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Antimicrobial exposure and the risk of delirium in critically ill patients.

ABSTRACT: BACKGROUND: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. METHODS: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. RESULTS: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). CONCLUSIONS: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.

SUBMITTER: Grahl JJ

PROVIDER: S-EPMC6291937 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Antimicrobial exposure and the risk of delirium in critically ill patients.

Grahl Jessica J JJ Stollings Joanna L JL Rakhit Shayan S Person Anna K AK Wang Li L Thompson Jennifer L JL Pandharipande Pratik P PP Ely E Wesley EW Patel Mayur B MB

Critical care (London, England) 20181212 1

<h4>Background</h4>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.<h4>Methods</h4>Our study was a nested cohort that enrolled non-neurological critically ill adults from a medical or surgical intensive care unit (ICU) with dail ...[more]

PMID: 30541600

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Project description:Delirium is associated with increased morbidity and mortality. We implemented a delirium prevention policy in intensive care unit (ICU) patients with a high risk of developing delirium, and evaluated if our policy resulted in quality improvement of relevant delirium outcome measures.This study was a before/after evaluation of a delirium prevention project using prophylactic treatment with haloperidol. Patients with a predicted risk for delirium of ? 50%, or with a history of alcohol abuse or dementia, were identified. According to the prevention protocol these patients received haloperidol 1 mg/8 h. Evaluation was primarily focused on delirium incidence, delirium free days without coma and 28-day mortality. Results of prophylactic treatment were compared with a historical control group and a contemporary group that did not receive haloperidol prophylaxis mainly due to non-compliance to the protocol mostly during the implementation phase.In 12 months, 177 patients received haloperidol prophylaxis. Except for sepsis, patient characteristics were comparable between the prevention and the historical (n = 299) groups. Predicted chance to develop delirium was 75 ± 19% and 73 ± 22%, respectively. Haloperidol prophylaxis resulted in a lower delirium incidence (65% vs. 75%, P = 0.01), and more delirium-free-days (median 20 days (IQR 8 to 27) vs. median 13 days (3 to 27), P = 0.003) in the intervention group compared to the control group. Cox-regression analysis adjusted for sepsis showed a hazard rate of 0.80 (95% confidence interval 0.66 to 0.98) for 28-day mortality. Beneficial effects of haloperidol appeared most pronounced in the patients with the highest risk for delirium. Furthermore, haloperidol prophylaxis resulted in less ICU re-admissions (11% vs. 18%, P = 0.03) and unplanned removal of tubes/lines (12% vs. 19%, P = 0.02). Haloperidol was stopped in 12 patients because of QTc-time prolongation (n = 9), renal failure (n = 1) or suspected neurological side-effects (n = 2). No other side-effects were reported. Patients who were not treated during the intervention period (n = 59) showed similar results compared to the untreated historical control group.Our evaluation study suggests that prophylactic treatment with low dose haloperidol in critically ill patients with a high risk for delirium probably has beneficial effects. These results warrant confirmation in a randomized controlled trial.clinicaltrial.gov Identifier: NCT01187667.

Project description:BACKGROUND:A common postoperative complication found among patients who are critically ill is delirium, which has a high mortality rate. A predictive model is needed to identify high-risk patients in order to apply strategies which will prevent and/or reduce adverse outcomes. OBJECTIVES:To identify the incidence of, and the risk factors for, postoperative delirium (POD) in surgical intensive care unit (SICU) patients, and to determine predictive scores for the development of POD. METHODS:This study enrolled adults aged over 18 years who had undergone an operation within the preceding week and who had been admitted to a SICU for a period that was expected to be longer than 24 h. The CAM - ICU score was used to determine the occurrence of delirium. RESULTS:Of the 250 patients enrolled, delirium was found in 61 (24.4%). The independent risk factors for delirium that were identified by a multivariate analysis comprised age, diabetes mellitus, severity of disease (SOFA score), perioperative use of benzodiazepine, and mechanical ventilation. A predictive score (age + (5 × SOFA) + (15 × Benzodiazepine use) + (20 × DM) + (20 × mechanical ventilation) + (20 × modified IQCODE > 3.42)) was created. The area under the receiver operating characteristic (ROC) curve (AUC) was 0.84 (95% CI: 0.786 to 0.897). The cut point of 125 demonstrated a sensitivity of 72.13% and a specificity of 80.95%, and the hospital mortality rate was significantly greater among the delirious than the non-delirious patients (25% vs. 6%, p < 0.01). CONCLUSIONS:POD was experienced postoperatively by a quarter of the surgical patients who were critically ill. A risk score utilizing 6 variables was able to predict which patients would develop POD. The identification of high-risk patients following SICU admission can provide a basis for intervention strategies to improve outcomes. TRIAL REGISTRATION:Thai Clinical Trials Registry TCTR20181204006 . Date registered on December 4, 2018. Retrospectively registered.

