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Association between incident delirium and 28- and 90-day mortality in critically ill adults: a secondary analysis.

ABSTRACT: BACKGROUND:While delirium prevalence and duration are each associated with increased 30-day, 6-month, and 1-year mortality, the association between incident ICU delirium and mortality remains unclear. We evaluated the association between both incident ICU delirium and days spent with delirium in the 28?days after ICU admission and mortality within 28 and 90?days. METHODS:Secondary cohort analysis of a randomized, double-blind, placebo-controlled trial conducted among 1495 delirium-free, critically ill adults in 14 Dutch ICUs with an expected ICU stay ?2?days where all delirium assessments were completed. In the 28?days after ICU admission, patients were evaluated for delirium and coma 3x daily; each day was coded as a delirium day [?1 positive Confusion Assessment Method for the ICU (CAM-ICU)], a coma day [no delirium and???1 Richmond Agitation Sedation Scale (RASS) score???-?4], or neither. Four Cox-regression models were constructed for 28-day mortality and 90-day mortality; each accounted for potential confounders (i.e., age, APACHE-II score, sepsis, use of mechanical ventilation, ICU length of stay, and haloperidol dose) and: 1) delirium occurrence, 2) days spent with delirium, 3) days spent in coma, and 4) days spent with delirium and/or coma. RESULTS:Among the 1495 patients, 28?day mortality was 17% and 90?day mortality was 21%. Neither incident delirium (28?day mortality hazard ratio [HR]?=?1.02, 95%CI?=?0.75-1.39; 90?day mortality HR?=?1.05, 95%CI?=?0.79-1.38) nor days spent with delirium (28?day mortality HR?=?1.00, 95%CI?=?0.95-1.05; 90?day mortality HR?=?1.02, 95%CI?=?0.98-1.07) were significantly associated with mortality. However, both days spent with coma (28?day mortality HR?=?1.05, 95%CI?=?1.02-1.08; 90?day mortality HR?=?1.05, 95%CI?=?1.02-1.08) and days spent with delirium or coma (28?day mortality HR?=?1.03, 95%CI?=?1.00-1.05; 90?day mortality HR?=?1.03, 95%CI?=?1.01-1.06) were significantly associated with mortality. CONCLUSIONS:This analysis suggests neither incident delirium nor days spent with delirium are associated with short-term mortality after ICU admission. TRIAL REGISTRATION:ClinicalTrials.gov, Identifier NCT01785290 Registered 7 February 2013.

SUBMITTER: Duprey MS

PROVIDER: S-EPMC7171767 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Association between incident delirium and 28- and 90-day mortality in critically ill adults: a secondary analysis.

Duprey Matthew S MS van den Boogaard Mark M van der Hoeven Johannes G JG Pickkers Peter P Briesacher Becky A BA Saczynski Jane S JS Griffith John L JL Devlin John W JW

Critical care (London, England) 20200420 1

<h4>Background</h4>While delirium prevalence and duration are each associated with increased 30-day, 6-month, and 1-year mortality, the association between incident ICU delirium and mortality remains unclear. We evaluated the association between both incident ICU delirium and days spent with delirium in the 28 days after ICU admission and mortality within 28 and 90 days.<h4>Methods</h4>Secondary cohort analysis of a randomized, double-blind, placebo-controlled trial conducted among 1495 delirium ...[more]

