Skip to main content
Top
Published in: BMC Clinical Pharmacology 1/2011

Open Access 01-12-2011 | Research article

Comparison of renal effects of ibuprofen versus indomethacin during treatment of patent ductus arteriosus in contiguous historical cohorts

Authors: Alla Kushnir, Joaquim MB Pinheiro

Published in: BMC Clinical Pharmacology | Issue 1/2011

Login to get access

Abstract

Background

Ibuprofen treatment of patent ductus arteriosus (PDA) has been shown to be as effective as indomethacin in small randomized controlled trials, with possibly fewer adverse effects. However, adverse renal effects of ibuprofen have been noted in some trials and suspected in our practice.
The purpose of this study was to examine whether ibuprofen and indomethacin treatment of PDA have comparable effects on renal function as evidenced by urine output and serum creatinine.

Methods

Retrospective chart review of 350 patients. Serum creatinine and urine output were recorded prior to start of treatment, during each course and after the last course of treatment. Pre-treatment mean creatinine and urine output values were compared to treatment and post treatment means using 2-factor repeated measures ANOVA.

Results

165 patients were treated with indomethacin (2005-2006) and 185 received ibuprofen (2007-2008). There was no difference between treatment groups in demographics or baseline renal function. For both groups, the number of treatment courses was inversely correlated with birth weight and gestational age. Analysis of the first course including all patients, revealed significant increase in creatinine and decrease in urine output with both drugs, with a more pronounced effect of indomethacin on creatinine. In the subgroup of 219 patients who received only one treatment course, there was a significant increase in creatinine after indomethacin, but not after ibuprofen. In the 131 who received 2 or more courses, the decrease in urine output and increase in creatinine were not different between drugs. There were significant decreases in urine output observed in the second and third courses of ibuprofen treatment (both by 0.9 mL/kg/hr).

