Differential renal adverse effects of ibuprofen and indomethacin in preterm infants: a review

Abstract

ObjectiveThe objective of this study was to evaluate the extent of renal adverse effects caused by ibuprofen or indomethacin in order to choose the safer drug to administer to preterm infants.MethodsThe following three parameters of renal function were taken into consideration: 1) the urine output; 2) the serum creatinine concentration; and 3) the frequency of oliguria. The bibliographic search was performed using PubMed and Embase databases as search engines.ResultsUrine output ranged from 3.5±1.2 to 4.0±1.4 mL/kg/h after ibuprofen treatment, and from 2.8±1.1 to 3.6±1.4 mL/kg/h after indomethacin treatment. The values for ibuprofen are significantly (P<0.05) higher than those for indomethacin. The serum creatinine concentrations ranged from 0.98±0.24 to 1.48±0.2 mg/dL after ibuprofen treatment, and from 1.06±0.24 and 2.03±2.10 mg/dL after indomethacin treatment. The values for ibuprofen are significantly (P<0.05) lower than those for indomethacin. The frequency of oliguria ranged from 1.0% to 9.6% (ibuprofen) and from 14.8% to 40.0% (indomethacin), and was significantly lower following ibuprofen than indomethacin administration. In infants with body weight lower than 1,000 g, oliguria appeared in 5% (ibuprofen) and 40% (indomethacin; P=0.02).ConclusionIndomethacin is associated with more severe renal adverse effects than ibuprofen. Ibuprofen is less nephrotoxic than indomethacin and should be used to treat patent ductus arteriosus in preterm infants. Immaturity increases the frequency of adverse effects of indomethacin.

Spontaneous Closure of the Ductus Arteriosus in Preterm Infants: A Systematic Review

“…Next to the ongoing discussion on the type of drug being either ibuprofen, indomethacin, or acetaminophen (117)(118)(119)(120)(121)(122)(123)(124), the timing of treatment initiation varies widely between studies, and might explain reported differences in efficacy. As spontaneous ductus closure increases with PNA, part of ductus closure reported in prophylactic and early treatment studies may be due to spontaneous closure rather than drug treatment.…”

Anti-Inflammatory Therapies for Treatment of Inflammation-Related Preterm Brain Injury

“…In the Trial of Indomethacin Prophylaxis in Preterm Infants, the prophylactic administration of indomethacin did not reduce the burden of white matter injury, and the surviving infants exhibited moderate-to-severe cognitive delays at a corrected aged of 18 months [ 202 ]. Additionally, contraindications to indomethacin treatment include nephrotoxicity [ 203 ], adverse cerebral hemodynamics [ 204 ], and an increased risk of serious neonatal complications (e.g., intracranial hemorrhage, necrotizing enterocolitis, and patent ductus arteriosus) [ 202 , 205 ] in preterm infants born before 30 weeks of gestation.…”

Potential neuroprotective strategies for perinatal infection and inflammation

“…By contrast, prophylaxis with indomethacin in extremely low birth weight infants did not improve the rate of survival without neurosensory impairment at 18 months, despite reducing the frequency of severe periventricular and intraventricular hemorrhage (Schmidt et al, 2001). Further, in a large cohort of preterm born infants, NSAIDs during pregnancy was associated with renal side effects (Pacifici, 2014) and an increased risk of quadriparetic and diparetic cerebral palsy (Tyler et al, 2012).…”