Delirium, an acute organ dysfunction, is common among critically ill patients leading to significant morbidity and mortality; its epidemiology in a mixed cardiology and cardiac surgery ICU is not ...well established. We sought to determine the prevalence and risk factors for delirium among cardiac surgery ICU patients.
Prospective observational study.
Twenty-seven-bed medical-surgical cardiac surgery ICU.
Two hundred consecutive patients with an expected cardiac surgery ICU length of stay >24 hrs.
None.
Baseline demographic data and daily assessments for delirium using the validated and reliable Confusion Assessment Method for the ICU were recorded, and quantitative tracking of delirium risk factors were conducted. Separate analyses studied the role of admission risk factors for occurrence of delirium during the cardiac surgery ICU stay and identified daily occurring risk factors for the development of delirium on a subsequent cardiac surgery ICU day.
Prevalence of delirium was 26%, similar among cardiology and cardiac surgical patients. Nearly all (92%) exhibited the hypoactive subtype of delirium. Benzodiazepine use at admission was independently predictive of a three-fold increased risk of delirium (odds ratio 3.1 1, 9.4, p = 0.04) during the cardiac surgery ICU stay. Of the daily occurring risk factors, patients who received benzodiazepines (2.6 1.2, 5.7, p = 0.02) or had restraints or devices that precluded mobilization (2.9 1.3, 6.5, p < 0.01) were more likely to have delirium the following day. Hemodynamic status was not associated with delirium.
Delirium occurred in one in four patients in the cardiac surgery ICU and was predominately hypoactive in subtype. Chemical restraints via use of benzodiazepines or the use of physical restraints/restraining devices predisposed patients to a greater risk of delirium, pointing to areas of quality improvement that would be new to the vast majority of cardiac surgery ICUs.
Delirium assessments in critically ill infants and young children pose unique challenges due to evolution of cognitive and language skills. The objectives of this study were to determine the validity ...and reliability of a fundamentally objective and developmentally appropriate delirium assessment tool for critically ill infants and preschool-aged children and to determine delirium prevalence.
Prospective, observational cohort validation study of the PreSchool Confusion Assessment Method for the ICU in a tertiary medical center PICU.
Participants aged 6 months to 5 years and admitted to the PICU regardless of admission diagnosis were enrolled.
An interdisciplinary team created the PreSchool Confusion Assessment Method for the ICU for pediatric delirium monitoring. To assess validity, patients were independently assessed for delirium daily by the research team using the PreSchool Confusion Assessment Method for the ICU and by a child psychiatrist using the Diagnostic and Statistical Manual of Mental Disorders criteria. Reliability was assessed using blinded, concurrent PreSchool Confusion Assessment Method for the ICU evaluations by research staff. A total of 530-paired delirium assessments were completed among 300 patients, with a median age of 20 months (interquartile range, 11-37) and 43% requiring mechanical ventilation. The PreSchool Confusion Assessment Method for the ICU demonstrated a specificity of 91% (95% CI, 90-93), sensitivity of 75% (95% CI, 72-78), negative predictive value of 86% (95% CI, 84-88), positive predictive value of 84% (95% CI, 81-87), and a reliability κ-statistic of 0.79 (0.76-0.83). Delirium prevalence was 44% using the PreSchool Confusion Assessment Method for the ICU and 47% by the reference rater. The rates of delirium were 53% versus 56% in patients younger than 2 years old and 33% versus 35% in patients 2-5 years old using the PreSchool Confusion Assessment Method for the ICU and reference rater, respectively. The short-form PreSchool Confusion Assessment Method for the ICU maintained a high specificity (87%) and sensitivity (78%) in post hoc analysis.
The PreSchool Confusion Assessment Method for the ICU is a highly valid and reliable delirium instrument for critically ill infants and preschool-aged children, in whom delirium is extremely prevalent.
The Sequential Organ Failure Assessment (SOFA) score is validated to measure severity of organ dysfunction in critically ill patients. However, in some practice settings, daily arterial blood gas ...data required to calculate the respiratory component of the SOFA score are often unavailable. The objectives of this study were to derive Spo2/Fio2 (SF) ratio correlations with the Pao2/Fio2 (PF) ratio to calculate the respiratory parameter of the SOFA score, and to validate the respiratory SOFA obtained using SF ratios against clinical outcomes.