Conclusion

Both drugs have a similar short-term effect on renal function. Indomethacin had a more prominent initial effect, while ibuprofen decreased renal function during the second and third courses similarly to indomethacin. The changes in renal function seen with ibuprofen treatment should be considered in fluid and electrolyte management, especially if treatment beyond one course is required.
Appendix
Available only for authorised users
Literature
1.
go back to reference Evans N, Kluckow M: Early ductal shunting and intraventricular haemorrhage in ventilated preterm infants. Arch Dis Child Fetal Neonatal Ed. 1996, 75 (3): F183-F186. 10.1136/fn.75.3.F183.CrossRefPubMedPubMedCentral Evans N, Kluckow M: Early ductal shunting and intraventricular haemorrhage in ventilated preterm infants. Arch Dis Child Fetal Neonatal Ed. 1996, 75 (3): F183-F186. 10.1136/fn.75.3.F183.CrossRefPubMedPubMedCentral
2.
go back to reference Martin CG, Snider AR, Katz SM, Peabody JL, Brady JP: Abnormal cerebral blood flow patterns in preterm infants with a large patent ductus arteriosus. J Pediatr. 1982, 101 (4): 587-93. 10.1016/S0022-3476(82)80715-4.CrossRefPubMed Martin CG, Snider AR, Katz SM, Peabody JL, Brady JP: Abnormal cerebral blood flow patterns in preterm infants with a large patent ductus arteriosus. J Pediatr. 1982, 101 (4): 587-93. 10.1016/S0022-3476(82)80715-4.CrossRefPubMed
3.
go back to reference Wong SN, Lo RN, Hui PW: Abnormal renal and splanchnic arterial Doppler pattern in premature babies with symptomatic patent ductus arteriosus. J Ultrasound Med. 1990, 9 (3): 125-30.PubMed Wong SN, Lo RN, Hui PW: Abnormal renal and splanchnic arterial Doppler pattern in premature babies with symptomatic patent ductus arteriosus. J Ultrasound Med. 1990, 9 (3): 125-30.PubMed
4.
go back to reference Cotton RB, Stahlman MT, Kovar I, Catterton WZ: Medical management of small preterm infants with symptomatic patent ductus arteriosus. J Pediatr. 1978, 92 (3): 467-73. 10.1016/S0022-3476(78)80451-X.CrossRefPubMed Cotton RB, Stahlman MT, Kovar I, Catterton WZ: Medical management of small preterm infants with symptomatic patent ductus arteriosus. J Pediatr. 1978, 92 (3): 467-73. 10.1016/S0022-3476(78)80451-X.CrossRefPubMed
5.
go back to reference Van Overmeire B, Smets K, Lecoutere D, Van de Broek H, Weyler J, Degroote K, Langhendries JP: A comparison of ibuprofen and indomethacin for closure of patent ductus arteriosus. N Engl J Med. 2000, 343 (10): 674-81. 10.1056/NEJM200009073431001.CrossRefPubMed Van Overmeire B, Smets K, Lecoutere D, Van de Broek H, Weyler J, Degroote K, Langhendries JP: A comparison of ibuprofen and indomethacin for closure of patent ductus arteriosus. N Engl J Med. 2000, 343 (10): 674-81. 10.1056/NEJM200009073431001.CrossRefPubMed
6.
go back to reference Friedman WF, Hirschklau MJ, Printz MP, Pitlick PT, Kirkpatrick SE: Pharmacologic closure of patent ductus arteriosus in the premature infant. N Engl J Med. 1976, 295 (10): 526-9. 10.1056/NEJM197609022951003.CrossRefPubMed Friedman WF, Hirschklau MJ, Printz MP, Pitlick PT, Kirkpatrick SE: Pharmacologic closure of patent ductus arteriosus in the premature infant. N Engl J Med. 1976, 295 (10): 526-9. 10.1056/NEJM197609022951003.CrossRefPubMed
7.
go back to reference Heymann MA, Rudolph AM, Silverman NH: Closure of the ductus arteriosus in premature infants by inhibition of prostaglandin synthesis. N Engl J Med. 1976, 295 (10): 530-3. 10.1056/NEJM197609022951004.CrossRefPubMed Heymann MA, Rudolph AM, Silverman NH: Closure of the ductus arteriosus in premature infants by inhibition of prostaglandin synthesis. N Engl J Med. 1976, 295 (10): 530-3. 10.1056/NEJM197609022951004.CrossRefPubMed
8.
