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Circulating cyclic adenosine monophosphate concentrations in milrinone treated paediatric patients after congenital heart surgery

Part of: Basic Science

Published online by Cambridge University Press:  03 February 2021

Katja M. Gist Open the ORCID record for Katja M. Gist [Opens in a new window] ,
Armin Korst ,
Stephanie J. Nakano ,
Brian L. Stauffer ,
Anis Karimpour-Fard ,
Wenru Zhou ,
Kristen Campbell ,
Michael F. Wempe ,
Carmen C. Sucharov  and
Shelley D. Miyamoto
Katja M. Gist*
Affiliation:
Department of Pediatrics, Division of Pediatric Cardiology, University of Colorado Denver, Anschutz Medical Campus, Children’s Hospital Colorado, Aurora, CO, USA
Armin Korst
Affiliation:
Research Institute, Children’s Hospital Colorado, Aurora, CO, USA
Stephanie J. Nakano
Affiliation:
Department of Pediatrics, Division of Pediatric Cardiology, University of Colorado Denver, Anschutz Medical Campus, Children’s Hospital Colorado, Aurora, CO, USA
Brian L. Stauffer
Affiliation:
Department of Medicine, Division of Cardiology, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
Anis Karimpour-Fard
Affiliation:
Department of Biostatistics and Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Wenru Zhou
Affiliation:
Department of Biostatistics and Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Kristen Campbell
Affiliation:
Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Michael F. Wempe
Affiliation:
Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
Carmen C. Sucharov
Affiliation:
Department of Medicine, Division of Cardiology, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
Shelley D. Miyamoto
Affiliation:
Department of Pediatrics, Division of Pediatric Cardiology, University of Colorado Denver, Anschutz Medical Campus, Children’s Hospital Colorado, Aurora, CO, USA
*
Address for correspondence: Katja M Gist, DO, MSCS, 13123 E 16th Ave, B100, Aurora, CO 80045, USA. Tel: +1 720 777 3614; Fax: +1 720 777 7290. E-mail: Katja.gist@childrenscolorado.org
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Abstract

Background:

Milrinone is a phosphodiesterase type 3 inhibitor that results in a positive inotropic effect in the heart through an increase in cyclic adenosine monophosphate. The purpose of this study was to evaluate circulating cyclic adenosine monophosphate and milrinone concentrations in milrinone treated paediatric patients undergoing congenital heart surgery.

Methods:

Single-centre prospective observational pilot study from January 2015 to December 2017 including children aged birth to 18 years. Milrinone and circulating cyclic adenosine monophosphate concentrations were measured at four time points through the first post-operative day and compared between patients with and without low cardiac output syndrome, defined using clinical and laboratory criteria.

Results:

Fifty patients were included. Nine (18%) developed low cardiac output syndrome. For all patients, 22% had single ventricle heart disease. The density and distribution of cyclic adenosine monophosphate concentrations varied between those with and without low cardiac output syndrome but were not significantly different. Milrinone concentrations increased in all patients. Paired t-tests demonstrated an increase in circulating cyclic adenosine monophosphate concentrations during the post-operative period among patients without low cardiac output syndrome.

Conclusions:

In this prospective observational study, circulating cyclic adenosine monophosphate concentrations increased in those without low cardiac output syndrome during the first 24 post-operative hours and milrinone concentrations increased in all patients. Further study of the utility of cyclic adenosine monophosphate concentrations in milrinone treated patients is necessary.

Keywords

Milrinonelow cardiac output syndromecAMPpediatricscongenital heart surgery
Type
Original Article
Information
Cardiology in the Young , Volume 31 , Issue 9 , September 2021 , pp. 1393 - 1400
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Copyright
© The Author(s), 2021. Published by Cambridge University Press

