Changes in acetylcholine receptor number in muscle from critically ill patients receiving muscle relaxants

Abstract

Previous reports have described prolonged paralysis after the administration of muscle relaxants in critically ill patients. The purpose of this study was to examine possible pathophysiologic causes for this paralysis by measuring muscle-type, nicotinic acetylcholine receptor number in necropsy muscle specimens from patients who had received muscle relaxants to facilitate mechanical ventilation before death. Prospective laboratory study of human muscle collected at autopsy. Medical and surgical intensive care units (ICUs) at a university hospital and a research laboratory. Fourteen critically ill patients, with a variety of diagnoses, all of whom required mechanical ventilatory support before their deaths in the ICU and who underwent post mortem examination. Patients were arbitrarily divided into three groups, according to their total vecuronium dose and number of days mechanically ventilated before death. Three patients were in the control group (defined as dying within 72 hrs of initiation of ventilatory support and receiving a total dose of < 5 mg of vecuronium). Six patients were in the low-dose group (defined as requiring ventilatory support for > 3 days before death and receiving a total vecuronium dose of < or = 200 mg). Five patients were in the high-dose group (defined as requiring ventilatory support for > 3 days before death and receiving a total vecuronium dose of > 200 mg). None. Nicotinic acetylcholine receptor numbers as measured by specific 125I-alpha-bungarotoxin binding to human rectus abdominis muscle obtained at autopsy were determined. In general, receptor number reflected the clinical requirements for the muscle relaxants of each patient. Patients who had increasing requirements for muscle relaxants before death had increases in receptor number, as compared with control values. The increase in nicotinic acetylcholine receptor number in muscle from patients with an increasing requirement for muscle relaxants before death suggests that nicotinic acetylcholine receptor up-regulation may underlie the increased requirements for muscle relaxants seen in some patients. Furthermore, these findings suggest that muscle relaxant-induced, denervation-like changes may at least be partially responsible for prolonged muscle paralysis after the long-term administration of muscle relaxants. This study may provide the first information into the molecular mechanisms underlying prolonged paralysis.