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Meta-Analysis
. 2020 Oct 12;10(10):CD013101.
doi: 10.1002/14651858.CD013101.pub2.

Prophylactic corticosteroids for paediatric heart surgery with cardiopulmonary bypass

Ben Gibbison  1 , José Carlos Villalobos Lizardi  2 , Karla Isis Avilés Martínez  2 , Daniel P Fudulu  3 , Miguel Angel Medina Andrade  4 , Giordano Pérez-Gaxiola  5 , Alvin Wl Schadenberg  6 , Serban C Stoica  7 , Stafford L Lightman  8 , Gianni D Angelini  3 , Barnaby C Reeves  9
Affiliations
Meta-Analysis

Prophylactic corticosteroids for paediatric heart surgery with cardiopulmonary bypass

Ben Gibbison et al. Cochrane Database Syst Rev. .

Abstract

Background: Corticosteroids are routinely given to children undergoing cardiac surgery with cardiopulmonary bypass (CPB) in an attempt to ameliorate the inflammatory response. Their use is still controversial and the decision to administer the intervention can vary by centre and/or by individual doctors within that centre.

Objectives: This review is designed to assess the benefits and harms of prophylactic corticosteroids in children between birth and 18 years of age undergoing cardiac surgery with CPB.

Search methods: We searched CENTRAL, MEDLINE, Embase and Conference Proceedings Citation Index-Science in June 2020. We also searched four clinical trials registers and conducted backward and forward citation searching of relevant articles.

Selection criteria: We included studies of prophylactic administration of corticosteroids, including single and multiple doses, and all types of corticosteroids administered via any route and at any time-point in the perioperative period. We excluded studies if steroids were administered therapeutically. We included individually randomised controlled trials (RCTs), with two or more groups (e.g. multi-drug or dose comparisons with a control group) but not 'head-to-head' trials without a placebo or a group that did not receive corticosteroids. We included studies in children, from birth up to 18 years of age, including preterm infants, undergoing cardiac surgery with the use of CPB. We also excluded studies in patients undergoing heart or lung transplantation, or both; studies in patients already receiving corticosteroids; in patients with abnormalities of the hypothalamic-pituitary-adrenal axis; and in patients given steroids at the time of cardiac surgery for indications other than cardiac surgery.

Data collection and analysis: We used the Covidence systematic review manager to extract and manage data for the review. Two review authors independently assessed studies for inclusion, extracted data, and assessed risks of bias. We resolved disagreements by consensus or by consultation with a third review author. We assessed the certainty of evidence with GRADE.

Main results: We found 3748 studies, of which 888 were duplicate records. Two studies had the same clinical trial registration number, but reported different populations and interventions. We therefore included them as separate studies. We screened titles and abstracts of 2868 records and reviewed full text reports for 84 studies to determine eligibility. We extracted data for 13 studies. Pooled analyses are based on eight studies. We reported the remaining five studies narratively due to zero events for both intervention and placebo in the outcomes of interest. Therefore, the final meta-analysis included eight studies with a combined population of 478 participants. There was a low or unclear risk of bias across the domains. There was moderate certainty of evidence that corticosteroids do not change the risk of in-hospital mortality (five RCTs; 313 participants; risk ratio (RR) 0.83, 95% confidence interval (CI) 0.33 to 2.07) for children undergoing cardiac surgery with CPB. There was high certainty of evidence that corticosteroids reduce the duration of mechanical ventilation (six RCTs; 421 participants; mean difference (MD) 11.37 hours lower, 95% CI -20.29 to -2.45) after the surgery. There was high-certainty evidence that the intervention probably made little to no difference to the length of postoperative intensive care unit (ICU) stay (six RCTs; 421 participants; MD 0.28 days lower, 95% CI -0.79 to 0.24) and moderate-certainty evidence that the intervention probably made little to no difference to the length of the postoperative hospital stay (one RCT; 176 participants; mean length of stay 22 days; MD -0.70 days, 95% CI -2.62 to 1.22). There was moderate certainty of evidence for no effect of the intervention on all-cause mortality at the longest follow-up (five RCTs; 313 participants; RR 0.83, 95% CI 0.33 to 2.07) or cardiovascular mortality at the longest follow-up (three RCTs; 109 participants; RR 0.40, 95% CI 0.07 to 2.46). There was low certainty of evidence that corticosteroids probably make little to no difference to children separating from CPB (one RCT; 40 participants; RR 0.20, 95% CI 0.01 to 3.92). We were unable to report information regarding adverse events of the intervention due to the heterogeneity of reporting of outcomes. We downgraded the certainty of evidence for several reasons, including imprecision due to small sample sizes, a single study providing data for an individual outcome, the inclusion of both appreciable benefit and harm in the confidence interval, and publication bias.