Project description:During critical illness, impaired endothelial vascular reactivity predicts prolonged acute brain dysfunction, but relationships between endothelial activation, blood-brain barrier/neurological injury, and acute brain dysfunction, including delirium, remain unexamined. We tested the hypothesis that elevated plasma markers of endothelial activation and blood-brain barrier/neurological injury are associated with delirium duration during critical illness.Prospective cohort study.Medical and surgical ICUs in an academic medical center.Adults in acute respiratory failure and/or shock.None.We enrolled subjects within 72 hours of organ failure diagnosis in the ICU. We measured plasma concentrations of plasminogen activator inhibitor-1, E-selectin, and angiopoietin-2 as markers of endothelial activation and S100B as a marker of blood-brain barrier/neurological injury in blood collected at enrollment. We assessed patients for delirium and coma twice daily after enrollment using the Confusion Assessment Method for the ICU and the Richmond Agitation-Sedation Scale. Among 134 patients with a median (interquartile) age of 57 years (46-66 yr) and Acute Physiology and Chronic Health Evaluation II of 26 (19-31), delirium occurred in 94 patients (70%) with a median duration of 2 days (0-4 d). Higher plasminogen activator inhibitor-1 (p = 0.002), E-selectin (p = 0.02), and S100B (p < 0.001) concentrations were associated with fewer delirium/coma-free days after adjusting for age, Charlson comorbidity index, modified Sequential Organ Failure Assessment score, and severe sepsis. Similarly, higher plasminogen activator inhibitor-1 (p = 0.007) and S100B (p = 0.01) concentrations were associated with longer delirium duration in survivors. Adjusting for S100B did not alter plasminogen activator inhibitor-1 and E-selectin associations with delirium, suggesting that these associations were not mediated by blood-brain barrier/neurological injury.Elevated plasma markers of endothelial activation and blood-brain barrier/neurological injury during critical illness are associated with prolonged delirium after biomarker measurement. Future research is needed to determine whether these processes have pathophysiologic roles in delirium and whether therapies targeted at the endothelium or blood-brain barrier can prevent and/or treat delirium during critical illness.

Project description:BackgroundCOVID-19 has been a devastating pandemic with little known of its neuropsychiatric complications. Delirium is one of the most common neuropsychiatric syndromes among hospitalized cancer patients with incidence ranging from 25% to 40% and rates of up to 85% in the terminally ill. Data on the incidence, risk factors, duration, and outcomes of delirium in critically ill cancer patients with COVID-19 are lacking.ObjectiveTo report the incidence, risks and outcomes of critically ill cancer patients who developed COVID-19.MethodsThis is a retrospective single-center study evaluating delirium frequency and outcomes in all critically ill cancer patients with COVID-19 admitted between March 1 and July 10, 2020. Delirium was assessed by Confusion Assessment Method for Intensive Care Unit, performed twice daily by trained intensive care unit (ICU) nursing staff. Patients were considered to have a delirium-positive day if Confusion Assessment Method for Intensive Care Unit was positive at least once per day.ResultsA total of 70 patients were evaluated. Of those 70, 53 (75.7%) were found to be positive for delirium. Patients with delirium were significantly older than patients without delirium (median age 67.5 vs 60.3 y, P = 0.013). There were no significant differences in demographic characteristics, chronic medical conditions, neuropsychiatric history, cancer type, or application of prone positioning between the 2 groups. Delirium patients were less likely to receive cancer-directed therapies (58.5% vs 88.2%, P = 0.038) but more likely to receive antipsychotics (81.1% vs 41.2%, P = 0.004), dexmedetomidine (79.3% vs 11.8%, P < 0.001), steroids (84.9% vs 58.8%, P = 0.039), and vasopressors (90.6% vs 58.8%, P = 0.006). Delirium patients were more likely to be intubated (86.8% vs 41.2%, P < 0.001), and all tracheostomies (35.9%) occurred in patients with delirium. ICU length of stay (19 vs 8 d, P < 0.001) and hospital length of stay (37 vs 12 d, P < 0.001) were significantly longer in delirium patients, but there was no statistically significant difference in hospital mortality (43.4% vs 58.8%, P = 0.403) or ICU mortality (34.0% vs 58.8%, P = 0.090).ConclusionsDelirium in critically ill cancer patients with COVID-19 was associated with less cancer-directed therapies and increased hospital and ICU length of stay. However, the presence of delirium was not associated with an increase in hospital or ICU mortality.