go back to reference Betkerur MV, Yeh TF, Miller K, Glasser RJ, Pildes RS: Indomethacin and its effect on renal function and urinary kallikrein excretion in premature infants with patent ductus arteriosus. Pediatrics. 1981, 68 (1): 99-102.PubMed Betkerur MV, Yeh TF, Miller K, Glasser RJ, Pildes RS: Indomethacin and its effect on renal function and urinary kallikrein excretion in premature infants with patent ductus arteriosus. Pediatrics. 1981, 68 (1): 99-102.PubMed
9.
go back to reference van Bel F, Guit GL, Schipper J, van de Bor M, Baan J: Indomethacin-induced changes in renal blood flow velocity waveform in premature infants investigated with color Doppler imaging. J Pediatr. 1991, 118 (4 (Pt 1)): 621-6.CrossRefPubMed van Bel F, Guit GL, Schipper J, van de Bor M, Baan J: Indomethacin-induced changes in renal blood flow velocity waveform in premature infants investigated with color Doppler imaging. J Pediatr. 1991, 118 (4 (Pt 1)): 621-6.CrossRefPubMed
10.
go back to reference Edwards AD, Wyatt JS, Richardson C, Potter A, Cope M, Delpy DT, Reynolds EO: Effects of indomethacin on cerebral haemodynamics in very preterm infants. Lancet. 1990, 335 (8704): 1491-5. 10.1016/0140-6736(90)93030-S.CrossRefPubMed Edwards AD, Wyatt JS, Richardson C, Potter A, Cope M, Delpy DT, Reynolds EO: Effects of indomethacin on cerebral haemodynamics in very preterm infants. Lancet. 1990, 335 (8704): 1491-5. 10.1016/0140-6736(90)93030-S.CrossRefPubMed
11.
go back to reference Varvarigou A, Bardin CL, Beharry K, Chemtob S, Papageorgiou A, Aranda JV: Early ibuprofen administration to prevent patent ductus arteriosus in premature newborn infants. JAMA. 1996, 275 (7): 539-44. 10.1001/jama.275.7.539.CrossRefPubMed Varvarigou A, Bardin CL, Beharry K, Chemtob S, Papageorgiou A, Aranda JV: Early ibuprofen administration to prevent patent ductus arteriosus in premature newborn infants. JAMA. 1996, 275 (7): 539-44. 10.1001/jama.275.7.539.CrossRefPubMed
12.
go back to reference Romagnoli C, De Carolis MP, Papacci P, Polimeni V, Luciano R, Piersigilli F, Delogu AB, Tortorolo G: Effects of prophylactic ibuprofen on cerebral and renal hemodynamics in very preterm neonates. Clin Pharmacol Ther. 2000, 67 (6): 676-83. 10.1067/mcp.2000.107048.CrossRefPubMed Romagnoli C, De Carolis MP, Papacci P, Polimeni V, Luciano R, Piersigilli F, Delogu AB, Tortorolo G: Effects of prophylactic ibuprofen on cerebral and renal hemodynamics in very preterm neonates. Clin Pharmacol Ther. 2000, 67 (6): 676-83. 10.1067/mcp.2000.107048.CrossRefPubMed
13.
go back to reference Pezzati M, Vangi V, Biagiotti R, Bertini G, Cianciulli D, Rubaltelli FF: Effects of indomethacin and ibuprofen on mesenteric and renal blood flow in preterm infants with patent ductus arteriosus. J Pediatr. 1999, 135 (6): 733-8. 10.1016/S0022-3476(99)70093-4.CrossRefPubMed Pezzati M, Vangi V, Biagiotti R, Bertini G, Cianciulli D, Rubaltelli FF: Effects of indomethacin and ibuprofen on mesenteric and renal blood flow in preterm infants with patent ductus arteriosus. J Pediatr. 1999, 135 (6): 733-8. 10.1016/S0022-3476(99)70093-4.CrossRefPubMed
14.
go back to reference Lago P, Bettiol T, Salvadori S, Pitassi I, Vianello A, Chiandetti L, Saia OS: Safety and efficacy of ibuprofen versus indomethacin in preterm infants treated for patent ductus arteriosus: a randomised controlled trial. Eur J Pediatr. 2002, 161 (4): 202-7. 10.1007/s00431-002-0915-y.CrossRefPubMed Lago P, Bettiol T, Salvadori S, Pitassi I, Vianello A, Chiandetti L, Saia OS: Safety and efficacy of ibuprofen versus indomethacin in preterm infants treated for patent ductus arteriosus: a randomised controlled trial. Eur J Pediatr. 2002, 161 (4): 202-7. 10.1007/s00431-002-0915-y.CrossRefPubMed
15.
go back to reference Mosca F, Bray M, Lattanzio M, Fumagalli M, Tosetto C: Comparative evaluation of the effects of indomethacin and ibuprofen on cerebral perfusion and oxygenation in preterm infants with patent ductus arteriosus. J Pediatr. 1997, 131 (4): 549-54. 10.1016/S0022-3476(97)70060-X.CrossRefPubMed Mosca F, Bray M, Lattanzio M, Fumagalli M, Tosetto C: Comparative evaluation of the effects of indomethacin and ibuprofen on cerebral perfusion and oxygenation in preterm infants with patent ductus arteriosus. J Pediatr. 1997, 131 (4): 549-54. 10.1016/S0022-3476(97)70060-X.CrossRefPubMed
