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, 40 (10), 2788-96

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

Christopher W Seymour et al. Crit Care Med.

Abstract

Objective: 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.

Design: Single-center, prospective cohort study nested within the Awakening and Breathing Controlled randomized trial.

Setting: Saint Thomas Hospital in Nashville, TN, from 2004 to 2006.

Patients: Adult patients receiving mechanical ventilation for >12 hrs with continuous recording of hourly sedation dosing.

Interventions: 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.

Measurements and main results: 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).

Conclusions: 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.

Conflict of interest statement

The authors have not disclosed any potential conflicts of interest

Figures

Figure 1
Figure 1
Cumulative sedative dosing during study period for patients receiving benzodiazepines (Panel A, mg) and propofol (Panel B, mg). Gray ribbons indicate the 95% confidence interval.
Figure 2
Figure 2
Probability of successful spontaneous breathing trial (SBT) on the day following sedative exposure, adjusted for parent study treatment group, age, SOFA score, and mental status on the day of sedative exposure, over plausible ranges of (A) daytime hourly average benzodiazepine dose, (B) daytime average hourly propofol dose, (C) the day-to-night change in hourly average benzodiazepine dose and (D) the day-to-night change in hourly average propofol dose. Gray ribbons represent 95% confidence bounds. All plots adjusted to the median (continuous variables) and mode (categorical variables) of model covariates. Interpretive examples: For patients in whom the average hourly dose of benzodiazpines is 1 mg/hr during the daytime, the probability of a successful SBT on the subsequent day is approximately 0.1 panel A after adjusting for other covariates. For patients in whom the average hourly dose of benzodiazepines is increased by 1 mg/hr at night, the probability of a successful SBT on the subsequent day is approximately 0.15 panel C after adjusting for covariates including daytime benzodiazepine dose.
Figure 3
Figure 3
Probability of successful extubation on the day following sedative exposure, adjusted for parent study treatment group age, SOFA score, and mental status on the day of sedative exposure, over plausible ranges of (A) daytime hourly average benzodiazepine dose, (B) daytime average hourly propofol dose, (C) the day-to-night change in hourly average benzodiazepine dose and (D) the day-to-night change in hourly average propofol dose. Gray ribbons represent 95% confidence bounds. All plots adjusted to the median (continuous variables) and mode (categorical variables) of model covariates. Interpretive examples: For patients in whom the average hourly dose of propofol is 30 mcg/kg/min during the daytime, the probability of a successful extubation on the subsequent day is approximately 0.2 panel B. For patients in whom the average hourly dose of benzodiazepines is increased by 1 mg/hr at night, the probability of a successful extubation on the subsequent day is approximately 0.1 panel C after adjusting for covariates including daytime benzodiazepine dose.
Figure 4
Figure 4
Probability of delirium on the day following sedative exposure, adjusted for parent study treatment group, age, SOFA score, and mental status on the day of sedative exposure, over plausible ranges of (A) daytime hourly average benzodiazepine dose, (B) daytime average hourly propofol dose, (C) the day-to-night change in hourly average benzodiazepine dose and (D) the day-to-night change in hourly average propofol dose. Gray ribbons represent 95% confidence bounds. All plots adjusted to the median (continuous variables) and mode (categorical variables) of model covariates. Interpretive examples: For patients in whom the average hourly dose of benzodiazpines is 2 mg/hr during the daytime and who are assessable for delirium the following day, the probability of experiencing delirium is approximately 1.0 panel A). For patients in whom the average hourly dose of propofol is increased by 10 mcg/kg/min at night, the probability of experiencing delirium on the subsequent day is approximately 0.1 panel D after adjusting for covariates including daytime propofol dose.

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