Abstract Background This study evaluated the efficacy of epidurally administered magnesium associated with local anesthetics on postoperative pain control. Methods The study protocol was registered in PROSPERO as CRD42021231910. Literature searches were conducted on Medline, Cochrane, EMBASE, CENTRAL, and Web of Science for randomized controlled trials comparing epidural administration of magnesium added to local anesthetics for postoperative pain in elective surgical adult patients. Primary outcomes were the time to the first Postoperative (PO) Analgesic Request (TFAR), 24-hour postoperative opioid consumption, and Visual Analog Scale (VAS) scores at the first six and 24 postoperative hours. Secondary outcomes included Postoperative Nausea and Vomiting (PONV), pruritus, and shivering. Quality of evidence was assessed using GRADE criteria. Results Seventeen studies comparing epidural were included. Effect estimates are described as weighted Mean Differences (MD) and 95% Confidence Intervals (95% CI) for the main outcomes: TFAR (MD = 72.4 min; 95% CI = 10.22-134.58 min; p < 0.001; I2= 99.8%; GRADE: very low); opioid consumption (MD = -7.2 mg (95% CI = -9.30 - -5.09; p < 0.001; I2= 98%; GRADE: very low). VAS pain scores within the first six PO hours (VAS) (MD = -1.01 cm; 95% CI = -1.40-0.64 cm; p < 0.001; I2= 88%; GRADE: very low), at 24 hours (MD = -0.56 cm; 95% CI = -1.14-0.01 cm; p= 0.05; I2= 97%; GRADE: very low). Conclusions Magnesium sulfate delayed TFAR and decreased 24-hour opioid consumption and early postoperative pain intensity. However, imprecision and inconsistency pervaded meta-analyses, causing very low certainty of effect estimates.

Abstract Background Up to 60% of pediatric surgical patients develop high levels of preoperative anxiety. This study compared the effects of oral combinations of midazolam and ketamine with oral midazolam alone for pediatric preanesthetic medication. Methods The study protocol was registered in PROSPERO as CRD42020172920. A systematic literature search was conducted using Medline, Cochrane, EMBASE, CENTRAL, and Web of Science for randomized controlled trials comparing oral combinations of midazolam and ketamine with midazolam alone as preanesthetic medication in elective surgical pediatric patients. Meta-analyses included the following outcomes: anxiety and sedation levels, child’s behavior during separation from parents, face mask acceptance, and venipuncture. The quality of evidence was assessed using GRADE criteria. Results Twenty studies were included. The following effects (RR (95% CI)) were observed for combinations of ketamine and midazolam relative midazolam alone: anxiolysis (1.2 (0.94-1.52); p= 0.15; I2 = 80%; GRADE = very low); satisfactory sedation (1.2 ( 1.10-1.31); p< 0.001; I2 = 71%; GRADE = very low); behavior during parental separation (1.2 (1.06-1.36); p= 0.003; I2 = 88%; GRADE = very low); facial mask acceptance (1.13 (1.04-1.24); p= 0.007; I2 = 49%; GRADE = very low); behavior during venipuncture (1.32 (1.11-1.57); p= 0.002; I2 = 66%; GRADE = very low). Conclusions While similar probabilities of obtaining anxiolysis were found, adequate sedation, calm behavior during child’s separation from parents, low levels of fear during face mask adaptation, and cooperative behavior during peripheral venous cannulation were more likely with midazolam-ketamine combinations.