Authors' conclusions: Corticosteroids probably do not change the risk of mortality for children having heart surgery using CPB at any time point. They probably reduce the duration of postoperative ventilation in this context, but have little or no effect on the total length of postoperative ICU stay or total postoperative hospital stay. There was inconsistency in the adverse event outcomes reported which, consequently, could not be pooled. It is therefore impossible to provide any implications and policy-makers will be unable to make any recommendations for practice without evidence about adverse effects. The review highlighted the need for well-conducted RCTs powered for clinical outcomes to confirm or refute the effect of corticosteroids versus placebo in children having cardiac surgery with CPB. A core outcome set for adverse event reporting in the paediatric major surgery and intensive care setting is required.

Trial registration: ClinicalTrials.gov NCT00490828 NCT00590018 NCT02615262 NCT03229538.

PubMed Disclaimer

Conflict of interest statement

BG: Dr Gibbison's institution is in receipt of project grants from the UK National Institute of Health Research and the British Heart Foundation to carry out research surrounding the topics of cardiac surgery, perioperative care and perioperative hypothalamic‐pituitary‐adrenal function including corticosteroids.

JCVL: none known.

KIAM: none known.

DPF: none known.

MAMA: none known.

GPG: none known.

AWLS: none known.

SCS: none known.

SLL: none known.

GDA: none known.

BCR: Prof Barnaby Reeves is funded (both part salary and research consumables) in part by the Cardiovascular theme of the NIHR Bristol Biomedical Research Centre.

Figures

1
1
PRISMA diagram
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1: Corticosteroid vs Placebo, Outcome 1: In‐hospital postoperative mortality
1.2
1.2. Analysis
Comparison 1: Corticosteroid vs Placebo, Outcome 2: Duration of postoperative mechanical ventilation (hours)
1.3
1.3. Analysis
Comparison 1: Corticosteroid vs Placebo, Outcome 3: Length of postoperative ICU stay (days)
1.4
1.4. Analysis
Comparison 1: Corticosteroid vs Placebo, Outcome 4: Length of postoperative hospital stay
1.5
1.5. Analysis
Comparison 1: Corticosteroid vs Placebo, Outcome 5: All‐cause mortality at longest follow‐up
1.6
1.6. Analysis
Comparison 1: Corticosteroid vs Placebo, Outcome 6: Cardiovascular mortality at longest follow‐up
1.7
1.7. Analysis
Comparison 1: Corticosteroid vs Placebo, Outcome 7: Failure to separate from CPB
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD013101

