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Clinical phenotypes of delirium during critical illness and severity of subsequent long-term cognitive impairment: a prospective cohort study.

ABSTRACT: BACKGROUND:Delirium 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. METHODS:In 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. FINDINGS:Between 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). INTERPRETATION:Our 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. FUNDING:National Institutes of Health and the Department of Veterans Affairs.

SUBMITTER: Girard TD

PROVIDER: S-EPMC6709878 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Clinical phenotypes of delirium during critical illness and severity of subsequent long-term cognitive impairment: a prospective cohort study.

Girard Timothy D TD Thompson Jennifer L JL Pandharipande Pratik P PP Brummel Nathan E NE Jackson James C JC Patel Mayur B MB Hughes Christopher G CG Chandrasekhar Rameela R Pun Brenda T BT Boehm Leanne M LM Elstad Mark R MR Goodman Richard B RB Bernard Gordon R GR Dittus Robert S RS Ely E W EW

The Lancet. Respiratory medicine 20180301 3

<h4>Background</h4>Delirium 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.<h4>Methods</h4>In this multicentre, prospective cohort study, ...[more]

PMID: 29508705

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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.).

Project description:ObjectivesDelirium, a heterogenous syndrome, is associated with worse long-term cognition after critical illness. We sought to determine if duration of motoric subtypes of delirium are associated with worse cognition.DesignSecondary analysis of prospective multicenter cohort study.SettingAcademic, community, and Veteran Affairs hospitals.PatientsFive-hundred eighty-two survivors of respiratory failure or shock.InterventionsWe assessed delirium and level of consciousness using the Confusion Assessment Method-ICU and Richmond Agitation Sedation Scale daily during hospitalization. We defined a day with hypoactive delirium as a day with positive Confusion Assessment Method-ICU and corresponding Richmond Agitation Sedation Scale score less than or equal to 0 and a day with hyperactive delirium as a day with positive Confusion Assessment Method-ICU and corresponding Richmond Agitation Sedation Scale score greater than 0. At 3 and 12 months, we assessed global cognition with the Repeatable Battery for the Assessment of Neurologic Status and executive function with the Trail Making Test Part B. We used multivariable regression to examine the associations between days of hypoactive and hyperactive delirium with cognition outcomes. We allowed for interaction between days of hypoactive and hyperactive delirium and adjusted for baseline and in-hospital covariates.Measurements and resultsHypoactive delirium was more common and persistent than hyperactive delirium (71% vs 17%; median 3 vs 1 d). Longer duration of hypoactive delirium was associated with worse global cognition at 3 (-5.13 [-8.75 to -1.51]; p = 0.03) but not 12 (-5.76 [-9.99 to -1.53]; p = 0.08) months and with worse executive functioning at 3 (-3.61 [-7.48 to 0.26]; p = 0.03) and 12 (-6.22 [-10.12 to -2.33]; p = 0.004) months; these associations were not modified by hyperactive delirium. Hyperactive delirium was not associated with global cognition or executive function in this cohort.ConclusionsLonger duration of hypoactive delirium was independently associated with worse long-term cognition. Assessing motoric subtypes of delirium in the ICU might aid in prognosis and intervention allocation. Future studies should consider delineating motoric subtypes of delirium.