PMID: 32312288

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Project description:Background and purposeDeep sedation is associated with acute brain dysfunction and increased mortality. We had previously shown that early-assessed brainstem reflexes may predict outcome in deeply sedated patients. The primary objective was to determine whether patterns of brainstem reflexes might predict mortality in deeply sedated patients. The secondary objective was to generate a score predicting mortality in these patients.MethodsObservational prospective multicenter cohort study of 148 non-brain injured deeply sedated patients, defined by a Richmond Assessment sedation Scale (RASS) <-3. Brainstem reflexes and Glasgow Coma Scale were assessed within 24 hours of sedation and categorized using latent class analysis. The Full Outline Of Unresponsiveness score (FOUR) was also assessed. Primary outcome measure was 28-day mortality. A "Brainstem Responses Assessment Sedation Score" (BRASS) was generated.ResultsTwo distinct sub-phenotypes referred as homogeneous and heterogeneous brainstem reactivity were identified (accounting for respectively 54.6% and 45.4% of patients). Homogeneous brainstem reactivity was characterized by preserved reactivity to nociceptive stimuli and a partial and topographically homogenous depression of brainstem reflexes. Heterogeneous brainstem reactivity was characterized by a loss of reactivity to nociceptive stimuli associated with heterogeneous brainstem reflexes depression. Heterogeneous sub-phenotype was a predictor of increased risk of 28-day mortality after adjustment to Simplified Acute Physiology Score-II (SAPS-II) and RASS (Odds Ratio [95% confidence interval] = 6.44 [2.63-15.8]; p<0.0001) or Sequential Organ Failure Assessment (SOFA) and RASS (OR [95%CI] = 5.02 [2.01-12.5]; p = 0.0005). The BRASS (and marginally the FOUR) predicted 28-day mortality (c-index [95%CI] = 0.69 [0.54-0.84] and 0.65 [0.49-0.80] respectively).ConclusionIn this prospective cohort study, around half of all deeply sedated critically ill patients displayed an early particular neurological sub-phenotype predicting 28-day mortality, which may reflect a dysfunction of the brainstem.

Project description:BACKGROUND:Mortality rates associated with acute kidney injury (AKI) vary among critically ill patients. Outcomes are often not corrected for severity or duration of AKI. Our objective was to analyse whether a new variable, AKI burden, would outperform 1) presence of AKI, 2) highest AKI stage, or 3) AKI duration in predicting 90-day mortality. METHODS:Kidney Diseases: Improving Global Outcomes (KDIGO) criteria using creatinine, urine output and renal replacement therapy were used to diagnose AKI. AKI burden was defined as AKI stage multiplied with the number of days that each stage was present (maximum five), divided by the maximum possible score yielding a proportion. The AKI burden as a predictor of 90-day mortality was assessed in two independent cohorts (Finnish Acute Kidney Injury, FINNAKI and Simple Intensive Care Studies I, SICS-I) by comparing four multivariate logistic regression models that respectively incorporated either the presence of AKI, the highest AKI stage, the duration of AKI, or the AKI burden. RESULTS:In the FINNAKI cohort 1096 of 2809 patients (39%) had AKI and 90-day mortality of the cohort was 23%. Median AKI burden was 0.17 (IQR 0.07-0.50), 1.0 being the maximum. The model including AKI burden (area under the receiver operator curve (AUROC) 0.78, 0.76-0.80) outperformed the models using AKI presence (AUROC 0.77, 0.75-0.79, p?=?0.026) or AKI severity (AUROC 0.77, 0.75-0.79, p?=?0.012), but not AKI duration (AUROC 0.77, 0.75-0.79, p?=?0.06). In the SICS-I, 603 of 1075 patients (56%) had AKI and 90-day mortality was 28%. Median AKI burden was 0.19 (IQR 0.08-0.46). The model using AKI burden performed better (AUROC 0.77, 0.74-0.80) than the models using AKI presence (AUROC 0.75, 0.71-0.78, p?=?0.001), AKI severity (AUROC 0.76, 0.72-0.79. p?=?0.008) or AKI duration (AUROC 0.76, 0.73-0.79, p?=?0.009). CONCLUSION:AKI burden, which appreciates both severity and duration of AKI, was superior to using only presence or the highest stage of AKI in predicting 90-day mortality. Using AKI burden or other more granular methods may be helpful in future epidemiological studies of AKI.

