Single dose perioperative intrathecal ketamine as an adjuvant to intrathecal bupivacaine: A systematic review and meta-analysis of adult human randomized controlled trials

Study objective: To identify whether adding intrathecal ketamine to intrathecal bupivacaine prolongs the time to first analgesic request in adult humans. Design: A meta-analysis of randomized controlled trials in humans. Setting: The majority of data was obtained in an operating room and postoperative recovery area. Patients: A total of 750 ASA physical status I and II patients were included in the study. Procedures performed include: cesarean section, lower abdominal surgery, lower limb surgery, and urologic surgery. Interventions: Databases including PubMed, Embase, Web of Science, and Cochrane were searched. Google Scholar was also queried. Multiple reviewers screened the papers for inclusion. Measurements: The primary outcome assessed was time to first analgesic request. Secondary outcomes included onset of sensory blockade, onset of motor blockade, duration of sensory blockade, and duration of motor blockade. Data were extracted to include means, 95% confidence intervals, tests for heterogeneity, and use of the Cochrane Collaboration guidelines to assess for publication bias. Main results: Eleven randomized controlled trials met inclusion criteria. When comparing intrathecal bupivacaine plus ketamine to intrathecal bupivacaine alone, the time to first analgesic request was prolonged (effect size = 58.23 min (95% CI 37.36 to 79.10) p < 0.0001). Secondary outcomes showed the onset time of sensory blockade was shortened (effect size = -0.87 min (95% CI -1.361 to 0.378) p = 0.0005), the onset time of motor blockade was reduced (effect size = -0.88 min (95% CI -1.77 to 0.013) p = 0.05), the duration of sensory blockade was prolonged (effect size = 39.73 min (95% CI 15.97 to 63.50) p = 0.001), and the duration of motor blockade was prolonged (effect size = 4.02 min (95% CI 3.27 to 4.78) p < 0.0001). Studies were shown to have high heterogeneity. Egger tests for all outcomes were non-significant and funnel plots assessing publication bias were all asymmetrical. Conclusions: The studies analyzed suggest there may be a benefit to using intrathecal ketamine as an adjunct to bupivacaine. Additional studies are warranted to optimize dosing, clarify the safety and efficacy of this intrathecal drug combination, and examine the various ketamine formulations as intrathecal bupivacaine adjuvants.