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Diurnal sedative changes during intensive care: impact on liberation from mechanical ventilation and delirium.

ABSTRACT: To determine whether benzodiazepine and propofol doses are increased at night and whether daytime and nighttime sedative doses are associated with delirium, coma, and delayed liberation from mechanical ventilation.Single-center, prospective cohort study nested within the Awakening and Breathing Controlled randomized trial.Saint Thomas Hospital in Nashville, TN, from 2004 to 2006.Adult patients receiving mechanical ventilation for >12 hrs with continuous recording of hourly sedation dosing.We measured hourly doses of benzodiazepine and propofol exposure during the daytime (7 AM to 11 PM) and nighttime (11 PM to 7 AM) for 5 days. We quantified nighttime dose increases by subtracting the average hourly daytime dose on the preceding day from subsequent average hourly nighttime dose. We used multivariable logistic regression to determine whether daytime and nighttime dose increases were independently associated with delirium, coma, and delayed liberation from mechanical ventilation.Among 140 patients, the median Acute Physiology and Chronic Health Evaluation II score was 27 (interquartile range 22-33). Among those receiving the sedatives, benzodiazepine and propofol doses were increased at night on 40% and 41% of patient-days, respectively. Of 485 patient-days, delirium was present on 160 (33%) and coma on 206 (42%). In adjusted models, greater daytime benzodiazepine dose was independently associated with failed spontaneous breathing trial and extubation, and subsequent delirium (p<.02 for all). Nighttime increase in benzodiazepine dose was associated with failed spontaneous breathing trial (p<.01) and delirium (p=.05). Daytime propofol dose was marginally associated with subsequent delirium (p=.06).Nearly half of mechanically ventilated intensive care unit patients received greater doses of sedation at night, a practice associated with failed spontaneous breathing trials, coma, and delirium. Over the first 5 days in our study, patients spent 75% of their time in coma or delirium, outcomes that may be reduced by efforts to decrease sedative exposure during both daytime and nighttime hours in the intensive care unit.

SUBMITTER: Seymour CW

PROVIDER: S-EPMC3576216 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Diurnal sedative changes during intensive care: impact on liberation from mechanical ventilation and delirium.

Seymour Christopher W CW Pandharipande Pratik P PP Koestner Tyler T Hudson Leonard D LD Thompson Jennifer L JL Shintani Ayumi K AK Ely E Wesley EW Girard Timothy D TD

Critical care medicine 20121001 10

<h4>Objective</h4>To determine whether benzodiazepine and propofol doses are increased at night and whether daytime and nighttime sedative doses are associated with delirium, coma, and delayed liberation from mechanical ventilation.<h4>Design</h4>Single-center, prospective cohort study nested within the Awakening and Breathing Controlled randomized trial.<h4>Setting</h4>Saint Thomas Hospital in Nashville, TN, from 2004 to 2006.<h4>Patients</h4>Adult patients receiving mechanical ventilation for ...[more]

PMID: 22824928

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Project description:BackgroundIn the intensive care unit (ICU), critical illness delirium occurs in the context of multiple comorbidities, multi-organ failure, and invasive management techniques, such as mechanical ventilation, sedation, and lack of sleep. Delirium is characterized by an acute confusional state defined by fluctuating mental status, inattention, and either disorganized thinking or an altered level of consciousness. The long-term cognitive and psychosocial function of patients that experience delirium in the ICU is of crucial interest because preliminary data suggest a strong association between ICU-related delirium and long-term cognitive impairment.ObjectiveThe aim of this study is to explore the relationship between delirium in the ICU and adverse outcomes by following mechanically ventilated patients for one year following their discharge from the ICU and collecting data on their long-term cognition and psychosocial function.MethodsThis study will be conducted by enrolling patients in two tertiary ICUs in Australia. We aim to recruit 200 patients who have been mechanically ventilated for more than 24 hours. Data will be collected at the following three time points: (1) at discharge where they will be administered the Mini-Mental State Examination (MMSE); (2) at 6 months after discharge from the ICU discharge where the Impact of Events Scale Revised (IES-R) and the Telephone Inventory for Cognitive Status (TICS) tests will be administered; and (3) at 12 months after discharge from the ICU where the patients will be administered the TICS and IES-R tests, as well as the Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE). The IQCODE will be administered to their "person responsible" or the significant other of the patient.ResultsLong-term cognition and psychosocial function will be the primary outcome of this study. Mortality will also be investigated as a secondary outcome. Active enrollment will take place until the end of September 2016 and data collection will conclude at the end of September 2017. The analysis and results are expected to be available by March 2018.ConclusionDelirium during mechanical ventilation has been linked to longer ICU and hospital stays, higher financial burdens, increased risks of long-term cognitive impairment (ie, dementia), poor functional outcomes and quality of life, and decreased survival. However, delirium during mechanical ventilation in the ICU is not well understood. This study will advance our knowledge of the comprehensive, long-term effects of delirium on cognitive and psychosocial function.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12616001116415; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=371216 (Archived by WebCite at http://www.webcitation.org/ 6nfDkGTcW).

