(1200) Impact of Sedation and Neuromuscular Blocker Strategy on Ventilated Patients With Severe COVID-19

Introduction: There is limited evidence to guide management of patients receiving mechanical ventilation (MV) who experience ventilator asynchrony with light sedation. High doses of sedative medications can achieve ventilator compliance and neuromuscular blocking agents (NMBAs) eliminate asynchrony but both strategies have potential complications. The purpose of this study was to compare a strategy of high-dose sedatives (beyond deep sedation) to a strategy of deep sedation and early NMBAs in patients receiving MV with severe hypoxemic respiratory failure secondary to COVID-19 pneumonia.

Methods: In this retrospective, multi-center, observational cohort study we evaluated adult patients admitted to an intensive care unit (ICU) for COVID-19 pneumonia receiving both MV and deep sedation. Patients were separated into a "high sedative dosing" cohort if they received at least 2 mg/hr of hydromorphone (HM) equivalent or at least 5 mg/hr midazolam equivalent with no use of NMBA infusion, and a “low sedative dosing + NMBA” cohort if they received a NMBA infusion for at least 12 hours and lower doses of sedation than previously described. Demographic variables, COVID-19 related data points, and outcomes data were collected. The primary outcome was MV-free days to day 28. Secondary outcomes included duration of opioid therapy, length of stay (LOS), and mortality.

Results: Each cohort included 85 patients. Imbalances at baseline included numerically higher Sequential Organ Failure Assessment (SOFA) Score, oxygen requirement prior to intubation, and vasopressor use in the NMBA cohort. Patients received a median of 449 mg and 362 mg HM equivalents per day in the high sedative dose and NMBA cohorts, respectively. The high dose cohort and NMBA cohort experienced a median of 16 (IQR 3-21) and 8 (IQR 0-18) MV-free days at day 28 in patients who survived to 28 days, respectively. ICU mortality was 35% and 64% and ICU LOS was 13 days (IQR 9-21) and 17 days (IQR 10-17) in the high dose cohort and NMBA cohort, respectively.

Conclusions: Significant baseline imbalances complicated interpretation of these results; however, there does not appear to be a signal for harm with the use of a high sedative dosing strategy for management of ventilator asynchrony. Future randomized, prospective studies are needed to guide management.