CONTEXT: No pharmacological therapeutic protocol has been found effective in modifying the clinical course of acute respiratory distress syndrome (ARDS) and mortality remains greater than 50%. OBJECTIVE: To determine the effects of prolonged methylprednisolone therapy on lung function and mortality in patients with unresolving ARDS. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING:Medical intensive care units of 4 medical centers. PARTICIPANTS: Twenty-four patients with severe ARDS who had failed to improve lung injury score (LIS) by the seventh day of respiratory failure. INTERVENTIONS: Sixteen patients received methylprednisolone and 8 received placebo. Methylprednisolone dose was initially 2 mg/kg per day and the duration of treatment was 32 days. Four patients whose LIS failed to improve by at least 1 point after 10 days of treatment were blindly crossed over to the alternative treatment. MAIN OUTCOME MEASURES: Primary outcome measures were improvement in lung function and mortality. Secondary outcome measures were improvement in multiple organ dysfunction syndrome (MODS) and development of nosocomial infections. RESULTS: Physiological characteristics at the onset of ARDS were similar in both groups. At study entry (day 9 [SD, 3] of ARDS), the 2 groups had similar LIS, ratios of PaO2 to fraction of inspired oxygen (FIO2), and MODS scores. Changes observed by study day 10 for methylprednisolone vs placebo were as follows: reduced LIS (mean [SEM], 1.7 [0.1] vs 3.0 [0.2]; P<.001); improved ratio of PaO2 to FIO2 (mean [SEM], 262 [19] vs 148 [35]; P<.001); decreased MODS score (mean [SEM], 0.7 [0.2] vs 1.8 [0.3]; P<.001); and successful extubation (7 vs 0; P=.05). For the treatment group vs the placebo group, mortality associated with the intensive care unit was 0 (0%) of 16 vs 5 (62%) of 8 (P=.002) and hospital-associated mortality was 2 (12%) of 16 vs 5 (62%) of 8 (P=.03). The rate of infections per day of treatment was similar in both groups, and pneumonia was frequently detected in the absence of fever. CONCLUSIONS: In this study, prolonged administration of methylprednisolone in patients with unresolving ARDS was associated with improvement in lung injury and MODS scores and reduced mortality.
RCT Entities:
CONTEXT: No pharmacological therapeutic protocol has been found effective in modifying the clinical course of acute respiratory distress syndrome (ARDS) and mortality remains greater than 50%. OBJECTIVE: To determine the effects of prolonged methylprednisolone therapy on lung function and mortality in patients with unresolving ARDS. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Medical intensive care units of 4 medical centers. PARTICIPANTS: Twenty-four patients with severe ARDS who had failed to improve lung injury score (LIS) by the seventh day of respiratory failure. INTERVENTIONS: Sixteen patients received methylprednisolone and 8 received placebo. Methylprednisolone dose was initially 2 mg/kg per day and the duration of treatment was 32 days. Four patients whose LIS failed to improve by at least 1 point after 10 days of treatment were blindly crossed over to the alternative treatment. MAIN OUTCOME MEASURES: Primary outcome measures were improvement in lung function and mortality. Secondary outcome measures were improvement in multiple organ dysfunction syndrome (MODS) and development of nosocomial infections. RESULTS: Physiological characteristics at the onset of ARDS were similar in both groups. At study entry (day 9 [SD, 3] of ARDS), the 2 groups had similar LIS, ratios of PaO2 to fraction of inspired oxygen (FIO2), and MODS scores. Changes observed by study day 10 for methylprednisolone vs placebo were as follows: reduced LIS (mean [SEM], 1.7 [0.1] vs 3.0 [0.2]; P<.001); improved ratio of PaO2 to FIO2 (mean [SEM], 262 [19] vs 148 [35]; P<.001); decreased MODS score (mean [SEM], 0.7 [0.2] vs 1.8 [0.3]; P<.001); and successful extubation (7 vs 0; P=.05). For the treatment group vs the placebo group, mortality associated with the intensive care unit was 0 (0%) of 16 vs 5 (62%) of 8 (P=.002) and hospital-associated mortality was 2 (12%) of 16 vs 5 (62%) of 8 (P=.03). The rate of infections per day of treatment was similar in both groups, and pneumonia was frequently detected in the absence of fever. CONCLUSIONS: In this study, prolonged administration of methylprednisolone in patients with unresolving ARDS was associated with improvement in lung injury and MODS scores and reduced mortality.
Authors: F López-Jiménez; M Brito; Y W Aude; P Scheinberg; M Kaplan; D A Dixon; N Schneiderman; J F Trejo; L H López-Salazar; E J Ramírez-Barba; R Kalil; C Ortiz; J Goyos; A Buenaño; S Kottiech; G A Lamas Journal: Arch Med Res Date: 2000 Jul-Aug Impact factor: 2.235
Authors: Laura E Fredenburgh; Mark A Perrella; Diana Barragan-Bradford; Dean R Hess; Elizabeth Peters; Karen E Welty-Wolf; Bryan D Kraft; R Scott Harris; Rie Maurer; Kiichi Nakahira; Clara Oromendia; John D Davies; Angelica Higuera; Kristen T Schiffer; Joshua A Englert; Paul B Dieffenbach; David A Berlin; Susan Lagambina; Mark Bouthot; Andrew I Sullivan; Paul F Nuccio; Mamary T Kone; Mona J Malik; Maria Angelica Pabon Porras; Eli Finkelsztein; Tilo Winkler; Shelley Hurwitz; Charles N Serhan; Claude A Piantadosi; Rebecca M Baron; B Taylor Thompson; Augustine Mk Choi Journal: JCI Insight Date: 2018-12-06
Authors: Matthew P Schreiber; Elizabeth Colantuoni; Oscar J Bienvenu; Karin J Neufeld; Kuan-Fu Chen; Carl Shanholtz; Pedro A Mendez-Tellez; Dale M Needham Journal: Crit Care Med Date: 2014-06 Impact factor: 7.598