TY - JOUR
T1 - Sedative polypharmacy mediates the effect of mechanical ventilation on delirium in critically ill COVID-19 patients
T2 - A retrospective cohort study
AU - Bose, Somnath
AU - Kelly, Lauren
AU - Shahn, Zachary
AU - Novack, Lena
AU - Banner-Goodspeed, Valerie
AU - Subramaniam, Balachundhar
N1 - Publisher Copyright:
© 2022 Acta Anaesthesiologica Scandinavica Foundation.
PY - 2022/10/1
Y1 - 2022/10/1
N2 - Background: Polypharmacy of sedatives (PP) is a potentially modifiable, iatrogenic risk factor for ICU delirium. The extent to which sedative PP influenced development of high rates of delirium among critically ill COVID-19 patients is unknown. We tested the hypothesis that PP, defined as the use of four or more classes of intravenous agents, is a mediator in the causal pathway of mechanical ventilation and delirium. Methods: Retrospective cohort study of adults admitted with a primary diagnosis of RT-PCR+ for SARS-CoV2 to ICUs of a tertiary-level academic medical center between February 2020 and April 2021. Mediation analysis was conducted with bootstrap estimation to assess whether an association between mechanical ventilation and delirium was mediated by PP. Analyses were adjusted for potential confounders related to mechanical ventilation, mediator, and outcome, including age, gender, vasopressor use, median RASS scores, SOFA score within 24 h of admission, and maximum CRP levels. Results: A total of 212 patients were included in the analysis. Of total patients, 72.6%(154/212) of patients had delirium (CAM-ICU+) during ICU stay. 54.7%(116/212) patients received PP. Mechanical ventilation (OR 3.81 [1.16–12.52]) and PP (OR 7.38 [2.4–22.68]) were identified as risk factors for development of ICU delirium after adjusting for prespecified confounders. PP acts as a mediator in the causal pathway between mechanical ventilation and delirium. 39% (95% CI: 17%–94%) of the effect of mechanical ventilation on delirium was mediated through PP. Conclusion: PP mediates approximately 39% of the effect of mechanical ventilation on delirium, which is clinically and statistically significant. Studies should assess whether mitigating PP could lead to reduction in ICU delirium. Implication Statement: PP of sedatives (defined as use of four or more intravenous agents) mediates approximately 39% of the effect of mechanical ventilation on development of ICU delirium. Avoidance of sedative PP may represent a viable strategy for reduction of ICU delirium.
AB - Background: Polypharmacy of sedatives (PP) is a potentially modifiable, iatrogenic risk factor for ICU delirium. The extent to which sedative PP influenced development of high rates of delirium among critically ill COVID-19 patients is unknown. We tested the hypothesis that PP, defined as the use of four or more classes of intravenous agents, is a mediator in the causal pathway of mechanical ventilation and delirium. Methods: Retrospective cohort study of adults admitted with a primary diagnosis of RT-PCR+ for SARS-CoV2 to ICUs of a tertiary-level academic medical center between February 2020 and April 2021. Mediation analysis was conducted with bootstrap estimation to assess whether an association between mechanical ventilation and delirium was mediated by PP. Analyses were adjusted for potential confounders related to mechanical ventilation, mediator, and outcome, including age, gender, vasopressor use, median RASS scores, SOFA score within 24 h of admission, and maximum CRP levels. Results: A total of 212 patients were included in the analysis. Of total patients, 72.6%(154/212) of patients had delirium (CAM-ICU+) during ICU stay. 54.7%(116/212) patients received PP. Mechanical ventilation (OR 3.81 [1.16–12.52]) and PP (OR 7.38 [2.4–22.68]) were identified as risk factors for development of ICU delirium after adjusting for prespecified confounders. PP acts as a mediator in the causal pathway between mechanical ventilation and delirium. 39% (95% CI: 17%–94%) of the effect of mechanical ventilation on delirium was mediated through PP. Conclusion: PP mediates approximately 39% of the effect of mechanical ventilation on delirium, which is clinically and statistically significant. Studies should assess whether mitigating PP could lead to reduction in ICU delirium. Implication Statement: PP of sedatives (defined as use of four or more intravenous agents) mediates approximately 39% of the effect of mechanical ventilation on development of ICU delirium. Avoidance of sedative PP may represent a viable strategy for reduction of ICU delirium.
KW - delirium
KW - intensive care unit
KW - mechanical ventilation
KW - mediation analysis
KW - polypharmacy
UR - http://www.scopus.com/inward/record.url?scp=85136915820&partnerID=8YFLogxK
U2 - 10.1111/aas.14119
DO - 10.1111/aas.14119
M3 - Article
C2 - 35900078
AN - SCOPUS:85136915820
SN - 0001-5172
VL - 66
SP - 1099
EP - 1106
JO - Acta Anaesthesiologica Scandinavica
JF - Acta Anaesthesiologica Scandinavica
IS - 9
ER -