Sedation practices and clinical outcomes in mechanically ventilated patients in a prospective multicenter cohort

Abstract

Objectives: We sought to study the association between sedation status, medications (benzodiazepines, opioids, and antipsychotics), and clinical outcomes in a resource-limited setting.

Design: A longitudinal study of critically ill participants on mechanical ventilation.

Setting: Five intensive care units (ICUs) in four public hospitals in Lima, Peru.

Patients: One thousand six hundred fifty-seven critically ill participants were assessed daily for sedation status during 28 days and vital status by day 90.

Results: After excluding data of participants without a Richmond Agitation Sedation Scale score and without sedation, we followed 1338 (81%) participants longitudinally for 18,645 ICU days. Deep sedation was present in 98% of participants at some point of the study and in 12,942 ICU days. Deep sedation was associated with higher mortality (interquartile odds ratio (OR) = 5.42, 4.23-6.95; p < 0.001) and a significant decrease in ventilator (- 7.27; p < 0.001), ICU (- 4.38; p < 0.001), and hospital (- 7.00; p < 0.001) free days. Agitation was also associated with higher mortality (OR = 39.9, 6.53-243, p < 0.001). The most commonly used sedatives were opioids and benzodiazepines (9259 and 8453 patient days respectively), and the latter were associated with a 41% higher mortality in participants with a higher cumulative dose (75th vs 25th percentile, interquartile OR = 1.41, 1.12-1.77; p < 0.01). The overall cumulative dose of benzodiazepines and opioids was high, 774.5 mg and 16.8 g, respectively, by day 7 and by day 28; these doses approximately doubled. Haloperidol was only used in 3% of ICU days; however, the use of it was associated with a 70% lower mortality (interquartile OR = 0.3, 0.22-0.44, p < 0.001).

Conclusions: Deep sedation, agitation, and cumulative dose of benzodiazepines were all independently associated with higher 90-day mortality. Additionally, deep sedation was associated with less ventilator-, ICU-, and hospital-free days. In contrast, haloperidol was associated with lower mortality in our study.

Keywords: Clinical outcomes; Critical illness; Sedation.

Fig. 1

Cumulative incidence plots evaluating sedation status and vital status during ICU stay. In this figure, we plot the cumulative incidence of death (represented by a broken red line), unassisted breathing (represented by a broken blue line), and sedation status (shaded areas) among those who are receiving assisting breathing using a Berezina plot (see Additional file 1). The shaded areas were proportional to the percentage of participants who were deeply (dark blue), moderately (blue) or adequately sedated (light blue), and agitated (pink). Our categorization of sedation is based on the Richmond Agitation Sedation Scale score (RASS), and if unavailable, it is based on a conversion based on the Ramsay Scale score or the Glasgow Coma Scale score to RASS as shown in Additional file 1: Table S2. This graph excludes ICU days where a sedation score (e.g., RASS) was not recorded, giving a total number of 17,364 ICU days

Fig. 2

Individual-trajectory plot of sedation status, vital status, or tracheostomy status during their ICU stay. In this figure, we plot individual daily trajectories of sedation status (deep in dark blue, moderate in blue, adequate in light blue, agitated in pink), vital status (death before 28 days in red, achieved unassisted breathing by 28 days and alive in navy blue), and if the participant received a tracheostomy (in green) using a Causa plot (see Additional file 1). Our categorization of sedation is based on the Richmond Agitation Sedation Scale score (RASS), and if unavailable, it is based on a conversion based on the Ramsay Scale score or the Glasgow Coma Scale score to RASS as shown in Additional file 1: Table S2. Each row represents a study participant, and each column represents an ICU day between enrollment and day 28. We stratified the rows by vital status or if the participant was alive at 28 days but received unassisted breathing. If the patient was neither dead nor receiving unassisted breathing, they were shown as the “Neither” category by 28 days, which includes patients that were still intubated or that had a tracheostomy

Fig. 3

a, b Cumulative dose of pharmacological agents. We plotted individual cumulative doses of benzodiazepines (panel a) and opioids (panel b) per ICU day. Each dot represents one patient at each time point. The x-axis represents ICU day, and the y-axis the cumulative benzodiazepine or opioid dose. The broken lines represent percentiles of the cumulative doses (10^th, 25^th, 50^th, 75^th, and 90^th percentile, respectively)