Haloperidol, clonidine and resolution of delirium in critically ill patients: a prospective cohort study

Purpose: Haloperidol and clonidine are commonly used to treat agitation in delirious intensive care unit (ICU) patients, but it is unclear whether these agents may shorten the duration of delirium. The objective of this study was to determine whether haloperidol, clonidine, or their combined administration to delirious ICU patients results in delirium resolution. Methods: This was a cohort study on a mixed ICU, excluding patients with a primary neurological disorder. The main outcome was the probability of delirium resolution, using propensity score matching and Markov multinomial logistic regression models for daily transitions. Secondary outcomes were delirium duration, number of delirium days, ventilation days, length of stay in the ICU and hospital, and ICU mortality. Results: A total of 3614 patients were included (1165 delirious [32%]; 2449 non-delirious [68%]). Delirium occurred on 4708 (18.9%) of 24,906 days. The probability of delirium resolution was lower in delirious patients who received haloperidol (OR 0.47, 95% CI 0.39–0.57), clonidine (OR 0.78, 95% CI 0.63–0.97), or both (OR 0.45, 95% CI 0.36–0.56) compared to untreated delirious patients. Delirious patients who received haloperidol, clonidine, or both had generally longer delirium duration, more delirium and ventilation days, and spent more time in the ICU and in hospital than untreated delirious patients. These agents had no effect on ICU mortality. Conclusion: Haloperidol and clonidine use in delirious ICU patients may be associated with reduced probability of delirium resolution. This finding, however, merits further investigation given inherent limitations of this observational analysis

A systematic review of risk factors for delirium in the ICU

Objective: Although numerous risk factors for delirium in the ICU have been proposed, the strength of evidence supporting each risk factor remains unclear. This study systematically identifies risk factors for delirium in critically ill adults where current evidence is strongest. Data Sources: CINAHL, EMBASE, MEDLINE, the Cochrane Central Register for Controlled Trials, and the Cochrane Database of Systematic Reviews. Study Selection: Studies published from 2000 to February 2013 that evaluated critically ill adults, not undergoing cardiac surgery, for delirium, and used either multivariable analysis or randomization to evaluate variables as potential risk factors for delirium. Data Extraction: Data were abstracted in duplicate, and quality was scored using Scottish Intercollegiate Guidelines Network checklists (i.e., high, acceptable, and low). Using a best-evidence synthesis each variable was evaluated using 3 criteria: the number of studies investigating it, the quality of these studies, and whether the direction of association was consistent across the studies. Strengths of association were not summarized. Strength of evidence was defined as strong (consistent findings in ≥2 high quality studies), moderate (consistent findings in 1 high quality study and ≥1 acceptable quality studies), inconclusive (inconsistent findings or 1 high quality study or consistent findings in only acceptable quality/low quality studies) or no evidence available. Data Synthesis: Among 33 studies included, 70% were high quality. There was strong evidence that age, dementia, hypertension, pre-ICU emergency surgery or trauma, Acute Physiology and Chronic Health Evaluation II score, mechanical ventilation, metabolic acidosis, delirium on the prior day, and coma are risk factors for delirium, that gender is not associated with delirium, and that use of dexmedetomidine is associated with a lower delirium prevalence. There is moderate evidence that multiple organ failure is a risk factor for delirium. Conclusions: Only 11 putative risk factors for delirium are supported by either strong or moderate level of evidence. These factors should be considered when designing delirium prevention strategies or controlling for confounding in future etiologic studies

