The Comparison of Efficiency of Oral Ibuprofen and Intravenous Indomethacin for Patent Ductus Arteriosus in Very Low Birth Weight Infants

Jong Woan Yun; Hyun A Park; Jong Hee Hwang

doi:10.14734/PN.2018.29.01.33

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Yun, Park, and Hwang: The Comparison of Efficiency of Oral Ibuprofen and Intravenous Indomethacin for Patent Ductus Arteriosus in Very Low Birth Weight Infants

Original Article

Perinatology 2018;29(1):33-38.

Published online: 19 March 2018

DOI: https://doi.org/10.14734/PN.2018.29.01.33

The Comparison of Efficiency of Oral Ibuprofen and Intravenous Indomethacin for Patent Ductus Arteriosus in Very Low Birth Weight Infants

Jong Woan Yun, MD, Hyun A Park, MD, Jong Hee Hwang, MD, PhD

Department of Pediatrics, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea

Correspondence to Jong Hee Hwang, MD, PhD Department of Pediatrics, Ilsan Paik Hospital, Inje University College of Medicine, 170 Juhwa-ro, Ilsanseogu, Goyang 10380, Korea Tel: +82-31-910-7583 Fax: +82-31-910-7108 E-mail: jhhwang@paik.ac.kr

Received 20 September 201721 October 2017 Accepted 27 October 2017

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

Intravenous indomethacin is the conventional treatment for closure of patent ductus arteriosus (PDA) in preterm infants. However, there are very few studies about oral ibuprofen in preterm infants with PDA. Therefore, this study was done to evaluate the efficacy and side effects of oral ibuprofen compared to intravenous indomethacin in very low birth weight (VLBW) infants.

Methods

From March 2008 to August 2012, medical records of 103 infants with VLBW who had PDA in Inje University Ilsan Paik Hospital were reviewed retrospectively. The medical treatment was given to the 90 infants with hemodynamically significant PDA. Patients were divided into the intravenous indomethacin (IV indo) group (n=27) and the oral ibuprofen (per oral [PO] ibu) group (n=63). Demographic findings and factors associated with PDA were compared between these groups.

Results

There were no significant differences in the mean gestational age, birth weight, and demographic findings between the two groups. The conditions such as respiratory distress syndrome and PDA size were not different before treatment. The rate of ductal closure was 100% in IV indo and 95% in PO ibu. 3 infants in only PO ibu needed surgical closure. Blood urea nitrogen and Creatinine levels did not increase significantly in PO ibu compared with IV indo, and there was no notable increase in necrotizing enterocolitis or oliguria incidence in this group either. There were no significant differences in the mortality and late complications.

Conclusion

Oral ibuprofen is as efficacious as intravenous indomethacin with similar adverse effects.

Keywords: Ductus arteriosus, Patent, Ibuprofen, Indomethacin

REFERENCES

1). Koch J., Hensley G., Roy L., Brown S., Ramaciotti C., Rosenfeld CR. Prevalence of spontaneous closure of the ductus arteriosus in neonates at a birth weight of 1000 grams or less. Pediatrics. 2006. 117:1113–21.

2). Ellison RC., Peckham GJ., Lang P., Talner NS., Lerer TJ., Lin L, et al. Evaluation of the preterm infant for patent ductus arteriosus. Pediatrics. 1983. 71:364–72.

3). Benitz WE., Bhombal S. The use of non-steroidal anti-inflammatory drugs for patent ductus arteriosus closure in preterm infants. Semin Fetal Neonatal Med. 2017. 22:302–7.

4). Hamrick SE., Hansmann G. Patent ductus arteriosus of the preterm infant. Pediatrics. 2010. 125:1020–30.

5). Lee JA., Kim MJ., Oh S., Choi BM. Current status of therapeutic strategies for patent ductus arteriosus in very-low-birth-weight infants in Korea. J Korean Med Sci. 2015. 30(Suppl 1):S59–66.

6). Ohlsson A., Walia R., Shah SS. Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight infants. Cochrane Database Syst Rev. 2010. 4:CD003481.

7). Keating P., Verhagen E., van Hoften J., ter Horst H., Bos AF. Effect of indomethacin infused over 30 minutes on cerebral fractional tissue oxygen extraction in preterm newborns with a patent ductus arteriosus. Neonatology. 2010. 98:232–7.

8). Patel J., Roberts I., Azzopardi D., Hamilton P., Edwards AD. Randomized double-blind controlled trial comparing the effects of ibuprofen with indomethacin on cerebral hemodynamics in preterm infants with patent ductus arteriosus. Pediatr Res. 2000. 47:36–42.

