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Effect of steroids on inflammatory markers and clinical parameters in congenital open heart surgery: a randomised controlled trial

Published online by Cambridge University Press:  28 April 2015

Muhammad M. Amanullah ,
Mohammad Hamid ,
Hashim M. Hanif ,
Marium Muzaffar ,
Maria T. Siddiqui ,
Fatima Adhi ,
Khabir Ahmad ,
Shahjahan Khan  and
Zahra Hasan
Muhammad M. Amanullah*
Affiliation:
Department of Surgery, AKUH, Karachi, Pakistan
Mohammad Hamid
Affiliation:
Department of Cardiac Anaesthesia, AKUH, Karachi, Pakistan
Hashim M. Hanif
Affiliation:
Department of Surgery, AKUH, Karachi, Pakistan
Marium Muzaffar
Affiliation:
Department of Surgery, AKUH, Karachi, Pakistan
Maria T. Siddiqui
Affiliation:
Department of Surgery, AKUH, Karachi, Pakistan
Fatima Adhi
Affiliation:
Department of Surgery, AKUH, Karachi, Pakistan
Khabir Ahmad
Affiliation:
Department of Surgery, AKUH, Karachi, Pakistan
Shahjahan Khan
Affiliation:
Medical College, Agha Khan University, AKUH, Karachi, Pakistan
Zahra Hasan
Affiliation:
Department of Pathology and Microbiology, AKUH, Karachi, Pakistan
*
Correspondence to: M. M. Amanullah, Congenital Cardiac Surgery, Department of Surgery, The Aga Khan University Hospital, Stadium Road, PO Box 3500, Karachi 74800, Pakistan. Tel: +922134930051, ext. 4708; Fax: +922134932095; E-mail: [email protected]
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Abstract

Background

Cardiopulmonary bypass is associated with systemic inflammatory response. Steroids suppress this response, although the therapeutic evidence remains controversial. We hypothesised that intravenous steroids in children undergoing open-heart surgery would decrease inflammation leading to better early post-operative outcomes. We conducted a randomised controlled trial to evaluate the trends in the levels of immunomodulators and their effects on clinical parameters.

Objective

To assess the effects of intravenous steroids on early post-operative inflammatory markers and clinical parameters in children undergoing open-heart surgery.

Materials and methods

A randomised controlled trial involving 152 patients, from one month up to 18 years of age, who underwent open-heart surgery for congenital heart disease from April 2010–2012 was carried out. Patients were randomised and administered either three scheduled intravenous pulse doses of dexamethasone (1 mg/kg) or placebo. Blood samples were drawn at four time intervals and serum levels of inflammatory cytokines – Interleukin-6, 8, 10, 18, and tumour necrosis factor-alpha – were measured. Clinical parameters were also assessed.

Results

Blood cytokine levels were compared between the dexamethasone (n=65) and placebo (n=64) groups. Interleukin-6 levels were lower at 6 and 24 hours post-operatively (p<0.001), and Interleukin-10 levels were higher 6 hours post-operatively (p<0.001) in the steroid group. Interleukin-8, 18, and tumour necrosis factor-alpha levels did not differ between the groups at any time intervals. The clinical parameters were similar in both the groups.

Conclusion

Dexamethasone caused quantitative suppression of Interleukin-6 and increased Interleukin-10 activation, contributing to reduced immunopathology, but it did not translate into clinical benefit in the short term.

Keywords

Cardiopulmonary bypasscongenital heart diseasesteroidsinflammatory markers
Type
Original Articles
Information
Cardiology in the Young , Volume 26 , Issue 3 , March 2016 , pp. 506 - 515
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Copyright
© Cambridge University Press 2015 

