Use of dexmedetomidine in patients with sepsis: a systematic review and meta-analysis of randomized-controlled trials

Purpose: Dexmedetomidine is widely used in patients with sepsis. However, its effect on septic patients remains controversial. Therefore, the objective of this study is to summarize all randomized-controlled trials examining the use of dexmedetomidine in patients with sepsis. Methods: In this systematic review and meta-analysis, we searched for randomized-controlled trials comparing dexmedetomidine with other sedatives in adults with sepsis. We generated pooled relative risks and mean differences, and performed trial-sequential-analysis as well as cumulative meta-analysis. The primary outcome was mortality, whereas the secondary outcomes were ICU stays, duration of mechanical ventilation and ventilation-free days, incidence of total adverse events, incidence of delirium and levels of IL-6, TNF-α, alanine transaminase. Results: Twenty-three randomized-controlled trials with 2,293 involved patients were identified. Compared to other sedatives, dexmedetomidine could decrease the all-cause mortality (RR 0.81; 95% Confidence Interval (CI) 0.71–0.93; P < 0.05) and inflammatory response (levels of IL-6 and TNF-α at 24 h: SMD: -1.46; 95% CI -2.10, -0.83 , p＜0.05； SMD: -1.20; 95% CI -1.78, -0.62 , p＜0.05, respectively). Trial-sequential-analysis showed that it is not up to required information size but the cumulative Z curve crossed the trial sequential monitoring boundary for benefit. Using cumulative meta-analysis, a steady reduction in mortality was observed after 2020. Risks of total adverse events were similar between dexmedetomidine and the other sedatives (OR = 1.06, 95% CI 0.50, 2.25, p = 0.87), but dexmedetomidine increases the risk of arrhythmias (OR 2.36, 95% CI 1.15, 4.8; P = 0.02; I2 = 0%). ICU stays (SMD: −0.26; 95% CI −0.70,0.18, p = 0.24), duration of mechanical ventilation, incidence of delirium (RR 0.89; 95% CI 0.66 to 1.19, low certainty; P = 0.43)，the levels of alanine transaminase and creatinine changes at 24 h (Respectively: p = 0.17 and 0.30) were all not significantly reduced. Conclusion: The use of dexmedetomidine in comparison to other sedative agent reduces significantly the all-cause mortality and inflammatory response in patients with sepsis. Dexmedetomidine might lead to an increased incidence of arrhythmias, but its safety profile did not show significant differences in the incidence of the total adverse events.