Ibuprofen For Patent Ductus Arteriosus Closure Research Articles

Evaluation the Effectiveness of Ibuprofen in Improving Patent Ductus Arteriosus

Background and Aim: Patent Ductus Arteriosus (PDA) is a common problem in premature neonates, especially in neonate’s low birth weight (LBW). This study aimed to compare the effectiveness of oral and intravenous ibuprofen in the management of PDA. Methods & Materials: We enrolled 40 low birth weight neonates (gestational age <37 weeks) with PDA into semi-experimental study. the LBW neonates received ibuprofen as an initial dose of 10 mg/kg, followed by 5 mg/kg at 24 and 48 hours later. The exclusion criteria were congenital chromosome anomalies, congenital heart disease, asphyxia, sepsis. The PDA was initially confirmed by echocardiography. Treatment efficacy was evaluated by echocardiography after the treatment. Ethical Considerations: This study was approved by the Ethics Committee of Arak University of Medical Sciences (Code: IR.ARAKMU.REC.1396.265). Results: Of the total participants 37.5% (female 25) were girls. Gestational age ranges from 29 to 36 weeks. The average birth weight was 1639±616 gr and the minimum of weight 750 gr. the mean gestational age was 30.4±4.0 weeks. After the first dose of ibuprofen, closure of PDA was observed in 32 patients (80%), PDA closed in eight patients (20%) with to repeat course ibuprofen. There was no significant relationship between the frequency of ibuprofen use with gestational age (P=0.06), birth weight (P=0.08), type of delivery (P=0.068) and multiple births (P=0.061). Conclusion: Most LBW neonate with PDA responded to using the first course of ibuprofen. extremely, all LBW infants responded to the second course. it seems that ibuprofen is as effective as ibuprofen for PDA closure even in LBW infants.

Comparison of intravenous Paracetamol with oral Ibuprofen for medical closure of PDA (patent ductus arteriosus) in preterm newborns – can it be an effective, safe and preferable choice?

Introduction: In prematurely born newborns, the ductus arteriosus frequently fails to close and more than half of preterms might have Patent Ductus Arteriosus (PDA) after birth during the first 24hours. About 70% of infants born before 28 weeks may require medical or surgical closure of PDA. Objectives: To compare the effect of i/v PCM and oral Ibuprofen on PDA closure rate in preterm neonates with a gestational age of > 37 weeks and evaluate the side effect profile of both drugs. Material and Methods: This time-bound prospective observational study for comparison of the efficacy of the two drugs on the closure of PDA in preterms admitted during 1.5 years of the study period in a neonatal ICU caring for inborn as well as outborn neonates in central India. After approval of the institutional ethics committee, initial clinical screening included all preterms but only those with PDA (open ductus arteriosus) confirmed by 2D-echocardiography were allocated to receive either of two treatment regimens (3-day courses of each oral Ibuprofen and i/v PCM) which already exist as evidence-based therapeutic practice options. Result: Out of a total of 43 cases clinically suspected on initial screening, 30 preterm babies confirmed by 2D-Echo to have PDA were finally enrolled and analysed. Twenty-one patients received i/v PCM with a resultant PDA closure rate of 85.7 % (n = 18/21), while nine cases could be allocated oral Ibuprofen arm and ductus closure was obtained in seven patients (77.78%). Although the PDA closure rate between two drug regimens was not statistically significant (p=0.593), i/v PCM resulted in slightly higher efficacy and fewer adverse effects. Conclusion: Paracetamol, preferably by the intravenous route, seems to be an effective, cheap, easily available and safe first-line alternative to oral Ibuprofen for the closure of PDA, especially in newborns with extreme prematurity, who are initially intolerant to oral feeds or drugs.