References

References to studies included in this review

Amanullah 2016 {published data only}
    1. Amanullah MM, Hamid M, Hanif HM, Muzaffar M, Siddiqui MT, Adhi F, et al. Effect of steroids on inflammatory markers and clinical parameters in congenital open heart surgery: a randomised controlled trial. Cardiology in the Young 2016;26(3):506-15. [DOI: ] - PubMed
Ando 2005 {published data only}
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Bronicki 2000 {published data only}
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Checchia 2003 {published data only}
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Dalili 2015 {published data only}
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Graham 2019 {published data only}
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Heying 2012 {published data only}
    1. Heying R, Wehage E, Schumacher K, Tassani P, Haas F, Lange R, et al. Dexamethasone pretreatment provides antiinflammatory and myocardial protection in neonatal arterial switch operation. Annals of Thoracic Surgery 2012;93(3):869-76. [DOI: ] - PubMed
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Keski Nisula 2015 {published data only}
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Lindberg 2003 {published data only}
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Malagon 2005 {published data only}
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Mott 2001 {published data only}
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Suominen 2017 {published data only}
    1. Jahnukainen T, Keski-Nisula J, Tainio J, Valkonen H, Patila T, Jalanko H, et al. Efficacy of corticosteroids in prevention of acute kidney injury in neonates undergoing cardiac surgery-A randomized controlled trial. Acta Anaesthesiologica Scandinavica 2018;17:17. [DOI: ] - PubMed
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References to studies excluded from this review

