TY - JOUR
T1 - Adjuvant treatment with a mammalian target of rapamycin inhibitor, sirolimus, and steroids improves outcomes in patients with severe H1N1 pneumonia and acute respiratory failure
AU - Wang, Chun Hua
AU - Chung, Fu Tsai
AU - Lin, Shu Min
AU - Huang, Shu Yi
AU - Chou, Chun Liang
AU - Lee, Kang Yun
AU - Lin, Tzou Yien
AU - Kuo, Han Pin
PY - 2014/2
Y1 - 2014/2
N2 - OBJECTIVES:: 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. DESIGN:: Open-label prospective randomized controlled trial. SETTING:: A tertiary medical center, Chang Gung Memorial Hospital, located in Taiwan. PATIENTS:: Between 2009 and 2011, of 4,012 H1N1-infected patients, 38 patients with severe H1N1 pneumonia and acute respiratory failure were enrolled. MEASUREMENTS AND MAIN RESULTS:: 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 PaO 2/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. CONCLUSIONS:: 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.
AB - OBJECTIVES:: 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. DESIGN:: Open-label prospective randomized controlled trial. SETTING:: A tertiary medical center, Chang Gung Memorial Hospital, located in Taiwan. PATIENTS:: Between 2009 and 2011, of 4,012 H1N1-infected patients, 38 patients with severe H1N1 pneumonia and acute respiratory failure were enrolled. MEASUREMENTS AND MAIN RESULTS:: 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 PaO 2/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. CONCLUSIONS:: 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.
KW - H1N1
KW - Outcomes
KW - Rapamycin
KW - Respiratory Failure
KW - Virus Clearance
KW - Virus Pneumonia
KW - H1N1
KW - Outcomes
KW - Rapamycin
KW - Respiratory Failure
KW - Virus Clearance
KW - Virus Pneumonia
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U2 - 10.1097/CCM.0b013e3182a2727d
DO - 10.1097/CCM.0b013e3182a2727d
M3 - Article
C2 - 24105455
AN - SCOPUS:84893289257
SN - 0090-3493
VL - 42
SP - 313
EP - 321
JO - Critical Care Medicine
JF - Critical Care Medicine
IS - 2
ER -