Differential Effects of Gamma-Aminobutyric Acidergic Sedatives on Risk of Post-Extubation Delirium in the ICU: A Retrospective Cohort Study from a New England Health Care Network

Omid Azimaraghi, Karuna Wongtangman, Luca J. Wachtendorf, Peter Santer, Sandra Rumyantsev, Curie Ahn, Michael E. Kiyatkin, Bijan Teja, Todd Sarge, Balachundhar Subramaniam, Matthias Eikermann

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

OBJECTIVES: To evaluate whether different gamma-aminobutyric acidergic (GABAergic) sedatives such as propofol and benzodiazepines carry differential risks of post-extubation delirium in the ICU. DESIGN: Retrospective cohort study. SETTING: Seven ICUs in an academic hospital network, Beth Israel Deaconess Medical Center (Boston, MA). PATIENTS: Ten thousand five hundred and one adult patients mechanically ventilated for over 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We tested the hypothesis that benzodiazepine versus propofol-based sedation is associated with fewer delirium-free days within 14 days after extubation. Further, we hypothesized that the measured sedation level evoked by GABAergic drugs is a better predictor of delirium than the drug dose administered. The proportion of GABAergic drug-induced deep sedation was defined as the ratio of days with a mean Richmond Agitation-Sedation Scale of less than or equal to -3 during mechanical ventilation. Multivariable regression and effect modification analyses were used. Delirium-free days were lower in patients who received a high proportion of deep sedation using benzodiazepine compared with propofol-based sedation (adjusted absolute difference, -1.17 d; 95% CI, -0.64 to -1.69; p < 0.001). This differential effect was magnified in elderly patients (age > 65) and in patients with liver or kidney failure (p-for-interaction < 0.001) but not observed in patients who received a low proportion of deep sedation (p = 0.95). GABAergic-induced deep sedation days during mechanical ventilation was a better predictor of post-extubation delirium than the GABAergic daily average effective dose (area under the curve 0.76 vs 0.69; p < 0.001). CONCLUSIONS: Deep sedation during mechanical ventilation with benzodiazepines compared with propofol is associated with increased risk of post-extubation delirium. Our data do not support the view that benzodiazepine-based compared with propofol-based sedation in the ICU is an independent risk factor of delirium, as long as deep sedation can be avoided in these patients.

Original languageEnglish (US)
Pages (from-to)E434-E444
JournalCritical care medicine
Volume50
Issue number5
DOIs
StatePublished - May 1 2022

Keywords

  • benzodiazepines
  • critical care
  • delirium
  • intensive care unit
  • propofol
  • sedation

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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