Molecular mechanisms of muscular and non-muscular actions of neuromuscular blocking agents in critical illness.

ABSTRACT

Despite frequent use of neuromuscular blocking agents in critical illness, changes in neuromuscular transmission with critical illness are not well appreciated. Recent studies have provided greater insights into the molecular mechanisms for beneficial muscular effects and non-muscular anti-inflammatory properties of neuromuscular blocking agents. This review summarises the normal structure and function of the neuromuscular junction and its transformation to a 'denervation-like' state in critical illness, the underlying cause of aberrant neuromuscular blocking agent pharmacology. We also address the important favourable and adverse consequences and molecular bases for these consequences during neuromuscular blocking agent use in critical illness. This review, therefore, provides an enhanced understanding of clinical therapeutic effects and novel pathways for the salutary and aberrant effects of neuromuscular blocking agents when used during acquired pathologic states of critical illness.