Effect of Extracorporeal Membrane Oxygenation Use on Sedative Requirements in Patients with Severe Acute Respiratory Distress Syndrome

Study Objectives: To compare sedative dose requirements during the 6-hour period when they are greatest in patients with severe acute respiratory distress syndrome (ARDS), as well as the time from severe ARDS onset to reach this maximum sedation exposure, between patients with severe ARDS who were managed either with or without extracorporeal membrane oxygenation (ECMO). Also, to explore factors other than ECMO use that may influence sedation requirements during this period of maximum sedation. Design: Retrospective comparative cohort analysis. Data Sources: Two academic centers, one with an adult ECMO program and one without. Patients: Consecutive adults with severe ARDS who were receiving continuous-infusion sedative therapy for at least 48 hours from the time of severe ARDS diagnosis and who were managed with ECMO (34 patients) or without ECMO (60 patients) between 2009 and 2013. Measurements and Main Results: Among patients managed with ECMO, the maximum median (interquartile range [IQR]) 6-hr sedative exposure (in midazolam equivalents) was nearly twice as high (118 [IQR 48–225] mg vs 60 [37–99] mg, p=0.004) and was reached, on average, 3 days later (4 [IQR 1–8] vs 1 [IQR 0.5–6] days, p=0.003) than patients not managed with ECMO. Patients managed with ECMO were younger, had a higher Sequential Organ Failure Assessment score, and, in the 24 hours prior to the period of maximum sedative exposure, had a higher ratio of partial pressure of oxygen in arterial blood to fraction of inspired oxygen and were more likely to receive renal replacement and high-dose fentanyl (2000 μg or more/24 hrs) therapy. An adjusted multivariable linear regression model using the natural logarithmic value of the maximum sedative exposure in a 6-hour period revealed that patient age (p=0.04) and administration of high-dose fentanyl in the 24 hours prior to the 6-hour period of maximum sedative use (p<0.0001) were each independently associated with the maximum 6-hour sedative requirement reached, but the use of ECMO was not (p=0.52). Conclusion: Although the application of ECMO during severe ARDS resulted in a period of maximum sedation exposure that was both greater and took longer to reach, factors other than ECMO, particularly high-dose opioid administration, appeared more likely to account for this maximum sedation use. Further research surrounding sedative requirements, clearance, and patient response during ECMO is required.