Abstract
Haemodynamic instability affects 22% to 29% of very low birth weight infants in the acute period following ligation of the ductus arteriosus and contributes to the mortality seen in this group. Since the sudden elevation of systemic vascular resistance has been recognised to be one of the factors contributing to this instability, milrinone, an afterload reducing agent, might potentially be of significant therapeutic benefit. This report presents the clinical course of an infant born at 26 weeks gestation who required surgical ligation of a haemodynamically significant patent ductus arteriosus after two unsuccessful 6-day courses of intravenous indomethacin. The post-operative period was characterized by oxygenation failure, rising blood pressure and echocardiographic signs indicative of diastolic dysfunction. The infant was successfully managed with milrinone, a phosphodiesterase inhibitor, which acts both as an “inodilator” and has lusitropy properties. Post-duct ligation haemodynamic instability in a preterm infant was successfully managed with milrinone. The role of afterload-reducing agents such as milrinone in this setting should, therefore, be systematically analyzed.
This is a preview of subscription content, log in via an institution to check access.
References
Artman M, Kithas PA, Wike JS et al (1989) Inotropic responses change during postnatal maturation in rabbit. Am J Physiol 255:H335–H342
Bailey JM, Miller BE, Lu W et al (1999) The pharmacokinetics of milrinone in pediatric patients after cardiac surgery. Anesthesiology 90:1012–1019
Barton P, Garcia J, Koutali A et al (1996) Hemodynamic effects of IV milrinone lactate in pediatric patients with septic shock. Chest 109:1302–1312
Benotti JR, Grossman W, Braunwald E (1978) Hemodynamic assessment of amrinone: a new inotropic agent. N Engl J Med 199:1373–1377
Binah O, Sodowick B, Vulliemoz Y et al (1986) The inotropic effects of amrinone and milrinone on neonatal and young canine cardiac muscle. Circulation 73:46–51
Chang AC, Atz AM, Wernovsky G et al (1995) Milrinone: systemic and pulmonary hemodynamic effects in neonates after cardiac surgery. Crit Care Med 23:1907–1914
Fowlie PW, Davis PG (2002) Prophylactic intravenous indomethacin for preventing mortality and morbidity in preterm infants. Cochrane Database Syst Rev. 2. Art. No.: CD000174. doi:10.1002/14651858.CD000174
Francis JV, Padmanabhan S, Jacques L et al (2010) Respiratory and cardiovascular morbidity in the first 48 hours post duct ligation surgery. Pediatric Academic Societies meeting, Vancouver E-PAS 2845.236
Harting MT, Blakely ML, Cox CS Jr et al (2008) Acute hemodynamic decompensation following patent ductus arteriosus ligation in premature infants. J Invest Surg 21:133–138
Hoffman TM, Wernovsky G, Atz AM et al (2003) Efficacy and safety of milrinone in preventing low cardiac output syndrome in infants and children after corrective surgery for congenital heart disease. Circulation 107:996–1002
Jentzer JH, LeJemtel TH, Sonnenblick EH et al (1981) Beneficial effect of amrinone on myocardial oxygen consumption during acute left ventricular failure in dogs. Am J Cardiol 48:75–83
McNamara PJ, Stewart L, Shivananda SP et al (2010) Patent ductus arteriosus ligation is associated with impaired left ventricular systolic performance in premature infants weighing less than 1,000 g. J Thorac Cardiovasc Surg 140:150–157
Noori S, Friedlich P, Seri I et al (2007) Changes in myocardial function and hemodynamics after ligation of the ductus arteriosus in preterm infants. J Pediatr 150:597–602
Ogawa S, Nakanishi T, Kamata K et al (1987) Effect of milrinone on myocardial mechanical function and cyclic AMP content in the fetal rabbit. Pediatr Res 22:282–285
Oquist NL, Strada SJ, Artman M (1992) Inotropic responses to selective (RO 20–1724 and SQ 65, 442) and nonselective (trequinsin) inhibitors of cyclic AMP-specific class IV phosphodiesterase in newborn, immature, and adult rabbit myocardium. Pediatr Res 31:300–304
Paradisis M, Evans N, Kluckow M et al (2006) Pilot study of milrinone for low systemic blood flow in very preterm infants. J Pediatr 148:306–313
Paradisis M, Jiang X, McLachlan AJ et al (2007) Population pharmacokinetics and dosing regimen design of milrinone in preterm infants. Arch Dis Child Fetal Neonatal Ed 92:F204–F209
Paradisis M, Evans N, Kluckow M et al (2009) Randomized trial of milrinone versus placebo for prevention of low systemic blood flow in very preterm infants. J Pediatr 154:189–195
Sehgal A, McNamara PJ (2007) Coronary artery hypo-perfusion is associated with impaired diastolic dysfunction in preterm infants after patent ductus arteriosus (PDA) ligation. Pediatric Academic Societies Annual Meeting E-PAS 615896.15
Sehgal A, Francis JV, James A et al (2010) Patent ductus arteriosus ligation and post-operative hemodynamic instability: case report and framework for enhanced neonatal care. Ind J Pediatr. doi:10.1007/s12098-010-0137-7
Silver PJ, Harris AJ, Canniff PC et al (1989) Phosphodiesterase isozyme inhibition, activation of the cyclic AMP system, and positive inotropy mediated by milrinone in isolated guinea pig cardiac muscle. J Cardiovasc Pharmacol 13:530–540
Stevens B, Johnston C, Pteryshen P et al (1996) Premature infant pain profile: development and initial validation. Clin J Pain 12:13–22
Wynands JE (1989) Amrinone: is it the inotrope of choice? J Cardiothorac Anesth 3:45–57
Conflict of interest
None.
Author information
Authors and Affiliations
Corresponding author
Additional information
Dr. Arvind Sehgal has more than 6 years of experience in functional echocardiography and accreditation in Clinician Performed Ultrasound by the Australasian Society for Ultrasound in Medicine.
Rights and permissions
About this article
Cite this article
Sehgal, A., Francis, J.V. & Lewis, A.I. Use of milrinone in the management of haemodynamic instability following duct ligation. Eur J Pediatr 170, 115–119 (2011). https://doi.org/10.1007/s00431-010-1296-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00431-010-1296-2