16.
go back to reference Su BH, Lin HC, Chiu HY, Hsieh HY, Chen HH, Tsai YC: Comparison of ibuprofen and indometacin for early-targeted treatment of patent ductus arteriosus in extremely premature infants: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. 2008, 93 (2): F94-F99.CrossRefPubMed Su BH, Lin HC, Chiu HY, Hsieh HY, Chen HH, Tsai YC: Comparison of ibuprofen and indometacin for early-targeted treatment of patent ductus arteriosus in extremely premature infants: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. 2008, 93 (2): F94-F99.CrossRefPubMed
17.
go back to reference Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, Brotherton T: Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg. 1978, 187 (1): 1-7. 10.1097/00000658-197801000-00001.CrossRefPubMedPubMedCentral Bell MJ, Ternberg JL, Feigin RD, Keating JP, Marshall R, Barton L, Brotherton T: Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg. 1978, 187 (1): 1-7. 10.1097/00000658-197801000-00001.CrossRefPubMedPubMedCentral
18.
go back to reference Vermont Oxford Network Database: Manual of Operations. 2007, Burlington, VT: Vermont Oxford Network, Release 12.0 Vermont Oxford Network Database: Manual of Operations. 2007, Burlington, VT: Vermont Oxford Network, Release 12.0
19.
go back to reference International Committee for the Classification of Retinopathy of Prematurity: The International Classification of Retinopathy of Prematurity Revisited. 2005, 991-9. 123 International Committee for the Classification of Retinopathy of Prematurity: The International Classification of Retinopathy of Prematurity Revisited. 2005, 991-9. 123
20.
go back to reference Papile LA, Burstein J, Burstein R, Koffler H: Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr. 1978, 92 (4): 529-34. 10.1016/S0022-3476(78)80282-0.CrossRefPubMed Papile LA, Burstein J, Burstein R, Koffler H: Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr. 1978, 92 (4): 529-34. 10.1016/S0022-3476(78)80282-0.CrossRefPubMed
21.
go back to reference Clyman RI: Ibuprofen and patent ductus arteriosus. N Engl J Med. 2000, 343 (10): 728-30. 10.1056/NEJM200009073431009.CrossRefPubMed Clyman RI: Ibuprofen and patent ductus arteriosus. N Engl J Med. 2000, 343 (10): 728-30. 10.1056/NEJM200009073431009.CrossRefPubMed
22.
go back to reference 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 (1): 36-42. 10.1203/00006450-200001000-00009.CrossRefPubMed 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 (1): 36-42. 10.1203/00006450-200001000-00009.CrossRefPubMed
23.
go back to reference Van Overmeire B, Follens I, Hartmann S, Creten WL, Van Acker KJ: Treatment of patent ductus arteriosus with ibuprofen. Arch Dis Child Fetal Neonatal Ed. 1997, 76 (3): F179-F184. 10.1136/fn.76.3.F179.CrossRefPubMedPubMedCentral Van Overmeire B, Follens I, Hartmann S, Creten WL, Van Acker KJ: Treatment of patent ductus arteriosus with ibuprofen. Arch Dis Child Fetal Neonatal Ed. 1997, 76 (3): F179-F184. 10.1136/fn.76.3.F179.CrossRefPubMedPubMedCentral
24.
go back to reference Tiker F, Yildirim SV: Acute renal impairment after oral ibuprofen for medical closure of patent ductus arteriosus. Indian Pediatr. 2007, 44 (1): 54-5.PubMed Tiker F, Yildirim SV: Acute renal impairment after oral ibuprofen for medical closure of patent ductus arteriosus. Indian Pediatr. 2007, 44 (1): 54-5.PubMed
25.
go back to reference Vieux R, Desandes R, Boubred F, Semama D, Guillemin F, Buchweiller MC, Fresson J, Hascoet JM: Ibuprofen in very preterm infants impairs renal function for the first month of life. Pediatr Nephrol. 2010, 25 (2): 267-74. 10.1007/s00467-009-1349-9.CrossRefPubMed Vieux R, Desandes R, Boubred F, Semama D, Guillemin F, Buchweiller MC, Fresson J, Hascoet JM: Ibuprofen in very preterm infants impairs renal function for the first month of life. Pediatr Nephrol. 2010, 25 (2): 267-74. 10.1007/s00467-009-1349-9.CrossRefPubMed
