A Comparison of Remifentanil and Morphine Sulfate for Acute Postoperative Analgesia after Total Intravenous Anesthesia with Remifentanil and Propofol
Authors: Yarmush Joel , D'Angelo Robert , Kirkhart Barbara , O'Leary Colleen , Pitts Melvin C. , Graf George , Sebel Peter , Watkins W. David , Miguel Rafael , Streisand James , Maysick Laurie K. , Vujic Dragomir 
Published: November 2003

Background
The transition from remifentanil intraoperative anesthesia to postoperative analgesia must be planned carefully due to the short duration of action (3-10 min) of remifentanil hydrochloride, a potent, esterase-metabolized mu-opioid agonist. This study compared the efficacy and safety of transition regimens using remifentanil or morphine sulfate for immediate postoperative pain relief in patients who had surgery under general anesthesia with remifentanil/propofol.

Methods
One hundred fifty patients who had received open-label remifentanil and propofol for intraoperative anesthesia participated in this multicenter, double-blind, double-dummy study and were randomly assigned to either the remifentanil (R) group or the morphine sulfate (M) group. Twenty minutes before the anticipated end of surgery, the propofol infusion was decreased by 50%, and patients received either a placebo bolus (R group) or a bolus of 0.15 mg/kg morphine (M group). At the end of surgery, the propofol and remifentanil maintenance infusions were discontinued and the analgesic infusion was started: either 0.1 microg x kg(-1) x min(-1) remifentanil (R group) or placebo analgesic infusion (M group). During the 25 min after tracheal extubation, remifentanil titrations in increments of 0.025 microg x kg(-1) x min(-1) and placebo boluses (R group), or 2 mg intravenous morphine boluses and placebo rate increases (M group) were administered as necessary at 5-min intervals to control pain. Patients received the 0.075 mg/kg intravenous morphine bolus (R group) or placebo (M group) at 25 and 30 min after extubation, and the analgesic infusion was discontinued at 35 min. From 35 to 65 minutes after extubation, both groups received 2-6 mg open-label morphine analgesia every 5 min as needed.

Results
Successful analgesia, defined as no or mild pain with adequate respiration (respiratory rate [RR] > or =8 breaths/min and pulse oximetry > or = 90%), was achieved in more patients in the R group than in the M group (58% vs. 33%, respectively) at 25 min after extubation (P < 0.05). The median remifentanil rate for successful analgesia was 0.125 microg x kg(-1) x min(-1) (range, 0.05-0.23 microg x kg(-1) x min(-1)), and the median number of 2-mg morphine boluses used was 2 (range, 0-5 boluses). At 35 min after extubation, > or = 74% of patients in both groups experienced moderate to severe pain. Median recovery times from the end of surgery were similar between groups. Transient respiratory depression, apnea, or both were the most frequent adverse events (14% for the R group vs. 6% for the M group; P > 0.05).

Conclusions
Remifentanil provided safe and effective postoperative analgesia when administered at a final rate of 0.05-0.23 microg x kg(-1) x min(-1) in the immediate postextubation period. Remifentanil provided more effective postoperative analgesia than did intraoperative treatment with morphine (0.15 mg/kg) followed by morphine boluses (< or = five 2-mg boluses). The effects of remifentanil dissipated rapidly after ending the infusion, and alternate analgesia was required. Further studies are underway to define transition regimens that will improve postoperative analgesia in patients receiving anesthesia with remifentanil.