Baseline cardiac output and its alterations during ibuprofen treatment for patent ductus arteriosus in preterm infants

BackgroundInfants with hemodynamically significant patent ductus arteriosus (PDA) may physiologically compensate with a supranormal cardiac output (CO). As such, a supranormal CO may be a surrogate marker for a significant PDA or indicate a failed response to PDA closure by ibuprofen. Electrical cardiometry (EC) is an impedance-based monitor that can continuously and non-invasively assess CO (COEC). We aimed to trend COEC through ibuprofen treatment for PDA in preterm infants.MethodsWe reviewed our database of preterm infants receiving ibuprofen for PDA closure. Response to ibuprofen was defined as no ductal flow in echocardiography ≤24 h after treatment. Responders were compared with gestational age (GA) and postnatal age matched non-responders and their trends of COEC were compared. Both groups’ baseline COEC were further compared to the reference infants without PDA.ResultsEighteen infants (9 responders and 9 non-responders) with median (interquatile range) GA 27.5 (26.6–28.6) weeks, birthweight 1038 (854–1218) g and age 3.5 (3.0–4.0) days were studied. There were positive correlations between COEC and ductal diameter and left atrium/ aortic root ratio (r = 0.521 and 0.374, p < 0.001, respectively). Both responders and non-responders had significantly higher baseline COEC than the reference. Although there was no significant within-subject alteration of COEC during ibuprofen treatment, there was a between-subject difference indicating non-responders had generally higher COEC.ConclusionsThe changes of COEC during pharmacological closure of PDA is less drastic compared to surgical closure. Infants with PDA had higher baseline COEC compared to those without PDA, and non-responders had higher COEC especially at baseline compared to responders.

Use of acetaminophen for patent ductus arteriosus treatment: a single center experience

Purpose: Patent ductus arteriosus (PDA) continues to be one of the most common complications associated with preterm birth. Up to 70% of infants born before 28 weeks gestational age may require some form of medical or surgical treatment for PDA closure. Recent studies have suggested acetaminophen to be a promising new alternative to indomethacin and ibuprofen for closure of PDA with potentially fewer adverse effects. Our aim for the study was to report our experience regarding the efficacy of acetaminophen compared to indomethacin for treatment of hemodynamically significant PDA (hs-PDA) in infants born in our institution.Material and methods: Retrospective cohort study of all preterm infants born <34-week gestation with hs-PDA, treated with acetaminophen or indomethacin as the first line medication for hs-PDA. Primary outcome of successful PDA closure rate (small or no PDA) and secondary outcomes of short-term morbidities and immediate adverse events were compared between the two cohorts.Results: Of the 43 infants, 25 were treated with acetaminophen and 18 with indomethacin, as first line for hs-PDA. Successful PDA closure rate was slightly lower for acetaminophen compared to indomethacin, although statistically not significant (acetaminophen: 40% versus indomethacin: 55.5%, p = .31). No significant differences in short-term morbidities including necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), late onset sepsis (LOS), retinopathy of prematurity (ROP) and intraventricular hemorrhage (IVH), or immediate side effects including oliguria, hyponatremia, elevated BUN/creatinine, thrombocytopenia were found between the two cohorts.Conclusions: Acetaminophen treatment of hs-PDA resulted in similar successful PDA closure rate compared to indomethacin in our small cohort of patients.

Oral pharmacological treatment for patent ductus arteriosus in premature neonates with hemodynamic repercussions.

To evaluate the efficacy of oral indomethacin, ibuprofen, and paracetamol in oral dosage form on patent ductus arteriosus (PDA) in premature neonates with significant clinical and hemodynamic repercussions (CHRs) and to determine the effect of these respective treatments on renal function. A retrospective study of cases of PDA in premature neonates in the Neonatal Intensive Care Unit was conducted. The treatments consisted of indomethacin [0.2mg/(kg·d), 3-day cycle], ibuprofen [10mg/(kg·d) followed by 5mg/(kg·d), 3-day cycle], and paracetamol (15mg/kg every 6h, 5-day cycle). The drugs were administered as an oral solution. The following variables were considered: gestational age, newborn weight at birth, Apgar score, diuresis, serum creatinine and urea levels, and serum electrolyte levels (sodium and potassium). Treatment with indomethacin presented efficacy of 87.5% in closure of the ductus with a mean outcome period of 3.5d. In premature neonates with CHRs and contraindications for indomethacin, the initial treatment with either ibuprofen or paracetamol failed to close the ductus. However, when this treatment was followed by indomethacin, closure occurred in 66.7% of the neonates, with an outcome period of 9.66d. The initial treatment with one cycle of ibuprofen followed by one or two cycles of paracetamol failed to close the ductus. Oral indomethacin was effective for closure of the PDA in premature neonates with severe CHRs. Oral paracetamol or ibuprofen for PDA closure in premature neonates with severe CHRs and contraindications for indomethacin was ineffective. However, results in clinical improvements of neonates allowed the subsequent use of indomethacin and successful closure of the ductus. A significant reduction of diuresis occurred in neonates who were treated with indomethacin, either as a first-line treatment or after the failure of ibuprofen or paracetamol.

