Dexmedetomidine in prevention and treatment of postoperative and intensive care unit delirium: a systematic review and meta-analysis

Abstract

BackgroundTo determine the preventive and therapeutic effect of dexmedetomidine on intensive care unit (ICU) delirium.MethodsThe literature search using PubMed and the Cochrane Central Register of Controlled Trials was performed (August 1, 2018) to detect all randomized controlled trials (RCTs) of adult ICU patients receiving dexmedetomidine. Articles were included if they assessed the influence of dexmedetomidine compared to a sedative agent on incidence of ICU delirium or treatment of this syndrome. Accordingly, relevant articles were allocated to the following two groups: (1) articles that assessed the delirium incidence (incidence comparison) or articles that assessed the treatment of delirium (treatment comparison). Incidence of delirium and delirium resolution were the primary outcomes. We combined treatment effects comparing dexmedetomidine versus (1) placebo, (2) standard sedatives, and (3) opioids in random-effects meta-analyses. Risk of bias for each included RCT was assessed following Cochrane standards.ResultsThe literature search resulted in 28 articles (25 articles/4975 patients for the incidence comparison and three articles/166 patients for the treatment comparison). In the incidence comparison, heterogeneity was present in different subgroups. Administration of dexmedetomidine was associated with significantly lower overall incidence of delirium when compared to placebo (RR 0.52; 95% CI 0.39–0.70; I2 = 37%), standard sedatives (RR 0.63; 95% CI 0.46–0.86; I2 = 69%), as well as to opioids (RR 0.61; 95% CI 0.44–0.83; I2 = 0%). Use of dexmedetomidine significantly increased the risks of bradycardia and hypotension. Limited data were available on circulatory insufficiency and mortality. In the treatment comparison, the comparison drugs in the three RCTs were placebo, midazolam, and haloperidol. The resolution of delirium was measured differently in each study. Two out of the three studies indicated clear favorable effects for dexmedetomidine (i.e., compared to placebo and midazolam). The study comparing dexmedetomidine with haloperidol was a pilot study (n = 20) with high variability in the results.ConclusionFindings suggest that dexmedetomidine reduces incidence and duration of ICU delirium. Furthermore, our systematic searches show that there is limited evidence if a delirium shall be treated with dexmedetomidine.Electronic supplementary materialThe online version of this article (10.1186/s13613-018-0437-z) contains supplementary material, which is available to authorized users.

A prospective randomized study to see the effects of combined administration of dexmedetomidine plus propofol versus propofol alone in cardiac surgical patients.

“…24 However, a large meta-analysis proved DEX more effective in reducing incidence of delirium in comparison to propofol or sevoflourane. 25 our study indicated more incidence of delirium in group 1 than in group 2 thus indicating that when DEX was combined with propofol the incidence of delirium became more as compared to propofol alone in group 1.…”

Serum biomarkers of delirium in the elderly: a narrative review

“…Dopamine excess and inflammation are important assumptions competing with or contributing to the hypothesis of cholinergic deficiency [57], but the focus should lie on modifiable factors causing delirium [18]. This includes stress reduction due to minimization of light and noise disturbances at night and adequate pain management among other things, but also preventive drug therapy in high-risk cohorts [58, 59]. Most importantly, the pathophysiology of delirium remains poorly understood [60] despite being first described by Hippocrates more than 2500 years ago [61].…”

Delirium in the acute hospital setting: the role of psychiatry

“…Finally, there is no evidence to support the use of benzodiazepines in managing delirium not associated with alcohol withdrawal (Lonergan 2009). There is limited emerging evidence to suggest that dexmedetomidine (an alpha-2 adrenergic agonist) may be a reasonable alternative to antipsychotics to manage agitation in ventilated ICU patients (Flükiger 2018). More recent studies have proposed that novel substances such as melatonin may have clinical utility due to its effect on sleep, but there is insufficient evidence to endorse this in the mainstream approach to delirium (Chen 2016).…”