Andreas Schwingshackl1, Dai Kimura2, Cynthia R Rovnaghi3, Jordy S Saravia2, Stephania A Cormier2, Bin Teng4, Alina N West2, Umberto G Meduri5, Kanwaljeet J S Anand6. 1. Department of Pediatrics, Mattel Children's Hospital at UCLA, Los Angeles, CA, United States. Electronic address: aschwingshackl@gmail.com. 2. Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, United States. 3. Pain Neurobiology Laboratory, University of Tennessee Health Science Center, Memphis, TN, United States. 4. Department of Physiology, University of Tennessee Health Science Center, Memphis, TN, United States. 5. Department of Internal Medicine, University of Tennessee Health Science Center, Memphis, TN, United States. 6. Department of Pediatrics, Stanford University, Stanford, CA, United States.
Abstract
OBJECTIVE: A double-blind, randomized controlled trial showed that low-dose glucocorticoid therapy in pediatric ARDS patients is feasible and may improve both ventilation and oxygenation indices in these patients. However, the molecular mechanisms underlying potential changes in outcomes remain unclear. Based on these clinical findings, this study was designed to examine the effects of intravenous methylprednisolone on circulating inflammatory biomarkers in pediatric ARDS patients. DESIGN: Double-blind, placebo-controlled randomized trial with blood collection on study entry and day 7. SETTING:Tertiary care children's hospital. PATIENTS: Children (0-18years) with ARDS undergoing mechanical ventilation. INTERVENTIONS:35 children were randomized within 72h of mechanical ventilation. The glucocorticoid group received methylprednisolone 2mg/kg loading dose followed by 1mg/kg/day continuous infusion from days 1 to 7. Both groups were ventilated following the ARDSnet recommendations. WBC and differential cell counts, plasma cytokines and CRP levels, and coagulation parameters were analyzed on days 0 and 7. RESULTS: At study entry, the placebo group had higher IL-15 and basophil levels. On day 7, in comparison to study entry, the placebo group had lower IL-1α, IFN-γ and IL-10 levels. The glucocorticoid group had lower INF-α, IL-6, IL-10, MCP-1, G-CSF and GM-CSF levels, and higher IL-17α levels on day 7 in comparison to study entry. Total and differential cell counts remained unchanged within the placebo group between days 0 and 7, whereas in the glucocorticoid group total WBC and platelets counts were increased on day 7. Pearson's correlation studies within the placebo and glucocorticoid groups revealed positive and negative correlations between cytokine levels, cell counts, coagulation parameters and relevant clinical parameters of disease severity identified in our previous study. Multiple regression models identified several cytokines as predictors for alterations in clinical parameters of disease severity. CONCLUSION: This pilot study shows the feasibility of simultaneously measuring multiple inflammatory cytokines, cell counts and coagulation parameters in pediatric ARDS patients. We report statistical models that may be useful for future, larger trials to predict ARDS severity and outcomes.
RCT Entities:
OBJECTIVE: A double-blind, randomized controlled trial showed that low-dose glucocorticoid therapy in pediatric ARDS patients is feasible and may improve both ventilation and oxygenation indices in these patients. However, the molecular mechanisms underlying potential changes in outcomes remain unclear. Based on these clinical findings, this study was designed to examine the effects of intravenous methylprednisolone on circulating inflammatory biomarkers in pediatric ARDS patients. DESIGN: Double-blind, placebo-controlled randomized trial with blood collection on study entry and day 7. SETTING: Tertiary care children's hospital. PATIENTS: Children (0-18years) with ARDS undergoing mechanical ventilation. INTERVENTIONS: 35 children were randomized within 72h of mechanical ventilation. The glucocorticoid group received methylprednisolone 2mg/kg loading dose followed by 1mg/kg/day continuous infusion from days 1 to 7. Both groups were ventilated following the ARDSnet recommendations. WBC and differential cell counts, plasma cytokines and CRP levels, and coagulation parameters were analyzed on days 0 and 7. RESULTS: At study entry, the placebo group had higher IL-15 and basophil levels. On day 7, in comparison to study entry, the placebo group had lower IL-1α, IFN-γ and IL-10 levels. The glucocorticoid group had lower INF-α, IL-6, IL-10, MCP-1, G-CSF and GM-CSF levels, and higher IL-17α levels on day 7 in comparison to study entry. Total and differential cell counts remained unchanged within the placebo group between days 0 and 7, whereas in the glucocorticoid group total WBC and platelets counts were increased on day 7. Pearson's correlation studies within the placebo and glucocorticoid groups revealed positive and negative correlations between cytokine levels, cell counts, coagulation parameters and relevant clinical parameters of disease severity identified in our previous study. Multiple regression models identified several cytokines as predictors for alterations in clinical parameters of disease severity. CONCLUSION: This pilot study shows the feasibility of simultaneously measuring multiple inflammatory cytokines, cell counts and coagulation parameters in pediatric ARDS patients. We report statistical models that may be useful for future, larger trials to predict ARDS severity and outcomes.
Authors: G R Bernard; A Artigas; K L Brigham; J Carlet; K Falke; L Hudson; M Lamy; J R Legall; A Morris; R Spragg Journal: Am J Respir Crit Care Med Date: 1994-03 Impact factor: 21.405
Authors: Bonny B Drago; Dai Kimura; Cynthia R Rovnaghi; Andreas Schwingshackl; Mark Rayburn; G Umberto Meduri; Kanwaljeet J S Anand Journal: Pediatr Crit Care Med Date: 2015-03 Impact factor: 3.624
Authors: Andreas Schwingshackl; Bin Teng; Manik Ghosh; Alina Nico West; Patrudu Makena; Vijay Gorantla; Scott E Sinclair; Christopher M Waters Journal: Am J Physiol Lung Cell Mol Physiol Date: 2011-09-23 Impact factor: 5.464
Authors: Douglas F Willson; Neal J Thomas; Robert Tamburro; Edward Truemper; Jonathon Truwit; Mark Conaway; Christine Traul; Edmund E Egan Journal: Pediatr Crit Care Med Date: 2013-09 Impact factor: 3.624