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Adjuvant Treatment with a Mammalian Target of Rapamycin Inhibitor, Sirolimus, and Steroids Improves Outcomes in Patients with Severe H1N1 Pneumonia and Acute Respiratory Failure
Study Question: Does the use of sirolimus improve outcomes in patients with severe H1N1 pneumonia?
Study Description: Patients with severe H1N1 pneumonia have an overproduction of T-cells, B-cells, and cytokines leading to inflammation and lung injury. Sirolimus may modulate the immune system and attenuate airway destruction leading to improved oxygenation for patients with severe H1N1 pneumonia. From winter 2009 through spring 2011 patients with confirmed H1N1 infection, and respiratory failure (A-aO2 gradient > 200 mmHg) requiring ventilator support were screened for enrollment. All study patients received oseltamivir 75 mg twice daily for 10 days with prednisolone 20 mg daily for 14 days. Patients were randomized to receive or not receive sirolimus 2 mg daily for 14 days. At ICU admission all patients received empiric moxfloxacin until results of microbiological studies were available.
Results: During the study period 11,026 patients were screened and 4,012 had confirmed H1N1 infection, of which 38 patients were randomized, (19 received sirolimus and 19 did not). Ventilatory support in survivors was shorter in the sirolimus group than non-sirolimus group, (13.8 ± 22.3 days vs. 33 ± 44.8 days, p = 0.03). The number of patients liberated from mechanical ventilation at 3 months was higher in the treatment group (84.2% vs. 47.4%, p = 0.04). PaO2/FiO2 and SOFA scores were significantly improved in the treatment group on days 3 and 7. Repeat PCR for H1N1 was negative in 12 of 16 sirolimus and 5 of 15 non-sirolimus patients (p < 0.05).
Conclusion(s): This study emphasizes the efficacy and safety of sirolimus in improving clinical outcomes of patients with severe H1N1 pneumonia.
Perspective: All patients in this study received corticosteroids. Since the start of this trial, literature has shown that high-dose corticosteroids may be harmful in the setting of ARDS due to H1N1. In other literature, patients receiving immunosuppressive therapy have tended to have worse outcomes. Although the results in this study’s treatment group seem very promising, they should be verified in at least one more, larger study of sirolimus, possibly without the use of corticosteroids, before sirolimus can be routinely recommended for H1N1 patients.