AbbasiTashnizi 2013 {published data only}
    1. Abbasi Tashnizi M, Soltani G, Moeinipour AA, Ayatollahi H, Tanha AS, Jarahi L, et al. Comparison between preoperative administration of methylprednisolone with its administration before and during congenital heart surgery on serum levels of IL-6 and IL-10. Iranian Red Crescent Medical Journal 2013;15(2):147-51. [DOI: ] - PMC - PubMed
AbdEl Hakeem 2003 {published data only}
    1. Abd El-Hakeem EE, Zareh ZE. Effects of dexamethasone on the incidence of shivering and recovery in patients undergoing valve replacement surgery. Egyptian Journal of Anaesthesia 2003;19(4):361-70.
Alten 2011 {published data only}
    1. Alten JA, Robert S, Borasino S, Dabal RJ. Random cortisol poorly predicts low cardiac output syndrome (LCOS) severity and hemodynamic response to hydrocortisone (HC) after cardiopulmonary bypass (CPB). Pediatric Critical Care Medicine 2011;1:S98. [DOI: ]
Anic 2004 {published data only}
    1. Anic D, Gasparovic H, Ivancan V, Batinic D. Effects of corticosteroids on inflammatory response following cardiopulmonary bypass. Croatian Medical Journal 2004;45(2):158-61. - PubMed
Brettner 2018 {published data only}
    1. Brettner F, Chappell D, Nebelsiek T, Hauer D, Schelling G, Becker BF, et al. Preinterventional hydrocortisone sustains the endothelial glycocalyx in cardiac surgery. Clinical hemorheology and microcirculation 2018;19:19. [DOI: ] - PubMed
Bronicki 2012 {published data only}
    1. Bronicki RA, Checchia PA, Stuart-Killion RB, Dixon DJ, Backer CL. The effects of multiple doses of glucocorticoids on the inflammatory response to cardiopulmonary bypass in children. World Journal for Pediatric & Congenital Heart Surgery 2012;3(4):439-45. [DOI: ] - PubMed
Bunge 2014 {published data only}
    1. Bunge JJ, Osch D, Dieleman JM, Jacob KA, Kluin J, van Dijk D, et al. Dexamethasone for the prevention of postpericardiotomy syndrome: A DExamethasone for Cardiac Surgery substudy. American Heart Journal 2014;168(1):126-31.e1. [DOI: ] - PubMed
Carrel 2017 {published data only}
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Celik 2004 {published data only}
    1. Celik JB, Gormus N, Okesli S, Gormus ZI, Solak H. Methylprednisolone prevents inflammatory reaction occurring during cardiopulmonary bypass: effects on TNF-alpha, IL-6, IL-8, IL-10. Perfusion 2004;19(3):185-91. - PubMed
Chaney 2001 {published data only}
    1. Chaney MA, Durazo-Arvizu RA, Nikolov MP, Blakeman BP, Bakhos M. Methylprednisolone does not benefit patients undergoing coronary artery bypass grafting and early tracheal extubation. Journal of Thoracic and Cardiovascular Surgery 2001;121(3):561-9. - PubMed
Clarizia 2011 {published data only}
    1. Clarizia NA, Manlhiot C, Schwartz SM, Sivarajan VB, Maratta R, Holtby HM, Gruenwald CE, et al. Improved outcomes associated with intraoperative steroid use in high-risk pediatric cardiac surgery. Annals of Thoracic Surgery 2011;91(4):1222-7. [DOI: ] - PubMed
Corbi 2001 {published data only}
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Crawford 2017 {published data only}
    1. Crawford JH, Hull MS, Borasino S, Steenwyk BL, Hock KM, Wall K, Alten JA. Adrenal insufficiency in neonates after cardiac surgery with cardiopulmonary bypass. Paediatric Anaesthesia 2017;27(1):77-84. [DOI: ] - PubMed
delaMotte 2014 {published data only}
    1. de la Motte L, Kehlet H, Vogt K, Nielsen CH, Groenvall JB, Nielsen HB, et al. Preoperative methylprednisolone enhances recovery after endovascular aortic repair: a randomized, double-blind, placebo-controlled clinical trial. Annals of Surgery 2014;260(3):540-8; discussion 548-9. [DOI: ] - PubMed
Demir 2009 {published data only}
    1. Demir T, Demir H, Tansel T, Kalko Y, Tireli E, Dayioglu E, et al. Influence of methylprednisolone on levels of neuron-specific enolase in cardiac surgery: a corticosteroid derivative to decrease possible neuronal damage. Journal of Cardiac Surgery 2009;24(4):397-403. [DOI: ] - PubMed
