We found substantial agreement among a large, interdisciplinary cohort of international experts regarding evidence supporting recommendations, and the remaining literature gaps in the assessment, prevention, and treatment of Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) in critically ill adults. Highlighting this evidence and the research needs will improve Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) management and provide the foundation for improved outcomes and science in this vulnerable population.

Background Critical illness is associated with cognitive impairment, but mental health and functional disabilities in general intensive care unit (ICU) survivors are inadequately characterized and there are a paucity of data regarding the relationship between age and delirium and these outcomes. Methods In this prospective, multisite cohort study, we enrolled medical/surgical ICU patients with respiratory failure or shock, collected detailed demographics and in-hospital variables, and assessed survivors at 3 and 12 months with measures of depression, posttraumatic stress disorder (PTSD) and functional disability. We used linear and proportional odds logistic regression to examine the independent associations between age and delirium duration versus mental health and functional disabilities. Findings We enrolled 821 patients with a median (interquartile range) age of 61 (51, 71), assessing 448 patients and 382 patients 3 and 12 months after discharge. At 3- and 12-month follow-up, 37% (149/407) and 33% (116/347) of subjects reported at least mild depression, driven primarily by somatic rather than cognitive symptoms. Depressive symptoms were common even among those with no proxy reported history of depression, reported at 3- and 12-month follow-up by 30% (76/255) and 29% (62/217) of these individuals. At either follow-up assessment, only 7% (27/415, 24/361) of subjects had symptoms consistent with PTSD. Disabilities in basic activities of daily living (ADLs) and instrumental activities of daily living (IADLs) were present in 32% (139/428) and 26% (108/422) of individuals at 3 months and in 27% (102/374) and 23%(87/372) at 12 months. Mental health and functional difficulties were prevalent in young and old patients. Although older age was frequently associated with mental health and functional disabilities, no consistent association was observed between delirium and these outcomes. Interpretation In contrast with early single-center reports, data from this large, multicenter investigation reveal depression is much more common than PTSD after critical illness and is driven by somatic symptoms indicative of physical disabilities rather than by cognitive symptoms. Poor mental health and functional disability were common, and persistent in up to a quarter of patients.

In this multicenter cohort study, one or more post-intensive care syndrome problems were present in the majority of survivors, but co-occurring problems were present in only one out of four. Education was protective from post-intensive care syndrome problems and frailty predictive of the development of post-intensive care syndrome problems. Future studies are needed to understand better the heterogeneous subtypes of post-intensive care syndrome and to identify modifiable risk factors.

BACKGROUND There are conflicting data on the effects of antipsychotic medications on delirium in patients in the intensive care unit (ICU). METHODS In a randomized, double-blind, placebo-controlled trial, we assigned patients with acute respiratory failure or shock and hypoactive or hyperactive delirium to receive intravenous boluses of haloperidol (maximum dose, 20 mg daily), ziprasidone (maximum dose, 40 mg daily), or placebo. The volume and dose of a trial drug or placebo was halved or doubled at 12-hour intervals on the basis of the presence or absence of delirium, as detected with the use of the Confusion Assessment Method for the ICU, and of side effects of the intervention. The primary end point was the number of days alive without delirium or coma during the 14-day intervention period. Secondary end points included 30-day and 90-day survival, time to freedom from mechanical ventilation, and time to ICU and hospital discharge. Safety end points included extrapyramidal symptoms and excessive sedation. RESULTS Written informed consent was obtained from 1183 patients or their authorized representatives. Delirium developed in 566 patients (48%), of whom 89% had hypoactive delirium and 11% had hyperactive delirium. Of the 566 patients, 184 were randomly assigned to receive placebo, 192 to receive haloperidol, and 190 to receive ziprasidone. The median duration of exposure to a trial drug or placebo was 4 days (interquartile range, 3 to 7). The median number of days alive without delirium or coma was 8.5 (95% confidence interval [CI], 5.6 to 9.9) in the placebo group, 7.9 (95% CI, 4.4 to 9.6) in the haloperidol group, and 8.7 (95% CI, 5.9 to 10.0) in the ziprasidone group (P=0.26 for overall effect across trial groups). The use of haloperidol or ziprasidone, as compared with placebo, had no significant effect on the primary end point (odds ratios, 0.88 [95% CI, 0.64 to 1.21] and 1.04 [95% CI, 0.73 to 1.48], respectively). There were no significant between-group differences with respect to the secondary end points or the frequency of extrapyramidal symptoms. CONCLUSIONS The use of haloperidol or ziprasidone, as compared with placebo, in patients with acute respiratory failure or shock and hypoactive or hyperactive delirium in the ICU did not significantly alter the duration of delirium. (Funded by the National Institutes of Health and the VA Geriatric Research Education and Clinical Center; MIND-USA ClinicalTrials.gov number, NCT01211522.)

National Institutes of Health and the Department of Veterans Affairs.