Risk factors for delirium after on-pump cardiac surgery : A systematic review

Introduction: As evidence-based effective treatment protocols for delirium after cardiac surgery are lacking, efforts should be made to identify risk factors for preventive interventions. Moreover, knowledge of these risk factors could increase validity of etiological studies in which adjustments need to be made for confounding variables. This review aims to systematically identify risk factors for delirium after cardiac surgery and to grade the evidence supporting these associations. Method: A prior registered systematic review was performed using EMBASE, CINAHL, MEDLINE and Cochrane from 1990 till January 2015 (http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42014007371). All studies evaluating patients for delirium after cardiac surgery with cardiopulmonary bypass (CPB) using either randomization or multivariable data analyses were included. Data was extracted and quality was scored in duplicate. Heterogeneity impaired pooling of the data; instead a semi-quantitative approach was used in which the strength of the evidence was graded based on the number of investigations, the quality of studies, and the consistency of the association reported across studies. Results: In total 1462 unique references were screened and 34 were included in this review, of which 16 (47 %) were graded as high quality. A strong level of evidence for an association with the occurrence of postoperative delirium was found for age, previous psychiatric conditions, cerebrovascular disease, pre-existent cognitive impairment, type of surgery, peri-operative blood product transfusion, administration of risperidone, postoperative atrial fibrillation and mechanical ventilation time. Postoperative oxygen saturation and renal insufficiency were supported by a moderate level of evidence, and there is no evidence that gender, education, CPB duration, pre-existent cardiac disease or heart failure are risk factors. Conclusion: Of many potential risk factors for delirium after cardiac surgery, for only 11 there is a strong or moderate level of evidence. These risk factors should be taken in consideration when designing future delirium prevention strategies trials or when controlling for confounding in future etiological studies

Temperature variability during delirium in ICU patients: an observational study.

INTRODUCTION:Delirium is an acute disturbance of consciousness and cognition. It is a common disorder in the intensive care unit (ICU) and associated with impaired long-term outcome. Despite its frequency and impact, delirium is poorly recognized by ICU-physicians and -nurses using delirium screening tools. A completely new approach to detect delirium is to use monitoring of physiological alterations. Temperature variability, a measure for temperature regulation, could be an interesting component to monitor delirium, but whether temperature regulation is different during ICU delirium has not yet been investigated. The aim of this study was to investigate whether ICU delirium is related to temperature variability. Furthermore, we investigated whether ICU delirium is related to absolute body temperature. METHODS:We included patients who experienced both delirium and delirium free days during ICU stay, based on the Confusion Assessment method for the ICU conducted by a research- physician or -nurse, in combination with inspection of medical records. We excluded patients with conditions affecting thermal regulation or therapies affecting body temperature. Daily temperature variability was determined by computing the mean absolute second derivative of the temperature signal. Temperature variability (primary outcome) and absolute body temperature (secondary outcome) were compared between delirium- and non-delirium days with a linear mixed model and adjusted for daily mean Richmond Agitation and Sedation Scale scores and daily maximum Sequential Organ Failure Assessment scores. RESULTS:Temperature variability was increased during delirium-days compared to days without delirium (β(unadjuste)d=0.007, 95% confidence interval (CI)=0.004 to 0.011, p<0.001). Adjustment for confounders did not alter this result (β(adjusted)=0.005, 95% CI=0.002 to 0.008, p<0.001). Delirium was not associated with absolute body temperature (β(unadjusted)=-0.03, 95% CI=-0.17 to 0.10, p=0.61). This did not change after adjusting for confounders (β(adjusted)=-0.03, 95% CI=-0.17 to 0.10, p=0.63). CONCLUSIONS:Our study suggests that temperature variability is increased during ICU delirium

Heart rate variability in intensive care unit patients with delirium

Sympathovagal balance, assessed with heart rate variability (HRV), may be altered in intensive care unit (ICU) delirium. HRV was measured in the frequency domain [low frequencies (LF)=0.04-0.15 Hz and high frequencies (HF)=0.15-0.40 Hz] with HF in normalized units (HFnu) to evaluate parasympathetic tone and LF:HF ratio for sympathovagal balance. The authors assessed 726 ICU patients and excluded patients with conditions affecting HRV. No difference could be found between patients with (N=13) and without (N=12) delirium by comparing the mean (±standard deviation) of the HFnu (75±7 versus 68±23) and the LF:HF ratio (-0.7±1.0 versus -0.1±1.1). This study suggests that autonomic function is not altered in ICU delirium

Systemic Corticosteroids And Transition To Delirium in Critically Ill Patients

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