9). Aly H., Lotfy W., Badrawi N., Ghawas M., Abdel-Meguid IE., Hammad TA. Oral Ibuprofen and ductus arteriosus in premature infants: a randomized pilot study. Am J Perinatol. 2007. 24:267–70.

10). Lee CH., Chen HN., Tsao LY., Hsiao CC., Lee ML. Oral ibuprofen versus intravenous indomethacin for closure of patent ductus arteriosus in very low birth weight infants. Pediatr Neonataol. 2012. 53:346–53.

11). Lee SJ., Kim JY., Park E., Sohn S. The pharmacological treatment of patent ductus arteriosus in premature infants with respiratory distress syndrome: oral ibuprofen vs. indomethacin. Korean J Pediatr. 2008. 51:95663.

12). Lee J., Choi M., Shim GH., Song YH., Chey MJ. Oral ibuprofen versus intravenous indomethacin for the treatment of patent ductus arteriosus in very low birth weight infants. Neonatal Med. 2013. 20:67–74.

13). Yang EM., Song ES., Choi YY. Comparison of oral ibuprofen and intravenous indomethacin for the treatment of patent ductus arteriosus in extremely low birth weight infants. J Pediatr (Rio J). 2013. 89:33–9.

14). Ohlsson A., Walia R., Shah SS. Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight infants. Cochrane Database Syst Rev. 2013. 4:CD003481.

15). Ohlsson A., Walia R., Shah SS. Ibuprofen for the treatment of patent ductus arteriosus in preterm or low birth weight (or both) infants. Cochrane Database Syst Rev. 2015. 2:CD003481.

16). Cherif A., Khrouf N., Jabnoun S., Mokrani C., Amara MB., Guellouze N, et al. Randomized pilot study comparing oral ibuprofen with intravenous ibuprofen in very low birth weight infants with patent ductus arteriosus. Pediatrics. 2008. 122:e1256–61.

17). Gokmen T., Erdeve O., Altug N., Oguz SS., Uras N., Dilmen U. Efficacy and safety of oral versus intravenous ibuprofen in very low birth weight preterm infants with patent ductus arteriosus. J Pediatr. 2011. 158:54954. .e1.

18). Oncel MY., Erdeve O. Oral medications regarding their safety and efficacy in the management of patent ductus arteriosus. World J Clin Pediatr. 2016. 5:75–81.

19). Erdeve O., Yurttutan S., Altug N., Ozdemir R., Gokmen T., Dilmen U, et al. Oral versus intravenous ibuprofen for patent ductus arteriosus closure: a randomised controlled trial in extremely low birthweight infants. Arch Dis Child Fetal Neonatal Ed. 2012. 97:F279–83.

20). Barzilay B., Youngster I., Batash D., Keidar R., Baram S., Goldman M, et al. Pharmacokinetics of oral ibuprofen for patent ductus arteriosus closure in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2012. 97:F116–9.

21). Van Overmeire B., Touw D., Schepens PJ., Kearns GL., Anker JN. Ibuprofen pharmacokinetics in preterm infants with patent ductus arteriosus. Clin Pharmacol Ther. 2001. 70:336–43.

22). Sharma PK., Garg SK., Narang A. Pharmacokinetics of oral ibuprofen in premature infants. J Clin Pharmacol. 2003. 43:968–73.

23). Neumann R., Schulzke SM., Bührer C. Oral ibuprofen versus intravenous ibuprofen or intravenous indomethacin for the treatment of patent ductus arteriosus in preterm infants: a systematic review and metaanalysis. Neonatology. 2012. 102:9–15.

Fig. 1.

Diagram of patent ductus arteriosus in very low birth weight infants. PDA, patent ductus arteriosus; VLBW, very low birth weight; IV, intravenous; PO, per oral.

Table 1.

Characteristics of Very Low Birth Infants with Symptomatic Patent Ductus Arteriosus

	IV Indomethacin		Oral Ibuprofen		P-value
	BW <1,500 g (n=27)	BW <1,000 g (n=12)	BW <1,500 g (n=63)	BW <1,000 g (n=34)	BW <1,500 g	BW <1,000 g
Gestational age (wks)	27±3	25±2	27±3	25±1	0.979	0.985
Birth weight (g)	1,014±269	759±133	976±306	730±149	0.584	0.554
Apgar score
1 minute	4±2	3±2	4±2	3±2	0.309	0.362
5 minutes	7±2	6±1	7±1	6±1	0.851	0.960
Male	11 (41)	10 (83)	34 (54)	16 (47)	0.250	0.030
Inborn	26 (96)	12 (100)	60 (95)	34 (100)	0.823	0.739
Cesarean section	16 (59)	6 (50)	44 (70)	25 (74)	0.329	0.129
PIH	2 (7)	1 (10)	10 (16)	4 (13)	0.308	0.659
PROM	15 (44)	7 (64)	11 (20)	6 (18)	0.015	0.007
Pathologic chorioamnionitis	9 (33)	5 (46)	16 (25)	13 (41)	0.251	0.525
Prenatal steroid	11 (41)	5 (46)	23 (36)	10 (32)	0.866	0.333
RDS	26 (96)	12 (100)	63 (100)	34 (100)	0.125	0.261
PPHN	2 (3)	1 (8)	3 (5)	0 (0)	0.616	0.537
Intubation duration (days)	51±49	71±57	49±38	66±41	0.861	0.765
Oxygen duration (days)	68±50	86±57	44±54	65±67	0.059	0.323
PCVC duration (days)	54±36	66±46	49±27	57±27	0.540	0.537

