Ketamine as adjuvant analgesic to opioids: a quantitative and qualitative systematic review.
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.
Department of Anesthesiology, Critical Care & Pain Management, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA. kathirvels@yahoo.com
Kathirvel
K
Subramaniam
Balachundhar
B
Subramaniam
Richard A
RA
Steinbrook
D000328:Adult; D015360:Analgesia, Epidural; D016058:Analgesia, Patient-Controlled; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000778:Anesthetics, Dissociative / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006801:Humans; D007262:Infusions, Intravenous; D007649:Ketamine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D020250:Postoperative Nausea and Vomiting / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic
D000701:Analgesics, Opioid; D000778:Anesthetics, Dissociative; D007649:Ketamine