Dose Response Study of Intrathecal Morphine for Off-Pump Coronary Artery Bypass Grafting: a pilot Prospective Randomized Double-Blinded Controlled Clinical Trial

Abstract

Objective: To determine the optimal dose of intrathecal morphine in patients undergoing off-pump coronary artery bypass grafting (OPCAB) surgery.Design: A prospective, randomized, double-blinded, placebo-controlled study. Setting:A tertiary-level university teaching hospital.Participants: 31 adult patients scheduled for elective primary OPCAB surgery.Interventions: Patients were randomized to receive 2.5µg/kg (ITM-2.5) or 5µg/kg (ITM-5) intrathecal morphine or sham-control preoperatively. Anaesthesia was induced and maintained with sufentanil (limited to 1µg/kg), propofol, rocuronium and isoflurane. Blinded observer-caregivers extubated the patients using protocol-defined criteria, and on-demand intravenous morphine (IVM) was administered to patients using a standardized protocol.Measurements and Results: Blinded observers measured the time to extubation, the amount of supplemental IVM used in the first 48hours post-extubation, satisfaction with pain control, ICU discharge time, hospital discharge time, the incidence of vomiting, pruritus, urinary retention. Pain at rest (VASR) and during movement (VASM) were scored using the Visual Analogue Scale at 2, 4, 8, 24, 36 and 48 hours from extubation. ITM 2.5μg/kg was as effective as 5μg/kg, and superior to on demand IVM alone. VAS values in ITM-2.5 and ITM-5 groups were similar, and significantly lower in first 24hours comparing to the control group at rest as well as during coughing (p<0.05). The 48hour cumulative dose of IVM was 22±12mg, 28±14mg, and 36±18mg in ITM-5, ITM-2.5, and control groups respectively. Fewer cases of pruritus, PONV and urinary retention were reported in the ITM-2.5 compared with the ITM-5 group. There were no differences among the study groups with regard to extubation time, ICU discharge and hospital discharge time. Conclusion:ITM of 2.5μg/kg was superior to IVM analgesia regimen. Furthermore, it had similar effectiveness and fewer side effects compared to ITM of 5μg/kg. This study suggests that the optimal effective dose of ITM is 2.5μg/kg for OPCAB surgery for postoperative analgesia.