Dhar 2012 {published data only}
    1. Dhar S, Rahman Z, Hasan K, Hoque MF, Sultana A. Effect of pre-bypass methylprednisolone on post-operative renal function following correction of atrial septal defect under cardiopulmonary bypass. Mymensingh Medical Journal 2012;21(1):72-9. - PubMed
Dreher 2015 {published data only}
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Ebrahimi 2010 {published data only}
    1. Ebrahimi L, Kheirandish M, Foroughi M, Aghaeii Pour M, Ahmadi Nejad M, Samarghandi N, et al. The effect of methylprednizolone on platelet aggregation during cardiopulmonary bypass surgery. Vox Sanguinis 2010;1:446. [DOI: ]
Ebrahimi 2016 {published data only}
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Fernandez 2011 {published data only}
    1. Fernandez AB, Kilger E, Heyn J, Kur F, Vicol C, Reichart B, et al. Stress doses of hydrocortisone reduce severe systemic inflammatory response in patients undergoing cardiac surgery without cardiopulmonary bypass. Innovations: Technology and Techniques in Cardiothoracic and Vascular Surgery 2011;6(3):189. [DOI: ]
Fillinger 2002 {published data only}
    1. Fillinger MP, Rassias AJ, Guyre PM, Sanders JH, Beach M, Pahl J, et al. Glucocorticoid effects on the inflammatory and clinical responses to cardiac surgery. Journal of Cardiothoracic and Vascular Anesthesia 2002;16(2):163-9. - PubMed
Fontela 2011 {published data only}
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Garg 2014 {published data only}
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Gessler 2005 {published data only}
    1. Gessler P, Hohl V, Carrel T, Pfenninger J, Schmid ER, Baenziger O, et al. Administration of steroids in pediatric cardiac surgery: impact on clinical outcome and systemic inflammatory response. Pediatric Cardiology 2005;26(5):595-600. - PubMed
Glumac 2017 {published data only}
    1. Glumac S, Kardum G, Sodic L, Supe-Domic D, Karanovic N. Effects of dexamethasone on early cognitive decline after cardiac surgery: a randomised controlled trial. European Journal of Anaesthesiology 2017;34(11):776-84. [DOI: ] - PubMed
Graham 2011 {published data only}
    1. Graham EM, Atz AM, Butts RJ, Baker NL, Zyblewski SC, Deardorff RL, et al. Standardized preoperative corticosteroid treatment in neonates undergoing cardiac surgery - results from a randomized trial. Pediatric Critical Care Medicine 2011;1:S87. [DOI: ] - PMC - PubMed
    1. Graham EM, Atz AM, Butts RJ, Baker NL, Zyblewski SC, Deardorff RL, et al. Standardized preoperative corticosteroid treatment in neonates undergoing cardiac surgery: results from a randomized trial. Journal of Thoracic and Cardiovascular Surgery 2011;142(6):1523-9. [DOI: ] - PMC - PubMed
    1. Graham EM, Atz AM, McHugh KE, Butts RJ, Baker NL, Stroud RE, et al. Preoperative steroid treatment does not improve markers of inflammation after cardiac surgery in neonates: results from a randomized trial. Journal of Thoracic and Cardiovascular Surgery 2014;147(3):902-8. [DOI: ] - PMC - PubMed
Hauer 2012 {published data only}
    1. Hauer D, Weis F, Campolongo P, Schopp M, Beiras-Fernandez A, Strewe C, et al. Glucocorticoid-endocannabinoid interaction in cardiac surgical patients: relationship to early cognitive dysfunction and late depression. Reviews in the Neurosciences 2012;23(5-6):681-90. - PubMed
Heckmann 2002 {published data only}
    1. Heckmann M, Pohlandt F. Hydrocortisone in preterm infants. Pediatrics 2002;109(6):1184-5; author reply 1184-5. - PubMed
Juneja 2000 {published data only}
    1. Juneja R, Dhar A, Raizada A, Mehta Y. Methylprednisolone-immunomodulation and outcome following CPB. British Journal of Anaesthesia 2000;84(Suppl 1):9.
Keski Nisula 2016 {published data only}
    1. Keski-Nisula J, Pesonen E, Olkkola KT, Ahlroth T, Puntila J, Andersson S, et al. High-dose methylprednisolone has no benefit over moderate dose for the correction of Tetralogy of Fallot. Annals of Thoracic Surgery 2016;102(3):870-6. [DOI: ] - PubMed
