Add Steroids to H1N1-Related ARDS Therapy

SAN DIEGO — Patients with suspected pandemic influenza A(H1N1)–associated acute respiratory distress syndrome responded favorably overall to an ICU treatment course of high-dose oseltamivir and prolonged low- to moderate-dose corticosteroids in a pilot study.

A marked improvement in lung injury scores was seen in 11 of 13 patients by day 7, and the 15% in-hospital mortality rate was lower than expected in such a critically ill population, Dr. G. Umberto Meduri said at the annual meeting of the American College of Chest Physicians.

On the basis of these findings and the extensive basic science rationale supporting prolonged steroid therapy in acute respiratory distress syndrome, the French Ministry of Health has announced it will fund a randomized controlled trial of this treatment protocol in patients with H1N1 influenza–associated ARDS. However, the results won't be in until after the current seasonal outbreak of 2009 H1N1 flu has ebbed, according to Dr. Meduri of the University of Tennessee, Memphis.

He reported on 13 consecutive patients who presented to an ICU in a tertiary-care hospital in Buenos Aires with suspected H1N1 influenza and hypoxemic respiratory failure during a 3-week period. Eight were in septic shock. Six had severe ARDS as defined by a PaO₂/FiO₂ (partial pressure of oxygen in arterial blood to the fraction of inspired oxygen) ratio of 120 or less and a positive end-expiratory pressure of at least 12 cm H₂O; patients this ill typically have an in-hospital mortality of about 55%, he said.

By day 7 in the ICU, 11 of 13 patients showed significantly improved lung function as defined by at least a 1-point drop on the 4-point Lung Injury Scale, or a score below 2. The degree of improvement was similar among patients with severe ARDS and those with more moderate hypoxemic respiratory failure.

Five patients were extubated by day 7, another 6 by day 14, and 2 later. The mean hospital length of stay was 18.7 days. Four patients developed ventilator-associated pneumonia, and 5 nondiabetic patients required insulin therapy, but there were no cases of GI bleeding or neuromuscular weakness. All 13 survivors were discharged home with no supplemental oxygen requirement.

One patient, an alcoholic with cirrhosis who developed septic shock and severe ARDS, died from progressive multiorgan failure on day 15. The other death was believed to be caused by a pulmonary embolism in a patient with comorbid chronic obstructive pulmonary disease, an outcome that underscores the importance of continuing thrombotic prophylaxis at least until hospital discharge, Dr. Meduri noted.

Upon ICU admission, the treatment protocol entails starting oseltamivir (Tamiflu) via nasogastric tube at 150 mg twice daily for 5 days, followed by 75 mg twice daily for 3–5 days as dictated by the patient's clinical course.

Although Dr. Meduri's protocol originally called for reserving methylprednisolone for patients with severe ARDS and using hydrocortisone at 300 mg/day in the others, he now believes it's simpler to use methylprednisolone in all patients, bearing in mind that those with severe ARDS need higher doses.

Upon ICU admission, patients receive a 60-mg intravenous bolus of methylprednisolone, then a continuous infusion at 60 mg/day for days 1–14, tapering to 30 mg/day on days 15–21, 15 mg/day on days 22–25, and 10 mg/day on days 26–28.

If a patient presents with severe ARDS or worsens to that status at any point, the methylprednisolone dose is 1 mg/kg per day, tapered as detailed in Dr. Meduri's earlier randomized trial involving patients with early severe ARDS unrelated to H1N1 flu (Chest 2007;131:954–63). In the H1N1 flu pilot study, patients remained on steroids for an average of 21 days.

One audience member noted that the 15% hospital mortality in the pilot study was comparable to mortality in patients with extremely severe ARDS using extracorporeal membrane oxygenation (ECMO).

“Most of the ICUs in the world don't have ECMO. Steroids are a good alternative,” Dr. Meduri replied.

'Most of the ICUs in the world don't have ECMO. Steroids are a good alternative.'

Source DR. MEDURI