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

Adverse effects of excessive sedation in critically ill mechanically ventilated patients are well described. Although guidelines strongly recommend minimizing sedative use, additional agents are added as infusions, often empirically. The tradeoffs associated with such decisions remain unclear.

To test the hypothesis that a pragmatic propofol-based sedation regimen with restricted polypharmacy (RP; ie, prohibits additional infusions unless a predefined propofol dosage threshold is exceeded) would increase coma-and ventilator-free days compared with usual care (UC), we performed a retrospective cohort study of adults admitted to intensive care units (ICUs) of a tertiary-level medical center who were mechanically ventilated, initiated on propofol infusion, and had >50% probability of need for continued ventilation for the next 24 hours. We compared RP to UC, adjusting for baseline and time-varying confounding (demographics, care unit, calendar time of admission, vitals, laboratories, other interventions such as vasopressors and fluids, and more) through inverse probability weighting in a target trial framework. Ventilator-free days and coma-free days within 30 days of intubation and in-hospital mortality were the outcomes of interest.

A total of 7974 patients were included in the analysis, of which 3765 followed the RP strategy until extubation. In the full cohort under UC, mean coma-free days were 23.5 (95% confidence interval [CI], [23.3-23.7]), mean ventilator-free days were 20.6 (95% CI, [20.4-20.8]), and the in-hospital mortality rate was 22.0% (95% CI, [21.2-22.8]). We estimated that an RP strategy would increase mean coma-free days by 1.0 days (95% CI, [0.7-1.3]) and ventilator-free days by 1.0 days (95% CI, [0.7-1.3]) relative to UC in our cohort. Our estimate of the confounding-adjusted association between RP and in-hospital mortality was uninformative (-0.5%; 95% CI, [-3.0 to 1.9]).

Compared with UC, RP was associated with more coma- and ventilator-free days. Restricting addition of adjunct infusions to propofol may represent a viable strategy to reduce duration of coma and mechanical ventilation. These hypothesis-generating findings should be confirmed in a randomized control trial.