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Low-dose S-ketamine has no effect on post-op morphine use

Pearl Toh
09 Mar 2019

The need for postoperative morphine consumption was not reduced even with the concurrent use of low-dose S-ketamine in patients who were undergoing major open gynaecological surgeries using remifentanil–propofol target-controlled infusion (TCI), a local study finds.

As the use of opioids, especially remifentanil, was associated with hyperalgesia which may lead to greater opioid consumption, the researchers led by Professor Sng Ban Leong from KK Women’s and Children’s Hospital, Singapore sought to find out if concurrent use of ketamine can prevent opioid-induced hyperalgesia. Ketamine is a noncompetitive antagonist for NMDA* receptor, which is activated by opioids.

The double-blind clinical trial recruited 90 women (mean age 48 years) who underwent elective open abdominal hysterectomy with remifentanil–propofol TCI as general anaesthesia and randomized them in a 1:1 ratio to receive intravenous boluses of S-ketamine 0.25 mg/kg or normal saline as control. [Indian J Anaesth 2019;63:126-133]  

Low-dose ketamine did not significantly reduce the cumulative morphine consumption over 24 hours after surgery compared with control (16.4 vs 21.0 mg; p=0.0547), although the log-transformed value of the total morphine consumption was significantly lower in the S-ketamine group (2.5 vs 2.9 mg; p=0.0263).

There was also no significant difference in pain scores at rest between the two groups recorded on the visual analogue scale over 24 hours postoperatively, except at 15 minutes after surgery (mean difference, -1.965; p=0.0359).   

“It is possible that the negative findings from our study could be due to the inappropriately low dosage (0.25 mg/kg) of S-ketamine adopted,” said Sng and co-authors. “In this study, we chose a conservative regimen to reduce the risk of psychotomimetic side effects resulting in a lower dose of S-ketamine.”

In terms of psychotomimetic side effects, there were no significant differences between groups, with 51.7 percent of patients overall reporting “feelings of altered physical strength”, 39.3 percent with dizziness, and 12.4 percent experiencing “abnormal movements” (defined as involuntary twitches) within the first 24 hours after surgery.

The two groups showed similar mood states, including anger, depression, anxiety, and fatigue as measured using the Profile of Mood Scale.

Opioid-related side effects such as nausea (40.0 percent vs 31.8 percent; p=0.5092), vomiting (13.6 percent vs 28.9 percent; p=0.1198), and pruritus (13.6 percent vs 11.1 percent; p=0.7578) were also not significantly different between the two groups.

In addition, patients who received S-ketamine were slower to emerge from general anaesthesia compared with those in the control group (14.6 vs 11.6 seconds; p=0.0308), which the researchers attributed to the sedative effects of S-ketamine. Nonetheless, they noted that “this may not be clinically significant given that the difference in recovery time was 3 seconds.”  

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