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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*
- Source :
- Critical Care Medicine. 42:313-321
- Publication Year :
- 2014
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2014.
-
Abstract
- Severe H1N1 pneumonia with acute respiratory failure results in infiltration of lungs due to the presence of hyperactive immune cells. Rapamycin and corticosteroids inhibit this immune response by blocking the activation of T and B cells.Open-label prospective randomized controlled trial.A tertiary medical center, Chang Gung Memorial Hospital, located in Taiwan.Between 2009 and 2011, of 4,012 H1N1-infected patients, 38 patients with severe H1N1 pneumonia and acute respiratory failure were enrolled.Thirty-eight patients with confirmed H1N1 pneumonia and on mechanical ventilatory support were randomized to receive adjuvant treatment of corticosteroids with an mTOR inhibitor, either with sirolimus (Rapamune 2 mg/d) (sirolimus group, n = 19) for 14 days or without sirolimus (nonsirolimus group, n = 19). The clinical values measured included PaO2/FIO2, Sequential Organ Failure Assessment score, duration of ventilatory support, and mortality. The baseline demography was similar between the two groups. After treatment, the PaO2/FIO2 values on day 3 (167.5 [95% CI, 86.7-209.2 mm Hg], n = 19 vs 106.8 [95% CI, 73.0-140.7 mm Hg], n = 19; p = 0.025] and day 7 (241.6 [95% CI, 185.2-297.9 mm Hg], n = 19 vs 147.0 [95% CI, 100.7-193.7 mm Hg], n = 17; p = 0.008) in the sirolimus group were significantly better over the nonsirolimus group. Similarly, the Sequential Organ Failure Assessment score on day 3 (4.3 [95% CI, 3.1-5.5]; p = 0.029) and day 7 (5.9 [95% CI, 4.8-6.9], n = 19 and 6.2 [95% CI, 4.7-7.8], n = 17, respectively) significantly improved in the sirolimus group. The liberation from a mechanical ventilator at 3 months was also better in the sirolimus combined with corticosteroids treatment. Similarly, the duration of ventilator use was significantly shorter in the sirolimus group (median, 7 vs 15 d; p = 0.03 by log-rank test). In the sirolimus combined with corticosteroids treatment group, a rapid clearance of virus also occurred after 7 days of treatment.In patients with severe H1N1 pneumonia, early adjuvant treatment with corticosteroids and an mTOR inhibitor was associated with improvement in outcomes, such as hypoxia, multiple organ dysfunction, virus clearance, and shortened liberation of ventilator and ventilator days.
- Subjects :
- Male
Prednisolone
medicine.medical_treatment
Pneumonia, Viral
Critical Care and Intensive Care Medicine
Severity of Illness Index
law.invention
Influenza A Virus, H1N1 Subtype
Pharmacotherapy
Immune system
Randomized controlled trial
law
Influenza, Human
medicine
Humans
Prospective Studies
Prospective cohort study
Glucocorticoids
Sirolimus
Chemotherapy
business.industry
Middle Aged
biochemical phenomena, metabolism, and nutrition
respiratory tract diseases
Treatment Outcome
Respiratory failure
Chemotherapy, Adjuvant
Acute Disease
Immunology
Drug Therapy, Combination
Female
Respiratory Insufficiency
business
Adjuvant
Immunosuppressive Agents
medicine.drug
Subjects
Details
- ISSN :
- 00903493
- Volume :
- 42
- Database :
- OpenAIRE
- Journal :
- Critical Care Medicine
- Accession number :
- edsair.doi.dedup.....af15546d1292ed1c33a4c4b31c2bfc2b