Keski‐Nisula 2020 {published data only}
    1. Keski-Nisula J, Arvola O, Jahnukainen T, Andersson S, Pesonen E. Reduction of inflammation by high-dose methylprednisolone does not attenuate oxidative stress in children undergoing bidirectional Glenn Procedure with or without aortic arch or pulmonary arterial repair. Journal of Cardiothoracic and Vascular Anesthesia 2020;34(6):1542-7. - PubMed
Kilger 2003 {published data only}
    1. Kilger E, Weis F, Briegel J, Frey L, Goetz AE, Reuter D, et al. Stress doses of hydrocortisone reduce severe systemic inflammatory response syndrome and improve early outcome in a risk group of patients after cardiac surgery. Critical Care Medicine 2003;31(4):1068-74. - PubMed
Kilger 2011 {published data only}
    1. Kilger E, Heyn J, Beiras-Fernandez A, Luchting B, Weis F. Stress doses of hydrocortisone reduce systemic inflammatory response in patients undergoing cardiac surgery without cardiopulmonary bypass. Minerva Anestesiologica 2011;77(3):268-74. - PubMed
Liakopoulos 2007 {published data only}
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Liu 2007 {published data only}
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Loef 2004 {published data only}
    1. Loef BG, Henning RH, Epema AH, Rietman GW, Oeveren W, Navis GJ, et al. Effect of dexamethasone on perioperative renal function impairment during cardiac surgery with cardiopulmonary bypass. British Journal of Anaesthesia 2004;93(6):793-8. - PubMed
Maeda 2016 {published data only}
    1. Maeda T, Takeuchi M, Tachibana K, Nishida T, Kagisaki K, Imanaka H. Steroids improve hemodynamics in infants with adrenal insufficiency after cardiac surgery. Journal of Cardiothoracic and Vascular Anesthesia 2016;30(4):936-41. [DOI: ] - PubMed
Malagon 2005a {published data only}
    1. Malagon I, Onkenhout W, Klok M, Linthorst L, van der Poel PF, Bovill JG, et al. Dexamethasone reduces gut permeability in pediatric cardiac surgery.[Retraction in J Thorac Cardiovasc Surg. 2007 Sep;134(3):771; PMID: 17726800]. Journal of Thoracic Cardiovascular Surgery 2005;130(2):265-71. - PubMed
Mardani 2012 {published data only}
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    1. Mardani D, Bigdelian H. The effect of dexamethasone prophylaxis on postoperative delirium after cardiac surgery: a randomized trial. Journal of Research in Medical Sciences 2012;17(1 SPL.1):S113-9. - PMC - PubMed
McClure 2017 {published data only}
    1. McClure GR, Belley-Cote EP, Harlock J, Lamy A, Stacey M, Devereaux PJ, et al. Steroids in cardiac surgery (SIRS): infection substudy. European Heart Journal 2017;38(Suppl 1):1276. [DOI: ]
Modan Moses 2010 {published data only}
    1. Modan-Moses D, Kanety H, Dagan O, Ehrlich S, Lotan D, Pariente C, et al. Leptin and the post-operative inflammatory response. More insights into the correlation with the clinical course and glucocorticoid administration. Journal of Endocrinological Investigation 2010;33(10):701-6. [DOI: ] - PubMed
Murphy 2011 {published data only}
    1. Murphy G, Sherwani SS, Szokol J, Avram MJ. Small-dose dexamethasone improves patient-perceived quality of recovery after cardiac surgery. Anesthesia and Analgesia 2011;112(5 SUPPL. 1):S-41. [DOI: ]
    1. Murphy G, Sherwani SS, Szokol J, Avram MJ, Patel K. The effect of small-dose dexamethasone on clinical recovery after cardiac surgery. Anesthesia and Analgesia 2011;112(5 SUPPL. 1):S-40. [DOI: ]
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Namdari 2011 {published data only}
    1. Namdari M, Ghafarzadeh M, Nikoo MA. Efficacy of intramuscular methyl prednisolone in preventing restenosis after coronary artery stenting with bare-metal stainless steel stent: a double-blind, randomised, controlled clinical trial. Cardiovascular Journal of Africa 2011;22(2):67-9. [DOI: ] - PMC - PubMed
NCT00293592 {published data only}
    1. NCT00293592. Dexamethasone for cardiac surgery trial. clinicaltrials.gov/ct2/show/NCT00293592 (first posted 17 February 2006).
