Benefit and Harm of Adding Epinephrine to a Local Anesthetic for Neuraxial and Locoregional Anesthesia: A Meta-analysis of Randomized Controlled Trials With Trial Sequential Analyses

BACKGROUND: This systematic review examines the benefit and harm of adding epinephrine to local anesthetics for epidural, intrathecal, or locoregional anesthesia. METHODS: We searched electronic databases to October 2017 for randomized trials comparing any local anesthetic regimen combined with epinephrine, with the same local anesthetic regimen without epinephrine, reporting on duration of analgesia, time to 2 segments regression, or any adverse effects. Trial quality was assessed using the Cochrane risk of bias tool and a random-effects model was used. Trial sequential analyses (TSA) were applied to identify the information size (IS; number of patients needed to reach a definite conclusion) and were set to detect an increase or decrease of effect of 30%-50%, depending on the end point considered. Alpha levels were adjusted (1%) for multiple outcome testing. RESULTS: We identified 70 trials (3644 patients, 17 countries, from 1970 to 2017). Median number of patients per trial was 44 (range, 9-174). Thirty-seven trials (1781 patients) tested epinephrine for epidural, 27 (1660) for intrathecal, and 6 (203) for locoregional anesthesia (sciatic, femoral, popliteal, axillary blocks). TSA enabled us to conclude that adding epinephrine to epidural local anesthetics could not decrease postoperative pain intensity by 30%, and did not impact the risk of intraoperative arterial hypotension. IS was insufficient to conclude on the impact of epinephrine on the risk of motor block (IS, 4%), arterial hypotension (20%), urinary retention (23%), or pain intensity at rest (27%) during labor. TSA confirmed that adding epinephrine to intrathecal local anesthetics increased the duration of motor block (weighted mean difference [WMD] 64 minutes; 99% CI, 37-91), analgesia (WMD 34 minutes; 99% CI, 6-62), and the time to 2 segments regression (WMD 20 minutes; 99% CI, 11-28). IS was insufficient to conclude on its impact on arterial hypotension (IS, 15%), or when administrated in a combined spinal-epidural, on motor block (IS, 11%) or arterial hypotension (IS, 11%). Adding epinephrine to local anesthetics for a locoregional block increased the duration of analgesia (WMD 66 minutes; 98% CI, 32-100]). CONCLUSIONS: Adding epinephrine to intrathecal or locoregional local anesthetics prolongs analgesia and motor block by no more than 60 minutes. The impact of adding epinephrine to epidural local anesthetics or to a combined spinal-epidural remains uncertain.