#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Improved oxygenation following methylprednisolone therapy and survival in paediatric acute respiratory distress syndrome


Autoři: Rebecca B. Mitting aff001;  Samiran Ray aff002;  Michael Raffles aff001;  Helen Egan aff001;  Paul Goley aff001;  Mark Peters aff002;  Simon Nadel aff001
Působiště autorů: Paediatric Intensive Care Unit, Imperial College Healthcare NHS Trust, London, United Kingdom aff001;  Paediatric and Neonatal Intensive Care Unit, Great Ormond Street Hospital NHS Trust, London, United Kingdom aff002;  Respiratory, critical care and anaesthesia section, UCL Great Ormond Street Institute of Child Health, London, United Kingdom aff003
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0225737

Souhrn

Background

Methylprednisolone remains a commonly used ancillary therapy for paediatric acute respiratory distress syndrome (PARDS), despite a lack of level 1 evidence to justify its use. When planning prospective trials it is useful to define response to therapy and to identify if there is differential response in certain patients, i.e. existence of ‘responders’ and ‘non responders’ to therapy. This retrospective, observational study carried out in 2 tertiary referral paediatric intensive care units aims to characterize the change in Oxygen Saturation Index, following the administration of low dose methylprednisolone in a cohort of patients with PARDS, to identify what proportion of children treated demonstrated response, whether any particular characteristics predict response to therapy, and to determine if a positive response to corticosteroids is associated with reduced Paediatric Intensive Care Unit mortality.

Methods

All patients who received prolonged, low dose, IV methylprednisolone for the specific indication of PARDS over a 5-year period (2011–2016) who met the PALICC criteria for PARDS at the time of commencement of steroid were included (n = 78).OSI was calculated four times per day from admission until discharge from PICU (or death). Patients with ≥20% improvement in their mean daily OSI within 72 hours of commencement of methylprednisolone were classified as ‘responders’. Primary outcome measure was survival to PICU discharge.

Results

Mean OSI of the cohort increased until the day of steroid commencement then improved thereafter. 59% of patients demonstrated a response to steroids. Baseline characteristics were similar between responders and non-responders. Survival to PICU discharge was significantly higher in ‘responders’ (74% vs 41% OR 4.14(1.57–10.87) p = 0.004). On multivariable analysis using likely confounders, response to steroid was an independent predictor of survival to PICU discharge (p = 0.002). Non-responders died earlier after steroid administration than responders (p = 0.003).

Conclusions

An improvement in OSI was observed in 60% of patients following initiation of low dose methylprednisolone therapy in this cohort of patients with PARDS. Baseline characteristics fail to demonstrate a difference between responders and non-responders. A 20% improvement in OSI after commencement of methylprednisolone was independently predictive of survival, Prospective trials are needed to establish if there is a benefit from this therapy.

Klíčová slova:

Pediatrics – Immune response – Steroids – Steroid therapy – Intensive care units – Acute respiratory distress syndrome – Corticosteroid therapy – Neuromuscular blockade


Zdroje

1. Yehya N, Servaes S, Thomas NJ, Nadkarni VM, Srinivasan V. Corticosteroid exposure in paediatric acute respiratory distress syndrome. Intensive Care Med. 2015 Sept; 41(9): 1658–66. doi: 10.1007/s00134-015-3953-4 26160728

2. Santschi M, Jouvet P, Leclerc F, Gauvin F, Newth CJ, Carroll CL et al. Acute lung injury in children: therapeutic practice and feasibility of international clinical trials. Pediatr Crit Care Med (2010) 11(6):681–9. doi: 10.1097/PCC.0b013e3181d904c0 20228688

3. Tamburro RF, Kneyber MC. Pulmonary specific ancillary treatment for paediatric acute respiratory distress syndrome: proceedings from the paediatric acute lung injury consensus conference. Paediatr Critl Care Med: June 2015;16(5s): s61–S72.

