Urinary protein profiling in hyperactive delirium and non-delirium cardiac surgery ICU patients.
ABSTRACT: BACKGROUND:Suitable biomarkers associated with the development of delirium are still not known. Urinary proteomics has successfully been applied to identify novel biomarkers associated with various disease states, but its value has not been investigated in delirium patients. RESULTS:In a prospective explorative study hyperactive delirium patients after cardiac surgery were included for urinary proteomic analyses. Delirium patients were matched with non-delirium patients after cardiac surgery on age, gender, severity of illness score, LOS-ICU, Euro-score, C-reactive protein, renal function and aorta clamping time. Urine was collected within 24 hours after the onset of delirium. Matrix-assisted laser desorption/ionisation-time of flight mass spectrometry (MALDI-TOF MS) was applied to detect differences in the urinary proteome associated with delirium in these ICU patients. We included 10 hyperactive delirium and 10 meticulously matched non-delirium post-cardiac surgery patients. No relevant differences in the urinary excretion of proteins could be observed. CONCLUSIONS:We conclude that MALDI-TOF MS of urine does not reveal a clear hyperactive delirium proteome fingerprint in ICU patients. TRIAL REGISTRATION:Clinical Trial Register number: NCT00604773.
Project description:Postoperative delirium in the intensive care unit (ICU) is a frequent complication after cardiac or thoracic surgery and is associated with increased morbidity and mortality.In this single-center substudy of the BAG-RECALL trial (NCT00682825), we screened patients after cardiac or thoracic surgery in the ICU twice daily for delirium using the Confusion Assessment Method for the ICU. The primary outcome was the incidence of delirium in patients who had been randomized to intraoperative Bispectral Index (BIS)-guided and end-tidal anesthetic concentration-guided depth of anesthesia protocols. As a secondary analysis, a Bayesian stochastic search variable selection strategy was used to rank a field of candidate risk factors for delirium, followed by binary logistic regression.Of 310 patients assessed, 28 of 149 (18.8%) in the BIS group and 45 of 161 (28.0%) in the end-tidal anesthetic concentration group developed postoperative delirium in the ICU (odds ratio 0.60, 95% confidence interval, 0.35-1.02, P= 0.058). Low average volatile anesthetic dose, intraoperative transfusion, ASA physical status, and European System for Cardiac Operative Risk Evaluation were identified as independent predictors of delirium.A larger randomized study should determine whether brain monitoring with BIS or an alternative method decreases delirium after cardiac or thoracic surgery. The association between low anesthetic concentration and delirium is a surprising finding and could reflect that patients with poor health are both more sensitive to the effects of volatile anesthetic drugs and are also more likely to develop postoperative delirium. Investigation of candidate methods to prevent delirium should be prioritized in view of the established association between postoperative delirium and adverse patient outcomes.
Project description:<h4>Objectives</h4>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.<h4>Design</h4>Secondary analysis of prospective multicenter cohort study.<h4>Setting</h4>Academic, community, and Veteran Affairs hospitals.<h4>Patients</h4>Five-hundred eighty-two survivors of respiratory failure or shock.<h4>Interventions</h4>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.<h4>Measurements and results</h4>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.<h4>Conclusions</h4>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.
