Korean Circulation Journal

The Korean Society of Cardiology (대한심장학회)
권호 표지
DOI QR코드

DOI QR Code

Safety and Efficacy of the Off-Label Use of Milrinone in Pediatric Patients with Heart Diseases

  • Lee, Joowon (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Kim, Gi Beom (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Kwon, Hye Won (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Kwon, Bo Sang (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Bae, Eun Jung (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Noh, Chung Il (Department of Pediatrics, Seoul National University Children's Hospital) ;
  • Lim, Hong Gook (Department of Thoracic and Cardiovascular Surgery, Seoul National University Children's Hospital) ;
  • Kim, Woong Han (Department of Thoracic and Cardiovascular Surgery, Seoul National University Children's Hospital) ;
  • Lee, Jeong Ryul (Department of Thoracic and Cardiovascular Surgery, Seoul National University Children's Hospital) ;
  • Kim, Yong Jin (Department of Thoracic and Cardiovascular Surgery, Seoul National University Children's Hospital)
  • Received : 2014.06.09
  • Accepted : 2014.08.19
  • Published : 2014.05.30
⟨ Previous Next ⟩

Abstract

Background and Objectives: Milrinone is often used in children to treat acute heart failure and prevent low cardiac output syndrome after cardiac surgery. Due to the lack of studies on the long-term milrinone use in children, the objective of this study was to assess the safety and efficacy of the current patterns of milrinone use for ${\geq}3$ days in infants and children with heart diseases. Subjects and Methods: We retrospectively reviewed the medical records of patients aged <13 years who received milrinone for ${\geq}3$ days from January 2005 to December 2012. Patients' characteristics including age, sex, height, weight, and body surface area were recorded. The following parameters were analyzed to identify the clinical application of milrinone: initial infusion rate, maintenance continuous infusion rate, total duration of milrinone therapy, and concomitantly infused inotropes. The safety of milrinone was determined based on the occurrence of adverse events such as hypotension, arrhythmia, chest pain, headache, hypokalemia, and thrombocytopenia. Results: We assessed 730 admissions (684 patients) during this period. Ventricular septal defects were the most common diagnosis (42.4%) in these patients. Milrinone was primarily used after cardiac surgery in 715 admissions (97.9%). The duration of milrinone treatment varied from 3 to 64.4 days (${\geq}7$ days in 149 admissions). Ejection fraction and fractional shortening of the left ventricle improved in patients receiving milrinone after cardiac surgery. Dose reduction of milrinone due to hypotension occurred in only 4 admissions (0.5%). Although diverse arrhythmias occurred in 75 admissions (10.3%), modification of milrinone infusion to manage arrhythmia occurred in only 3 admissions (0.4%). Multivariate analysis indicated that the development of arrhythmia was not influenced by the pattern of milrinone use. Conclusion: Milrinone was generally administered for ${\geq}3$ days in children with heart diseases. The use of milrinone for ${\geq}3$ days was effective in preventing low cardiac output after cardiac surgery when combined with other inotropes, suggesting that milrinone could be safely employed in pediatric patients with heart diseases.

