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Intensive Care Medicine

, Volume 41, Issue 9, pp 1658–1666 | Cite as

Corticosteroid exposure in pediatric acute respiratory distress syndrome

  • Nadir YehyaEmail author
  • Sabah Servaes
  • Neal J. Thomas
  • Vinay M. Nadkarni
  • Vijay Srinivasan
Original

Abstract

Purpose

Use of systemic corticosteroids in acute respiratory distress syndrome (ARDS) remains controversial, and studies in children are lacking.

Methods

We performed an observational, single-center study in a prospectively enrolled cohort of children meeting criteria for ARDS (both Berlin 2012 and AECC 1994 acute lung injury) and pediatric ARDS (PARDS, as defined by PALICC 2015). Comprehensive analysis of corticosteroid utilization was planned, and detailed information collected on corticosteroid use, timing, treatment duration, and cumulative dose while mechanically ventilated. We assessed the association between corticosteroid exposure >24 h and outcomes.

Results

Of the 283 children with PARDS (37 deaths, 13 %), 169 (60 %) received corticosteroids for >24 h while ventilated: 51 % hydrocortisone, 41 % methylprednisolone, 5 % dexamethasone, 3 % combination of corticosteroids. Corticosteroid exposure >24 h was associated with increased mortality, fewer ventilator-free days at 28 days (VFD), and longer duration of ventilation in survivors in unadjusted analyses (all p < 0.05). Multivariate and propensity score adjusted analyses confirmed independent association of corticosteroid exposure with fewer VFD and longer duration of ventilation in survivors, but not with mortality. In planned analyses of high-risk subgroups, no benefit was seen with corticosteroids exposure, with fewer VFD associated with corticosteroid exposure >24 h in patients with ≥3 organ failures and immunocompromised patients.

Conclusions

Corticosteroid exposure >24 h was independently associated with fewer VFD and longer duration of ventilation in survivors, even after adjustment for key potential confounders, including severity of illness, oxygenation index, immunocompromised status, and number of organ failures.

Keywords

Pediatric Acute respiratory distress syndrome ARDS PARDS Children Corticosteroids 

Notes

Acknowledgments

We would like to thank Xuemei Zhang and our colleagues at Westat Biostatistics and Data Management Core for statistical support and analysis. We thank the CHOP Virtual PICU Systems team for assistance with PRISM III scoring.

Conflicts of interest

Dr. Neal J. Thomas reports personal fees from Discovery Labs, personal fees from Ikaria, and grants from the US Food and Drug Administration, all outside of the submitted work. The remaining authors declare no conflicts of interest.

Supplementary material

134_2015_3953_MOESM1_ESM.doc (88 kb)
Supplementary material 1 (DOC 88 kb)

