Aida et al. randomly assigned patients scheduled for gastrectomy to receive epidural morphine, intravenous low-dose ketamine, or combinations thereof to evaluate patient postsurgical pain. All 121 patients were administered standard general anesthesia. The 30 patients assigned to the epidural morphine group received the opioid as a bolus dose of 0.06 mg/kg 40 min before skin closure, maintained at 0.02 mg · kg−1· h−1until closing of the incision. Intravenous ketamine was administered in another group of 29 patients as a bolus dose of 1.0 mg/kg 10 min before closure, maintained at a dose of 0.5 mg · kg−1· h−1until close of the incision. A group of 31 patients received a combination of the two drugs and the control group (n = 31) received intravenous and epidural saline. The anesthesiologist was blinded as to which drug solution was administered. Another physician blinded to study drug assessed patients for their postsurgical pain at rest using the visual analog scale (VAS) scores at 6, 12, 24, and 48 after surgery. Twelve hours postsurgery, pain with movement (trying to change position) was also assessed.
Epidural morphine alone administered before incision closure reduced VAS values at 24 and 48 h after surgery, and decreased patient consumption of morphine via patient-controlled analgesia pumps at 6 and 12 h postoperatively. Low-dose intravenous ketamine also lowered VAS values at rest and decreased morphine consumption compared with those in the control group. However, patients in the combination group who received epidural morphine and intravenous ketamine showed the lowest VAS values both at rest and with movement, compared with all other groups. The results may suggest that epidural morphine affects the spinal cord segmentally, and intravenous ketamine may block brain stem sensitization via the vagus or phrenic nerve during upper abdominal surgery. To effectively provide postsurgical pain relief after upper abdominal surgery, drugs that affect the brain, spinal cord, and peripheral nervous system may be necessary.