Project description:ImportanceThere is limited evidence on the optimal strategy for liberating infants and children from invasive mechanical ventilation in the pediatric intensive care unit.ObjectiveTo determine if a sedation and ventilator liberation protocol intervention reduces the duration of invasive mechanical ventilation in infants and children anticipated to require prolonged mechanical ventilation.Design, setting, and participantsA pragmatic multicenter, stepped-wedge, cluster randomized clinical trial was conducted that included 17 hospital sites (18 pediatric intensive care units) in the UK sequentially randomized from usual care to the protocol intervention. From February 2018 to October 2019, 8843 critically ill infants and children anticipated to require prolonged mechanical ventilation were recruited. The last date of follow-up was November 11, 2019.InterventionsPediatric intensive care units provided usual care (n = 4155 infants and children) or a sedation and ventilator liberation protocol intervention (n = 4688 infants and children) that consisted of assessment of sedation level, daily screening for readiness to undertake a spontaneous breathing trial, a spontaneous breathing trial to test ventilator liberation potential, and daily rounds to review sedation and readiness screening and set patient-relevant targets.Main outcomes and measuresThe primary outcome was the duration of invasive mechanical ventilation from initiation of ventilation until the first successful extubation. The primary estimate of the treatment effect was a hazard ratio (with a 95% CI) adjusted for calendar time and cluster (hospital site) for infants and children anticipated to require prolonged mechanical ventilation.ResultsThere were a total of 8843 infants and children (median age, 8 months [interquartile range, 1 to 46 months]; 42% were female) who completed the trial. There was a significantly shorter median time to successful extubation for the protocol intervention compared with usual care (64.8 hours vs 66.2 hours, respectively; adjusted median difference, -6.1 hours [interquartile range, -8.2 to -5.3 hours]; adjusted hazard ratio, 1.11 [95% CI, 1.02 to 1.20], P = .02). The serious adverse event of hypoxia occurred in 9 (0.2%) infants and children for the protocol intervention vs 11 (0.3%) for usual care; nonvascular device dislodgement occurred in 2 (0.04%) vs 7 (0.1%), respectively.Conclusions and relevanceAmong infants and children anticipated to require prolonged mechanical ventilation, a sedation and ventilator liberation protocol intervention compared with usual care resulted in a statistically significant reduction in time to first successful extubation. However, the clinical importance of the effect size is uncertain.Trial registrationisrctn.org Identifier: ISRCTN16998143.

Project description:BackgroundPolypharmacy of sedatives (PP) is a potentially modifiable, iatrogenic risk factor for ICU delirium. The extent to which sedative PP influenced development of high rates of delirium among critically ill COVID-19 patients is unknown. We tested the hypothesis that PP, defined as the use of four or more classes of intravenous agents, is a mediator in the causal pathway of mechanical ventilation and delirium.MethodsRetrospective cohort study of adults admitted with a primary diagnosis of RT-PCR+ for SARS-CoV2 to ICUs of a tertiary-level academic medical center between February 2020 and April 2021. Mediation analysis was conducted with bootstrap estimation to assess whether an association between mechanical ventilation and delirium was mediated by PP. Analyses were adjusted for potential confounders related to mechanical ventilation, mediator, and outcome, including age, gender, vasopressor use, median RASS scores, SOFA score within 24 h of admission, and maximum CRP levels.ResultsA total of 212 patients were included in the analysis. Of total patients, 72.6%(154/212) of patients had delirium (CAM-ICU+) during ICU stay. 54.7%(116/212) patients received PP. Mechanical ventilation (OR 3.81 [1.16-12.52]) and PP (OR 7.38 [2.4-22.68]) were identified as risk factors for development of ICU delirium after adjusting for prespecified confounders. PP acts as a mediator in the causal pathway between mechanical ventilation and delirium. 39% (95% CI: 17%-94%) of the effect of mechanical ventilation on delirium was mediated through PP.ConclusionPP mediates approximately 39% of the effect of mechanical ventilation on delirium, which is clinically and statistically significant. Studies should assess whether mitigating PP could lead to reduction in ICU delirium.Implication statementPP of sedatives (defined as use of four or more intravenous agents) mediates approximately 39% of the effect of mechanical ventilation on development of ICU delirium. Avoidance of sedative PP may represent a viable strategy for reduction of ICU delirium.