References

  1. 1.
    Meduri GU, Headley AS, Golden E, Carson SJ, Umberger RA, Kelso T, Tolley EA (1998) Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome: a randomized controlled trial. JAMA 280:159–165CrossRefPubMedGoogle Scholar
  2. 2.
    Steinberg KP, Hudson LD, Goodman RB, Hough CL, Lanken PN, Hyzy R, Thompson BT, Ancukiewicz M (2006) Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med 354:1671–1684CrossRefPubMedGoogle Scholar
  3. 3.
    Meduri GU, Golden E, Freire AX, Taylor E, Zaman M, Carson SJ, Gibson M, Umberger R (2007) Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial. Chest 131:954–963CrossRefPubMedGoogle Scholar
  4. 4.
    Drago BB, Kimura D, Rovnaghi CR, Schwingshackl A, Rayburn M, Meduri GU, Anand KJ (2015) Double-blind, placebo-controlled pilot randomized trial of methylprednisolone infusion in pediatric acute respiratory distress syndrome. Pediatr Crit Care Med 16:e74–e81CrossRefPubMedGoogle Scholar
  5. 5.
    Kim SH, Hong SB, Yun SC, Choi WI, Ahn JJ, Lee YJ, Lee HB, Lim CM, Koh Y, Korean Society of Critical Care Medicine HNC (2011) Corticosteroid treatment in critically ill patients with pandemic influenza A/H1N1 2009 infection: analytic strategy using propensity scores. Am J Respir Crit Care Med 183:1207–1214CrossRefPubMedGoogle Scholar
  6. 6.
    Brun-Buisson C, Richard JC, Mercat A, Thiebaut AC, Brochard L, Group R-SAHNvR (2011) Early corticosteroids in severe influenza A/H1N1 pneumonia and acute respiratory distress syndrome. Am J Respir Crit Care Med 183:1200–1206CrossRefPubMedGoogle Scholar
  7. 7.
    Wong JJ, Loh TF, Testoni D, Yeo JG, Mok YH, Lee JH (2014) Epidemiology of pediatric acute respiratory distress syndrome in Singapore: risk factors and predictive respiratory indices for mortality. Front Pediatr 2:78PubMedCentralCrossRefPubMedGoogle Scholar
  8. 8.
    Peter JV, John P, Graham PL, Moran JL, George IA, Bersten A (2008) Corticosteroids in the prevention and treatment of acute respiratory distress syndrome (ARDS) in adults: meta-analysis. BMJ 336:1006–1009PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    Wong HR, Cvijanovich NZ, Allen GL, Thomas NJ, Freishtat RJ, Anas N, Meyer K, Checchia PA, Weiss SL, Shanley TP, Bigham MT, Banschbach S, Beckman E, Harmon K, Zimmerman JJ (2014) Corticosteroids are associated with repression of adaptive immunity gene programs in pediatric septic shock. Am J Respir Crit Care Med 189:940–946PubMedCentralCrossRefPubMedGoogle Scholar
  10. 10.
    Trachsel D, McCrindle BW, Nakagawa S, Bohn D (2005) Oxygenation index predicts outcome in children with acute hypoxemic respiratory failure. Am J Respir Crit Care Med 172:206–211CrossRefPubMedGoogle Scholar
  11. 11.
    Flori HR, Glidden DV, Rutherford GW, Matthay MA (2005) Pediatric acute lung injury: prospective evaluation of risk factors associated with mortality. Am J Respir Crit Care Med 171:995–1001CrossRefPubMedGoogle Scholar
  12. 12.
    Erickson S, Schibler A, Numa A, Nuthall G, Yung M, Pascoe E, Wilkins B, Paediatric Study Group, Australian, New Zealand Intensive Care Society (2007) Acute lung injury in pediatric intensive care in Australia and New Zealand: a prospective, multicenter, observational study. Pediatr Crit Care Med 8:317–323CrossRefPubMedGoogle Scholar
  13. 13.
    Khemani RG, Markovitz BP, Curley MA (2009) Characteristics of children intubated and mechanically ventilated in 16 PICUs. Chest 136:765–771PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Lopez-Fernandez Y, Azagra AM, de la Oliva P, Modesto V, Sanchez JI, Parrilla J, Arroyo MJ, Reyes SB, Pons-Odena M, Lopez-Herce J, Fernandez RL, Kacmarek RM, Villar J, Pediatric Acute Lung Injury Epidemiology and Natural History (PED-ALIEN) Network (2012) Pediatric Acute Lung Injury Epidemiology and Natural History study: incidence and outcome of the acute respiratory distress syndrome in children. Crit Care Med 40:3238–3245CrossRefPubMedGoogle Scholar
  15. 15.
    De Luca D, Piastra M, Chidini G, Tissieres P, Calderini E, Essouri S, Medina Villanueva A, Vivanco Allende A, Pons-Odena M, Perez-Baena L, Hermon M, Tridente A, Conti G, Antonelli M, Kneyber M, Respiratory Section of the European Society for Pediatric Neonatal Intensive Care (2013) The use of the Berlin definition for acute respiratory distress syndrome during infancy and early childhood: multicenter evaluation and expert consensus. Intensive Care Med 39:2083–2091CrossRefPubMedGoogle Scholar
  16. 16.
    Yehya N, Servaes S, Thomas NJ (2015) Characterizing degree of lung injury in pediatric acute respiratory distress syndrome. Crit Care Med 43:937–946CrossRefPubMedGoogle Scholar
  17. 17.
