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Persistence of Delirium after Cessation of Sedatives and Analgesics and Impact on Clinical Outcomes in Critically Ill Patients.

Pharmacotherapy 2017 November
STUDY OBJECTIVE: As delirium is a common manifestation in critically ill patients and is associated with worse clinical outcomes, we sought to characterize the reversibility of delirium after discontinuation of sedation and to determine whether sedation-associated delirium that rapidly reverses impacts clinical outcomes.

DESIGN: Post hoc subgroup analysis of prospectively collected data from a previously published study.

PATIENTS: Seventy adults admitted to a medical intensive care unit (ICU) between March and July 2012 who required mechanical ventilation with continuous analgesia and/or sedation and underwent a spontaneous awakening trial (SAT).

MEASUREMENTS AND MAIN RESULTS: Patients were grouped into four categories: delirium free, rapidly reversible delirium (RRD; defined as delirium always resolving within 4 hrs of stopping sedatives), persistent delirium (PD; defined as delirium always persisting for ≥ 4 hours after stopping sedatives), or mixed delirium (consisting of RRD and PD episodes). The incidence of the four delirium subtypes and their associations with clinical outcomes were evaluated. A validated, guideline-recommended, bedside delirium monitoring instrument-the Confusion Assessment Method for the ICU (CAM-ICU)-was used to assess for the presence or absence of delirium. Clinical outcomes included ventilator-free days at day 28, ICU and hospital length of stay, 28-day mortality, and patient disposition; time to first CAM-ICU becoming negative (delirium free) for a continuous 48-hour duration was also assessed. A total of 103 SATs were performed in the 70 patients. Of the 103 SATs, 28 (27.2%) were CAM-ICU negative before the SAT. Of the remaining 75 SATs, PD was present for the majority of SATs (62 [82.7%]); RRD was present after 13 (17.3%) SATs. On a patient level, 17 patients (24.3%) were always delirium free before cessation of medications for continuous sedation. Of the 53 patients with delirium before undergoing an SAT, 11 (20.8%) had RRD, 2 (3.8%) had mixed delirium, and 40 (75.5%) had PD. Proportional odds logistic regression adjusting for age, Acute Physiology and Chronic Health Evaluation II score, sepsis, and preexisting hypertension showed that patients with PD had a higher probability of longer ICU length of stay (odds ratio 4.01 [95% confidence interval 1.36-11.77], p=0.011), but those with RRD did not.

CONCLUSION: Despite the cessation of medications for continuous sedation, delirium persisted for the majority of patients and was associated with worse outcomes, which attests to the importance of strategies to minimize sedation.

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