Low-dose intravenous ketamine and clonidine for poor postoperative opioid responsiveness : a double blind randomized study

In the immediate postoperative period, some patients present with pain that responds poorly to intravenous opioids. In a double-blind randomized study, we tested the hypothesis that administering small doses of intravenous ketamine (0.125 mg/kg) combined with clonidine (0.5 mu g/kg) would enhance the speed of onset and the quality of an opioid analgesic regimen in patients who initially responded poorly to opioids. We enrolled 68 patients in the study, all physical status I to III according to the American Society of Anesthesiologists classification. If the patient's numerical rating scale (NRS) score remained a >= 5 after an initial intravenous injection of 10 mg piritramide (2-mg boluses every 5 minutes) in the post-anesthesia care unit, patients were randomized to either intravenous placebo (sodium chloride 0.9%) or active substances (ketamine 0.125 mg/kg plus clonidine 0.5 mu g/kg). Fifteen minutes after administration of either placebo or active agents, patients with severe pain (NRS > 4) again received intravenous opioids until NRS < 4. The primary endpoint of the study was to reduce by 20 minutes the time necessary to achieve an NRS < 4. There was no statistically significant difference between the two groups regarding the time required for patients to achieve an NRS < 4. It was concluded that in the immediate postoperative period, the acute administration of small combined doses of intravenous ketamine (0.125 mg/kg) and clonidine (0.5 mu g/kg) does not reduce the onset of an opioid-based analgesia in patients with an initial poor response to intravenous opioids.