Pulmonary Disorders I

conducted a meta-analysis of seven randomized clinical trials involving 1703 critically ill patients

with COVID-19. It should be noted most patients included in pooled analysis did not meet a strict

definition of ARDS but were considered critically ill. This meta-analysis evaluated the impact of

systemic corticosteroids, including dexamethasone, methylprednisolone, or hydrocortisone, on 28-

corticosteroids significantly reduced the risk of all-cause mortality (summary OR 0.66; 95% CI,

0.53–0.82; p<0.001) using a fixed-effects model. However, no association was observed between

corticosteroids and controls using a random-effects meta-analysis approach (OR 0.70; 95% CI,

0.48–1.01). Subgroup analysis showed the survival benefit favored dexamethasone over no steroids

according to pooled data from three clinical trials. Of note, this benefit with dexamethasone was

largely driven by the RECOVERY trial consisting of 57% of the overall pooled data. The remaining

clinical trials consisting of hydrocortisone (n=3) and methylprednisolone (n=1) showed that these

agents did not affect survival according to subgroup analysis. In addition, no increased risk of

adverse events was found between corticosteroid and control groups.

The optimal dexamethasone dosing strategy remains unknown, though most clinicians have adopted

the 6-mg/day approach used in the RECOVERY trial. In other words, higher dexamethasone dosing

strategies (20 mg/day) have not shown additional beneficial effects compared with lower doses (6

Inhaled pulmonary vasodilators

Inhaled nitric oxide and inhaled epoprostenol have improved gas exchange, despite their lack of

effect on clinical outcomes (length of stay and mortality). Limited data suggest these agents are

equally efficacious. A meta-analysis of randomized clinical trials comparing inhaled nitric oxide

and placebo showed no effect on mortality in patients with ARDS (RR 1.10; 95% CI, 0.94–1.29),

patients with a baseline Pao2/ Fio2 of 100 mm Hg or less (RR 1.01; 95% CI, 0.78–1.32), or patients

2014;42:404-12).

Institutions have used inhaled epoprostenol as a more cost-effective option over inhaled nitric

oxide. Direct comparisons between these studies suggest safety and efficacy were similar. However,

inhaled epoprostenol has been associated with significant cost savings over inhaled nitric oxide.

Major limitations of widespread inhaled nitric oxide use for ARDS include high costs and dedicated

equipment for drug delivery. Given that cost is the primary differentiating factor between these

two agents, many institutions have transitioned from inhaled nitric oxide to inhaled epoprostenol.

Implementation of inhaled epoprostenol delivery systems and processes requires continuous

education and pharmacovigilance to mitigate the risk of medication errors and preventable adverse

drug events.

The 2023 ESICM guideline and the 2024 ATS guideline did not evaluate inhaled epoprostenol;

thus, they do not provide any recommendations on its use in ARDS. However, one of the 2019

guidelines states to avoid inhaled epoprostenol in ARDS because of weak quality of evidence

for consideration in severe ARDS for patients currently receiving lung-protective ventilation and