A role for extracorporeal treatment in severe influenza?

Influenza occurs worldwide as a seasonal infection. The influenza virus is enclosed in an envelope containing the glycoproteins hemagglutinin and neuraminidase. It has been known for many decades that the virus mutates to form new subtypes and strains, which are named according to the antigenic types of hemagglutinin and neuraminidase, thus influenza A (H3N2), etc. A gradual change (antigenic drift) in the antigenic properties produces new strains; influenza vaccines are reformulated every year to take this antigenic drift into account. A more abrupt change (antigenic shift) may produce a new subtype. Usually, these mutations do not produce any significant change in virulence. Occasionally the mutated virus may be devastating in terms of morbidity and mortality, as was seen in the great flu pandemic of 1918– 1919, caused by an influenza A (H1N1) virus, when nearly 20 million people are believed to have died worldwide. A second pandemic of influenza A (H2N2) occurred in 1957–1958, accounting for nearly 70,000 deaths in the US, followed by a third pandemic of influenza A (H3N2) in 1968. In early 2009, an increase in hospitalizations for pneumonia associated with influenza in Mexico and the finding of a novel influenza A virus from children in the United States heralded the arrival of what came to be known as “swine flu. ” Younger age groups and pregnant women were particularly vulnerable to developing severe forms of influenza with this virus. The World Health Organization (WHO) raised the likelihood of a pandemic, and an international effort began to develop and vaccinate vulnerable populations. The actual mortality caused by the virus has been much less than feared, and currently debate rages on whether the WHO acted appropriately. The current strain of influenza A (H1N1) virus can lead to severe hypoxic respiratory failure and acute respiratory distress syndrome (ARDS). The usual treatment modality is the use of artificial ventilation to support the patient until the lungs begin to heal and oxygenation improves. In this issue of the Southern Medical Journal, Homsi et al report the successful treatment of severe acute respiratory failure in a 44year-old patient with influenza A (H1N1). The patient was morbidly obese, and a number of reports have also observed an increased prevalence in obese individuals. The treatment of this morbidly obese patient was unusual in some respects with the use of very high doses of steroids and high peak end expiratory pressure (PEEP) levels ( 25 cm H20), and this report’s management recommendations bring into focus the question of the role of extracorporeal membrane oxygenation (ECMO) in treating respiratory failure associated with influenza A (H1N1). The use of ECMO in these patients has been described by Davies et al. One hundred eighty six patients with confirmed influenza A (H1N1) infection received mechanical ventilation for hypoxic respiratory failure. In 53 of these patients in whom ECMO was applied in addition to standard mechanical ventilation, the mortality rate was 21%, whereas in the 133 patients in whom ECMO was not applied, the mortality rate was 13%. However, the patients who received ECMO were more severely hypoxemic. Unfortunately, this is a case report, with no control arm for comparison, ie, matched patients with equal severity of respiratory failure, treated only with standard techniques with mechanical ventilation. While it is possible that the mortality rate would have been higher in the absence of ECMO, no definitive statement can be made on the role of ECMO in severe respiratory failure induced by influenza A (H1N1) based on this study. Others have reported on the use of ECMO in small numbers of influenza A (H1N1)-infected patients; again, these are case reports which do not allow an assessment of ECMO against standard treatment in these patients. However, the vast majority of patients with influenza A (H1N1) infection develop either no symptoms or relatively mild, typical symptoms of influenza (upper airway symptoms, fever, and gastrointestinal symptoms) without any complications. Nevertheless, vaccination is recommended, especially for children and pregnant women. In symptomatic patients, the recommended treatment is with antiviral drugs From the Division of Pulmonary and Critical Care Medicine, University of Connecticut Health Center, Farmington, CT.