Background Dexmedetomidine is widely used in patients with sepsis. However, its effect on septic patients remains controversial. The objective of this study was to summarize all randomized controlled trials (RCTs) examining dexmedetomidine use in sepsis patients. Methods This systematic review and meta-analysis included RCTs comparing dexmedetomidine with other sedatives in adult sepsis patients. We generated pooled relative risks (RRs) and standardized mean differences and performed trial sequential analysis and a cumulative meta-analysis. The primary outcome was mortality, and the secondary outcomes were the length of the intensive care unit stay, duration of mechanical ventilation, number of ventilation-free days, incidence of total adverse event, incidence of delirium, and levels of interleukin 6, tumor necrosis factor alpha, and alanine aminotransferase. Results We included 19 RCTs that enrolled 1929 patients. Compared with other sedatives, dexmedetomidine decreased the all-cause mortality (RR 0.83; 95% confidence interval [CI] [0.69, 0.99]) and inflammatory response (interleukin 6 and tumor necrosis factor alpha levels at 24 h: standardized mean difference (SMD) − 2.15; 95% CI [− 3.25, − 1.05] and SMD − 1.07, 95% CI [− 1.92, − 0.22], respectively). Trial sequential analysis showed that it is not up to required information size. The overall risk adverse events was similar between dexmedetomidine and the other sedatives (RR 1.27, 95% CI [0.69, 2.36]), but dexmedetomidine increased the risk of arrhythmias (RR 1.43, 95% CI [0.59, 3.51]). Length of intensive care unit stay (SMD − 0.22; 95% CI [− 0.85, − 0.41]), duration of mechanical ventilation (SMD 0.12; 95% CI [− 1.10, 1.35]), incidence of delirium (RR 0.98; 95% CI [0.72, 1.33]), and levels of alanine aminotransferase and creatinine at 24 h were not significantly reduced. Conclusions Dexmedetomidine in sepsis patients could significantly reduce mortality compared with benzodiazepines but not with propofol. In addition, dexmedetomidine can significantly decrease inflammatory response in patients with sepsis compared with other sedatives. Dexmedetomidine might lead to an increased incidence of arrhythmias, but its safety profile did not show significant differences in the incidence of total adverse events. Future RCTs are needed to determine the sepsis patient population that would benefit most from dexmedetomidine and its optimal dosing regimen.

PurposeDexmedetomidine 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.MethodsIn 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.ResultsTwenty-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.ConclusionThe 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.