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

Abstract

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.

Effect of age and ICU types on mortality in invasive mechanically ventilated patients with sepsis receiving dexmedetomidine: a retrospective cohort study with propensity score matching

“…Cox proportional hazards regression results also supported that dexmedetomidine was related to lower 28-day mortality. These results were consistent with previous studies ( Song et al, 2019 ; Aso et al, 2021 ; Zhang et al, 2022 ). However, the DESIRE trial indicated that dexmedetomidine treatment did not improve 28-day mortality in patients requiring mechanical ventilation with sepsis ( Kawazoe et al, 2017 ).…”

Dexmedetomidine Attenuates Lipopolysaccharide-Induced Sympathetic Activation and Sepsis via Suppressing Superoxide Signaling in Paraventricular Nucleus

“…There was no significant difference in outcomes between the septic adults treated with DEX and those treated with propofol [ 63 ]. However, a recent meta-analysis of 19 randomized controlled trials that enrolled 1929 patients showed the benefit of DEX in septic patients [ 64 ]. Future randomized controlled trials need to identify the population of patients with sepsis who can benefit most from DEX and its optimal regimen.…”

Multiple uses of dexmedetomidine in small animals: a mini review

“…Morelli et colleagues demonstrated that using dexmedetomidine for the sedation of septic patients guarantees a comparable level of sedation and reduces the dosage of norepinephrine required compared to propofol ( 68 ), and from a recent meta-analysis resulted that dexmedetomidine, in human patients with sepsis, could significantly reduce mortality compared with benzodiazepines but not with propofol ( 69 ).…”