Objectives We assessed the evidence from reviews and meta-analyses of randomised clinical trials on the effects of pharmacological prevention and management of delirium in intensive care unit (ICU) patients. Methods We searched for reviews in July 2017 in: Cochrane Library, MEDLINE, Embase, Science Citation Index, BIOSIS Previews, CINAHL and LILACS. We assessed whether reviews were systematic according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and assessed the methodological quality using ROBIS. Outcome measures Primary outcomes: all-cause mortality, serious adverse events, prevention of delirium and management of delirium. Secondary outcomes: quality of life; non-serious adverse events and cognitive function. Results We included 378 reviews: 369 narrative reviews, eight semisystematic reviews which failed on a maximum of two arbitrary PRISMA criteria and one systematic review fulfilling all 27 PRISMA criteria. For the prevention of delirium, we identified the one systematic review and eight semisystematic reviews all assessing the effects of alpha-2-agonists. None found evidence of a reduction of mortality (systematic review RR 0.99, 95% CI 0.79 to 1.24). The systematic review and three semisystematic reviews found no evidence of an effect for the prevention of delirium (systematic review RR 0.85, 0.63 to 1.14). Conversely, four semisystematic reviews found a beneficial effect. Serious adverse events, quality of life, non-serious adverse events and cognitive function were not assessed. We did not identify any systematic or semisystematic reviews addressing other pharmacological interventions for the prevention of delirium. For the management of manifest delirium, we did not identify any systematic or semisystematic review assessing any pharmacological agents. Conclusion Based on systematic reviews, the evidence for the use of pharmacological interventions for prevention or management of delirium is poor or sparse. A systematic review with low risk of bias assessing the effects of pharmacological prevention of delirium and management of manifest delirium in ICU patients is urgently needed. PROSPERO registration number CRD42016046628.

The prevalence of delirium in intensive care unit (ICU) patients is high. Delirium has been associated with morbidity and mortality including more ventilator days, longer ICU stay, increased long-term mortality and cognitive impairment. Thus, the burden of delirium for patients, relatives and societies is considerable. Today, reviews of randomised clinical trials are produced in large scales sometimes making it difficult to get an overview of the available evidence. A preliminary search identified several reviews investigating the effects of pharmacological interventions for the management and prevention of delirium in ICU patients. The conclusions of the reviews showed conflicting results. Despite this unclear evidence, antipsychotics, in particular, haloperidol is often the recommended pharmacological intervention for delirium in ICU patients. The objective of this overview of reviews is to critically assess the evidence of reviews of randomised clinical trials on the effect of pharmacological management and prevention of delirium in ICU patients. We will search for reviews in the following databases: Cochrane Library, MEDLINE, EMBASE, Science Citation Index, BIOSIS, Cumulative Index to Nursing and Allied Health Literature, Latin American and Caribbean Health Sciences Literature, and Allied and Complementary Medicine Database. Two authors will independently select references for inclusion using Covidence, extract data and assess the methodological quality of the included systematic reviews using the ROBIS tool. Any disagreement will be resolved by consensus. We will present the data as a narrative synthesis and summarise the main results of the included reviews. In addition, we will present an overview of the bias risk assessment of the systematic reviews. Results of this overview may establish a way forward to find and update or to design a high quality systematic review assessing the effects of the most promising pharmacological intervention for delirium in ICU patients. PROSPERO - CRD42016046628 .