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Patients admitted to the ICU with critical COVID-19 often require prolonged periods of mechanical ventilation. Difficulty weaning, lack of progress, and clinical deterioration are commonly encountered. These conditions should prompt a thorough evaluation for persistent or untreated manifestations of COVID-19, as well as complications from COVID-19 and its various treatments. Inflammation may persist and lead to fibroproliferative changes in the lungs. Infectious complications may arise including bacterial superinfection in the earlier stages of disease. Use of immunosuppressants may lead to the dissemination of latent infections, and to opportunistic infections. Venous thromboembolic disease is common, as are certain neurologic manifestations of COVID-19 including delirium and stroke. High levels of ventilatory support may lead to ventilator-induced injury to the lungs and diaphragm. We present diagnostic and therapeutic considerations for the mechanically ventilated patient with COVID-19 who shows persistent or worsening signs of critical illness, and we offer an approach to treating this complex but common scenario., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Mortality has long been used as a primary end point for randomized controlled trials in critical care. Recently, a plurality of trials targeting mortality end points as their primary outcome has failed to detect a difference between study arms. While there are a number of reasons for the preponderance of such neutral trials, the use of mortality as an outcome is one important consideration. We explore some of the reasons why such trials may be biased toward a neutral result, as well as reasons to consider alternative end points that are better coupled to the expected therapeutic effect. We also discuss to what extent mortality as a binary outcome is patient-important in the ICU., (Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)