NCT00490828 {published data only}
    1. Influence of hydrocortisone on immunologic markers and health care related quality of life in patients after cardiac surgery. clinicaltrials.gov/ct2/show/NCT00490828 (first posted 25 June 2007).
NCT00879931 {published data only}
    1. NCT00879931. Influence of corticoids on renal function in cardiac surgery. clinicaltrials.gov/show/nct00879931 (first posted 13 April 2009).
NCT01296074 {published data only}
    1. NCT01296074. Corticosteroid prophylaxis on the cardiopulmonary bypass-induced systemic inflammatory response. clinicaltrials.gov/show/nct01296074 (first posted 15 February 2011).
NCT03002259 {published data only}
    1. NCT03002259. Dexamethasone for cardiac surgery-II trial. clinicaltrials.gov/show/nct03002259 (first posted 23 December 2016).
Oliver 2004 {published data only}
    1. Oliver WC Jr Nuttall GA, Orszulak TA, Bamlet WR, Abel MD, Ereth MH, et al. Hemofiltration but not steroids results in earlier tracheal extubation following cardiopulmonary bypass: a prospective, randomized double-blind trial. Anesthesiology 2004;101(2):327-39. - PubMed
Ottens 2013 {published data only}
    1. Ottens TH, Dieleman JM, Van Dijk D, Nijsten MW, Van Der Maaten JM. The influence of dexamethasone on intraoperative and postoperative lactate levels and glycaemic control in cardiac surgery patients. Applied Cardiopulmonary Pathophysiology 2013;17(2):185-6.
Paparella 2017 {published data only}
    1. Paparella D, Parolari A, Rotunno C, Vincent J, Myasoedova V, Guida P, et al. The effects of steroids on coagulation dysfunction induced by cardiopulmonary bypass: a Steroids in Cardiac Surgery (SIRS) trial substudy. Seminars in Thoracic and Cardiovascular Surgery 2017;29(1):35-44. [DOI: ] - PubMed
Poyrazoglu 2016 {published data only}
    1. Poyrazoglu HH, Duman Z, Demir S, Avsar MK, Atalay A, Ciftci B, et al. Investigating the impacts of preoperative steroid treatment on tumor necrosis factor-alpha and duration of extubation time underwent ventricular septal defect surgery. Balkan Medical Journal 2016;33(2):158-63. [DOI: ] - PMC - PubMed
Rahman 2010 {published data only}
    1. Rahman Z, Dhar S, Hasan K, Sultana A. Effect of pre-bypass methylprednisolone on post-operative renal function in cardiac ICU following correction of atrial septal deffect under cardiopulmonary bypass. Intensive Care Medicine 2010;2):S316. [DOI: ] - PubMed
Robert 2015 {published data only}
    1. Robert SM, Borasino S, Dabal RJ, Cleveland DC, Hock KM, Alten JA. Effect of postoperative steroids on cardiovascular/respiratory function in neonates undergoing cardiopulmonary bypass. Paediatric Critical Care Medicine 2015;16(7):629-36. [NCT01595386] - PubMed
    1. Robert SM, Borasino S, Dabal RJ, Cleveland DC, Hock KM, Alten JA. Postoperative hydrocortisone infusion reduces the prevalence of low cardiac output syndrome after neonatal cardiopulmonary bypass. Pediatric Critical Care Medicine 2015;16(7):629-36. [DOI: ] - PubMed
SanchezCanovas 2016 {published data only}
    1. Sanchez Canovas S, Garcia Candel A. Methylprednisolone in patients undergoing cardiopulmonary bypass (SIRS): a randomised, double-blind, placebo-controlled trial. Cirugia Cardiovascular 2016;23(5):270-1. [DOI: ]
Santarpino 2009 {published data only}
    1. Santarpino G, Caroleo S, Onorati F, Rubino AS, Dardano A, Gulletta E, et al. Inflammatory response after cardiopulmonary bypass: a randomized comparison between conventional hemofiltration and steroids. Journal of Cardiovascular Surgery 2009;50(4):555-64. - PubMed
Sauer 2013 {published data only}
    1. Sauer AC, Slooter AJ, Veldhuijzen DS, Van Eijk MM, Van Dijk D. Intraoperative dexamethasone and delirium after cardiac surgery: a randomized clinical trial. Critical Care 2013;2):S148. [DOI: ] - PubMed
Schelling 2004 {published data only}
    1. Schelling G, Kilger E, Roozendaal B, de Quervain DJ, Briegel J, Dagge A, et al. Stress doses of hydrocortisone, traumatic memories, and symptoms of posttraumatic stress disorder in patients after cardiac surgery: a randomized study. Bioligal Psychiatry 2004;55(6):627-33. - PubMed