4. Meduri GU, Bridges L, Shih MC, Marik PE, Siemenieniuk RAC, Kocak M. Prolonged glucocorticoid treatment is associated with improved ARDS outcomes: analysis of individual patients’ data from four randomised trials and trial-level meta-analysis of the updated literature. Intensive Care Med. 2016 May;42(5):829–40 doi: 10.1007/s00134-015-4095-4 26508525

5. Steinberg KP, Hudson LD, Goodman RB Hough CL, Lenka PN, Hyzy R et al; National Heart, Lung and Blood Institute Acute Respiratory Distress Syndrome Clinical Trials Network. N Eng J Med. 2006 Apr 20;354(16):1671–84

6. Meduri GU, Belenchia JM, Estes RJ, Wunderink RG, el Torky M, Leeper KVJ. Fibroproliferative phase of ARDS. Clinical findings and effects of corticosteroids. Chest. 1991 Oct;100(4): 943–52 doi: 10.1378/chest.100.4.943 1914609

7. Field-Ridley A, Dharmar M, Steinhorn D, McDonald C, Moran JP. ICU-acquired weakness is associated with differences in clinical outcomes in critically ill children. Pediatr Crit Care Med. 2016 Jan;17(1):53–7 doi: 10.1097/PCC.0000000000000538 26492063

8. Martinot A, Fourier C, Cremer R, Hu V, Deschildre A, Leclerc F. Short-course, high-dose corticosteroid treatment in six children with late ARDS. Pediatr Pulmonol. 1997;23:314–316 9141118

9. Peters MJ, Ray S, Kneyber M. Corticosteroids for paediatric ARDS: unjustified–even unjustifiable? Intensive Care Med. 2015 Sep;41(9):1685–7. doi: 10.1007/s00134-015-3963-2 26160730

10. Luo L, Shaver C, Zhao Z, Koyama T, Calfee CS, Bastarache JA et al. Clinical predictors of hospital mortality differ between direct and indirect ARDS. Chest 2017 Apr; 151(4):755–763 doi: 10.1016/j.chest.2016.09.004 27663180

11. Calfee CS, Janz Dr, Bernard GR, May AK Kangelaris KN, Matthay MA et al. Distinct molecular phenotypes of direct vs indirect ARDS in single-center and multicentre studies. Chest 2015 Jun;147(6):1539– doi: 10.1378/chest.14-2454 26033126

12. Goligher EC1, Kavanagh BP, Rubenfeld GD, Aahikari NK, Pinto R, Fan E et al. Oxygenation response to positive end expiratory pressure predicts mortality in acute respiratory distress syndrome. A secondary analysis of the LOVS and ExPress trials. Am J Respir Crit Care Med. 2014 Jul;190(1):70–6 1548. doi: 10.1164/rccm.201404-0688OC 24919111

13. Goligher EC, Kavanagh BP, Rubenfeld GD, Ferguson ND. Physiological Responsiveness should guide entry into randomized controlled trials. Am J Respir Crit Care Med. 2015 Dec; 192(12):1416–1419 doi: 10.1164/rccm.201410-1832CP 25580530

14. Gebistorf F, Karam O, Wetterslev J, Afshari A. Inhaled nitric oxide for acute respiratory distress syndrome (ARDS) in children and adults. Cochrane Database Syst Rev. 2016 Jun 27;(6):CD002787. doi: 10.1002/14651858.CD002787.pub3 27347773

15. Leteurtre S, Martinot A, Duhamel A, Leung D, Erickson S, Smith LS. Validation of paediatric logistic organ dysfunction (PELOD) score:prospective, observational multicentre study. Lancet 2003 Jul 18;362(9379):192–7 doi: 10.1016/S0140-6736(03)13908-6 12885479

16. Khemani RG, Smith LS, Zimmerman JJ, Erikson S. Paediatric Acute Respiratory Distress Syndrome: Definition, Incidence, and Epidemiology: Proceedings from the Paediatric Acute Lung Injury Consensus Conference. Pediatr Crit Care Med. 16(5_suppl):S23–S40, June 2015.

17. Khemani RG, Thomas NJ, Venkatachalam V, Scimeme JP, Berutti T, Schneider JB et al. Pediatric Acute Lung Injury and Sepsis Network Investigators (PALISI). Comparison of SpO2 to PaO2 based markers of lung disease severity for children with acute lung injury. Crit Care Med. 2012;40:1309–1316 doi: 10.1097/CCM.0b013e31823bc61b 22202709

18. Des Prez K, McNeil B, Wang C, Bastarache JA, Shaver CM, Ware LB. Oxygen Saturation Index predicts clinical outcomes in ARDS. Chest. 2017;152(6):1151–8 doi: 10.1016/j.chest.2017.08.002 28823812

19. Khemani RG, Rubin S, Belani S et al. Pulse oximetry vs PaO2 metrics in mechanically ventilated children: Berlin definition of ARDS and mortality risk. Intensive Care med. 2015; 41(1):94–102 doi: 10.1007/s00134-014-3486-2 25231293

