HONOLULU – The jury is still out on whether patients with acute lung injury and adult respiratory distress syndrome derive any benefit from the use of corticosteroids, according to Dr. Stephen M. Pastores.
"This is probably the most controversial topic in acute lung injury and ARDS," Dr. Pastores of the department of anesthesiology and critical care medicine at Memorial Sloan-Kettering Cancer Center, New York, said at the annual meeting of the American College of Chest Physicians. "For those of us who might believe in the use of corticosteroids, we base that on the pretty good evidence that they are effective anti-inflammatory agents. There have been a few positive trials for the use of prolonged corticosteroid treatment in ALI [acute lung injury]-ARDS, with significantly less side effects in comparison to older trials investigating massive doses," such as methylprednisolone 120 mg/kg per day.
Renewed interest in this topic came about 4 years ago, he said, after publication of a study that evaluated the effects of low-dose methylprednisolone infusion on lung function in 91 patients with early ARDS (within 72 hours). About two-thirds of the patients (66%) had sepsis (Chest 2007;131:954-63). Patients were randomized to receive methylprednisolone infusion (1 mg/kg per day) or placebo for up to 28 days. The primary end point was a 1-point reduction in the lung injury score or successful extubation by day 7.
"An important piece of this study was that [the researchers] did regular infection surveillance with regular bronchoscopies, and they avoided the use of neuromuscular blockers," said Dr. Pastores, who is also professor of medicine and anesthesiology at Cornell University in New York.
The researchers found that patients in the treatment arm had a greater than 1-point drop in their lung injury score. The researchers also found no significant increase in complications such as infection, "and because they avoided neuromuscular blockers, there was hardly any incidence of neuromuscular weakness or neuropathy," Dr. Pastores said.
In a subsequent review of five trials on the use of steroids for the treatment of ARDS that enrolled a total of 518 patients, Dr. Pastores and his associates observed that the steroid dosing and treatment duration were different across the trials, and that infection surveillance was not routine (Intensive Care Med. 2008;34:61-9). However, three of the trials in which patients received steroids before day 14 of ARDS found a slight benefit to this approach, with a number needed to treat of six.
"If you look at the patients who were randomized to the methylprednisolone arm, the mortality rate was 24%, which is about 16% less than the control arm that did not receive steroids," Dr. Pastores said of the 245 patients in these three trials. "From this review, we concluded that prolonged glucocorticoid treatment substantially and significantly improves meaningful patient-centered outcomes in terms of less ventilator days, less days in the ICU, and perhaps a distinct survival benefit – only in patients who have steroids early in the course of acute lung injury, however."
A more recent systematic review that factored in additional trials concluded that prolonged glucocorticoid treatment has a "distinct survival benefit" when initiated before day 14 of ARDS, with a number needed to treat of four (Crit. Care Med. 2009;37:1594-603). No significant differences in the rate of neuromyopathy or other major events were seen between the treatment and control groups. "However, we have to be cautious," Dr. Pastores said of the findings. "There are limitations in all of the systematic reviews on this topic. There are marked differences in study designs, patient characteristics, varying doses of steroids that were used, dosing strategies, and duration of therapy."
In 2008, a task force convened by the American College of Critical Care Medicine concluded that moderate-dose glucocorticoids should be considered in patients with early severe ARDS (PaO2/FiO2 of less than 200) and before day 14 in patients with unresolving ARDS (Crit. Care Med. 2008;36:1937-49). "We could not come to a definitive conclusion or recommendation on patients with less-severe ALI," said Dr. Pastores, who was a member of the task force. "Keep in mind that the recommendation is based on level 2B evidence for a mortality benefit. It’s a weak recommendation because the quality of the evidence was moderate; it wasn’t very strong because we didn’t have enough good randomized, controlled trials. For reduction in duration of mechanical ventilation, however, the evidence is strong (1B), with the aggregate of data showing a doubling of extubation, in comparison to controls, by day 7 and 14."
"Prolonged glucocorticoid treatment substantially and significantly improves meaningful patient-centered outcomes."