We obtained matched measurements of Spo2 and Pao2 from two populations: group 1-patients undergoing general anesthesia and group 2-patients from the acute respiratory distress syndrome network-low-vs. high-tidal volume for the acute respiratory management of acute respiratory distress syndrome database. Using a linear regression model, we first determined SF ratios corresponding to PF ratios of 100, 200, 300, and 400. Second, we evaluated the contribution of positive end-expiratory pressure (PEEP) on the relationship between SF and PF, for patients on PEEP in centimeters of water (cm H2O) of <8, 8-12, and >12. Third, we calculated the SOFA scores in a separate cohort of intensive care unit patients using the derived SF ratios and validated them against clinical outcomes.
The total SOFA scores calculated using SF ratios and PF ratios were highly correlated (Spearman's rho 0.85, p < 0.001) in all patients and in the three stratified PEEP categories (<8 cm H2O, Spearman's rho 0.87, p < 0.001; PEEP 8-12 cm H20, Spearman's rho 0.85, p < 0.001; PEEP >12 cm H2O, Spearman's rho 0.85, p < 0.001). The respiratory SOFA scores based on SF ratios and PF ratios correlated similarly with intensive care unit length of stay and ventilator-free days, when validated in a cohort of critically ill patients.
The total and respiratory SOFA scores obtained with imputed SF values correlate with the corresponding SOFA score using PF ratios. Both the derived and original respiratory SOFA scores similarly predict outcomes.
Delirium, 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.
Secondary analysis of prospective multicenter cohort study.
Academic, community, and Veteran Affairs hospitals.
Five-hundred eighty-two survivors of respiratory failure or shock.
We 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.
Hypoactive 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.
Longer 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.
To survey the recent medical literature examining the pathophysiology of acute brain dysfunction (delirium and coma) in the ICU.
Clinical risk factors for brain dysfunction in the ICU continue to be ...elucidated and prediction models developed. Multiple studies have identified sedatives, especially benzodiazepines, as modifiable risk factors for delirium. Imaging studies examining global brain disorders have demonstrated white matter lesions and brain atrophy to be associated with delirium. Endothelial dysfunction, increased blood-brain barrier permeability, and reduced blood flow have also been implicated in cerebral perfusion abnormalities associated with brain dysfunction. The response of the brain to inflammation, including activation of microglia and neuronal apoptosis, leads to synaptic and neurochemical disturbances. Decreased availability of acetylcholine during critical illness leads to decreased counter-regulatory activity in response to inflammatory disease states, likely causing additional injury and further neurotransmitter imbalances. Dopamine, norepinephrine, and serotonin excess and their respective amino acid precursors have also been associated with brain dysfunction.
The multifactorial pathophysiology of acute brain dysfunction remains incompletely understood. Multiple clinical risk factors have been identified and numerous pathophysiologic pathways have been hypothesized. Future research is required to investigate the roles of these pathways on differing clinical presentations, potential therapeutic options, and patient outcomes.
To evaluate the safety, feasibility, and efficacy of combined adrenergic blockade with propranolol and clonidine in patients with severe traumatic brain injury (TBI).
Administration of adrenergic ...blockade after severe TBI is common. To date, no prospective trial has rigorously evaluated this common therapy for benefit.
This phase II, single-center, double-blinded, pilot randomized placebo-controlled trial included patients aged 16-64 years with severe TBI (intracranial hemorrhage and Glasgow Coma Scale score ≤ 8) within 24 h of ICU admission. Patients received propranolol and clonidine or double placebo for 7 days. The primary outcome was ventilator-free days (VFDs) at 28 days. Secondary outcomes included catecholamine levels, hospital length of stay, mortality, and long-term functional status. A planned futility assessment was performed mid-study.
