Efficacy and safety of ketamine as an adjuvant to regional anesthesia: A systematic review and meta-analysis of randomized controlled trials.

Study Objective: To identify whether adding ketamine to the local anesthetics (LA) in the regional anesthesia could prolong the duration of analgesia.

Design: A Systematic review and meta-analysis of randomized controlled trials.

Setting: The major dates were obtained in the operating room and the postoperative recovery ward.

Patients: A total of 1011 patients at ASA physical status I and II were included in the analysis. Procedure performed including cesarean section, orthopedic, radical mastectomy, urological or lower abdominal surgery and intracavitary brachytherapy implants insertion.

Interventions: After an extensive search of the electronic database, patients received regional anesthesia combined or not combined general anesthesia and with or without adding ketamine to LA were included in the analysis. The regional anesthesia includes spinal anesthesia, brachial plexus block, pectoral nerve block, transversus abdominis plane block and femoral and sciatic nerve block.

Measurement: The primary outcome was the duration of analgesia. Secondary outcomes were the duration and onset time of motor and sensory block as well as the ketamine-related adverse effect. Data are expressed in mean differences in continuous data and odds ratios (OR) for dichotomous data with 95% confidence intervals. The risk of bias of the included studies was evaluated using the revised Cochrane risk of bias tool for randomized trials. The quality of evidence for each outcome was rated according to the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) Working Group system.

Main Result: Twenty randomized controlled trials were included in the analysis. When ketamine was used as an adjuvant to LA, the duration of analgesia could be prolonged(172.21 min, 95% CI, 118.20 to 226.22; P<0.00001, I = 98%), especially in the peripheral nerve block(366.96 min, 95% CI, 154.19 to 579.74; P = 0.0007, I = 98%). Secondary outcomes showed ketamine could prolong the duration of sensory block(29.12 min, 95% CI, 10.22 to 48.01; P = 0.003, I = 96%) but no effect on the motor block(6.94 min, 95% CI,-2.65 to 16.53;P = 0.16, I = 84%), the onset time of motor and sensory block (motor onset time, -1.17 min, 95% CI, -2.67 to 0.34; P = 0.13, I = 100%; sensory onset time, -0.33 min, 95% CI,-0.87 to 0.20; P = 0.23, I = 96%) as well as the ketamine-related adverse effect(OR, 1.97, 95% CI,0.93 to 4.17;P = 0.08, I = 57%).

Conclusion: This study indicates that ketamine could be an ideal adjuvant to local anesthetics regardless of the types of anesthesia. Overall, the quality of the evidence is low.