He went on to note that physicians should give steroids in conjunction with infection surveillance, "avoiding neuromuscular blockers if you can, and being concerned about the phenomenon of rebound inflammation if you stop steroids abruptly."
Inhaled nitric oxide has also been studied as a nonventilatory strategy in ALI/ARDS. A Cochrane review of 13 randomized, controlled trials involving 1,303 patients found no significant effect with this approach in overall mortality, but did show a transient improvement in oxygenation in the first 24 hours. The review also found that inhaled nitric oxide had no significant effect on duration of ventilation, ventilator-free days, and ICU and hospital length of stay. An increased risk of renal impairment among adults was also noted (Cochrane Database Syst. Rev. 2010 Oct. 23 [doi:10.1002/14651858.CD002787.pub2]).
"The conclusion from this meta-analysis was that there was no mortality benefit, and in fact [nitric oxide] might even be harmful," Dr. Pastores said.
Intriguing findings on the use of neuromuscular blockers in severe, early ARDS were presented in 2010 by French researchers after a multicenter trial of 340 patients who were randomized to IV cisatracurium infusion or placebo for 48 hours (N. Engl. J. Med. 2010;363:1107-16). The primary outcome was 90-day mortality and ventilator-free days.
Patients in the treatment group had lower 90-day mortality and more ventilator-free days, compared with those in the placebo group.
"Neuromuscular blockers may facilitate lung-protective ventilation in this patient population by improving patient-ventilator synchrony," Dr. Pastores said. "They may also improve chest wall compliance and reduce oxygen consumption, and possibly cause a decrease in lung or systemic inflammation."
The study’s limitations were that "it only involved cisatracurium and therefore may not apply to other neuromuscular blockers. There were also no data on conditions known to antagonize or potentiate neuromuscular blockers," he added.
Another treatment strategy for ALI/ARDS – the routine use of aerosolized beta2-agonists – cannot be recommended at this time because of the results of a recent trial in which patients were randomized to 5-mg aerosolized albuterol or saline placebo every 4 hours for up to 10 days. The primary outcome was ventilator-free days. "The trial had to be stopped for futility because there was no improvement in ventilator-free days," Dr. Pastores said. "In fact, there was a suggestion of a slight trend of increasing morbidity among patients in the treatment group. The investigators theorized that the lung-protective ventilation and conservative fluid management reduced lung injury and water to the extent that additional lung fluid clearance with beta2-agonists had no additional beneficial effect."
"This is probably the most controversial topic in acute lung injury and ARDS."
The role of pharmaconutrition has also been studied in this patient population. According to Dr. Pastores, three previous trials of continuous omega-3 enteral feeds showed improved PaO2/FiO2 ratio, shorter ventilator time and ICU stay, and fewer organ failures and lower mortality. However, a more recent randomized, controlled trial of 272 adults found that twice-daily administration of omega-3 fatty acids plus antioxidant supplementation did not improve ventilator-free days or other clinical outcomes (JAMA 2011;306:1574-81). "There was some suggestion that perhaps it was harmful to these patients," Dr. Pastores said. For example, 60-day hospital mortality was higher among the patients in the treatment group, compared with those in the placebo group (27% vs. 16%, respectively; P = .054).
Future nonventilatory therapies that might hold promise for patients with ALI/ARDS, he said, include inhaled protein C, tissue factor inhibition, statins, and the extended use of steroids in severe community-acquired pneumonia.
Dr. Pastores disclosed that he has received grant support from Altor Bioscience Corp. and from Spectral Diagnostics Inc.