Project description:BackgroundTo understand delirium heterogeneity, prior work relied on psychomotor symptoms or risk factors to identify subtypes. Data-driven approaches have used machine learning to identify biologically plausible, treatment-responsive subtypes of other acute illnesses but have not been used to examine delirium.MethodsWe conducted a secondary analysis of a large, multicenter prospective cohort study involving adults in medical or surgical ICUs with respiratory failure or shock who experienced delirium per the Confusion Assessment Method for the ICU. We used data collected before delirium diagnosis in an unsupervised latent class model to identify delirium subtypes and then compared demographics, clinical characteristics, and outcomes between subtypes in the final model.FindingsThe 731 patients who developed delirium during critical illness had a median age of 63 [IQR, 54-72] years, a median Sequential Organ Failure Assessment score of 8.0 [6.0-11.0] and 613 [83.4%] were mechanically ventilated at delirium identification. A four-class model best fit the data with 50% of patients in subtype (ST) 1, 18% in subtype 2, 17% in subtype 3, and 14% in subtype 4. Subtype 2-which had more shock and kidney impairment-had the highest mortality (33% [ST2] vs. 17% [ST1], 25% [ST3], and 17% [ST4], p = 0.003). Subtype 4-which received more benzodiazepines and opioids-had the longest duration of delirium (6 days [ST4] vs. 3 [ST1], 4 [ST2], and 3 days [ST3], p < 0.001) and coma (4 days [ST4] vs. 2 [ST1], 1 [ST2], and 2 days [ST3], p < 0.001). Each of the four data-derived delirium subtypes was observed within previously identified psychomotor and risk factor-based delirium subtypes. Clinically significant cognitive impairment affected all subtypes at follow-up, but its severity did not differ by subtype (3-month, p = 0.26; 12-month, p = 0.80).InterpretationThe four data-derived delirium subtypes identified in this study should now be validated in independent cohorts, examined for differential treatment effects in trials, and inform mechanistic work evaluating treatment targets.FundingNational Institutes of Health (T32HL007820, R01AG027472).

Project description:ObjectiveTo determine the feasibility of conducting a longitudinal prospective study to evaluate functional recovery and predictors of impaired functional recovery in critically ill children.DesignProspective pilot study.SettingSingle-center PICU at McMaster Children's Hospital, Hamilton, Canada.PatientsChildren aged 12 months to 17 years, with at least one organ dysfunction, limited mobility or bed rest during the first 48 hours of PICU admission, and a minimum 48-hour PICU length of stay, were eligible. Patients transferred from a neonatal ICU prior to ever being discharged home, already mobilizing well or at baseline functional status at time of screening, with an English language barrier, and prior enrollment into this study, were excluded.InterventionsNone.Measurements and main resultsThe primary outcome was feasibility, as defined by the ability to screen, enroll eligible patients, and execute the study procedures and measurements on participants. Secondary outcomes included functional status at baseline, 3 and 6 months, PICU morbidity, and mortality. Functional status was measured using the Pediatric Evaluation of Disability Inventory and the Participation and Environment Measure for Children and Youth. Thirty-three patients were enrolled between October 2012 and April 2013. Consent rate was 85%, and follow-up rates were 93% at 3 months and 71% at 6 months. We were able to execute the study procedures and measurements, demonstrating feasibility of conducting a future longitudinal study. Functional status deteriorated following critical illness. Recovery appears to be influenced by baseline health or functional status and severity of illness.ConclusionLongitudinal research is needed to understand how children recover after a critical illness. Our results suggest factors that may influence the recovery trajectory and were used to inform the methodology, outcomes of interest, and appropriate sample size of a larger multicenter study evaluating functional recovery in this population.

Project description:BackgroundDelirium during critical illness results from numerous insults, which might be interconnected and yet individually contribute to long-term cognitive impairment. We sought to describe the prevalence and duration of clinical phenotypes of delirium (ie, phenotypes defined by clinical risk factors) and to understand associations between these clinical phenotypes and severity of subsequent long-term cognitive impairment.MethodsIn this multicentre, prospective cohort study, we included adult (≥18 years) medical or surgical ICU patients with respiratory failure, shock, or both as part of two parallel studies: the Bringing to Light the Risk Factors and Incidence of Neuropsychological Dysfunction in ICU Survivors (BRAIN-ICU) study, and the Delirium and Dementia in Veterans Surviving ICU Care (MIND-ICU) study. We assessed patients at least once a day for delirium using the Confusion Assessment Method-ICU and identified a priori-defined, non-mutually exclusive phenotypes of delirium per the presence of hypoxia, sepsis, sedative exposure, or metabolic (eg, renal or hepatic) dysfunction. We considered delirium in the absence of hypoxia, sepsis, sedation, and metabolic dysfunction to be unclassified. 3 and 12 months after discharge, we assessed cognition with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). We used multiple linear regression to separately analyse associations between the duration of each phenotype of delirium and RBANS global cognition scores at 3-month and 12-month follow-up, adjusting for potential confounders.FindingsBetween March 14, 2007, and May 27, 2010, 1048 participants were enrolled, eight of whom could not be analysed. Of 1040 participants, 708 survived to 3 months of follow-up and 628 to 12 months. Delirium was common, affecting 740 (71%) of 1040 participants at some point during the study and occurring on 4187 (31%) of all 13 434 participant-days. A single delirium phenotype was present on only 1355 (32%) of all 4187 participant-delirium days, whereas two or more phenotypes were present during 2832 (68%) delirium days. Sedative-associated delirium was most common (present during 2634 [63%] delirium days), and a longer duration of sedative-associated delirium predicted a worse RBANS global cognition score 12 months later, after adjusting for covariates (difference in score comparing 3 days vs 0 days: -4·03, 95% CI -7·80 to -0·26). Similarly, longer durations of hypoxic delirium (-3·76, 95% CI -7·16 to -0·37), septic delirium (-3·67, -7·13 to -0·22), and unclassified delirium (-4·70, -7·16 to -2·25) also predicted worse cognitive function at 12 months, whereas duration of metabolic delirium did not (1·14, -0·12 to 3·01).InterpretationOur findings suggest that clinicians should consider sedative-associated, hypoxic, and septic delirium, which often co-occur, as distinct indicators of acute brain injury and seek to identify all potential risk factors that may impact on long-term cognitive impairment, especially those that are iatrogenic and potentially modifiable such as sedation.FundingNational Institutes of Health and the Department of Veterans Affairs.

