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San Francisco—Anesthesiologists looking to reduce the consumption of morphine after scoliosis surgery in pediatric patients may want to consider ketamine, Japanese researchers have found.
In a retrospective study, a group from Keio University School of Medicine, in Tokyo, concluded that although ketamine had a morphine-sparing effect after low-dose remifentanil-based anesthesia, this was not the case after high-dose remifentanil-based anesthesia.
“General anesthesia maintained with high-dose remifentanil is associated with acute opioid tolerance and/or hyperalgesia, which is usually manifested by increased postoperative pain and opioid requirement,” said Rie Minoshima, MD, professor of anesthesiology at Keio. “Although ketamine could reduce morphine requirement after scoliosis surgery, the morphine-sparing effect of ketamine is controversial because higher doses of remifentanil could induce more severe acute opioid tolerance, thus overcoming the clinical effect of ketamine.”
To better grasp the relationship between intraoperative remifentanil dose and clinical effect of ketamine, Dr. Minoshima and her colleagues enrolled 74 patients (ages 7-19 years) into the trial. Each patient underwent scoliosis surgery under anesthesia with propofol and remifentanil. Patients received either low-dose remifentanil (<0.2 mcg/kg per minute) or high-dose remifentanil (>0.3 mcg/kg per minute) during surgery, along with IV morphine by patient-controlled analgesia. Some patients also received a continuous infusion of ketamine at 1 mcg/kg per minute for 48 hours after surgery.
The investigators measured a variety of parameters—including postoperative morphine consumption, pain scores at rest and with movement, and sedation scores—at six, 12, 24 and 48 hours after surgery.
The four groups were comparable with respect to duration of anesthesia and dose of propofol.
The investigators found that postoperative 24-hour cumulative morphine consumption was significantly lower in the ketamine plus low-dose remifentanil (KL) group (0.40±0.17 mg/kg) than the ketamine plus high-dose remifentanil (KH) group (0.59±0.27 mg/kg), low-dose remifentanil-only (NL) group (0.63 mg/kg) or the high-dose remifentanil-only (NH) group (0.73±0.28 mg/kg; P=0.011).
“We also found that NRS [numeric rating scale] scores on movement were significantly lower in group KL and group KH than in groups NH and NL at our various time points after surgery,” Dr. Minoshima added. “There was, however, no difference in NRS at rest and sedation score between the groups.”
Several previous studies failed to show the morphine-sparing effect of ketamine after remifentanil-based anesthesia, Dr. Minoshima continued, “likely because the dose of remifentanil was relatively high and the ketamine infusion was stopped at the end of surgery. In our report, opioid-tolerance hyperalgesia induced by low-dose remifentanil could be attenuated by intraoperative and postoperative ketamine infusion.”
Dr. Minoshima was quick to point out that the retrospective trial had several limitations, beginning with the fact that the starting point of the remifentanil infusion and the loading dose of ketamine were not determined. “There were also a variety of regimens of intraoperative fentanyl that might have affected postoperative analgesic use,” she added. “As such, further prospective studies are required to evaluate our results.”

Scott Byram, MD, assistant director of anesthesiology and medical director of the acute pain service at Loyola University, in Chicago, questioned whether a larger sample size might have generated statistically significant results. “To me, it to me looks like the morphine consumption just keeps going down as you add ketamine. So I wonder if that’s just a statistical anomaly, and more sample size would make a difference. With that in mind, it seems like [the] conclusion should be that high-dose remifentanil increases postoperative morphine consumption, independent of whether or not you use ketamine.”
—Michael Vlessides