Meta-Analysis to Assess Efficacy and Safety of High-Dose Ibuprofen Compared with Standard Treatment of Patent Ductus Arteriosus in Premature Infants

Background: Patent ductus arteriosus (PDA) is a common congenital heart defect in premature infants. Intravenous injection of ibuprofen is used for PDA treatment, but its optimum dose, efficacy, and safety are unclear. Objectives: This meta-analysis aimed to access randomized controlled trials that compared high- or low-dose ibuprofen with a standard dose of ibuprofen for closure of PDA in preterm infants. Methods: The standard search methods of the Cochrane neonatal review group were used to screen ibuprofen versus indomethacin trials. All groups that used ibuprofen in those trials were filtered out. The high-dose group was defined as those using an average dose of ibuprofen greater than or equal to 10 mg/kg in the first three days. Results: We identified 14 studies of good methodological quality comparing ibuprofen to indomethacin trials among neonates. Results showed that high-dose ibuprofen could remarkably raise the closure rate (relative risk = 0.90, 95% CI = [0.81, 1.00], P = 0.04). No significant differences were found in adverse effects, bleeding disorders, or oliguria. The closure rate in neonates with PDA increased with the ibuprofen dosage (R2 = 0.9990). The loading dose produced a significant closure rate compared with the low-dose group (relative risk = 1.91, 95% CI = [1.25, 2.92], P = 0.003), with no increase in toxic side effects. Conclusions: Loading dose is a necessary strategy for infants with PDA. A high dose of ibuprofen for PDA closure was more effective than a normal dose of ibuprofen. The side effects in both treatment groups were not significantly different. Given the small sample size and risk of bias in all trials, the tolerability and safety of the dose regimen should be assessed in a large population before considering the use of these doses for PDA.

ORAL VERSUS INTRAVENOUS IBUPROFEN FOR THE EARLY CLOSURE OF PATENT DUCTUS ARTERIOSUS IN LOW BIRTH WEIGHT PRETERM INFANTS

Background Patent ductus arteriosus (PDA) is common in very premature infants. Pharmacological closure of PDA with indomethacin, a prostaglandin inhibitor, has remained the mainstay of treatment in premature infants over the last three decades. Intravenous ibuprofen was recently shown to be as effective and to have fewer adverse reaction in preterm infants. If equally effective, then oral ibuprofen for PDA closure would have several important advantages over the intravenous route.This study was designed to assess the efficacy and safety of oral ibuprofen and intravenous ibuprofen for the early pharmacological treatment of PDA in LBW preterm infants with respiratory distress syndrome.MethodsA randomized, single-blinded, controlled study was performed on premature neonates at the neonatal care unit of the University Hospital for Obstetrics and Gynecology”Koco Gliozheni”, Tirana, Albania, from January 2010 to December 2012. The study enrolled 68 preterm infants with gestational age between 28-32 weeks, birth weight ≤ 2000 g, postnatal age 48-96 h, and had echocardiographically confirmed significant PDA. The preterm infants received either intravenous or oral ibuprofen randomly as an initial dose of 10 mg/kg, followed by 5 mg/kg at 24 and 48 h. After the first dose of treatment in both groups, echocardiographic evaluation was performed, to determine the need for a second or third dose. The rate of ductal closure, adverse effects, complications, and the patient’s clinical course were recorded.Results All patients were born after 28 until 32 weeks’ gestation. 36 patients were treated with oral ibuprofen and 32 with intravenous ibuprofen in this period. After the first course of the treatment, the PDA closed in 30 (83.3%) of the patients assigned to the oral ibuprofen group versus 23 (71.8%) of those enrolled in the intravenous ibuprofen group (p = 0.355). There was no difference between treatment groups in demographics or baseline renal function. In the evaluation of renal tolerance, none of the patients had oliguria. There were no significant differences with respect to complications during the stay.Conclusions In low birth weight infants, the rate of early ductal closure with oral ibuprofen is at least as good as with the intravenous route. Oral ibuprofen is associated with fewer adverse effects

Efficacy and safety of oral ibuprofen for closure of patent ductus arteriosus in preterm infants: a meta-analysis