20. Dowell JC, Thomas NJ and Yehya N; Association of response to inhaled nitric oxide and duration of mechanical ventilation in paediatric acute respiratory distress syndrome. Paediatric Critical Care Medicine 2017;18(11);1019–26

21. Goldman AP, Tasker RC, Hosiasson S, Henricksen T, Macrae DJ. Early response to inhaled nitric oxide and its relationship to outcome in children with severe hypoxemic respiratory failure. Chest. 1997 Sep;112(3):752–8. doi: 10.1378/chest.112.3.752 9315811

22. Guerin C, Reignier J, Richard JC et al. Prone positioning in severe acute respiratory distress syndrome. N Engl J Med 2013; 368(23): 2159–2168. doi: 10.1056/NEJMoa1214103 23688302

23. Meduri GU, Bridges L, Siemieniuk RAC, Kocak M. An exploratory reanalysis of the randomized trial on efficacy of corticosteroids as rescue therapy for the late phase of acute respiratory distress syndrome. Crit Care Med. 2018 Feb 9. doi: 10.1097/CCM.0000000000003021 [Epub ahead of print] 29432350

24. Onland W, de Jaegere AP, Offringa M, Van Kaam A. Systemic corticosteroid regimens for prevention of bronchopulmonary dyplasia in preterm infants. Cochran Database Syst Rev. 2017 Jan 31;1 CD010941.

25. O’Brien S, Nadel S, Almossawi O, Inwald DP. The Impact of Chronic Health conditions on length of stay and mortality in a General PICU. Pediatr Crit Care Med. 2017 Jan; 18(1):1-

26. O’Donnell D, Parslow R and Draper ES. Deprivation, ethnicity and prematurity in infant respiratory failure in PICU in the UK. Acta Paediatr. 2010 Aug;99(8):1186–91 doi: 10.1111/j.1651-2227.2010.01803.x 20236254

27. Annane D, Pastores S, Rochwerg Bet al. Guidelines for the diagnosis and management of critical illness related corticosteroid insufficiency (CIRCI) in critically ill patients (Part I): Society of Critical Care Medicine SCCM) and European Society of Intensive Care Medicine (ESICM) 2017. Critical Care Medicine. 45(12):2078–2088. doi: 10.1097/CCM.0000000000002737 28938253

28. Quasney M, Lopez-Fernanez Y, Santschi M, Watson RS. The outcomes of children with Pediatric acute respiratory distress syndrome: Proceedings from the pediatric acute lung injury consensus conference.Pediatr Crit Care Med: June 2015—Volume 16—Issue 5_suppl—p S118–S131

29. Wong JJ, Jit M, Sultant R, Mok YH, Yeo JG, Koh JWJC et al. Mortality in pediatric acute respiratory distress syndrome: A systematic review and meta-analysis. J Intensive Care Med. 2017 Jan 1:885066617705109

30. Valentine SL, Sapru A, Higgerson RA, Spinella PC, Flori HR, Graham DA et al. Pediatric Acute Lung Injury and Sepsis Investigator’s (PALISI) Network; Acute Respiratory Distress Syndrome Clinical Research Network (ARDSNet). Fluid balance in critically ill children with acute lung injury. Crit Care Med. 2012;40:2883–2889 doi: 10.1097/CCM.0b013e31825bc54d 22824936

31. Rowan CM, Loomis A, McArthur J, Smith LS, Gertz SJ, Fitzgeral JC et al. High-frequency Oscillatory Ventilation use and severe pediatric ARDS in the pediatric hematopoietic cell transplant recipient. Respir Care. 2018 Apr;63(4): 404–411 doi: 10.4187/respcare.05765 29279362

32. Madotto F, Pham T, Bellani G, Bos LD, Simonis FD, Fan E et al. Resolved versus confirmed ARDS after 24 h: insights from the LUNG SAFE study. Intensive Care Med. 2018 April. 2018 Apr 9. doi: 10.1007/s00134-018-5152-6 29632996

33. Kimura D, Saravia J, Rovnaghi CR, Meduri GU, Schwingshackl A Cormier SA et al. Plasma biomarker analysis in paediatric ARDS: Generating future framework from a pilot randomised control trial of Methylprednisolone:A framework for identifying plasma biomarkers related to clinical outcomes in paediatric ARDS. Front Paediatr 2016;4:31

34. Prone and Oscillation paediatric clinical trial. 2018. PROSPECT trial protocol [ONLINE] Available at: http://www.prospect-network.org/about/. Accessed May 9, 2018.


Článok vyšiel v časopise

PLOS One


2019 Číslo 11
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#