Project description:OBJECTIVES:Catatonia, a condition characterized by motor, behavioral, and emotional changes, can occur during critical illness and appear as clinically similar to delirium, yet its management differs from delirium. Traditional criteria for medical catatonia preclude its diagnosis in delirium. Our objective in this investigation was to understand the overlap and relationship between delirium and catatonia in ICU patients and determine diagnostic thresholds for catatonia. DESIGN:Convenience cohort, nested within two ongoing randomized trials. SETTING:Single academic medical center in Nashville, TN. PATIENTS:We enrolled 136 critically ill patients on mechanical ventilation and/or vasopressors, randomized to two usual care sedation regimens. MEASUREMENTS AND MAIN RESULTS:Patients were assessed for delirium and catatonia by independent and masked personnel using Confusion Assessment Method for the ICU and the Bush Francis Catatonia Rating Scale mapped to Diagnostic Statistical Manual 5 criterion A for catatonia. Of 136 patients, 58 patients (43%) had only delirium, four (3%) had only catatonia, 42 (31%) had both, and 32 (24%) had neither. In a logistic regression model, more catatonia signs were associated with greater odds of having delirium. For example, patient assessments with greater than or equal to three Diagnostic Statistical Manual 5 symptoms (75th percentile) had, on average, 27.8 times the odds (interquartile range, 12.7-60.6) of having delirium compared with patient assessments with zero Diagnostic Statistical Manual 5 criteria (25th percentile) present (p < 0.001). A cut-off of greater than or equal to 4 Bush Francis Catatonia Screening Instrument items was both sensitive (91%; 95% CI, 82.9-95.3) and specific (91%; 95% CI, 87.6-92.9) for Diagnostic Statistical Manual 5 catatonia. CONCLUSIONS:Given that about one in three patients had both catatonia and delirium, these data prompt reconsideration of Diagnostic Statistical Manual 5 criteria for "Catatonic Disorder Due to Another Medical Condition" that preclude diagnosing catatonia in the presence of delirium.

Project description:ObjectiveTo determine the attributable mortality caused by delirium in critically ill patients.DesignProspective cohort study.Setting32 mixed bed intensive care unit in the Netherlands, January 2011 to July 2013.Participants1112 consecutive adults admitted to an intensive care unit for a minimum of 24 hours.ExposuresTrained observers evaluated delirium daily using a validated protocol. Logistic regression and competing risks survival analyses were used to adjust for baseline variables and a marginal structural model analysis to adjust for confounding by evolution of disease severity before the onset of delirium.Main outcome measureMortality during admission to an intensive care unit.ResultsAmong 1112 evaluated patients, 558 (50.2%) developed at least one episode of delirium, with a median duration of 3 days (interquartile range 2-7 days). Crude mortality was 94/558 (17%) in patients with delirium compared with 40/554 (7%) in patients without delirium (P<0.001). Delirium was significantly associated with mortality in the multivariable logistic regression analysis (odds ratio 1.77, 95% confidence interval 1.15 to 2.72) and survival analysis (subdistribution hazard ratio 2.08, 95% confidence interval 1.40 to 3.09). However, the association disappeared after adjustment for time varying confounders in the marginal structural model (subdistribution hazard ratio 1.19, 95% confidence interval 0.75 to 1.89). Using this approach, only 7.2% (95% confidence interval -7.5% to 19.5%) of deaths in the intensive care unit were attributable to delirium, with an absolute mortality excess in patients with delirium of 0.9% (95% confidence interval -0.9% to 2.3%) by day 30. In post hoc analyses, however, delirium that persisted for two days or more remained associated with a 2.0% (95% confidence interval 1.2% to 2.8%) absolute mortality increase. Furthermore, competing risk analysis showed that delirium of any duration was associated with a significantly reduced rate of discharge from the intensive care unit (cause specific hazard ratio 0.65, 95% confidence interval 0.55 to 0.76).ConclusionsOverall, delirium prolongs admission in the intensive care unit but does not cause death in critically ill patients. Future studies should focus on episodes of persistent delirium and its long term sequelae rather than on acute mortality.Trial registration Clinicaltrials.gov NCT01905033.

Dataset Information

Antimicrobial exposure and the risk of delirium in critically ill patients.

Publications

Antimicrobial exposure and the risk of delirium in critically ill patients.

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