Dose compliance was 99%, blinding was intact, and no open-label agents were used. No treatment patient experienced dysrhythmia, myocardial infarction, or cardiac arrest. The study was stopped for futility after enrolling 47 patients (26 placebo, 21 treatment), per a priori stopping rules. There was no significant difference in VFDs between treatment and control groups 0.3 days, 95% CI (- 5.4, 5.8), p = 1.0. Other than improvement of features related to sympathetic hyperactivity (mean difference in Clinical Features Scale (CFS) 1.7 points, CI (0.4, 2.9), p = 0.012), there were no between-group differences in the secondary outcomes.
Despite the safety and feasibility of adrenergic blockade with propranolol and clonidine after severe TBI, the intervention did not alter the VFD outcome. Given the widespread use of these agents in TBI care, a multi-center investigation is warranted to determine whether adrenergic blockade is of therapeutic benefit in patients with severe TBI. Trial Registration Number NCT01322048.
Acute kidney injury may contribute to distant organ dysfunction. Few studies have examined kidney injury as a risk factor for delirium and coma.
To examine whether acute kidney injury is associated ...with delirium and coma in critically ill adults.
In a prospective cohort study of intensive care unit patients with respiratory failure and/or shock, we examined the association between acute kidney injury and daily mental status using multinomial transition models adjusting for demographics, nonrenal organ failure, sepsis, prior mental status, and sedative exposure. Acute kidney injury was characterized daily using the difference between baseline and peak serum creatinine and staged according to Kidney Disease Improving Global Outcomes criteria. Mental status (normal vs. delirium vs. coma) was assessed daily with the Confusion Assessment Method for the ICU and Richmond Agitation-Sedation Scale.
Among 466 patients, stage 2 acute kidney injury was a risk factor for delirium (odds ratio OR, 1.55; 95% confidence interval CI, 1.07-2.26) and coma (OR, 2.04; 95% CI, 1.25-3.34) as was stage 3 injury (OR for delirium, 2.56; 95% CI, 1.57-4.16) (OR for coma, 3.34; 95% CI, 1.85-6.03). Daily peak serum creatinine (adjusted for baseline) values were also associated with delirium (OR, 1.35; 95% CI, 1.18-1.55) and coma (OR, 1.44; 95% CI, 1.20-1.74). Renal replacement therapy modified the association between stage 3 acute kidney injury and daily peak serum creatinine and both delirium and coma.
Acute kidney injury is a risk factor for delirium and coma during critical illness.
Prior retrospective cross-sectional work has associated antimicrobials with a non-specific phrase: encephalopathy without seizures. The purpose of this study is to determine whether different classes ...of antimicrobials have differential associations with the daily risk of delirium after critical illness is adjusted for.
Our study was a nested cohort that enrolled non-neurological critically ill adults from a medical or surgical intensive care unit (ICU) with daily follow-up to 30 days. Our independent variable was exposure to previous-day antimicrobial class: beta-lactams (subclasses: penicillins, first- to third-generation cephalosporins, fourth-generation cephalosporins, and carbapenems), macrolides, fluoroquinolones, and other. We adjusted for baseline covariates (age, comorbidities, cognition scores, sepsis, and mechanical ventilation), previous-day covariates (delirium, doses of analgesics/sedatives, and antipsychotic use), and same-day covariates (illness severity). Our primary outcome of delirium was measured by using the Confusion Assessment Method for the ICU. A daily delirium logistic regression model was used with an ICU time-restricted sensitivity analysis including daily adjustment for sepsis and mechanical ventilation.
Of 418 ICU patients, delirium occurred in 308 (74%) with a median of 3 days (interquartile range 2-6) among those affected and 318 (76%) were exposed to antimicrobials. When covariates and ICU type were adjusted for, only first- to third-generation cephalosporins were associated with delirium (logistic regression model odds ratio (OR) = 2.2, 95% confidence interval (CI) 1.28-3.79, P = 0.004; sensitivity analysis OR = 2.13, 95% CI 1.10-4.10, P = 0.024).
First-, second-, and third-generation cephalosporins doubled the odds of delirium after baseline co-morbidities, ICU type, the course of critical care, and other competing antimicrobial and psychotropic medication risks were adjusted for. We did not find an association between delirium and cefepime, penicillins, carbapenems, fluoroquinolones, or macrolides.
The 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.
We 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.
Among 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.
Delirium 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.
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