Center for Excellence in Critical Care Am J Respir Crit Care Med 2005;171:242-8 Hydrocortisone Infusion for Severe Community- acquired Pneumonia A Preliminary Randomized Study Marco Confalonieri, Rosario Urbino, Alfredo Potena, Marco Piattella, Piercarlo Parigi, Giacomo Puccio, Rossana Della Porta, Carbone Giorgio, Francesco Blasi, Reba Umberger and G. Umberto Meduri Ospedale di Trieste, Trieste; Ospedale Gradenigo-Torino; Ospedale Molinette di Torino; Arcispedale S. Anna di Ferrara; Ospedale di Crema; Ospedale di Paderno Dugnano-Milano; Institute of Respiratory Diseases, University of Milan, Milan, Italy; and Memphis Lung Research Program, Memphis, Tennessee Correspondence and requests for reprints should be addressed to Dr. Marco Confalonieri, Azienda Ospedaliero-Universitaria di Trieste, Strada di Fiume 447, Trieste, Italy.

Center for Excellence in Critical Care Am J Respir Crit Care Med 2005;171:242-8 Hydrocortisone Infusion for Severe Community-acquired Pneumonia A Preliminary Randomized Study Objective: hydrocortisone administered early in severe Community Acquired Pneumonia attenuates pulmonary and systemic inflammation and reduces sepsis related complications and mortality Design: Prospective, placebo-controlled, randomized, double-blind trial on two parallel groups Setting: 6 hospitals in Italy from July 2000 to March 2003

Center for Excellence in Critical Care Am J Respir Crit Care Med 2005;171:242-8 Hydrocortisone Infusion for Severe Community-acquired Pneumonia Entry Criteria Patients with clinical and X-ray evidence of pneumonia plus 2 minor or 1 major 1993 American Thoracic Society criteria for severe pneumonia –Minor criteria: (1) respiratory rate > 30 breaths at admission; (2) PaO2/FiO2 < 250; (3) CXR showing bilateral or multilobar involvement; (4) SBP < 90 mm Hg; or (5) DBP < 60 mm Hg. –Major criteria: (1) mechanical ventilation; (2) increase in the size of opacities on CXR of > 50% at 48 hours; (3) vasopressors > 4 hours; or (4) serum creatinine >2 mg/dl.

Center for Excellence in Critical Care Am J Respir Crit Care Med 2005;171:242-8 Hydrocortisone Infusion for Severe Community-acquired Pneumonia Exclusion Criteria nosocomial pneumonia; severe immunosuppression; acute burn injury; a preexisting medical condition with a life expectancy less than 3 months; pregnancy; a major gastrointestinal bleed within 3 months of the current hospitalization; or a condition requiring more than 0.5 mg/kg/day of prednisone equivalent (i.e., acute asthma or chronic obstructive pulmonary disease [COPD]).

Center for Excellence in Critical Care Am J Respir Crit Care Med 2005;171:242-8 Hydrocortisone Infusion for Severe Community-acquired Pneumonia Randomization Placebo (n=23) Hydrocortisone 200 mg IV load followed by 10 mg/hr X 7 days (n=23) Primary end-points were improvement in PaO2:FIO2 (PaO2:FIO2 > 300 or 100 increase from study entry) and multiple organ dysfunction syndrome (MODS) score by Study Day 8 and development of delayed septic shock. The secondary end-points were duration of mechanical ventilation, length of ICU/RIU and hospital stay, and survival to hospital discharge and to 60 days

Center for Excellence in Critical Care Am J Respir Crit Care Med 2005;171:242-8 Results Hydrocortisone treated patients had significant: improvement in PaO2:FIO2 (p = 0.002) improvement in CXR score (p < ), reduction in C-reactive protein levels (p = 0.01) reduction in MODS score (p = 0.003) reduction in delayed septic shock (p = 0.001). reduction in length of hospital stay (p = 0.03) reduction in mortality (p = 0.009).

Center for Excellence in Critical Care Am J Respir Crit Care Med 2005;171:242-8 Placebo Hydrocortisone p = 0.009

Center for Excellence in Critical Care Am J Respir Crit Care Med 2005;171:242-8 Conclusion prolonged low-dose hydrocortisone infusion hastens resolution of pneumonia and prevents the development of sepsis- related complications. a 7-day course of low-dose hydrocortisone infusion was associated with a significant reduction in duration of mechanical ventilation, hospital length of stay, and hospital mortality

Center for Excellence in Critical Care Am J Respir Crit Care Med 2005;171:242-8 Hydrocortisone Placebo P=0.009