Background Delirium is an extremely common hospital complication. No study to date has assessed whether a priori defined covariates; type of hospital setting and year of study publication, influence the relationship between delirium and mortality. This is also the first study to examine the longitudinal trend of delirium-associated mortality over recent decades, to analyse the trajectory of our efforts in combating this disease. Methods MEDLINE, EMBASE and PsycINFO, were searched from January 1981 to May 2018 for English-language primary articles. Rigorous title and abstract screen and full-text screen were conducted independently by two reviewers. This paper adhered to MOOSE guidelines. Data was extracted independently by one reviewer using standardised data-collection sheets, with a separate reviewer verifying for accuracy. The quality of included studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. Unadjusted effect sizes and event counts were analysed with a random effects model in primary meta-analysis and meta-regression, whereas a mixed effect model was used in secondary sub-group analysis. Mortality data at longest follow-up and cumulative mortality (hospital mortality combined with mortality at longest follow-up) data were analysed. Results As part of a larger project, 446 of 6790 articles were retrieved, including 71 studies that measured mortality. Our results demonstrate that elderly inpatients with delirium had significantly greater odds of mortality (OR 3.18 [95%CI: 2.73, 3.70]) compared to non-delirious controls. Patients with delirium in the ICU had the highest odds for mortality (OR: 7.09 [95%CI: 3.60, 14.0]); double the risk compared to the average. Curiously, despite advancements in delirium research, delirium associated in-hospital odds of mortality has not changed in 30 years. Conclusion This is the largest meta-analysis to confirm the association between delirium and mortality, in older (age ≥ 65) hospital inpatients. The current meta-analysis highlights the significant odds of mortality after an episode of delirium, and these odds are much higher for ICU patients. However, in contrast to other medical conditions that have seen a decrease in associated mortality over the past few decades, delirium associated mortality remains unchanged. These findings underscore the urgent need for better delirium treatments. PROSPERO Registration Number: CRD42018098627, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=98627

BACKGROUND Delirium is common in the ICU, with incidence rates reported to be upwards of 70%. Due to the significant morbidity and mortality associated with delirium, it is hypothesised that a delirium-free sedative agent will improve outcomes in older adults admitted to the ICU. OBJECTIVES To assess if dexmedetomidine sedation is associated with a reduction in ICU delirium among older adults, and to evaluate its risks and benefits compared with propofol sedation. DESIGN Systematic review of randomised controlled trials and cohort studies with meta-analyses. DATA SOURCES Articles published from database inception to 8 April 2019 were retrieved from Medline, EMBASE, Evidence-based Medicine Reviews, International Pharmaceutical Abstracts, Scopus, ClinicalTrials.gov and WHO Trials. ELIGIBILITY Studies were included if they compared dexmedetomidine sedation with propofol in the ICU, reported the incidence of delirium as an outcome and had a mean/median sample age of at least 60. Studies that examined dexmedetomidine and propofol use intra-operatively or as part of general anaesthesia were excluded. RESULTS Dexmedetomidine sedation was associated with a lower incidence of delirium when compared with propofol: seven studies, n=1249; risk ratio 0.70; 95% confidence interval (CI) 0.52 to 0.95; P = 0.02. There was no statistically significant difference in the incidence of bradycardia: three studies, n=278; risk ratio 1.52; 95% CI 0.85 to 2.72; P = 0.16, and hypotension: six studies, n=867 patients; risk ratio 1.12; 95% CI 0.86 to 1.45; P = 0.42. Dexmedetomidine sedation did not reduce hospital length of stay, ICU length of stay or duration of mechanical ventilation compared with propofol. CONCLUSION Compared with propofol, dexmedetomidine sedation in the ICU is associated with lower delirium incidence among older adults with no significant increase in adverse events. In older adult ICU patients at risk of developing delirium, sedation with dexmedetomidine should be considered. Further research is warranted to elucidate and explain the mechanisms underlying this process, and to confirm our findings with large, multicentre trials. TRIAL REGISTRATION The study protocol has been registered in PROSPERO (CRD42018099339).