Nitric Oxide Administration During Pediatric Cardiopulmonary Bypass Surgery to Prevent Platelet Activation
Summary
Open heart surgery requires the use of a cardiopulmonary bypass (CPB) circuit. As blood flows across the artificial surfaces of the CPB circuit, platelets are activated and consumed. This activation results in a profound inflammatory reaction and need for transfusion. This reaction is intensified in younger, smaller patients undergoing longer, more complex open heart surgery. Nitric oxide is naturally released by vascular endothelial surfaces and acts as a signaling molecule which prevents platelet activation. The investigators hypothesize that the addition of the nitric oxide to the sweep gas of the oxygenator during cardiopulmonary bypass surgery will replace this natural endothelial function and thus prevent platelet activation and consumption. The investigators plan to test this hypothesis with a pilot double blinded, randomized trial of 40 patients less than a year of age undergoing cardiac surgery requiring CPB.
Timeline
- Start
- 2018-04-25
- Primary completion
- 2019-04-20
- Completion
- 2019-05-05
Publications
- Background Despotis GJ, Avidan MS, Hogue CW Jr. Mechanisms and attenuation of hemostatic activation during extracorporeal circulation. Ann Thorac Surg. 2001 Nov;72(5):S1821-31. doi: 10.1016/s0003-4975(01)03211-8.
- Background Chambers LA, Cohen DM, Davis JT. Transfusion patterns in pediatric open heart surgery. Transfusion. 1996 Feb;36(2):150-4. doi: 10.1046/j.1537-2995.1996.36296181928.x.
- Background Petaja J, Lundstrom U, Leijala M, Peltola K, Siimes MA. Bleeding and use of blood products after heart operations in infants. J Thorac Cardiovasc Surg. 1995 Mar;109(3):524-9. doi: 10.1016/S0022-5223(95)70284-9.
- Background Rinder CS, Bonan JL, Rinder HM, Mathew J, Hines R, Smith BR. Cardiopulmonary bypass induces leukocyte-platelet adhesion. Blood. 1992 Mar 1;79(5):1201-5.
- Background Wan S, LeClerc JL, Vincent JL. Inflammatory response to cardiopulmonary bypass: mechanisms involved and possible therapeutic strategies. Chest. 1997 Sep;112(3):676-92. doi: 10.1378/chest.112.3.676.
- Background Radomski MW, Vallance P, Whitley G, Foxwell N, Moncada S. Platelet adhesion to human vascular endothelium is modulated by constitutive and cytokine induced nitric oxide. Cardiovasc Res. 1993 Jul;27(7):1380-2. doi: 10.1093/cvr/27.7.1380.
- Background Naseem KM, Roberts W. Nitric oxide at a glance. Platelets. 2011;22(2):148-52. doi: 10.3109/09537104.2010.522629. Epub 2010 Nov 4.
- Background Annich GM, Meinhardt JP, Mowery KA, Ashton BA, Merz SI, Hirschl RB, Meyerhoff ME, Bartlett RH. Reduced platelet activation and thrombosis in extracorporeal circuits coated with nitric oxide release polymers. Crit Care Med. 2000 Apr;28(4):915-20. doi: 10.1097/00003246-200004000-00001.
- Background de Graaf JC, Banga JD, Moncada S, Palmer RM, de Groot PG, Sixma JJ. Nitric oxide functions as an inhibitor of platelet adhesion under flow conditions. Circulation. 1992 Jun;85(6):2284-90. doi: 10.1161/01.cir.85.6.2284.
- Background Konishi R, Shimizu R, Firestone L, Walters FR, Wagner WR, Federspiel WJ, Konishi H, Hattler BG. Nitric oxide prevents human platelet adhesion to fiber membranes in whole blood. ASAIO J. 1996 Sep-Oct;42(5):M850-3. doi: 10.1097/00002480-199609000-00111.
- Background Mellgren K, Friberg LG, Mellgren G, Hedner T, Wennmalm A, Wadenvik H. Nitric oxide in the oxygenator sweep gas reduces platelet activation during experimental perfusion. Ann Thorac Surg. 1996 Apr;61(4):1194-8. doi: 10.1016/0003-4975(96)00017-3.
- Background Chung A, Wildhirt SM, Wang S, Koshal A, Radomski MW. Combined administration of nitric oxide gas and iloprost during cardiopulmonary bypass reduces platelet dysfunction: a pilot clinical study. J Thorac Cardiovasc Surg. 2005 Apr;129(4):782-90. doi: 10.1016/j.jtcvs.2004.06.049.
- Background Checchia PA, Bronicki RA, Muenzer JT, Dixon D, Raithel S, Gandhi SK, Huddleston CB. Nitric oxide delivery during cardiopulmonary bypass reduces postoperative morbidity in children--a randomized trial. J Thorac Cardiovasc Surg. 2013 Sep;146(3):530-6. doi: 10.1016/j.jtcvs.2012.09.100. Epub 2012 Dec 8.
- Background James C, Millar J, Horton S, Brizard C, Molesworth C, Butt W. Nitric oxide administration during paediatric cardiopulmonary bypass: a randomised controlled trial. Intensive Care Med. 2016 Nov;42(11):1744-1752. doi: 10.1007/s00134-016-4420-6. Epub 2016 Sep 30.
- Background Eisses MJ, Chandler WL. Cardiopulmonary bypass parameters and hemostatic response to cardiopulmonary bypass in infants versus children. J Cardiothorac Vasc Anesth. 2008 Feb;22(1):53-9. doi: 10.1053/j.jvca.2007.06.006. Epub 2007 Aug 22.
- Background Miller BE, Mochizuki T, Levy JH, Bailey JM, Tosone SR, Tam VK, Kanter KR. Predicting and treating coagulopathies after cardiopulmonary bypass in children. Anesth Analg. 1997 Dec;85(6):1196-202. doi: 10.1097/00000539-199712000-00003.
- Background Williams GD, Bratton SL, Riley EC, Ramamoorthy C. Coagulation tests during cardiopulmonary bypass correlate with blood loss in children undergoing cardiac surgery. J Cardiothorac Vasc Anesth. 1999 Aug;13(4):398-404. doi: 10.1016/s1053-0770(99)90210-0.
- Background Berger JT, Holubkov R, Reeder R, Wessel DL, Meert K, Berg RA, Bell MJ, Tamburro R, Dean JM, Pollack MM; Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. Morbidity and mortality prediction in pediatric heart surgery: Physiological profiles and surgical complexity. J Thorac Cardiovasc Surg. 2017 Aug;154(2):620-628.e6. doi: 10.1016/j.jtcvs.2017.01.050. Epub 2017 Feb 10.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Nitric Oxide | Other / unclassified | 20 ppm | — |