Objective To evaluate the efficacy and safety of oral ibuprofen for closure of patent ductus arteriosus (PDA) in preterm infants.Methods The related literatures till December 31st,2011 in Cochrane Library,PubMed,EMBASE,Ovid,Springer,China Academic Journal Full-text Database,Wanfang Database,VIP Database and China Biological Medical Literature Database were searched.The inclusion criteria were:(1) the subject of the research was preterm infants with birth weight less than 2500 g and/or gestational age less than 37 weeks; (2) randomized or semirandomized controlled trial; (3) the intervention group received oral ibuprofen,while the control group received oral placebos / intravenous indomethacin or ibuprofen; (4) the main outcome was the failure rate of PDA closure; (5) hemodynamic changes with PDA were detected by ultrasonography.Meta-analysis was performed by Review Manager 4.22 software.Results Eleven randomized controlled trials were included,among which,three were high quality reports.Meta-analysis showed lower failure rate of PDA closure in subjects received oral ibuprofen than in those received placebos orally (RR =0.22,95 ％ CI:0.14-0.35),while the number of infants required operative closure of PDA decreased significantly (RR =0.16,95％ CI:0.03-0.86).Further analysis showed the effect of oral ibuprofen was similar to intravenous indomethacin (RR =0.93,95 ％ CI:0.57-1.53),but better than intravenous ibuprofen (RR=0.42,95％CI:0.26-0.67).However,oral ibuprofen did not reduced the ratio of patients required operation compared with intravenous indomethacin or ibuprofen (RR=0.58,95％CI:0.24-1.41).The incidence of gastrointestinal hemorrhage was higher in oral ibuprofen group than that in placebos(RR=1.99,95％CI:1.13-3.50).The serum level of creatine was lower in oral ibuprofen group than in intravenous indomethacin or ibuprofen group (weighted average=-19.10,95％ CI:-25.12-12.31).Compared with intravenous indomethcin group,less necrotizing enterocolitis cases were identified in oral ibuprofen group,but no statistical significance was found (RR=0.57,95％ CI:0.30-1.09).No long-term outcome was reported in any selected literature.Conclusions Oral ibuprofen for PDA closure in preterm infants appears to be as effective as intravenous or indomethacin,and more effective than intraveous ibuproten.Oral ibuproten represents better safety. Key words: Ductus arteriosus, patent; Ibuprofen; Infant, premature; Indomethacin; Treatment outcome; Meta-analysis

Ibuprofen lysine administration to neonates with a patent ductus arteriosus: effect on platelet plug formation assessed by in vivo and in vitro measurements

Ibuprofen might have advantages over indomethacin, when used to effectuate closure of a neonate's patent ductus arteriosus (PDA). Several previous studies indicate that platelet plug formation is impaired after administration of indomethacin, but it is not clear whether a similar impairment occurs following ibuprofen dosing. We performed template bleeding times and PFA-100 tests (platelet function analyzer) on 20 neonates who had a PDA, before and again at various preset intervals following ibuprofen dosing. Patients ranged from 23 to 40 weeks gestation and weighed 511 to 2566 g. Their first dose of ibuprofen was administered at 72 h (18 to 363 h) after birth (median, range). None of the subjects had clinical bleeding problems noted during the days they received ibuprofen dosing. The template bleeding times before dosing ranged from 135 to 450 s. Repeat tests were performed in groups of four, at 2 h, 4 to 6 h, 12 to 18 h, 24 h after the first dose, and at 2 h after the third dose of ibuprofen. No changes in bleeding times were detected. (P=0.299) A PFA-100 time was performed on all 20 patients before and again after the ibuprofen administration. However, 3 of the 40 tests were unsuccessful, because of microclots in the blood sample (n=1) or failure of the analyzer for an unspecified reason (n=2). Before the dosing the PFA-100 time ranged from 52 to 300 s. A paired t-test showed a slight but statistically significant lengthening in PFA-100 time after the ibuprofen administration (P=0.019). The correlation between the bleeding time and the PFA-100 was poor (R(2)=0.212, P=0.576). On the basis of our present studies, we speculate that ibuprofen lysine administration to neonates with a PDA, when used according to the manufacturer's recommendations, has little adverse effect on platelet plug formation. This information might be a factor to consider when deciding whether to select indomethacin or ibuprofen for PDA closure.