Project description:Delirium is a well-known complication in cardiac surgery and intensive care unit (ICU) patients. However, in many other settings its prevalence and clinical consequences are understudied. The aims of this study were: (1) To assess delirium prevalence in a large, diverse cohort of acute care patients classified as either at risk or not at risk for delirium; (2) To compare these two groups according to defined indicators; and (3) To compare delirious with non-delirious patients regarding hospital mortality, ICU and hospital length of stay, nursing hours and cost per case.This cohort study was performed in a Swiss university hospital following implementation of a delirium management guideline. After excluding patients aged <?18 years or with a length of stay (LOS)?<?1 day, 29'278 patients hospitalized in the study hospital in 2014 were included. Delirium period prevalence was calculated based on a Delirium Observation Scale (DOS) score???3 and / or Intensive Care Delirium Screening Checklist (ICDSC) scores ?4.Of 10'906 patients admitted, DOS / ICDSC scores indicated delirium in 28.4%. Delirium was most prevalent (36.2-40.5%) in cardiac surgery, neurosurgery, trauma, radiotherapy and neurology patients. It was also common in geriatrics, internal medicine, visceral surgery, reconstructive plastic surgery and cranio-maxillo-facial surgery patients (prevalence 21.6-28.6%). In the unadjusted and adjusted models, delirious patients had a significantly higher risk of inpatient mortality, stayed significantly longer in the ICU and hospital, needed significantly more nursing hours and generated significantly higher costs per case. For the seven most common ICD-10 diagnoses, each diagnostic group's delirious patients had worse outcomes compared to those with no delirium.The results indicate a high number of patients at risk for delirium, with high delirium prevalence across all patient groups. Delirious patients showed significantly worse clinical outcomes and generated higher costs. Subgroup analyses highlighted striking variations in delirium period-prevalence across patient groups. Due to the high prevalence of delirium in patients treated in care centers for radiotherapy, visceral surgery, reconstructive plastic surgery, cranio-maxillofacial surgery and oral surgery, it is recommended to expand the current focus of delirium management to these patient groups.
Project description:<h4>Background</h4>Factors that may increase the risk for delirium and the firm knowledge around mechanism for delirium in noninvasive ventilation (NIV) patients is lacking. We investigated the incidence, characteristics, and outcomes of delirium in NIV patients.<h4>Methods</h4>A prospective observational study was performed in an intensive care unit (ICU) of a teaching hospital. Patients in whom NIV was used as a first-line intervention were enrolled. During NIV intervention, delirium was screened using the Confusion Assessment Method for the ICU each day. The association between delirium and poor outcomes (e.g., NIV failure, ICU and hospital mortality) was investigated using forward stepwise multivariate logistic regression analyses.<h4>Results</h4>We enrolled 1083 patients. Of these, 196 patients (18.1%) experienced delirium during NIV intervention. Patients with delirium had higher NIV failure rates (37.8% vs. 21.0%, p < 0.01), higher ICU mortality (33.2% vs. 14.3%, p < 0.01), and higher hospital mortality (37.2% vs. 17.0%, p < 0.01) than subjects without delirium. They also had a longer duration of NIV (median 6.3 vs. 3.7 days, p < 0.01), and stayed longer in the ICU (median 9.0 vs. 6.0 days, p < 0.01) and the hospital (median 14.5 vs. 11.0 days, p < 0.01). These results were confirmed in COPD and non-COPD cohorts. According to subtype, compared to hyperactive delirium patients, hypoactive and mixed delirium patients spent more days and many more days on NIV (median 3.4 vs. 6.5 vs. 10.1 days, p < 0.01). Similar outcomes were found for length of stay in the ICU and hospital. However, NIV failure, ICU mortality, and hospital mortality did not differ among the three subtypes.<h4>Conclusions</h4>Delirium is associated with increases in poor outcomes (NIV failure, ICU mortality, and hospital mortality) and the use of medical resources (duration of NIV, and lengths of stay in the ICU and hospital). Regarding subtype, hypoactive and mixed delirium are associated with higher, and much higher, consumption of medical resources, respectively, compared to hyperactive delirium.
Project description:To determine whether the postoperative administration of tryptophan would be beneficial for elderly adults undergoing surgery who are at risk of developing postoperative delirium.Randomized, double-blind, placebo-controlled trial.Denver Veterans Affairs Medical Center.Individuals aged 60 and older undergoing major elective operations requiring a postoperative intensive care unit (ICU) admission (n = 325).L-tryptophan, 1 g orally three times a day or placebo was started after surgery and continued for up to 3 days postoperatively.Delirium and its motor subtypes were measured using the Confusion Assessment Method-Intensive Care Unit (CAM-ICU) and the Richmond Agitation and Sedation Scale. The primary outcome for between-group comparison was the incidence of excitatory (mixed and hyperactive) postoperative delirium. The secondary outcomes for comparison were the incidence and duration of overall postoperative delirium.The overall incidence of postoperative delirium was 39% (95% confidence interval = 34-44%) (n = 116). Seventeen percent of participants in the tryptophan group and 9% in the placebo group had excitatory delirium (P = .18), and the duration of excitatory delirium was 3.3 ± 1.7 days for tryptophan and 3.1 ± 1.9 days for placebo (P = .74). Forty percent of participants in the tryptophan group and 37% in the placebo group had overall delirium (P = .60), and the duration of overall delirium was 2.9 ± 1.8 days for tryptophan and 2.4 ± 1.6 days for placebo (P = .17).Postoperative tryptophan supplementation in older adults undergoing major elective operations requiring postoperative ICU admission did not reduce the incidence or duration of postoperative excitatory delirium or overall delirium.
