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

  • Muhammad M. Amanullah (a1), Mohammad Hamid (a2), Hashim M. Hanif (a1), Marium Muzaffar (a1), Maria T. Siddiqui (a1), Fatima Adhi (a1), Khabir Ahmad (a1), Shahjahan Khan (a3) and Zahra Hasan (a4)...

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.

Copyright

Corresponding author

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: muneer.amanullah@aku.edu

References

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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: 845857.
2. Wan, S, LeClerc, JL, Vincent, JL. Inflammatory response to cardiopulmonary bypass: mechanisms involved and possible therapeutic strategies. Chest 1997; 112: 676692.
3. Edmunds, LH Jr. Inflammatory response to cardiopulmonary bypass. Ann Thorac Surg 1998; 66: S12S16; discussion S25–S28.
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: 9961002.
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: 10681074.
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: 16721678.
7. Casey, LC. Role of cytokines in the pathogenesis of cardiopulmonary-induced multisystem organ failure. Ann Thorac Surg 1993; 56: S92S96.
8. Drusin, LM, Engle, MA, Hagstrom, JW, Schwartz, MS. The postpericardiotomy syndrome: a six-year epidemiologic study. N Engl J Med 1965; 272: 597602.
9. Tarnok, A, Schneider, P. Pediatric cardiac surgery with cardiopulmonary bypass: pathways contributing to transient systemic immune suppression. Shock 2001; 16: 2432.
10. Chaney, MA. Corticosteroids and cardiopulmonary bypass: a review of clinical investigations. Chest 2002; 121: 921931.
11. Paparella, D, Yau, TM, Young, E. Cardiopulmonary bypass induced inflammation: pathophysiology and treatment. An update. Eur J Cardiothorac Surg 2002; 21: 232244.
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: 17121716.
13. Stayer, SA, Diaz, LK, East, DL, et al. Changes in respiratory mechanics among infants undergoing heart surgery. Anesth Analg 2004; 98: 4955.
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: 387393.
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.
16. Brunow de Carvalho, W, Fonseca, MC. Steroids use in pediatric cardiac surgery: more questions. Pediatr Crit Care Med 2007; 8: 503504.
17. Janeway, CA Jr, Flavell, RA. Immunology at Yale. Immunol Res 1999; 19: 105106.
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: 343348.
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: 437441.
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: 28232828.
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: 728732.
22. Checchia, PA, Backer, CL, Bronicki, RA, et al. Dexamethasone reduces postoperative troponin levels in children undergoing cardiopulmonary bypass. Crit Care Med 2003; 31: 17421745.
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: 595600.
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: 262268.
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: 6265.
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: 7477.
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: 4953.
28. Mayumi, H, Zhang, QW, Nakashima, A, et al. Synergistic immunosuppression caused by high-dose methylprednisolone and cardiopulmonary bypass. Ann Thorac Surg 1997; 63: 129137.
29. Morton, JR, Hiebert, CA, Lutes, CA, White, RL. Effect of methylprednisolone on myocardial preservation during coronary artery surgery. Am J Surg 1976; 13: 419422.
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: 13041313.
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: 14901495.
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: 499502.
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: 435442.

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