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. Electronic supplementary material The online version of this article (10.1186/s13054-019-2394-9) contains supplementary material, which is available to authorized users.

Comparative Effectiveness of Midazolam, Propofol, and Dexmedetomidine in Patients With or at Risk for Acute Respiratory Distress Syndrome: A Propensity Score-Matched Cohort Study

“…The administration of sedative drugs is a nearly universal intervention in mechanically ventilated intensive care unit (ICU) patients ( Patel and Kress, 2012 ). Appropriate sedation management is one effective method of improving patient tolerance of mechanical ventilation and reducing psychological stress in critically ill patients in the ICU ( Weinert and Calvin, 2007 ; Patel and Kress, 2012 ); however, the use of an inappropriate sedation strategy may increase the risk of all-cause mortality, delay ventilator weaning, and prolong the duration of hospitalization in ICU patients undergoing mechanical ventilation ( Shehabi et al, 2012 ; Shehabi et al, 2013b ; Shah et al, 2017 ; Shehabi et al, 2018 ; Aragón et al, 2019 ).…”

Effects of sedatives and opioids on trigger and cycling asynchronies throughout mechanical ventilation: an observational study in a large dataset from critically ill patients

“…Whereas one study found that light sedation with propofol did not affect the rate of asynchronies but deep sedation with propofol increased it [10], another found that deep sedation reduced but did not eliminate asynchronies [18]. A recent study showed that deep sedation, benzodiazepines, and cumulative doses of benzodiazepines were associated with higher mortality [19]. In another trial, patients on dexmedetomidine had slightly fewer asynchronies than those on propofol [20].…”

Inconsistent relationship between depth of sedation and intensive care outcome: systematic review and meta-analysis

“…Recently, a Peruvian multi-centre observational cohort study examining the relationship between benzodiazepine dose and mortality was published (45). In this study benzodiazepine dose was associated with a higher risk of mortality and a significant decrease in Vfd, although it should be noted that 98% of participants were deeply sedated at some point during the study and depth of sedation was assessed using either the Glasgow Coma Scale, Ramsay Sedation Scale or RASS.…”