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PAIN MEDICINE

Ketamine as Adjuvant Analgesic to Opioids: A Quantitative and Qualitative Systematic Review

From the Department of Anesthesiology, Critical Care & Pain Management, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts

Address correspondence and reprint requests to Kathirvel Subramaniam, MD, Department of Anesthesiology, Critical Care & Pain Management, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston MA 02215. Address email to kathirvels{at}yahoo.com

Animal studies on ketamine and opioid tolerance have shown promising results. Clinical trials have been contradictory. We performed a systematic review of randomized, double-blind clinical trials of ketamine added to opioid analgesia. Thirty-seven trials with 51 treatment arms and 2385 patients were included. Studies were divided into 5 subgroups: IV ketamine as single dose (n = 11), continuous infusion (n = 11), patient-controlled analgesia (PCA) (n = 6), epidural ketamine with opioids (n = 8), and studies in children (n = 4). Outcome measures included pain scores, time to first request for analgesia, supplemental analgesics, and adverse events. Efficacy was estimated by statistical significance (P < 0.05) of outcome measures as reported in studies and also by calculation of weighted mean difference for pain scores during the first 24 h after surgery. As compared to morphine alone, IV PCA with ketamine and morphine did not improve analgesia. Intravenous infusion of ketamine decreased IV and epidural opioid requirements in 6 of 11 studies. A single bolus dose of ketamine decreased opioid requirements in 7 of 11 studies. Five of 8 trials with epidural ketamine showed beneficial effects. Adverse effects were not increased with small dose ketamine. We conclude that small dose ketamine is a safe and useful adjuvant to standard practice opioid-analgesia.

IMPLICATIONS: Narcotics alone are not effective in all postoperative patients for adequate pain relief. They may also be associated with unacceptable side effects. Thus, there remains a need for additional pain medications. We found ketamine, an IV anesthetic drug, in small doses helped reduce narcotic use after surgery.

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