Keywords

Acknowledgement

Supported by : Ministry of Food and Drug safety

References

  1. Colucci WS. Cardiovascular effects of milrinone. Am Heart J 1991;121(6 Pt 2):1945-7. https://doi.org/10.1016/0002-8703(91)90829-7
  2. Monrad ES, McKay RG, Baim DS, et al. Improvement in indexes of diastolic performance in patients with congestive heart failure treated with milrinone. Circulation 1984;70:1030-7. https://doi.org/10.1161/01.CIR.70.6.1030
  3. Monrad ES, Baim DS, Smith HS, Lanoue A, Brauwald E, Grossman W. Effects of milrinone on coronary hemodynamics and myocardial energetics in patients with congestive heart failure. Circulation 1985;71: 972-9. https://doi.org/10.1161/01.CIR.71.5.972
  4. Vogt W, Laer S. Drug use patterns for the prevention of paediatric low cardiac output syndrome in Europe. Intensive Care Med 2011;37:1390-1. https://doi.org/10.1007/s00134-011-2266-5
  5. Klugman D, Berger JT, Sable CA, He J, Khandelwal SG, Slonim AD. Pediatric patients hospitalized with myocarditis: a multi-institutional analysis. Pediatr Cardiol 2010;31:222-8. https://doi.org/10.1007/s00246-009-9589-9
  6. Assad-Kottner C, Chen D, Jahanyar J, et al. The use of continuous milrinone therapy as bridge to transplant is safe in patients with short waiting times. J Card Fail 2008;14:839-43. https://doi.org/10.1016/j.cardfail.2008.08.004
  7. Lindsay CA, Barton P, Lawless S, et al. Pharmacokinetics and pharmacodynamics of milrinone lactate in pediatric patients with septic shock. J Pediatr 1998;132:329-34. https://doi.org/10.1016/S0022-3476(98)70454-8
  8. Pasquali SK, Hall M, Slonim AD, et al. Off-label use of cardiovascular medications in children hospitalized with congenital and acquired heart disease. Circ Cardiovasc Qual Outcomes 2008;1:74-83. https://doi.org/10.1161/CIRCOUTCOMES.108.787176
  9. Chang AC, Atz AM, Wernovsky G, Burke RP, Wessel DL. Milrinone: systemic and pulmonary hemodynamic effects in neonates after cardiac surgery. Crit Care Med 1995;23:1907-14. https://doi.org/10.1097/00003246-199511000-00018
  10. 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. https://doi.org/10.1161/01.CIR.0000051365.81920.28
  11. Duggal B, Pratap U, Slavik Z, Kaplanova J, Macrae D. Milrinone and low cardiac output following cardiac surgery in infants: is there a direct myocardial effect? Pediatr Cardiol 2005;26:642-5. https://doi.org/10.1007/s00246-005-0881-z
  12. Seino Y, Momomura S, Takano T, Hayakawa H, Katoh K. Multicenter, double-blind study of intravenous milrinone for patients with acute heart failure in Japan. Japan Intravenous Milrinone Investigators. Crit Care Med 1996;24:1490-7. https://doi.org/10.1097/00003246-199609000-00010
  13. Packer M, Carver JR, Rodeheffer RJ, et al. Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group. N Engl J Med 1991;325:1468-75. https://doi.org/10.1056/NEJM199111213252103
  14. Cuffe MS, Califf RM, Adams KF Jr, et al. Short-term intravenous milrinone for acute exacerbation of chronic heart failure: a randomized controlled trial. JAMA 2002;287:1541-7. https://doi.org/10.1001/jama.287.12.1541
  15. Fleming GA, Murray KT, Yu C, et al. Milrinone use is associated with postoperative atrial fibrillation after cardiac surgery. Circulation 2008; 118:1619-25. https://doi.org/10.1161/CIRCULATIONAHA.108.790162
  16. 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;108:1620-4. https://doi.org/10.1016/j.amjcard.2011.07.023
  17. Ramamoorthy C, Anderson GD, Williams GD, Lynn AM. Pharmacokinetics and side effects of milrinone in infants and children after open heart surgery. Anesth Analg 1998;86:283-9.
