Perioperative nimodipine and postoperative analgesia

There is experimental evidence that nimodipine, an L-type dihydropiridine calcium channel blocker with relatively high blood-brain barrier penetration, enhances the antinociceptive properties of morphine. We tested the hypothesis that oral nimodipine taken preoperatively and 6 hourly for 48 h postoperatively would reduce visual analog scale pain scores and morphine consumption in morphine-naive patients with acute postoperative pain. Forty patients undergoing total knee replacement surgery (age 70 +/- 7 yr, 28 male) were randomized by computer-generated numbers to receive capsules containing either nimodipine 30 mg or placebo in a double-blind study design. All patients received 3 capsules (nimodipine 90 mg or placebo) 1-2 h before induction of anesthesia followed by oral nimodipine 30 mg or placebo 6 hourly for 48 hours postoperatively. Spinal anesthesia was induced with hyperbaric bupivacaine 0.5% (2.4-3.0 mL) and fluids and ephedrine were given at the discretion of the anesthesiologist. Morphine patient-controlled analgesia (PCA, bolus 1 mg, lockout 5 min) was given for postoperative analgesia. Primary outcome measures were visual analog pain scores at rest and on moving (sitting forward) and PCA morphine consumption. Morphine consumption was significantly larger in nimodipine patients at 12 h (39 +/- 18 versus 29 +/- 15, P = 0.04), 24 h (62 +/- 23 versus 45 +/- 24; P = 0.02), and 48 h (88 +/- 34 versus 61 +/- 27; P = 0.01). There were no significant differences in pain scores at rest or moving or in time to first use of morphine analgesia. This study has demonstrated increased morphine consumption after 12 h in postoperative patients receiving nimodipine, suggesting that, in patients undergoing knee replacement surgery, it has no adjunctive analgesic effect and may actually inhibit the analgesic effect of morphine.