Corticosteroid use in ARDS and its application to evolving therapeutics for coronavirus disease 2019 (COVID-19): A systematic review.

Data regarding the use of corticosteroids for treatment of acute respiratory distress syndrome (ARDS) are conflicting. As the coronavirus disease 2019 (COVID-19) pandemic progresses, more literature supporting the use of corticosteroids for COVID-19 and non-COVID-19 ARDS have emerged. Glucocorticoids are proposed to attenuate the inflammatory response and prevent progression to the fibroproliferative phase of ARDS through their multiple mechanisms and anti-inflammatory properties. The purpose of this systematic review was to comprehensively evaluate the literature surrounding corticosteroid use in ARDS (non-COVID-19 and COVID-19) in addition to a narrative review of clinical considerations of corticosteroid use in these patient populations. OVID Medline and EMBASE were searched. Randomized controlled trials evaluating the use of corticosteroids for COVID-19 and non-COVID-19 ARDS in adult patients on mortality outcomes were included. Risk of bias was assessed with the Risk of Bias 2.0 tool. There were 388 studies identified, 15 of which met the inclusion criteria that included a total of 8877 patients. The studies included in our review reported a mortality benefit in 6/15 (40%) studies with benefit being seen at varying time points of mortality follow-up (ICU survival, hospital, and 28 and 60 days) in the COVID-19 and non-COVID-19 ARDS studies. The two non-COVID19 trials assessing lung injury score improvements found that corticosteroids led to significant improvements with corticosteroid use. The number of mechanical ventilation-free days significantly were found to be increased with the use of corticosteroids in all four studies that assessed this outcome. Corticosteroids are associated with improvements in mortality and ventilator-free days in critically ill patients with both COVID-19 and non-COVID-19 ARDS, and evidence suggests their use should be encouraged in these settings. However, due to substantial differences in the corticosteroid regimens utilized in these trials, questions still remain regarding the optimal corticosteroid agent, dose, and duration in patients with ARDS.

Review of Emerging Pharmacotherapy for the Treatment of Coronavirus Disease 2019.

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into an emergent global pandemic. Coronavirus disease 2019 (COVID-19) can manifest on a spectrum of illness from mild disease to severe respiratory failure requiring intensive care unit admission. As the incidence continues to rise at a rapid pace, critical care teams are faced with challenging treatment decisions. There is currently no widely accepted standard of care in the pharmacologic management of patients with COVID-19. Urgent identification of potential treatment strategies is a priority. Therapies include novel agents available in clinical trials or through compassionate use, and other drugs, repurposed antiviral and immunomodulating therapies. Many have demonstrated in vitro or in vivo potential against other viruses that are similar to SARS-CoV-2. Critically ill patients with COVID-19 have additional considerations related to adjustments for organ impairment and renal replacement therapies, complex lists of concurrent medications, limitations with drug administration and compatibility, and unique toxicities that should be evaluated when utilizing these therapies. The purpose of this review is to summarize practical considerations for pharmacotherapy in patients with COVID-19, with the intent of serving as a resource for health care providers at the forefront of clinical care during this pandemic.

Comparison of Hydromorphone versus Fentanyl-based Sedation in Extracorporeal Membrane Oxygenation: A Propensity-Matched Analysis.

INTRODUCTION: Data comparing sedatives in patients receiving extracorporeal membrane oxygenation (ECMO) are sparse. However, it is known that the ECMO circuit alters the pharmacokinetic properties of medications via drug sequestration of lipophilic agents and increased volume of distribution. OBJECTIVES: This study evaluated the difference in days alive without delirium or coma and the sedative requirements in patients receiving fentanyl versus hydromorphone in ECMO patients. METHODS: This single-center retrospective observational study evaluated adults receiving ECMO for more than 48 hours and continuous infusion of either fentanyl or hydromorphone for at least 6 hours. Of 148 patients evaluated, 88 received fentanyl and 60 received hydromorphone continuous infusion sedation. Outcomes included delirium-free and coma-free (DFCF) days, narcotic use, and sedative use. MAIN RESULTS: There was an increase in the number of DFCF days in the hydromorphone group at day 7 (p=0.07) and day 14 (p=0.08) and a significant reduction in daily fentanyl equivalent exposure. Propensity score matching yielded 54 matched pairs. An 11.1% increase was observed in the proportion of ECMO days alive without delirium or coma in the hydromorphone group at 7 days (53.2% vs 42.1%, p=0.006). Patients in the hydromorphone group received significantly fewer narcotics with a median of 555 µg (interquartile range [IQR] 287-905 µg) of fentanyl equivalents per day compared with 2291 µg (IQR 1053-4023 µg) in the fentanyl group (p<0.005). CONCLUSION: The use of hydromorphone-based sedation in ECMO patients resulted in more days alive without delirium or coma while significantly reducing narcotic requirements.

Oral Anticancer Therapy: Management of Drug Interactions.

Oral anticancer therapy is increasingly integrated into the care of patients with cancer. Recognition and management of drug-drug interactions (DDIs) is critical to providing efficacious and safe anticancer treatment. DDIs with QTc-prolonging agents, anticoagulants, enzyme inducers and inhibitors, antidepressants, and acid suppressants are commonly encountered with anticancer therapies. Here, we review frequently observed DDIs and outline literature-supported suggestions for their management.