Project description:BackgroundThe temporal association of delirium during critical illness with mortality is unclear, along with the associations of hypoactive and hyperactive motoric subtypes of delirium with mortality. We aimed to evaluate the relationship of delirium during critical illness, including hypoactive and hyperactive motoric subtypes, with mortality in the hospital and after discharge up to 1 year.MethodsWe analyzed a prospective cohort study of adults with respiratory failure and/or shock admitted to university, community, and Veterans Affairs hospitals. We assessed patients using the Richmond Agitation-Sedation Scale and the Confusion Assessment Method for the intensive care unit (ICU) and defined the motoric subtype according to the corresponding Richmond Agitation-Sedation Scale if delirium was present. We used Cox proportional hazard models, adjusted for baseline characteristics, coma, and daily hospital events, to determine whether delirium on a given day predicted mortality the following day in patients in the hospital and also to determine whether delirium presence and duration predicted mortality after discharge up to 1 year in patients who survived to hospital discharge. We performed similar analyses for hypoactive and hyperactive subtypes of delirium.ResultsAmong 1040 critically ill patients, 214 (21%) died in the hospital and 204 (20%) died out-of-hospital by 1 year. Delirium was common, occurring in 740 (71%) patients for a median (interquartile range [IQR]) of 4 (2-7) days. Hypoactive delirium occurred in 733 (70%) patients, and hyperactive occurred in 185 (18%) patients, with a median (IQR) of 3 (2-7) days and 1 (1-2) days, respectively. Delirium on a given day (hazard ratio [HR], 2.87; 95% confidence interval [CI], 1.32-6.21; P = .008), in particular the hypoactive subtype (HR, 3.35; 95% CI, 1.51-7.46; P = .003), was independently associated with an increased risk of death the following day in the hospital. Hyperactive delirium was not associated with an increased risk of death in the hospital (HR, 4.00; 95% CI, 0.49-32.51; P = .19). Among hospital survivors, neither delirium presence (HR, 1.01; 95% CI, 0.82-1.24; P = .95) nor duration (HR, 0.99; 95% CI, 0.97-1.01; P = .56), regardless of motoric subtype, was associated with mortality after hospital discharge up to 1 year.ConclusionsDelirium during critical illness is associated with nearly a 3-fold increased risk of death the following day for patients in the hospital but is not associated with mortality after hospital discharge. This finding appears primarily driven by the hypoactive motoric subtype. The independent relationship between delirium and mortality occurs early during critical illness but does not persist after hospital discharge.

Project description:BackgroundThere is an unmet public health need to understand better the relationship between baseline cognitive function, the occurrence and severity of delirium, and subsequent cognitive decline. Our aim was to quantify the relationship between baseline cognition and delirium and follow-up cognitive impairment.MethodsWe did a prospective longitudinal study in a stable representative community sample of adults aged 70 years or older who were registered with a Camden-based general practitioner in the London Borough of Camden (London, UK). Participants were recruited by invitation letters from general practice lists or by direct recruitment of patients from memory clinics or patients recently discharged from secondary care. We quantified baseline cognitive function with the modified Telephone Interview for Cognitive Status. In patients who were admitted to hospital, we undertook daily assessments of delirium using the Memorial Delirium Assessment Scale (MDAS). We estimated the association of pre-admission baseline cognitive function with delirium prevalence, severity, and duration. We assessed subsequent cognitive function 2 years after baseline recruitment using the Telephone Interview for Cognitive Status. Regression models were adjusted by age, sex, education, illness severity, and frailty.FindingsWe recruited 1510 participants (median age 77 [IQR 73-82], 57% women) between March, 2017, and October, 2018. 209 participants were admitted to hospital across 371 episodes (1999 person-days of assessment). Better baseline cognition was associated with a lower risk of delirium (odds ratio 0·63, 95% CI 0·45 to 0·89) and with less severe delirium (-1·6 MDAS point, 95% CI -2·6 to -0·7). Individuals with high baseline cognition (baseline Z score +2·0 SD) had demonstrable decline even without delirium (follow-up Z score +1·2 SD). However, those with a high delirium burden had an even larger absolute decline of 2·2 SD in Z score (follow-up Z score -0·2). Once individuals had more than 2 days of moderate delirium, the rates of death over 2 years were similar regardless of baseline cognition; a better baseline cognition no longer conferred any mortality benefit.InterpretationA higher baseline cognitive function is associated with a good prognosis with regard to likelihood and severity of delirium. However, those with a high baseline cognition and with delirium had the highest degree of cognitive decline, a change similar to the decline observed in individuals with a high amyloid burden in other cohorts. Older people with a healthy baseline cognitive function who develop delirium stand to lose the most after delirium. This group could benefit from targeted cognitive rehabilitation interventions after delirium.

Dataset Information

Clinical phenotypes of delirium during critical illness and severity of subsequent long-term cognitive impairment: a prospective cohort study.

Publications

Clinical phenotypes of delirium during critical illness and severity of subsequent long-term cognitive impairment: a prospective cohort study.

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