Relationship between Decrease in Urine Output following Treatment with Prostaglandin Inhibitors and PDA Closure

Abstract

Objective Prostaglandin inhibitors are used for the treatment of patent ductus arteriosus (PDA) and they often transiently decrease the urine output (UO) due to prostaglandin inhibition in the renal vasculature. We hypothesized that preterm infants whose renal vasculature shows greater sensitivity to prostaglandin inhibitors are likely to have ductal tissue with greater sensitivity to the same. Our objective was to determine whether the decrease in UO following treatment of PDA with a prostaglandin inhibitor is associated with a higher probability of PDA closure.

Study Design In a prospective, proof-of-concept, cohort study, we enrolled 40 preterm neonates with hemodynamically significant PDA (hsPDA), being treated with a prostaglandin inhibitor. The key predictor, UO, was measured at baseline and daily until 72 hours. We repeated echocardiography daily until PDA closure or the end of treatment. The key outcome was PDA closure. We compared “PDA-closed” (n = 28) and “PDA-open” (n = 12) groups for change in UO from baseline.

Results The median (Q1, Q3) percent decrease in UO (figures rounded off to integers) was greater in the “PDA-closed” versus “PDA-open” group: from baseline to 0 to 24 hours [−45% (−55%, +0.04%) vs. −15% (−28%, +49%)]; baseline to 24 to 48 hours [−41% (−53%, +14%) vs. −3% (−25%, +62%), p = 0.03] and baseline to 48 to 72 hours [−33% (−49%, +32%) vs. +21% (−7%, +98%), p = 0.02]. Decrease in UO preceded PDA closure. The “PDA-closed” group had significantly greater weight loss, despite a greater decrease in UO. A decrease in UO of 27 and 17% by 24 to 48 hours and 48 to 72 hours, respectively, best predicted PDA closure.

Conclusion A decrease in UO after treating hsPDA with a prostaglandin inhibitor is associated with successful closure of PDA.

Key Points

• Prostaglandin inhibition causes both decrease in urine output and PDA closure following medical treatment

• The association between drug-induced decrease in urine output and PDA closure has been inadequately studied.

• Decrease in urine output after treatment with prostaglandin inhibitors increases the chances of PDA closure.

Keywords

patent ductus arteriosus - preterm - prostaglandin inhibitor - oliguria

Ethical Approval

The protocol of the study was approved by the Institute Ethics Committee (approval number INT/IEC/2017/547 dated May 05, 2017).

Publication History

Received: 28 October 2021

Accepted: 13 April 2022

Accepted Manuscript online:
18 April 2022

Article published online:
31 May 2022

• References

• 1 Arlettaz R. Echocardiographic evaluation of patent ductus arteriosus in preterm infants. Front Pediatr 2017; 5: 147
• 2 Hermes-DeSantis ER, Clyman RI. Patent ductus arteriosus: pathophysiology and management. J Perinatol 2006; 26 (Suppl. 01) S14-S18 , discussion S22–S23
• 3 Mitra S, Florez ID, Tamayo ME. et al. Association of placebo, indomethacin, ibuprofen, and acetaminophen with closure of hemodynamically significant patent ductus arteriosus in preterm infants: a systematic review and meta-analysis. JAMA 2018; 319 (12) 1221-1238
• 4 Oncel MY, Erdeve O. Safety of therapeutics used in management of patent ductus arteriosus in preterm infants. Curr Drug Saf 2015; 10 (02) 106-112
• 5 Dang D, Wang D, Zhang C, Zhou W, Zhou Q, Wu H. Comparison of oral paracetamol versus ibuprofen in premature infants with patent ductus arteriosus: a randomized controlled trial. PLoS One 2013; 8 (11) e77888
• 6 Härkin P, Härmä A, Aikio O. et al. Paracetamol accelerates closure of the ductus arteriosus after premature birth: a randomized trial. J Pediatr 2016; 177: 72-77.e2
• 7 Ohlsson A, Shah PS. Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low birth weight infants. Cochrane Database Syst Rev 2018; 4: CD010061
• 8 Adamska E, Helwich E, Rutkowska M, Zacharska E, Piotrowska A. Comparison of the efficacy of ibuprofen and indomethacin in the treatment of patent ductus arteriosus in prematurely born infants. Med Wieku Rozwoj 2005; 9 (3 Pt 1): 335-354
• 9 El-Mashad AE, El-Mahdy H, El Amrousy D, Elgendy M. Comparative study of the efficacy and safety of paracetamol, ibuprofen, and indomethacin in closure of patent ductus arteriosus in preterm neonates. Eur J Pediatr 2017; 176 (02) 233-240
• 10 Ahamed MF, Verma P, Lee S. et al. Predictors of successful closure of patent ductus arteriosus with indomethacin. J Perinatol 2015; 35 (09) 729-734
• 11 Boo NY, Mohd-Amin I, Bilkis AA, Yong-Junina F. Predictors of failed closure of patent ductus arteriosus with indomethacin. Singapore Med J 2006; 47 (09) 763-768
• 12 Chorne N, Jegatheesan P, Lin E, Shi R, Clyman RI. Risk factors for persistent ductus arteriosus patency during indomethacin treatment. J Pediatr 2007; 151 (06) 629-634
• 13 Itabashi K, Ohno T, Nishida H. Indomethacin responsiveness of patent ductus arteriosus and renal abnormalities in preterm infants treated with indomethacin. J Pediatr 2003; 143 (02) 203-207
• 14 Tschuppert S, Doell C, Arlettaz-Mieth R. et al. The effect of ductal diameter on surgical and medical closure of patent ductus arteriosus in preterm neonates: size matters. J Thorac Cardiovasc Surg 2008; 135 (01) 78-82
• 15 Valerio E, Valente MR, Salvadori S, Frigo AC, Baraldi E, Lago P. Intravenous paracetamol for PDA closure in the preterm: a single-center experience. Eur J Pediatr 2016; 175 (07) 953-966
• 16 Yang CZ, Lee J. Factors affecting successful closure of hemodynamically significant patent ductus arteriosus with indomethacin in extremely low birth weight infants. World J Pediatr 2008; 4 (02) 91-96
• 17 Louis D, Dey A, Jain A. Association between changes in urine output and successful indomethacin treatment for patent ductus arteriosus in preterm neonates. J Paediatr Child Health 2021; 57 (04) 554-558