Soltani 2013 {published data only}
    1. Soltani G, Abbasi Tashnizi M, Moeinipour AA, Ganjifard M, Esfahanizadeh J, Sepehri Shamloo A, et al. Comparing the effect of preoperative administration of methylprednisolone and its administration before and during surgery on the clinical outcome in pediatric open heart surgeries. Iranian Red Crecent Medical Journal 2013;15(6):483-7. [DOI: ] - PMC - PubMed
Suezawa 2013 {published data only}
    1. Suezawa T, Aoki A, Kotani M, Tago M, Kobayashi O, Hirasaki A, et al. Clinical benefits of methylprednisolone in off-pump coronary artery bypass surgery. General Thoracic and Cardiovascular Surgery 2013;61(8):455-9. [DOI: ] - PubMed
Suominen 2005 {published data only}
    1. Suominen PK, Dickerson HA, Moffett BS, Ranta SO, Mott AR, Price JF, et al. Hemodynamic effects of rescue protocol hydrocortisone in neonates with low cardiac output syndrome after cardiac surgery. Pediatric Critical Care Medicine 2005;6(6):655-9. - PubMed
Varan 2002 {published data only}
    1. Varan B, Tokel K, Mercan S, Donmez A, Aslamaci S. Systemic inflammatory response related to cardiopulmonary bypass and its modification by methyl prednisolone: high dose versus low dose. Pediatric Cardiology 2002;23(4):437-41. - PubMed
vonSpiegel 2002 {published data only}
    1. von Spiegel T, Giannaris S, Wietasch GJ, Schroeder S, Buhre W, Schorn B, et al. Effects of dexamethasone on intravascular and extravascular fluid balance in patients undergoing coronary bypass surgery with cardiopulmonary bypass. Anesthesiology 2002;96(4):827-34. - PubMed
Weis 2006 {published data only}
    1. Weis F, Kilger E, Roozendaal B, Quervain DJ, Lamm P, Schmidt M, et al. Stress doses of hydrocortisone reduce chronic stress symptoms and improve health-related quality of life in high-risk patients after cardiac surgery: a randomized study. Journal of Thoracic and Cardiovascular Surgery 2006;131(2):277-82. - PubMed
    1. Weis F, Beiras-Fernandez A, Schelling G, Briegel J, Lang P, Hauer D, et al. Stress doses of hydrocortisone in high-risk patients undergoing cardiac surgery: effects on interleukin-6 to interleukin-10 ratio and early outcome. Critical Care Medicine 2009;37(5):1685-90. [DOI: ] - PubMed
Whitlock 2006 {published data only}
    1. Whitlock RP, Young E, Noora J, Farrokhyar F, Blackall M, Teoh KH. Pulse low dose steroids attenuate post-cardiopulmonary bypass SIRS; SIRS I. Journal of Surgery Research 2006;132(2):188-94. - PubMed
Withington 2014 {published data only}
    1. Withington DE, Fontela PS, Harrington KP, Tchervenkov C, Lands LC. A comparison of three dose timings of methylprednisolone in infant cardiopulmonary bypass. Springerplus 2014;3:484. [DOI: ] - PMC - PubMed
Yared 2000 {published data only}
    1. Yared JP, Starr NJ, Torres FK, Bashour CA, Bourdakos G, Piedmonte M, et al. Effects of single dose, postinduction dexamethasone on recovery after cardiac surgery. Annals of Thoracic Surgery 2000;69(5):1420-4. - PubMed
YasserMohamed 2009 {published data only}
    1. Yasser Mohamed A, Elmistekawy E, El-Serogy H. Effects of dexamethasone on pulmonary and renal functions in patients undergoing CABG with cardiopulmonary bypass. Seminars in Cardiothoracic and Vascular Anesthesia 2009;13(4):231-7. [DOI: ] - PubMed

References to ongoing studies

NCT02615262 {published data only}
    1. NCT02615262. Intraoperative dexamethasone in pediatric cardiac surgery. clinicaltrials.gov/ct2/show/NCT02615262 (first posted 26 November 2015).
STRESS 2021 {published and unpublished data}
    1. Hill KD, Baldwin HS, Bichel DP, Butts RJ, Chamberlain RC, Ellis AM, et al. Rationale and design of the steroids to reduce systemic inflammation after infant heart surgery (STRESS) trial. American Heart Journal 2020;220:192-202. - PMC - PubMed

Additional references

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