26.
go back to reference Gournay V, Roze JC, Kuster A, Daoud P, Cambonie G, Hascoet JM, Chamboux C, Blanc T, Fichtner C, Savagner C, Gouyon JB, Flurin V, Thiriez G: Prophylactic ibuprofen versus placebo in very premature infants: a randomised, double-blind, placebo-controlled trial. Lancet. 2004, 364 (9449): 1939-44. 10.1016/S0140-6736(04)17476-X.CrossRefPubMed Gournay V, Roze JC, Kuster A, Daoud P, Cambonie G, Hascoet JM, Chamboux C, Blanc T, Fichtner C, Savagner C, Gouyon JB, Flurin V, Thiriez G: Prophylactic ibuprofen versus placebo in very premature infants: a randomised, double-blind, placebo-controlled trial. Lancet. 2004, 364 (9449): 1939-44. 10.1016/S0140-6736(04)17476-X.CrossRefPubMed
27.
go back to reference Richards J, Johnson A, Fox G, Campbell M: A second course of ibuprofen is effective in the closure of a clinically significant PDA in ELBW infants. Pediatrics. 2009, 124 (2): e287-e293. 10.1542/peds.2008-2232.CrossRefPubMed Richards J, Johnson A, Fox G, Campbell M: A second course of ibuprofen is effective in the closure of a clinically significant PDA in ELBW infants. Pediatrics. 2009, 124 (2): e287-e293. 10.1542/peds.2008-2232.CrossRefPubMed
28.
go back to reference Aranda JV, Clyman R, Cox B, Van Overmeire B, Wozniak P, Sosenko I, Carlo WA, Ward RM, Shalwitz R, Baggs G, Seth A, Darko L: A randomized, double-blind, placebo-controlled trial on intravenous ibuprofen L-lysine for the early closure of nonsymptomatic patent ductus arteriosus within 72 hours of birth in extremely low-birth-weight infants. Am J Perinatol. 2009, 26 (3): 235-45. 10.1055/s-0028-1103515.CrossRefPubMed Aranda JV, Clyman R, Cox B, Van Overmeire B, Wozniak P, Sosenko I, Carlo WA, Ward RM, Shalwitz R, Baggs G, Seth A, Darko L: A randomized, double-blind, placebo-controlled trial on intravenous ibuprofen L-lysine for the early closure of nonsymptomatic patent ductus arteriosus within 72 hours of birth in extremely low-birth-weight infants. Am J Perinatol. 2009, 26 (3): 235-45. 10.1055/s-0028-1103515.CrossRefPubMed
29.
go back to reference Cotton RB, Stahlman MT, Bender HW, Graham TP, Catterton WZ, Kovar I: Randomized trial of early closure of symptomatic patent ductus arteriosus in small preterm infants. J Pediatr. 1978, 93 (4): 647-51. 10.1016/S0022-3476(78)80910-X.CrossRefPubMed Cotton RB, Stahlman MT, Bender HW, Graham TP, Catterton WZ, Kovar I: Randomized trial of early closure of symptomatic patent ductus arteriosus in small preterm infants. J Pediatr. 1978, 93 (4): 647-51. 10.1016/S0022-3476(78)80910-X.CrossRefPubMed
30.
go back to reference SUPPORT Study Group of the Eunice Kennedy Shriver NICHDNeonatal Research Network: Target Ranges of Oxygen Saturation in Extremely Preterm Infants. N Engl J Med. 2010, 362 (21): 1959-69.CrossRef SUPPORT Study Group of the Eunice Kennedy Shriver NICHDNeonatal Research Network: Target Ranges of Oxygen Saturation in Extremely Preterm Infants. N Engl J Med. 2010, 362 (21): 1959-69.CrossRef
31.
go back to reference Vermont Oxford Network: Vermont Oxford Network Database: 2009 Annual NICU Quality Management Report. 2010, Burlington, VT, Vermont Oxford Network Vermont Oxford Network: Vermont Oxford Network Database: 2009 Annual NICU Quality Management Report. 2010, Burlington, VT, Vermont Oxford Network
Metadata
Title
Comparison of renal effects of ibuprofen versus indomethacin during treatment of patent ductus arteriosus in contiguous historical cohorts
Authors
Alla Kushnir
Joaquim MB Pinheiro
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Clinical Pharmacology / Issue 1/2011
Electronic ISSN: 1472-6904
DOI
https://doi.org/10.1186/1472-6904-11-8

Other articles of this Issue 1/2011

BMC Clinical Pharmacology 1/2011 Go to the issue