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

Jan 4, 2022Critical care medicine

Different GABA-based Sedatives and Their Links to Delirium Risk After Breathing Tube Removal in ICU Patients

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Abstract

Delirium-free days were lower by 1.17 days in patients receiving deep sedation with benzodiazepines compared to those sedated with propofol.

High levels of deep sedation using benzodiazepines are associated with an increased risk of post-extubation delirium.
The effect of benzodiazepine sedation on delirium was more pronounced in patients over 65 years old and those with liver or kidney failure.
In patients receiving low levels of deep sedation, no significant difference in delirium-free days was observed between benzodiazepines and propofol.
The level of sedation during mechanical ventilation is a better predictor of post-extubation delirium than the total drug dose administered.

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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.

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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

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