Bronchomotor, haemodynamic and neuromuscular effects of atracurium and cis-atracurium [51/W89]: comparative experimental and clinical studies in critically ill mechanically ventilated patients

ABSTRACT

The effects of atracurium and cis-atracurium on histamine- induced submaximal contractions of isolated tracheal strips and on the airway resistance were tested in guinea pigs. Clinical studies included 24 chronic obstructive pulmonary disease [COPD] and 24 head injury patients, mechanically ventilated with the use of Puritan Bennett, 7200ae ventilator. Flow-volume loops were recorded and analyzed to determine the bronchomotor effects of atracurium 0.6 mg kg-1 or cis- atracurium 0.12 mg kg-1. Heart rate was monitored continuously and noninvasive blood pressure was recorded at specified time intervals. An acceleration piezo-electric transducer was used to monitor neuromuscular transmission. Atracurium produced potentiation of histamine-induced submaximal contractions of isolated tracheal strips and a dose-related increase in the airway resistance of intact anesthetized guinea pigs. The bronchoconstrictor effect of atracurium was abolished by mepyramine maleate. In clinical studies expiratory flow rates from a mean base-line value of 0.52 +/- SD 0.08 l sec-1 to reach 0.41 +/- 0.06 l sec-1, p <0.05. Further atracurium produced significant reductions in mean arterial pressure with a compensatory rise in heart rate in COPD and head injury patients. In contrast, cis-atracurium was not associated with any evidence of histamine-induced bronchospastic or hemodynamic effects. Cis- atracurium had significantly longer onset time than atracurium, with a mean difference ranging between 1.1-1.5 minutes. Time to 25% and 75% first twitch [T1] recovery, recovery index, and the time required for 70% recovery of train-of-4 ratio [T4/T1] were all shorter in head injury than COPD patients. Cis-atracurium appears to be the closest to the ideal neuromuscular blocking agent for use in critically ill patients