Project description:To compare the efficacy and safety of scheduled low-dose haloperidol versus placebo for the prevention of delirium (Intensive Care Delirium Screening Checklist ? 4) administered to critically ill adults with subsyndromal delirium (Intensive Care Delirium Screening Checklist = 1-3).Randomized, double-blind, placebo-controlled trial.Three 10-bed ICUs (two medical and one surgical) at an academic medical center in the United States.Sixty-eight mechanically ventilated patients with subsyndromal delirium without complicating neurologic conditions, cardiac surgery, or requiring deep sedation.Patients were randomly assigned to receive IV haloperidol 1 mg or placebo every 6 hours until delirium occurred (Intensive Care Delirium Screening Checklist ? 4 with psychiatric confirmation), 10 days of therapy had elapsed, or ICU discharge.Baseline characteristics were similar between the haloperidol (n = 34) and placebo (n = 34) groups. A similar number of patients given haloperidol (12/34 [35%]) and placebo (8/34 [23%]) developed delirium (p = 0.29). Haloperidol use reduced the hours per study day spent agitated (Sedation Agitation Scale ? 5) (p = 0.008), but it did not influence the proportion of 12-hour ICU shifts patients spent alive without coma (Sedation Agitation Scale ? 2) or delirium (p = 0.36), the time to first delirium occurrence (p = 0.22), nor delirium duration (p = 0.26). Days of mechanical ventilation (p = 0.80), ICU mortality (p = 0.55), and ICU patient disposition (p = 0.22) were similar in the two groups. The proportion of patients who developed corrected QT-interval prolongation (p = 0.16), extrapyramidal symptoms (p = 0.31), excessive sedation (p = 0.31), or new-onset hypotension (p = 1.0) that resulted in study drug discontinuation was comparable between the two groups.Low-dose scheduled haloperidol, initiated early in the ICU stay, does not prevent delirium and has little therapeutic advantage in mechanically ventilated, critically ill adults with subsyndromal delirium.
Project description: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 .).
Project description:<b>Background:</b> Postoperative delirium (POD) is common in patients following cardiac surgery. According to studies on non-cardiac surgery, males suffered from higher incidence of POD. However, there is no report about effect of gender differences on POD occurrence in cardiac surgery patients. The aim of this study was to investigate the effect of gender differences on POD occurrence in adult patients after cardiac valve surgery. <b>Methods:</b> This is a retrospective case-control study. We recorded the clinical data in adult patients who underwent elective cardiac valve surgery from May 2019 to October 2020. POD was assessed by the Confusion Assessment Method for Intensive Care Unit. Univariate analysis was used to screen the potential risk factors. Collinearity analysis was conducted to detect overlapping predictor variables on the outcomes. A multivariate logistic regression with odds ratio (OR) and 95% confidence interval (CI) was used to identify the independent risk factors. The Hosmer-Lemeshow test was performed to show the good calibration of the logistic regression model. <b>Results:</b> In total, we recorded the perioperative data in 431 adult patients, including 212 males and 219 females. Sixty patients suffered from POD, including 39 males and 21 females. Twenty-one perioperative variables were selected, and 11 were screened by univariate analysis. We did not detect the severe collinearity among the 11 variables. Male gender was identified as a significant risk factor in POD occurrence in patients undergoing cardiac surgery (Adjusted OR: 2.213, 95% CI: 1.049-4.670, <i>P</i> = 0.037). The Hosmer-Lemeshow test demonstrated good calibration of the logistic regression model (χ<sup>2</sup> = 7.238, <i>P</i> = 0.511). Besides, compared with females, the relationship of male and delirium subtypes was as follows: (1) hyperactive: adjusted OR: 3.384, 95% CI: 1.335-8.580, <i>P</i> = 0.010; (2) hypoactive: adjusted OR: 0.509, 95% CI: 0.147-1.766, <i>P</i> = 0.287. A Stratification analysis by age demonstrated that the males showed higher POD incidence in patients aged younger than 60 years (adjusted OR: 4.384, 95% CI: 1.318-14.586, <i>P</i> = 0.016). <b>Conclusions:</b> Male gender is an important risk factor in POD occurrence in patients following cardiac surgery. Furthermore, the incidence of hyperactive delirium is higher in males. Besides, the male patients aged younger than 60 years are at high risk of POD. We should pay more attention to the male patients to prevent their POD occurrence.