    Pediatric Acute Lung Injury Consensus Conference Group (2015) Pediatric acute respiratory distress syndrome: consensus recommendations from the pediatric acute lung injury consensus conference. Pediatr Crit Care Med 16:428–439CrossRefGoogle Scholar
  18. 18.
    Santschi M, Jouvet P, Leclerc F, Gauvin F, Newth CJ, Carroll CL, Flori H, Tasker RC, Rimensberger PC, Randolph AG, PALIVE Investigators, Pediatric Acute Lung Injury and Sepsis Investigators Network (PALISI), European Society of Pediatric and Neonatal Intensive Care (ESPNIC) (2010) Acute lung injury in children: therapeutic practice and feasibility of international clinical trials. Pediatr Crit Care Med 11:681–689CrossRefPubMedGoogle Scholar
  19. 19.
    Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS (2012) Acute respiratory distress syndrome: the Berlin definition. JAMA 307:2526–2533PubMedGoogle Scholar
  20. 20.
    Mager DE, Lin SX, Blum RA, Lates CD, Jusko WJ (2003) Dose equivalency evaluation of major corticosteroids: pharmacokinetics and cell trafficking and cortisol dynamics. J Clin Pharmacol 43:1216–1227CrossRefPubMedGoogle Scholar
  21. 21.
    Markovitz BP, Goodman DM, Watson RS, Bertoch D, Zimmerman J (2005) A retrospective cohort study of prognostic factors associated with outcome in pediatric severe sepsis: what is the role of steroids? Pediatr Crit Care Med 6:270–274CrossRefPubMedGoogle Scholar
  22. 22.
    Atkinson SJ, Cvijanovich NZ, Thomas NJ, Allen GL, Anas N, Bigham MT, Hall M, Freishtat RJ, Sen A, Meyer K, Checchia PA, Shanley TP, Nowak J, Quasney M, Weiss SL, Banschbach S, Beckman E, Howard K, Frank E, Harmon K, Lahni P, Lindsell CJ, Wong HR (2014) Corticosteroids and pediatric septic shock outcomes: a risk stratified analysis. PLoS One 9:e112702PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    Wernovsky G, Wypij D, Jonas RA, Mayer JE Jr, Hanley FL, Hickey PR, Walsh AZ, Chang AC, Castaneda AR, Newburger JW, Wessel DL (1995) Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants. A comparison of low-flow cardiopulmonary bypass and circulatory arrest. Circulation 92:2226–2235CrossRefPubMedGoogle Scholar
  24. 24.
    Goldstein B, Giroir B, Randolph A, International Consensus Conference on Pediatric Sepsis (2005) International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 6:2–8CrossRefPubMedGoogle Scholar
  25. 25.
    Yehya N, Topjian AA, Lin R, Berg RA, Thomas NJ, Friess SH (2014) High frequency oscillation and airway pressure release ventilation in pediatric respiratory failure. Pediatr Pulmonol 49:707–715PubMedCentralCrossRefPubMedGoogle Scholar
  26. 26.
    Yehya N, Topjian AA, Thomas NJ, Friess SH (2014) Improved oxygenation 24 hours after transition to airway pressure release ventilation or high-frequency oscillatory ventilation accurately discriminates survival in immunocompromised pediatric patients with acute respiratory distress syndrome. Pediatr Crit Care Med 15:e147–e156PubMedCentralCrossRefPubMedGoogle Scholar
  27. 27.
    Horan TC, Andrus M, Dudeck MA (2008) CDC/NHSN surveillance definition of health care-associated infection and criteria for specific types of infections in the acute care setting. Am J Infect Control 36:309–332CrossRefPubMedGoogle Scholar
  28. 28.
    Wong HR, Cvijanovich NZ, Anas N, Allen GL, Thomas NJ, Bigham MT, Weiss SL, Fitzgerald J, Checchia PA, Meyer K, Shanley TP, Quasney M, Hall M, Gedeit R, Freishtat RJ, Nowak J, Shekhar RS, Gertz S, Dawson E, Howard K, Harmon K, Beckman E, Frank E, Lindsell CJ (2015) Developing a clinically feasible personalized medicine approach to pediatric septic shock. Am J Respir Crit Care Med 191:309–315CrossRefPubMedGoogle Scholar
  29. 29.
    Pasquali SK, Hall M, Li JS, Peterson ED, Jaggers J, Lodge AJ, Marino BS, Goodman DM, Shah SS (2010) Corticosteroids and outcome in children undergoing congenital heart surgery: analysis of the pediatric health information systems database. Circulation 122:2123–2130PubMedCentralCrossRefPubMedGoogle Scholar
  30. 30.
    Annane D (2007) Glucocorticoids for ARDS: just do it! Chest 131:945–946CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg and ESICM 2015

Authors and Affiliations

  • Nadir Yehya
    • 1
    Email author
  • Sabah Servaes
    • 2
  • Neal J. Thomas
    • 3
  • Vinay M. Nadkarni
    • 1
  • Vijay Srinivasan
    • 1
  1. 1.Department of Anesthesiology and Critical Care MedicineChildren’s Hospital of Philadelphia and University of PennsylvaniaPhiladelphiaUSA
  2. 2.Department of RadiologyChildren’s Hospital of Philadelphia and University of PennsylvaniaPhiladelphiaUSA
  3. 3.Division of Pediatric Critical Care Medicine, Department of Pediatrics and Public Health SciencePenn State Hershey Children’s HospitalHersheyUSA

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