications, electrolyte, acid-base, and nutritional abnormalities, along with underlying nervous system and muscle pathology. Prolonged weakness after discontinuation of NMBAs is increasingly recognized after these agents are used for extended periods. This phenomenon may be related to alterations in the pharmacokinetics and pharmacodynamics, along with altered physiology of the neuromuscular junction, nervous system, or muscle, or other undefined toxic effects. A sound knowledge of the basic physiology of the neuromuscular junction, neuromuscular blocker pharmacology, and standard techniques to assess the degree of neuromuscular blockade provides the rationale for drug selection when paralysis is indicated in ICU patients.