Project description:Background:The aim of this clinical study was to evaluate the efficacy of neurobehavioral, hemodynamics and sedative characteristics of dexmedetomidine compared with morphine and midazolam-based regimen after cardiac surgery at equivalent levels of sedation and analgesia in improving clinically relevant outcomes such as delirium. Methods:Sixty patients were randomly allocated into one of two equal groups: group A = 30 patients received dexmedetomidine infusion (0.4-0.7 ?g/kg/h) and Group B = 30 patients received morphine in a dose of 10-50 ?g/kg/h as an analgesic with midazolam in a dose of 0.05 mg/kg up to 0.2 mg/kg as a sedative repeated as needed. Titration of the study medication infusions was conducted to maintain light sedation (Richmond agitation-sedation scale) (-2 to +1). Primary outcome was the prevalence of delirium measured daily through confusion assessment method for intensive care. Results:Group A was associated with shorter length of mechanical ventilation, significant shorter duration of intensive care unit (ICU) stay (P = 0.038), and lower risk of delirium following cardiac surgery compared to Group B. Group A showed statistically significant decrease in heart rate values 4 h after ICU admission (P = 0.015) without significant bradycardia. Group A had lower fentanyl consumption following cardiac surgery compared to Group B. Conclusion:Dexmedetomidine significantly reduced the length of stay in ICU in adult cardiac surgery with no significant reduction in the incidence of postoperative delirium compared to morphine and midazolam.
Project description:Introduction: Post-operative delirium remains a significant problem, particularly in the older surgical patient. Previous evidence suggests that the provision of supplementary visual feedback about ones environment via the use of a mirror may positively impact on mental status and attention (core delirium diagnostic domains). We aimed to explore whether use of an evidence-based mirrors intervention could be effective in reducing delirium and improving post-operative outcomes such as factual memory encoding of the Intensive Care Unit (ICU) environment in older cardiac surgical patients. Methods: This was a pilot time-cluster randomized controlled trial at a 32-bed ICU, enrolling 223 patients aged 70 years and over, admitted to ICU after elective or urgent cardiac surgery from October 29, 2012 to June 23, 2013. The Mirrors Group received a structured mirrors intervention at set times (e.g., following change in mental status). The Usual Care Group received the standard care without mirrors. Primary outcome was ICU delirium incidence; secondary outcomes were ICU delirium days, ICU days with altered mental status or inattention, total length of ICU stay, physical mobilization (balance confidence) at ICU discharge, recall of factual and delusional ICU memories at 12 weeks, Health-Related Quality of Life at 12 weeks, and acceptability of the intervention. Results: The intervention was not associated with a significant reduction in ICU delirium incidence [Mirrors: 20/115 (17%); Usual Care: 17/108 (16%)] or duration [Mirrors: 1 (1-3); Usual Care: 2 (1-8)]. Use of the intervention on ICU was predictive of significantly higher recall of factual (but not delusional) items at 12 weeks after surgery (p = 0.003) and acceptability was high, with clinicians using mirrors at 86% of all recorded hourly observations. The intervention did not significantly impact on other secondary outcomes. Conclusion: Use of a structured mirrors intervention on the post-operative ICU does not reduce delirium, but may result in improved factual memory encoding in older cardiac surgical patients. This effect may occur via mechanisms unrelated to delirium, altered mental status, or inattention. The intervention may provide a new means of improving outcomes in patients at risk of post-ICU anxiety and/or Post-Traumatic Stress Disorder. Trial Registration: Clinicaltrials.gov identifier NCT01599689.