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

Abstract

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.

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

“…Several systematic reviews and meta-analyses on this research topic have been previously conducted [11] [12] [13] [49] [14]. Among previous meta-analyses, Huang et al was the most comprehensive study [13], and it included 15 RCTs with 1,871 patients in the analysis.…”

“…Recent four meta-analyses have shown controversial results, where two of these studies [11] [12] suggested a positive effect of dexmedetomidine on mortality in sepsis patients, while two other studies [13] [14] did not find a significant difference in mortality between dexmedetomidine and the other sedative agents. However, these conclusions are limited by the number of included studies, and the effects of dexmedetomidine on the incidence of delirium, adverse events, and the length of intensive care unit (ICU) stay remains controversial.…”