Project description:Ketamine is increasingly being used for analgosedation, but its effect on delirium remains unclear. We compared delirium risk variables and ketamine analgosedation use between adults who developed incident delirium and those who did not, evaluated whether ketamine analgosedation increases delirium risk, and compared ICU delirium characteristics, treatments, and outcomes between ketamine and nonketamine patients with delirium.DesignSecondary, subgroup analysis of a cohort study.SettingSingle, 36-bed mixed medical-surgical ICU in the Netherlands from July 2016 to February 2020.PatientsConsecutive adults were included. Patients admitted after elective surgery, not expected to survive greater than or equal to 48 hours, admitted with delirium, or where delirium occurred prior to ketamine use were excluded.InterventionNone.Measurements and main resultsTrained ICU nurses evaluated patients without coma (Richmond Agitation Sedation Scale. -4/-5) every 8 hours with the Confusion Assessment Method ICU; a delirium day was defined by greater than or equal to1 + Confusion Assessment Method ICU and/or scheduled antipsychotic use. Among 11 variables compared between the delirium and nondelirium groups (Baseline: age, Charlson Comorbidity score, cognitive impairment, admission type, and Acute Physiology and Chronic Health Evaluation-IV score, daily ICU [until delirium occurrence or discharge]: Sequential Organ Failure Assessment score, coma, benzodiazepine, opioid, and ketamine use) and total ICU days, 7 (age, Charlson score, Sequential Organ Failure Assessment score, coma, benzodiazepine, opioid, and ketamine use) were significantly different and were entered, along with delirium occurrence, in a logistic regression model. A total of 332 of 925 of patients (36%) developed delirium. Ketamine use was greater in patients with delirium (54 [16%] vs 4 [0.7%]; p < 0.01). Ketamine use (adjusted odds ratio, 5.60; 95% CI, 1.09-29.15), age (adjusted odds ratio, 1.03; 95% CI, 1.01-1.06), coma (adjusted odds ratio, 2.10; 95% CI, 1.15-3.78), opioid use (adjusted odds ratio, 171.17; 95% CI, 66.45-553.68), and benzodiazepine use (adjusted odds ratio, 34.07; 95% CI, 8.12-235.34) were each independently and significantly associated with increased delirium. Delirium duration, motoric subtype, delirium treatments, and outcomes were not different between the ketamine and nonketamine groups.ConclusionsKetamine analgosedation may contribute to increased ICU delirium. The characteristics of ketamine and nonketamine delirium are similar. Further prospective research is required to evaluate the magnitude of risk for delirium with ketamine use.

Project description:IntroductionGut microbiota is associated with host characteristics such as age, sex, immune condition or frailty and is thought to be a key player in numerous human diseases. Nevertheless, its association with outcome in critically ill patients has been poorly investigated. The aim of this study is to assess the association between gut microbiota composition and Day-28 mortality in critically ill patients.MethodsRectal swab at admission of every patient admitted to intensive care unit (ICU) between October and November 2019 was frozen at - 80 °C. DNA extraction was performed thanks to QIAamp® PowerFecal® Pro DNA kit (QIAgen®). V3-V4 regions of 16SRNA and ITS2 coding genes were amplified by PCR. Sequencing (2x250 bp paired-end) was performed on MiSeq sequencer (Illumina®). DADA2 pipeline on R software was used for bioinformatics analyses. Risk factors for Day-28 mortality were investigated by logistic regression.ResultsFifty-seven patients were consecutively admitted to ICU of whom 13/57 (23%) deceased and 44/57 (77%) survived. Bacteriobiota α-diversity was lower among non-survivors than survivors (Shannon and Simpson index respectively, p < 0.001 and p = 0.001) as was mycobiota α-diversity (respectively p = 0.03 and p = 0.03). Both gut bacteriobiota and mycobiota Shannon index were independently associated with Day-28 mortality in multivariate analysis (respectively OR: 0.19, 97.5 CI [0.04-0.60], p < 0.01 and OR: 0.29, 97.5 CI [0.09-0.75], p = 0.02). Bacteriobiota β-diversity was significantly different between survivors and non-survivors (p = 0.05) but not mycobiota β-diversity (p = 0.57). Non-survivors had a higher abundance of Staphylococcus haemolyticus, Clostridiales sp., Campylobacter ureolyticus, Akkermansia sp., Malassezia sympodialis, Malassezia dermatis and Saccharomyces cerevisiae, whereas survivors had a higher abundance of Collinsella aerofaciens, Blautia sp., Streptococcus sp., Faecalibacterium prausnitzii and Bifidobacterium sp.ConclusionThe gut bacteriobiota and mycobiota α diversities are independently associated with Day-28 mortality in critically ill patients. The causal nature of this interference and, if so, the underlying mechanisms should be further investigated to assess if gut microbiota modulation could be a future therapeutic approach.

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Dataset Information

Association between incident delirium and 28- and 90-day mortality in critically ill adults: a secondary analysis.

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Association between incident delirium and 28- and 90-day mortality in critically ill adults: a secondary analysis.

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