ABSTRACT
Purpose: To systematically evaluate the effectiveness and safety of ketamine in preventing propofol injection pain (PIP). Patients and Methods: The electronic databases including PubMed, Embase, Web of Science, and Cochrane Library were searched from their inception until 2 August 2023. Randomized controlled trials (RCT) comparing ketamine with placebo or other interventions to alleviate PIP in adults were included. Fixed-effects or random-effects models were used to calculate pooled risk ratios (RR) and corresponding 95% confidence intervals (CI) based on the heterogeneity of the studies included. Results: Thirteen RCTs involving 2105 patients were included. In terms of reducing the incidence of PIP, ketamine is more effective than placebo (RR = 0.43, 95% CI = [0.34, 0.55], P < 0.00001), lidocaine (RR = 0.70, 95% CI = [0.55, 0.90], P = 0.005), dexmedetomidine (RR = 0.52, 95% CI = [0.40, 0.66], P < 0.00001), and thiopental (RR = 0.25, 95% CI = [0.08, 0.83], P = 0.02). In reducing the incidence of severe PIP, ketamine is superior to placebo (RR = 0.12, 95% CI = [0.08, 0.19], P < 0.00001), and lidocaine (RR = 0.34, 95% CI = [0.21, 0.56], P < 0.0001), except dexmedetomidine (RR = 0.20, 95% CI = [0.04, 1.13], P = 0.07), and thiopental (RR = 0.33, 95% CI = [0.04, 3.10], P = 0.33). Compared with mixed injection, separate injection of ketamine and propofol showed no significant difference in the incidence of PIP (RR = 0.96, 95% CI = [0.31, 3.00], P = 0.95) and severe PIP (RR = 1.19, 95% CI = [0.07, 21.29], P = 0.90). Based solely on the reports from the studies included, subanesthetic doses of ketamine are generally safe in preventing PIP. Conclusion: A subanesthetic dose of ketamine can effectively and safely reduce the incidence of PIP and severe PIP in adults, and is more effective than lidocaine, dexmedetomidine, and thiopental. Registration: PROSPERO CRD42023455093.
ABSTRACT
(1) Purpose: to systematically evaluate the recovery following sedation and anesthesia with remimazolam combined with flumazenil in comparison to propofol. (2) Methods: Electronic databases, including PubMed, Embase, Web of Science, and the Cochrane Library, were systematically searched from their inception up to 22 October 2023. Included in this analysis were randomized controlled trials (RCT) that compared remimazolam-flumazenil with propofol for the recovery from sedation and anesthesia in adults. The risk of bias was assessed using the Cochrane risk of bias tool. Pooled risk ratios (RR) or mean differences (MD) along with their corresponding 95% confidence intervals (CI) were calculated using either fixed-effects or random-effects models, and the results were visualized in forest plots. (3) Results: Nine RCTs involving 745 patients who underwent general anesthesia in three different countries were included. Compared to propofol, the remimazolam-flumazenil combination shortened the emergence time (MD = -4.34 min, 95% CI = [-6.88, -1.81], p = 0.0008, low certainty), extubation time (MD = -4.26 min, 95% CI = [-6.81, -1.7], p = 0.0011, low certainty), and the post-anesthesia care unit (PACU) stay (MD = -4.42 min, 95% CI = [-7.45, -1.38], p = 0.0044, low certainty), while reducing the incidence of respiratory depression (RR = 0.2, 95% CI = [0.04, 0.89], p = 0.03, high certainty) after general anesthesia. However, this combination was associated with a higher incidence of re-sedation (RR = 4.15, 95% CI = [1.31, 13.13], p = 0.01, moderate certainty). (4) Conclusions: Based on the existing evidence, the combination of remimazolam and flumazenil accelerates recovery from general anesthesia and lowers the risk of respiratory depression compared to propofol. However, it is important to consider the higher risk of re-sedation when using this combination in clinical practice. Due to limitations in the quality of the evidence, it is advisable to interpret the results of meta-analyses with caution.
