Sedation/DeliriumHaloperidol for the management of delirium in adult intensive care unit patients: A systematic review and meta-analysis of randomized controlled trials
Introduction
Delirium, a syndrome of acute brain dysfunction, is a common complication in patients undergoing treatment in the intensive care unit (ICU). It is characterized by a daily fluctuating symptoms of confusion, inattention, and consciousness disturbances [1]. The underlying cause of delirium is often multifactorial, and may be related to neurotransmitter pathway alterations, cerebral oxygen deprivation, and increased cerebral inflammatory cytokines [[2], [3], [4]]. In the ICU, the mean incidence of delirium is about 30% as shown in a recent systematic review [5], Of note, ICU patients have greater number of risk factors associated with ICU treatment, with patients averaging 11 delirium-associated risk factors [6].
ICU-related delirium is associated with poor clinical outcomes, including prolonged ICU and hospital length of stay (LOS), development of post-ICU cognitive impairment, and increased health-care costs [[7], [8], [9], [10], [11], [12]]. Current guidelines recommend the early instillation of non-pharmacological strategies for the prevention and treatment of ICU-associated delirium, such as early mobilization, avoidance of excess sedation and benzodiazepines, reorientation, as well as the use of eyeglasses and hearing aids [13].
Haloperidol is a typical antipsychotic with antidopaminergic, anticholinergic, and potential immunomodulatory properties. Use of haloperidol for the management of delirium has previously demonstrated beneficial outcomes in non-critically ill patients, however, its role in ICU patients is controversial [4,[14], [15], [16]]. Therefore, we conducted a meta-analysis of all randomized controlled trials (RCTs) in order to evaluate the efficacy and safety of haloperidol regarding management of delirium in ICU patients in comparison to placebo.
Section snippets
Study design and data sources
Our study is a systematic review and meta-analysis which was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) 2015 Statement [17]. The literature search and study selection were conducted independently by two reviewers (A.A. and L.R.). Any discrepancy was solved by a consensus with a third reviewer (Y.Z.). We systematically searched 3 electronic databases: PubMed, Cochrane Library, and Embase from inception through October 25th, 2018
Summary of the included studies
Electronic database search yielded 464 studies. After review, 6 RCTs met our inclusion criteria and were included in the final analysis [[19], [20], [21], [22], [23], [24]]. The search and study selection processes are shown in Fig. 1. All the included studies are of high quality (Fig. 2). Of note, in van den Boogaard et al. study, only haloperidol 2 mg group versus placebo were included since haloperidol 1 mg group was discontinued early during the study, and haloperidol dose of 2 mg was
Discussion
We performed a meta-analysis of only RCTs evaluating the role of haloperidol in the prevention and/or treatment of ICU associated delirium. Our study revealed that haloperidol does not significantly affect short-term mortality, incidence of delirium, ICU LOS, or delirium/coma-free days in critically ill patients. However, we found that haloperidol use was does not increase the incidence of serious adverse events, extrapyramidal symptoms, or QTc interval prolongation.
van den Boogaard et al.
Conclusion
In patients admitted to ICU, the use of haloperidol for the management of delirium (prophylaxis or treatment) has no significant reduction of short-term mortality, incidence of delirium, ICU LOS, increased delirium or coma-free days compared with placebo. However, haloperidol treated patients have no increased risks for development of serious adverse events, QTc prolongation, or extrapyramidal symptoms.
Declaration of interest
No financial support was received for this work and the authors have no conflicts of interest to declare.
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