Hemodynamic Effects of Doxacurium Chloride in Patients Receiving Oxygen Sufentanil Anesthesia for Coronary Artery Bypass Grafting or Valve Replacement

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Abstract
Doxacurium chloride is an investigational long-acting neuromuscular blocking drug, which has been shown to be devoid of cardiovascular side effects when administered in modest doses to healthy patients. This is the first hemodynamic study of doxacurium in adult patients with cardiac disease. Forty-one patients scheduled to undergo cardiac surgery were studied. Anesthesia consisted of induction with midazolam 0.2-0.3 mg/kg and sufentanil 0.01-0.03 mg followed by an infusion of sufentanil at 0.03-0.06 mg .cntdot. min-1. Baseline hemodynamic data were collected during a stable state of sufentanil anesthesia. Doxacurium was then administered in doses of 1, 2, or 3 times its ED95 of 0.025 mg/kg. Hemodynamic measurements were repeated at 2, 5, and 10 min after doxacurium injection in the absence of surgical stimulation. An additional group of control patients received saline instead of doxacurium. Baseline hemodynamic measurements were similar among groups. There was a slight decrease in heart rate in all groups over time. However, there was no significant difference between the groups of patients receiving doxacurium and the control group in which the heart rate decreased progressively from 52 beats/min at baseline to 49 beats/min 10 min after doxacurium administration. At no time was there any significant change in mean arterial pressure, right atrial pressure, or cardiac output. Likewise derived hemodynamic variables including cardiac index, stroke volume, and pulmonary vascular resistance were unchanged. In addition to the decrease in heart rate, the hemodynamic changes, which reached statistical significance, were clinically insignificant and occurred predominantly in the group of patients receiving doxacurium 0.08 mg/kg. Baseline pulmonary artery occlusion pressure was 13 mmHg, and it increased to 14, 15, and 15 mmHg at 2, 5, and 10 min, respectively. Accordingly, pulmonary vascular resistance fell from 139 dyne .cntdot. s .cntdot. cm-5 at baseline to 114, 103, and 102 dyne .cntdot. s .cntdot. cm-5 at 2, 5, and 10 min, respectively. There was also a significant increase in stroke volume from 67 to 74 ml at 10 min in this group of patients receiving the largest dose. It is concluded that doxacurium has no clinically significant effect on measured or derived hemodynamic variables at doses up to 3 times its ED95. This combination of a long duration of action and absence of circulatory effects makes doxacurium a potentially useful drug for patients with limited cardiac reserve undergoing prolonged operations.