  18. Bishara T, Seto WT, Trope A, Parshuram CS. Use of milrinone in critically ill children. Can J Hosp Pharm 2010;63:420-8.
  19. Delaney JW, Moltedo JM, Dziura JD, Kopf GS, Snyder CS. Early postoperative arrhythmias after pediatric cardiac surgery. J Thorac Cardiovasc Surg 2006;131:1296-300. https://doi.org/10.1016/j.jtcvs.2006.02.010
  20. Grosse-Wortmann L, Kreitz S, Grabitz RG, et al. Prevalence of and risk factors for perioperative arrhythmias in neonates and children after cardiopulmonary bypass: continuous holter monitoring before and for three days after surgery. J Cardiothorac Surg 2010;5:85. https://doi.org/10.1186/1749-8090-5-85
  21. Zampi JD, Hirsch JC, Gurney JG, et al. Junctional ectopic tachycardia after infant heart surgery: incidence and outcomes. Pediatr Cardiol 2012;33:1362-9. https://doi.org/10.1007/s00246-012-0348-y
  22. Makhoul M, Oster M, Fischbach P, Das S, Deshpande S. Junctional ectopic tachycardia after congenital heart surgery in the current surgical era. Pediatr Cardiol 2013;34:370-4. https://doi.org/10.1007/s00246-012-0465-7
  23. Hoffman TM, Bush DM, Wernovsky G, et al. Postoperative junctional ectopic tachycardia in children: incidence, risk factors, and treatment. Ann Thorac Surg 2002;74:1607-11. https://doi.org/10.1016/S0003-4975(02)04014-6
  24. Miyake CY, Teele SA, Chen L, et al. In-hospital arrhythmia development and outcomes in pediatric patients with acute myocarditis. Am J Cardiol 2014;113:535-40. https://doi.org/10.1016/j.amjcard.2013.10.021
  25. Ichikawa R, Sumitomo N, Komori A, et al. The follow-up evaluation of electrocardiogram and arrhythmias in children with fulminant myocarditis. Circ J 2011;75:932-8. https://doi.org/10.1253/circj.CJ-10-0918
  26. Friedman RA, Moak JP, Garson A Jr. Clinical course of idiopathic dilated cardiomyopathy in children. J Am Coll Cardiol 1991;18:152-6. https://doi.org/10.1016/S0735-1097(10)80233-5
  27. Weerasinghe A, Taylor KM. The platelet in cardiopulmonary bypass. Ann Thorac Surg 1998;66:2145-52. https://doi.org/10.1016/S0003-4975(98)00749-8
  28. Kikura M, Lee MK, Safon RA, Bailey JM, Levy JH. The effects of milrinone on platelets in patients undergoing cardiac surgery. Anesth Analg 1995;81:44-8.
  29. McMahon CJ, Murchan H, Prendiville T, Burch M. Long-term support with milrinone prior to cardiac transplantation in a neonate with left ventricular noncompaction cardiomyopathy. Pediatr Cardiol 2007; 28:317-8. https://doi.org/10.1007/s00246-007-0020-0
  30. Price JF, Towbin JA, Dreyer WJ, et al. Outpatient continuous parenteral inotropic therapy as bridge to transplantation in children with advanced heart failure. J Card Fail 2006;12:139-43. https://doi.org/10.1016/j.cardfail.2005.11.001

Cited by

  1. Milrinone : Chest pain and ectopic atrial tachycardia: 2 case reports vol.1525, pp.1, 2014, https://doi.org/10.1007/s40278-014-4600-5
  2. Prematuration Culture with Phosphodiesterase Inhibitors After Vitrification May Induce Recovery of Mitochondrial Activity in Vitrified Mouse Immature Oocytes vol.16, pp.4, 2014, https://doi.org/10.1089/bio.2018.0010
  3. Vasopresores e inotrópicos: uso en pediatría vol.88, pp.1, 2014, https://doi.org/10.1016/j.acmx.2017.02.005
  4. The effect of milrinone on hemodynamic and gas exchange parameters in children vol.30, pp.1, 2014, https://doi.org/10.1017/s1047951119002865
  5. Effects of Vasopressin Infusion After Pediatric Cardiac Surgery: A Meta-analysis vol.42, pp.2, 2014, https://doi.org/10.1007/s00246-020-02496-8
  6. Cryopreservation of Porcine Embryos: Recent Updates and Progress vol.19, pp.3, 2014, https://doi.org/10.1089/bio.2020.0074