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When compared with control patients without delirium, patients with delirium had significantly higher mortality during admission (risk ratio 2.19, 94% confidence interval 1.78 to 2.70; PA high proportion of adults admitted to hospital experience delirium, a pathological alteration in cognition associated with inattention, a fluctuating course, and an underlying systemic illness, metabolic imbalance, or association with a drug (or withdrawal).1 2 Delirium has been linked to adverse short term outcomes, including up to threefold increases hospital mortality and length of stay,3 4 5 which place considerable burdens on caregivers6 7 and healthcare services.8 9 Delirium can also have long term consequences, with studies indicating an association between delirium and a higher likelihood of death,10 functional disability,11 admission to residential care, cognitive impairment,12 and dementia after discharge.13 The risk of delirium is particularly high in selected subsets of hospital patients such as elderly people and those with pre-existing cognitive impairments,14 people with terminal illnesses,15 patients undergoing major surgery,16 and those who are admitted to an intensive care unit.17The identification, prevention, and treatment of delirium are increasingly regarded as major public health priorities.18 Delirium has been described as one of the most common types of organ dysfunction encountered in intensive care, though its prevalence is variable across studies.3 19 Delirium can be overlooked, misdiagnosed, and its significance underestimated by healthcare providers working in intensive care.20 21 Studies evaluating the relation between delirium and mortality have yielded inconsistent results, some reporting a significant association4 22 23 24 and others not.25 26 27Knowledge of the true magnitude of delirium and its associated burdens in critically ill patients would allow clinicians, researchers, and policymakers to allocate much needed resources towards reducing morbidity and mortality associated with delirium.We therefore conducted a systematic review of studies evaluating delirium in intensive care.Random effects models and meta-regression analyses were used to pool data from individual studies.
We selected risk ratio as a measure of effect for the binary outcome (death) as it is less prone to artificial inflation from heterogeneity than risk difference.35 Studies with zero events were entered in the analysis to include all data and reduce bias.36 To handle studies that reported zero outcomes for mortality, we performed a series of sensitivity analyses comparing Peto, Mantel-Haenszel, and inverse variance statistical methods with fixed and random effect with 0.5 continuity correction.37 38 Inverse variance and Mantel-Haenszel methods yielded identical results; we have shown the Mantel-Haenszel data in the mortality forest plot.
RDS, JIFS, and AD screened citations identified by the initial search and selected potentially relevant titles for review of abstracts.
From these, RDS, JIFS, and RBS then chose articles for review of full length reports.
We carried out a systematic review and meta-analysis of prospective observational studies following the recommendations of the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group.28 We searched Pub Med (1966-2015), Embase (1974-2015), CINAHL (1982-2015), the Cochrane Library (2015), and Psych INFO (up to 2015). We hand searched reference lists of retrieved articles, relevant review articles, and personal files. Search terms included delirium, acute confusional state, encephalopathy, organic brain syndrome, brain dysfunction, brain failure which were cross-referenced to the terms intensive care, intensive care unit, ICU, critical care, critical illness, critically ill, sepsis, acute respiratory distress, multiple organ system failure, and mechanical ventilation (see appendix 1 for details of search strategy).
To be considered for inclusion, studies had to meet the following criteria: We excluded articles if they did not have a control group of patients without delirium; if they were case studies or case series; if most enrolled patients (or the largest subgroup) had a primary central nervous system disorder (stroke, traumatic brain injury, central nervous system infections, brain tumors, recent intracranial surgery); if most enrolled patients were undergoing cardiac surgery or organ/tissue transplantation (patient subsets associated with pathophysiologically distinct forms of acute brain dysfunction); if most enrolled patients were experiencing alcohol or substance withdrawal; or if the primary study endpoint was the comparative efficacy or safety of different sedative drugs.