Inflammatory response after pediatric cardiac catheter interventions- preliminary proposal for a prospective study

Background
CPB components have been implicated in eliciting the inflammatory response.

Other Factors eliciting the inflammatory response: Ischemiareperfusion injury

Heparinprotamine interactions
Surgical trauma Blood transfusion

Impact of inflammation on clinical outcomes

Allan CK, Newburger JW, McGrath E, Elder J, Psoinos C, Laussen PC, del Nido PJ, Wypij D, McGowan FX Jr. The relationship between inflammatory activation and clinical outcome after infant cardiopulmonary bypass. Anesth Analg. 2010 Nov;111(5):1244-51.

IL-6 and CRP increased significantly after surgery

IL-6 and IL-8 correlated with intensive care unit length of stay and postoperative blood product administration Greater preoperative cytokine and CRP production in younger infants did not correlate with postoperative outcomes Correlation between postoperative inflammatory mediator production and clinical course was statistically significant but clinically modest. The contribution of inflammatory mediator production to postoperative morbidity is relatively limited.

Madhok AB, Ojamaa K, Haridas V, Parnell VA, Pahwa S, Chowdhury D. . Cytokine response in children undergoing surgery for congenital heart disease. Pediatr Cardiol. 2006 Jul-Aug;27(4):408-13

Serum levels of interleukin (IL)-6, IL-8, and IL-10 increased significantly. Serum levels of TNF-alpha, IL-1 and IL-12 were not raised. IL-6 and IL-8 levels correlated with increased inotrope requirement.

Impact of anti-inflammatory therapy

Pediatr Cardiol. 2005 Sep-Oct;26(5):595-600. Administration of steroids in pediatric cardiac surgery: impact on clinical outcome and systemic inflammatory response. Gessler P, Hohl V, Carrel T, Pfenninger J, Schmid ER, Baenziger O, Prtre R.

Postoperative recovery was similar in patients treated with or without steroids when corrected for the type of cardiac surgery performed. After CPB, there was an inflammatory reaction, especially in patients with a long CPB time. Postoperative plasma levels of interleukin-8 were correlated with the duration of CPB time . Administration of steroids had no significant impact on the laboratory parameters of inflammation. Administration of prednisolone into the priming solution of the CPB circuit had no measurable influence on postoperative recovery and did not suppress the inflammatory response.

Circulation. 2010 Nov 23;122(21):2123-30. Corticosteroids and outcome in children undergoing congenital heart surgery: analysis of the Pediatric Health Information Systems database. Pasquali SK, Hall M, Li JS, Peterson ED, Jaggers J, Lodge AJ, Marino BS, Goodman DM, Shah SS.

In this observational analysis of children undergoing congenital heart surgery, there was no significant benefit associated with corticosteroids Corticosteroids may be associated with increased morbidity, particularly in lower-risk patients.

Inflammatory response in the absence of CPB

Inflammatory response is also seen after

Administration of anaesthesia Minimally invasive procedures
Inflamm Res. 2013 Jun 22. Comparison of inflammatory cytokine profiles in plasma of patients undergoing otorhinological surgery with propofol or isoflurane anesthesia. Mazoti MA, Braz MG, de Assis Golim M, Braz LG, Dias NH, Salvadori DM, Braz JR, Fecchio D. Anaesth Intensive Care. 2008 Jan;36(1):74-8. A comparison of the effect of total intravenous anaesthesia with propofol and remifentanil and inhalational anaesthesia with isoflurane on the release of pro- and anti-inflammatory cytokines in patients undergoing open cholecystectomy.Ke JJ, Zhan J, Feng XB, Wu Y, Rao Y, Wang YL.

Anaesthesia. 1999 Aug;54(8):733-8. The effect of anaesthesia and surgery on plasma cytokine production. Helmy SA, Wahby MA, El-Nawaway M.

Trans catheter aortic valve implantations and endovascular procedures elicit an inflammatory response

Eur Heart J. 2012 Jun;33(12):1459-68. Systemic inflammatory response syndrome predicts increased mortality in patients after transcatheter aortic valve implantation. Sinning JM, Scheer AC, Adenauer V, Ghanem A, Hammerstingl C, Schueler R, Mller C, VasaNicotera M, Grube E, Nickenig G, Werner N. J Vasc Surg. 2013 Mar;57(3):668-77. The impact of endograft type on inflammatory response after endovascular treatment of abdominal aortic aneurysm. Moulakakis KG, Alepaki M, Sfyroeras GS, Antonopoulos CN, Giannakopoulos TG, Kakisis J, Karakitsos P, Liapis CD.

Hypothesis:
Interventional cardiac catheterisation in children elicits an
inflammatory response.

The magnitude of inflammatory response elicited is less than that

seen after open heart operations.

Study Proposal I:
Inclusion criteria:
Children > 1year who undergo catheter based interventional procedures.

Outcome:
Levels of inflammatory markers before and after the procedure.

Study Proposal II
ASD device closure vs surgical closure
Include all children who undergo isolated closure of ASD, either surgically or with a device.

Outcome:
Inflammatory markers before and after the procedure.

Inflammatory markers:

Total leukocyte count

hs-CRP IL-6 IL-8 TNF-alpha IL-1beta

Sampling:

Baseline before induction

After induction , before start of procedure At the end of procedure 6 hours after 24 hours after

Possible confounding factors

Effect of anaesthesia
Blood transfusion Effects of antifibrinolytic agents