Values are expressed as the mean±standard deviation and number of patients (%). Abbreviations: BW, birth weight; PIH, pregnancy induced hypertension; PROM, premature rupture of membrane; RDS, respiratory distress syndrome; PPHN, persistent pulmonary hypertension; PCVC, percutaneous central venous catheterization.

Table 2.

Efficacy of Intravenous Indomethacin versus Oral Ibuprofen for Patent Ductus Arteriosus in Very Low Birth Weight Infants

	IV indomethacin		Oral ibuprofen		P-value
	BW <1,500 g (n=27)	BW <1,000 g (n=12)	BW <1,500 g (n=63)	BW <1,000 g (n=34)	BW <1,500 g	BW <1,000 g
Initial PDA Size (mm)	1.9±0.8	1.6±0.5	2.0±0.6	1.8±0.4	0.392	0.183
1st cycle	23 (85)	10 (83)	47 (72)	21 (62)	0.392	0.550
≥2nd cycle	4 (15)	2 (17)	16 (28)	13 (38)	0.286	0.469
Ligation operation	0 (0)	0 (0)	3 (5)	2 (6)	0.245	0.542

Values are expressed as the mean±standard deviation and number of patients (%). Abbreviations: IV, intravenous; BW, birth weight; PDA, patent ductus arteriosus.

Table 3.

Side Effect of Intravenous Indomethacin versus Oral Ibuprofen for Patent Ductus Arteriosus in Very Low Birth Weight Infants

	IV Indomethacin		Oral Ibuprofen		P-value
	BW <1,500 g (n=27)	BW <1,000 g (n=12)	BW <1,500 g (n=63)	BW <1,000 g (n=34)	BW <1,500 g	BW <1,000 g
BUN after 1st cycle use (mg/dL)	21±10	23±13	20±10	23±11	0.834	0.971
Creatinine after 1st cycle use (mg/dL)	1.2±0.5	1.1±0.6	1.3±0.4	1.4±0.5	0.380	0.109
Oliguria	11 (21)	7 (64)	14 (42)	10 (74)	0.051	0.080
Pulmonary hemorrhage	0 (0)	0 (0)	3 (5)	3 (9)	0.245	0.553
GI hemorrhage	3 (11)	2 (17)	2 (3)	1 (3)	0.132	0.241
NEC	0 (0)	0 (0)	0 (0)	0 (0)	0.866	0.910

Values are expressed as the mean±standard deviation and number of patients (%). Abbreviations: IV, intravenous; BW, birth weight; BUN, blood urea nitrogen; GI, gastrointestinal; NEC, necrotizing enterocolitis.

Table 4.

Mortality and Morbidity of Intravenous Indomethacin versus Oral Ibuprofen for Patent Ductus Arteriosus in Very Low Birth Weight Infants

	IV Indomethacin		Oral Ibuprofen		P-value
	BW <1,500 g (n=27)	BW <1,000 g (n=12)	BW <1,500 g (n=63)	BW <1,000 g (n=34)	BW <1,500 g	BW <1,000 g
BPD (≥moderate)	8 (30)	3 (25)	28 (44)	12 (35)	0.051	0.468
Sepsis	7 (26)	5 (40)	17 (27)	14 (41)	0.917	0.501
ROP (≥stage 3)	6 (22)	5 (40)	8 (13)	6 (18)	0.455	0.179
ROP (laser operation)	7 (26)	5 (40)	8 (13)	6 (18)	0.127	0.120
IVH (≥grade III)	1 (4)	1 (8)	4 (6)	2 (6)	0.594	0.625
Cystic PVL	4 (15)	1 (8)	4 (6)	3 (9)	0.196	0.703
Mortality	4 (15)	2 (17)	8 (13)	9 (26)	0.758	0.701
Hospital stay (days)	90±51	106±58	91±52	109±58	0.956	0.878

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