Project description:BackgroundThere are conflicting data on the effects of antipsychotic medications on delirium in patients in the intensive care unit (ICU).MethodsIn 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.ResultsWritten 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.ConclusionsThe 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 .).

Project description:ObjectivesAdult ICU survivors that experience delirium are at high risk for developing new functional disabilities and mental health disorders. We sought to determine if individual motoric subtypes of delirium are associated with worse disability, depression, and/or post-traumatic stress disorder in ICU survivors.DesignSecondary analysis of a prospective multicenter cohort study.SettingAcademic, community, and Veteran Affairs hospitals.PatientsAdult ICU survivors of respiratory failure and/or shock.InterventionsWe assessed delirium and level of consciousness using the Confusion Assessment Method-ICU and Richmond Agitation and Sedation Scale daily during hospitalization. We classified delirium as hypoactive (Richmond Agitation and Sedation Scale ≤ 0) or hyperactive (Richmond Agitation and Sedation Scale > 0). At 3- and 12-month postdischarge, we assessed for dependence in activities of daily living and instrumental activities of daily living, symptoms of depression, and symptoms of post-traumatic stress disorder. Adjusting for baseline and inhospital covariates, multivariable regression examined the association of exposure to delirium motoric subtype and long-term outcomes.Measurements and main resultsIn our cohort of 556 adults with a median age of 62 years, hypoactive delirium was more common than hyperactive (68.9% vs 16.8%). Dependence on the activities of daily living was present in 37% at 3 months and 31% at 12 months, whereas dependence on instrumental activities of daily living was present in 63% at 3 months and 56% at 12 months. At both time points, depression and post-traumatic stress disorder rates were constant at 36% and 5%, respectively. Each additional day of hypoactive delirium was associated with higher instrumental activities of daily living dependence at 3 months only (0.24 points [95% CI, 0.07-0.41; p = 0.006]). There were no associations between the motoric delirium subtype and activities of daily living dependence, depression, or post-traumatic stress disorder.ConclusionsLonger duration of hypoactive delirium, but not hyperactive, was associated with a minimal increase in early instrumental activities of daily living dependence scores in adult survivors of critical illness. Motoric delirium subtype was neither associated with early or late activities of daily living functional dependence or mental health outcomes, nor late instrumental activities of daily living functional dependence.

Project description:BackgroundSurvivors of critical illness often have a prolonged and disabling form of cognitive impairment that remains inadequately characterized.MethodsWe enrolled adults with respiratory failure or shock in the medical or surgical intensive care unit (ICU), evaluated them for in-hospital delirium, and assessed global cognition and executive function 3 and 12 months after discharge with the use of the Repeatable Battery for the Assessment of Neuropsychological Status (population age-adjusted mean [±SD] score, 100±15, with lower values indicating worse global cognition) and the Trail Making Test, Part B (population age-, sex-, and education-adjusted mean score, 50±10, with lower scores indicating worse executive function). Associations of the duration of delirium and the use of sedative or analgesic agents with the outcomes were assessed with the use of linear regression, with adjustment for potential confounders.ResultsOf the 821 patients enrolled, 6% had cognitive impairment at baseline, and delirium developed in 74% during the hospital stay. At 3 months, 40% of the patients had global cognition scores that were 1.5 SD below the population means (similar to scores for patients with moderate traumatic brain injury), and 26% had scores 2 SD below the population means (similar to scores for patients with mild Alzheimer's disease). Deficits occurred in both older and younger patients and persisted, with 34% and 24% of all patients with assessments at 12 months that were similar to scores for patients with moderate traumatic brain injury and scores for patients with mild Alzheimer's disease, respectively. A longer duration of delirium was independently associated with worse global cognition at 3 and 12 months (P=0.001 and P=0.04, respectively) and worse executive function at 3 and 12 months (P=0.004 and P=0.007, respectively). Use of sedative or analgesic medications was not consistently associated with cognitive impairment at 3 and 12 months.ConclusionsPatients in medical and surgical ICUs are at high risk for long-term cognitive impairment. A longer duration of delirium in the hospital was associated with worse global cognition and executive function scores at 3 and 12 months. (Funded by the National Institutes of Health and others; BRAIN-ICU ClinicalTrials.gov number, NCT00392795.).

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Loud and Clear: Sensory Impairment, Delirium, and Functional Recovery in Critical Illness.

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Loud and Clear: Sensory Impairment, Delirium, and Functional Recovery in Critical Illness.

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