Project description:ObjectivesTo assess the reliability of codes relevant to critically ill patients in administrative data.DesignRetrospective cohort study linking data from Acute Physiology and Chronic Health Evaluation Outcomes, a clinical database of ICU patients with data from Medicare Provider Analysis and Review. We linked data based on matching for sex, date of birth, hospital, and date of admission to hospital.SettingForty-six hospitals in the United States participating in Acute Physiology and Chronic Health Evaluation Outcomes.PatientsAll patients in Acute Physiology and Chronic Health Evaluation Outcomes greater than or equal to 65 years old who could be linked with hospitalization records in Medicare Provider Analysis and Review from January 1, 2009, through September 30, 2012.Measurements and main resultsOf 62,451 patients in the Acute Physiology and Chronic Health Evaluation Outcomes dataset, 80.1% were matched with data in Medicare Provider Analysis and Review. All but 2.7% of Acute Physiology and Chronic Health Evaluation Outcomes ICU patients had either an ICU or coronary care unit charge in Medicare Provider Analysis and Review. In Acute Physiology and Chronic Health Evaluation Outcomes, 37.0% received mechanical ventilation during the ICU stay versus 24.1% in Medicare Provider Analysis and Review. The Medicare Provider Analysis and Review procedure codes for mechanical ventilation had high specificity (96.0%; 95% CI, 95.8-96.2), but only moderate sensitivity (58.4%; 95% CI, 57.7-59.1), with a positive predictive value of 89.6% (95% CI, 89.1-90.1) and negative predictive value of 79.7% (95% CI, 79.4-80.1). For patients with mechanical ventilation codes, Medicare Provider Analysis and Review overestimated the percentage with a duration greater than 96 hours (36.6% vs 27.3% in Acute Physiology and Chronic Health Evaluation Outcomes). There was discordance in the hospital discharge status (alive or dead) for only 0.47% of all linked records (κ = 1.00).ConclusionsMedicare Provider Analysis and Review data contain robust information on hospital mortality for patients admitted to the ICU but have limited ability to identify all patients who received mechanical ventilation during a critical illness. Estimates of use of mechanical ventilation in the United States should likely be revised upward.

Project description:BackgroundEndotheliopathy is suggested as pivotal pathophysiology of sepsis and trauma-associated organ failure, but its role in acute respiratory failure is not yet determined. We investigated if endotheliopathy biomarkers at ICU admission are associated with illness severity and clinical outcomes in patients with acute respiratory failure requiring mechanical ventilation.MethodsWe conducted a prospective single-center cohort study including 459 mechanically ventilated adults at ICU admission. Plasma levels of three endotheliopathy biomarkers were measured at ICU admission: Syndecan-1, soluble Thrombomodulin (sTM), and Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1). The primary outcome was the rate of liberation from mechanical ventilation, which is presented together with the rate of the competing risk of death while still on mechanical ventilation. Secondary outcomes were PaO2/FiO2-ratios on admission and on last measurement in patients dying within five days, and 30-day all-cause mortality. The primary outcome and 30-day all-cause mortality were analyzed using Cox regression, controlled for gender, age, chronic obstructive pulmonary disease, septic shock, heart failure, PaO2/FiO2-ratio at admission, respiratory infection, acute kidney injury, and bilirubin. PaO2/FiO2-ratios were analyzed using linear regression, controlled for age, chronic obstructive pulmonary disease, respiratory infection, and shock.ResultsPatients with high sTM were liberated from mechanical ventilation at a lower rate (adjusted hazard ratio (HR) 0.71, for an increase from the 25th to the 75th percentile, 95% confidence interval (CI) 0.54-0.93, p = 0.01). Patients with high PECAM-1 were liberated from mechanical ventilation at a lower rate, but only during the first 5 days (adjusted HR 0.72, for an increase from the 25th to the 75th percentile, 95% CI 0.58-0.9, p < 0.01). High levels of Syndecan-1 and PECAM-1 were associated with a higher rate of death while still on mechanical ventilation. sTM and PECAM-1 were negatively associated with PaO2/FiO2-ratio at ICU admission and no biomarker was associated with last measured PaO2/FiO2-ratio. High levels of all biomarkers were associated with higher 30-day all-cause mortality.ConclusionIn acute respiratory failure, endotheliopathy biomarkers are associated with lower rates of liberation from mechanical ventilation, hypoxemia at ICU admission, and 30-day all-cause mortality.

Dataset Information

Diurnal sedative changes during intensive care: impact on liberation from mechanical ventilation and delirium.

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Diurnal sedative changes during intensive care: impact on liberation from mechanical ventilation and delirium.

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