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References

Stroshane, RM, Koss, RF, Biddlecome, CE, Luczkowec, C, Edelson, J. Oral and intravenous pharmacokinetics of milrinone in human volunteers. J Pharm Sci 1984; 73: 1438–1441.CrossRefGoogle ScholarPubMed
DeWitt, ES, Black, KJ, Thiagarajan, RR, et al. Effects of commonly used inotropes on myocardial function and oxygen consumption under constant ventricular loading conditions. J Appl Physiol 2016; 121: 7–14.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Parr, GV, Blackstone, EH, Kirklin, JW. Cardiac performance and mortality early after intracardiac surgery in infants and young children. Circulation 1975; 51: 867–874.CrossRefGoogle ScholarPubMed
Wernovsky, G, Wypij, D, Jonas, RA, et al. Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants. A comparison of low-flow cardiopulmonary bypass and circulatory arrest. Circulation 1995; 92: 2226–2235.CrossRefGoogle ScholarPubMed
Ulate, KP, Yanay, O, Jeffries, H, Baden, H, Di Gennaro, JL, Zimmerman, J. An elevated low cardiac output syndrome score is associated ith morbidity in infants after congenital heart surgery. Pediatr Crit Care Med 2017; 18: 26–33.CrossRefGoogle Scholar
Gaies, M, Pasquali, SK, Donohue, JE, et al. Seminal postoperative complications and mode of death after pediatric cardiac surgical procedures. Ann Thorac Surg 2016; 102: 628–635.CrossRefGoogle ScholarPubMed
Bailey, JM, Hoffman, TM, Wessel, DL, et al. A population pharmacokinetic analysis of milrinone in pediatric patients after cardiac surgery. J Pharmacokinet Pharmacodyn 2004; 31: 43–59.CrossRefGoogle ScholarPubMed
Cox, ZL, Calcutt, MW, Morrison, TB, Akers, WS, Davis, MB, Lenihan, DJ. Elevation of plasma milrinone concentrations in stage D heart failure associated with renal dysfunction. J Cardiovasc Pharmacol Ther 2013; 18: 433–438.CrossRefGoogle Scholar
Gist, KM, Mizuno, T, Goldstein, SL, Vinks, A. Retrospective evaluation of milrinone pharmacokinetics in children with kidney injury. Ther Drug Monit 2015; 37: 792–796.CrossRefGoogle ScholarPubMed
Mizuno, T, Gist, KM, Gao, Z, et al. Developmental pharmacokinetics and age-appropriate dosing design of milrinone in neonates and infants with acute kidney injury following cardiac surgery. Clin Pharmacokinet 2019; 58: 793–803.CrossRefGoogle ScholarPubMed
Gist, KM, Cooper, DS, Wrona, J, et al. Acute kidney injury biomarkers predict an increase in serum milrinone concentration earlier than serum creatinine-defined acute kidney injury in infants after cardiac surgery. Ther Drug Monit 2018; 40: 186–194.CrossRefGoogle ScholarPubMed
Gist, KM, Goldstein, SL, Joy, MS, Vinks, AA. Milrinone dosing issues in critically Ill children with kidney injury: a review. J Cardiovasc Pharmacol 2016; 67: 175–181.CrossRefGoogle ScholarPubMed
Cone, J, Wang, S, Tandon, N, et al. Comparison of the effects of cilostazol and milrinone on intracellular cAMP levels and cellular function in platelets and cardiac cells. J Cardiovasc Pharmacol 1999; 34: 497–504.CrossRefGoogle ScholarPubMed
O’Brien, SM, Clarke, DR, Jacobs, JP, et al. An empirically based tool for analyzing mortality associated with congenital heart surgery. J Thorac Cardiovasc Surg 2009; 138: 1139–1153.CrossRefGoogle ScholarPubMed
Gaies, M, Gurney, J, Yen, A, et al. Vasoactive-inotropic score as a predictor of morbidity and mortality in infants after cardiopulmonary bypass. Pediatric Criti Care Med 2010; 11: 234–238.CrossRefGoogle ScholarPubMed
Ostchega, Y, Porter, KS, Hughes, J, Dillon, CF, Nwankwo, T. Resting pulse rate reference data for children, adolescents, and adults: United States, 1999–2008. Natl Health Stat Report 2011; 24: 1–16.Google Scholar
Kleinman, ME, de Caen, AR, Chameides, L, et al. Pediatric Basic and Advanced Life Support Chapter Collaborators. Part 10: Pediatric basic and advanced life support: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Circulation 2010; 122: S466–S515.CrossRefGoogle ScholarPubMed
Schwartz, GJ, Haycock, GB, Edelmann, CM, Jr., Spitzer, A. A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 1976; 58: 259–263.CrossRefGoogle ScholarPubMed
Sucharov, CC, Nakano, SJ, Slavov, D, et al. A PDE3A promoter polymorphism regulates cAMP-induced transcriptional activity in failing human myocardium. J Am Coll Cardiol 2019; 73: 1173–1184.CrossRefGoogle ScholarPubMed
Jimenez-Sabado, V, Herraiz-Martinez, A, Nolla-Colomer, C, et al. P5695 Inhibition of PDE3 but not PDE4 phosphodiesterases stimulate ryanodine receptor phosphorylation at Ser2808. Eur Heart J 2018; 39: ehy566.P5695.CrossRefGoogle Scholar
Shakur, Y, Fong, M, Hensley, J, et al. Comparison of the effects of cilostazol and milrinone on cAMP-PDE activity, intracellular cAMP and calcium in the heart. Cardiovasc Drugs Ther 2002; 16: 417–427.CrossRefGoogle ScholarPubMed
Lehnart, SE, Wehrens, XH, Reiken, S, et al. Phosphodiesterase 4D deficiency in the ryanodine-receptor complex promotes heart failure and arrhythmias. Cell 2005; 123: 25–35.CrossRefGoogle ScholarPubMed
Delaney, JW, Moltedo, JM, Dziura, JD, Kopf, GS, Snyder, CS. Early postoperative arrhythmias after pediatric cardiac surgery. J Thorac Cardiovasc Surg 2006; 131: 1296–1300.CrossRefGoogle ScholarPubMed
Gist, KM, Schuchardt, EL, Moroze, MK, et al. Tachyarrhythmia following norwood operation: a single-center experience. World J Pediatr Congenital Heart Surg 2014; 5: 206–210.CrossRefGoogle Scholar
McFerson, MC, McCanta, AC, Pan, Z, et al. Tachyarrhythmias after the Norwood procedure: relationship and effect of vasoactive agents. Pediatric Cardiol 2014; 35: 668–675.CrossRefGoogle ScholarPubMed
Smith, AH, Owen, J, Borgman, KY, Fish, FA, Kannankeril, PJ. Relation of milrinone after surgery for congenital heart disease to significant postoperative tachyarrhythmias. Am J Cardiol 2011; 108: 1620–1624.CrossRefGoogle ScholarPubMed
Gist, KM, Goldstein, SL, Joy, MS, Vinks, AA. Milrinone dosing issues in critically ill children with kidney injury: a review. J Cardiovasc Pharmacol 2016; 67: 175–181.CrossRefGoogle ScholarPubMed
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