Sedative polypharmacy mediates the effect of mechanical ventilation on delirium in critically ill COVID‐19 patients: A retrospective cohort study

Abstract

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 ) and PP ) 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.

Restricted Polypharmacy Compared to Usual Care in Mechanically Ventilated Patients: A Retrospective Cohort Study

“…7 The overall effects of sedation strategies involving multiple agents versus a single agent have not been thoroughly evaluated. [8][9][10][11] We tested the hypothesis that a pragmatic propofol-based sedation regimen prohibiting the addition of other sedative infusions unless a defined propofol dosage threshold was exceeded would be associated with more ventilator-and coma-free days when compared with usual care (UC). Propofol was chosen as the referent category because it is the most used sedative in intensive care units (ICUs).…”

“…7 The overall effects of sedation strategies involving multiple agents versus a single agent have not been thoroughly evaluated. 8–11…”

An Agitation Sedation Level Prediction Model for ICU Patients

“…When the patient's condition stabilizes and parameters such as HGB, HCT, SPO2, and CREAT show a tendency to stabilize, maintaining a mild sedation target (RASS score 0 to -2) is desired. Accordingly, sedative dosages are adjusted or discontinued based on RASS assessment scores to avoid overuse of sedative medications, which could prolong ventilator weaning time and increase the occurrence of delirium [37]. Therefore, the presence or absence of sedative medication usage, along with HGB, SPO2, and HCT levels, are the most influential features in the agitation classification and exhibit a positive correlation.…”