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References

1. Kirklin, JK, Westaby, S, Blackstone, EH, Kirklin, JW, Chenoweth, DE, Pacifico, AD. Complement and the damaging effects of cardiopulmonary bypass. J Thorac Cardiovasc Surg 1983; 86: 845–857.Google Scholar
2. Wan, S, LeClerc, JL, Vincent, JL. Inflammatory response to cardiopulmonary bypass: mechanisms involved and possible therapeutic strategies. Chest 1997; 112: 676–692.Google Scholar
3. Edmunds, LH Jr. Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg 1998; 66: S12–S16; discussion S25–S28.Google Scholar
4. Hoffman, TM, Wernovsky, G, Atz, AM, et al. Efficacy and safety of milrinone in preventing low cardiac output syndrome in infants and children after corrective surgery for congenital heart disease. Circulation 2003; 107: 996–1002.Google Scholar
5. Kilger, E, Weis, F, Briegel, J, 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. Crit Care Med 2003; 31: 1068–1074.Google Scholar
6. Ando, M, Park, IS, Wada, N, Takahashi, Y. Steroid supplementation: a legitimate pharmacotherapy after neonatal open heart surgery. The Ann Thorac Surg 2005; 80: 1672–1678.Google Scholar
7. Casey, LC. Role of cytokines in the pathogenesis of cardiopulmonary-induced multisystem organ failure. Ann Thorac Surg 1993; 56: S92–S96.Google Scholar
8. Drusin, LM, Engle, MA, Hagstrom, JW, Schwartz, MS. The postpericardiotomy syndrome: a six-year epidemiologic study. N Engl J Med 1965; 272: 597–602.Google Scholar
9. Tarnok, A, Schneider, P. Pediatric cardiac surgery with cardiopulmonary bypass: pathways contributing to transient systemic immune suppression. Shock 2001; 16: 24–32.CrossRefGoogle ScholarPubMed
10. Chaney, MA. Corticosteroids and cardiopulmonary bypass: a review of clinical investigations. Chest 2002; 121: 921–931.Google Scholar
11. Paparella, D, Yau, TM, Young, E. Cardiopulmonary bypass induced inflammation: pathophysiology and treatment. An update. Eur J Cardiothorac Surg 2002; 21: 232–244.Google Scholar
12. el-Barbary, M, Khabar, KS. Soluble tumor necrosis factor receptor p55 predicts cytokinemia and systemic inflammatory response after cardiopulmonary bypass. Crit Care Med 2002; 30: 1712–1716.Google Scholar
13. Stayer, SA, Diaz, LK, East, DL, et al. Changes in respiratory mechanics among infants undergoing heart surgery. Anesth Analg 2004; 98: 49–55.Google Scholar
14. Duval, EL, Kavelaars, A, Veenhuizen, L, van Vught, AJ, van de Wal, HJ, Heijnen, CJ. Pro- and anti-inflammatory cytokine patterns during and after cardiac surgery in young children. Eur J Pediatr 1999; 158: 387–393.Google Scholar
15. Hasan, Z, Zaidi, I, Jamil, B, Khan, MA, Kanji, A, Hussain, R. Elevated ex vivo monocyte chemotactic protein-1 (CCL2) in pulmonary as compared with extra-pulmonary tuberculosis. BMC Immunol 2005; 6: 14.Google Scholar
16. Brunow de Carvalho, W, Fonseca, MC. Steroids use in pediatric cardiac surgery: more questions. Pediatr Crit Care Med 2007; 8: 503–504.Google Scholar
17. Janeway, CA Jr, Flavell, RA. Immunology at Yale. Immunol Res 1999; 19: 105–106.Google Scholar
18. Trotter, A, Mück, K, Grill, HJ, Schirmer, U, Hannekum, A, Lang, D. Gender-related plasma levels of progesterone, interleukin-8 and interleukin-10 during and after cardiopulmonary bypass in infants and children. Crit Care 2001; 5: 343–348.Google Scholar
19. Varan, B, Tokel, K, Mercan, S, Dönmez, A, Aslamaci, S. Systemic inflammatory response related to cardiopulmonary bypass and its modification by methyl prednisolone: high dose versus low dose. Pediatr Cardiol 2002; 23: 437–441.Google Scholar
20. Schroeder, VA, Pearl, JM, Schwartz, SM, Shanley, TP, Manning, PB, Nelson, DP. Combined steroid treatment for congenital heart surgery improves oxygen delivery and reduces postbypass inflammatory mediator expression. Circulation 2003; 107: 2823–2828.Google Scholar
21. Lindberg, L, Forsell, C, Jögi, P, Olsson, AK. Effects of dexamethasone on clinical course, C-reactive protein, S100B protein and von Willebrand factor antigen after paediatric cardiac surgery. Br J Anaesth 2003; 90: 728–732.Google Scholar
22. Checchia, PA, Backer, CL, Bronicki, RA, et al. Dexamethasone reduces postoperative troponin levels in children undergoing cardiopulmonary bypass. Crit Care Med 2003; 31: 1742–1745.Google Scholar
23. Gessler, P, Hohl, V, Carrel, T, et al. Administration of steroids in pediatric cardiac surgery: impact on clinical outcome and systemic inflammatory response. Pediatr Cardiol 2005; 26: 595–600.Google Scholar
24. Niazi, Z, Flodin, P, Joyce, L, Smith, J, Mauer, H, Lillehei, RC. Effects of glucocorticosteroids in patients undergoing coronary artery bypass surgery. Chest 1979; 76: 262–268.Google Scholar
25. Wilson, NJ, Webber, SA, Patterson, MW, Sandor, GG, Tipple, M, LeBlanc, J. Double-blind placebo-controlled trial of corticosteroids in children with postpericardiotomy syndrome. Pediatr Cardiol 1994; 15: 62–65.Google Scholar
26. Iqbal, MP, Sharif, HM, Mehboobali, N, Yousuf, FA, Khan, AH, Sellke, FW. N-acetyl-B-D-glucosaminidase and inflammatory response after cardiopulmonary bypass. J Coll Physicians Surg Pak 2008; 18: 74–77.Google Scholar
27. Seghaye, MC, Engelhardt, W, Grabitz, RG, et al. Multiple system organ failure after open heart surgery in infants and children. Thorac Cardiovasc Surg 1993; 41: 49–53.Google Scholar
28. Mayumi, H, Zhang, QW, Nakashima, A, et al. Synergistic immunosuppression caused by high-dose methylprednisolone and cardiopulmonary bypass. Ann Thorac Surg 1997; 63: 129–137.Google Scholar
29. Morton, JR, Hiebert, CA, Lutes, CA, White, RL. Effect of methylprednisolone on myocardial preservation during coronary artery surgery. Am J Surg 1976; 13: 419–422.Google Scholar
30. Yeh, TF, Lin, YJ, Lin, HC. Outcomes at school age after postnatal dexamethasone therapy for lung disease of prematurity. N Engl J Med 2004; 350: 1304–1313.Google Scholar
31. Bronicki, RA, Backer, CL, Baden, HP, Mavroudis, C, Crawford, SE, Green, TP. Dexamethasone reduces the inflammatory response to cardiopulmonary bypass in children. Ann Thorac Surg 2000; 69: 1490–1495.Google Scholar
32. Amanullah, M, Hasan, A, Roe, J, Dunning, J. Is prophylactic administration of steroids of benefit to children undergoing cardiac surgery? Interact Cardiovasc Thorac Surg 2004; 3: 499–502.Google Scholar
33. Scrascia, G, Rotunno, C, Guida, P, et al. Perioperative steroids administration in pediatric cardiac surgery: a meta-analysis of randomized controlled trials. Pediatr Crit Care Med 2014; 15: 435–442.Google Scholar