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Efficacy and Safety of Oral Versus Intravenous Ibuprofen in Very Low Birth Weight Preterm Infants with Patent Ductus Arteriosus

OBJECTIVE To compare oral ibuprofen with intravenous ibuprofen for closure of patent ductus arteriosus in very low birth weight (VLBW) preterm infants. STUDY DESIGN In a prospective, randomized study, 102 VLBW preterm infants with patent ductus arteriosus received either intravenous or oral ibuprofen at an initial dose of 10 mg/kg, followed by 5 mg/kg at 24 and 48 hours. The success rate and evaluation of renal tolerance using cystatin-C were the major outcomes. RESULTS Patent ductus arteriosus closure rate was significantly higher with oral ibuprofen (84.6% versus 62%) after the first course of the treatment (P = .011). The cystatin-C level increased significantly after treatment in the oral group (P = .001), but did not change with intravenous ibuprofen (P = .4). CONCLUSIONS Oral ibuprofen is more effective than intravenous ibuprofen for ductal closure in VLBW infants. The increase in the cystatin-C level with oral treatment suggests that patients with borderline renal function should be evaluated and followed closely.

Intravenous Paracetamol Treatment in the Management of Patent Ductus Arteriosus in Extremely Low Birth Weight Infants

Background: Treatment options for the closure of a hemodynamically significant patent ductus arteriosus (hsPDA) include medical therapy such as ibuprofen and indomethacin and surgical ligation. Objective: To evaluate the efficacy of intravenous paracetamol in preterm infants with hsPDA whose feeding was contraindicated or had feeding intolerance. Methods: Preterm infants with hsPDA were started on intravenous paracetamol treatment with parental consent. Paracetamol was administered at a dose of 60 mg/kg/day, in four divided doses, for a period of 3 days. In the absence of closure of hsPDA, treatment was extended up to 6 days, after which echocardiographic examination was performed. Results: A total of 10 preterm infants were included in the study with a median gestational age of 274/7 weeks (minimum–maximum: 24–29) and a median birth weight of 775 g (590–990). The first dose of intravenous paracetamol was given after a median of 6 days (2–15). On echocardiographic examination, median internal ductal diameter was 2 mm (1.5–3), with a median left atrium-to-aortic root ratio of 1.95 (1.6–2.2). Intravenous paracetamol resulted in successful closure of hsPDA in all patients. Conclusions: This study is the first case series in the literature which used intravenous paracetamol treatment for hsPDA. We believe that intravenous paracetamol could be used as an alternative drug for infants. Further prospective randomized-controlled trials are needed to evaluate the efficacy of intravenous paracetamol for the closure of hsPDA.

Oral paracetamol versus oral ibuprofen in the management of patent ductus arteriosus in preterm infants: a randomized controlled trial.

OBJECTIVE To compare the efficacy and safety of oral paracetamol and oral ibuprofen for the pharmacological closure of patent ductus arteriosus (PDA) in preterm infants. STUDY DESIGN This prospective, randomized, controlled study enrolled 90 preterm infants with gestational age ≤ 30 weeks, birthweight ≤ 1250 g, and postnatal age 48 to 96 hours who had echocardiographically confirmed significant PDA. Each enrolled patient received either oral paracetamol (15 mg/kg every 6 hours for 3 days) or oral ibuprofen (initial dose of 10 mg/kg, followed by 5 mg/kg at 24 and 48 hours). RESULTS Spontaneous closure rate for the entire study group was 54%. After the first course of treatment, the PDA closed in 31 (77.5%) of the patients assigned to the oral ibuprofen group vs 29 (72.5%) of those enrolled in the oral paracetamol group (P = .6). The reopening rate was higher in the paracetamol group than in the ibuprofen group, but the reopening rates were not statistically different (24.1% [7 of 29] vs 16.1% [5 of 31]; P = .43). The cumulative closure rates after the second course of drugs were high in both groups. Only 2 patient (2.5%) in the paracetamol group and 3 patients (5%) in the ibuprofen group required surgical ligation. CONCLUSION This randomized, controlled clinical study compared oral paracetamol with ibuprofen in preterm infants and demonstrated that paracetamol may be a medical alternative in the management of PDA.

A different first-choice drug in the medical management of patent ductus arteriosus: oral paracetamol

Abstract Background and objectives: Patent ductus arteriosus (PDA) is a significant cause of morbidity and mortality in preterm infants. This case series was conducted to investigate the usefulness of paracetamol as a first choice for the treatment of PDA in preterm infants. Subjects and methods: Preterm infants were prospectively enrolled. Treatment with oral paracetamol was started at a dose of 15 mg/kg every 6 h for 3 d, with echocardiographic evaluation performed at the end of the treatment and 2 d after the treatment. Serum paracetamol levels were also evaluated for 24 h after the first dose to ensure the absorption and reaching the therapeutic level. Results: A total of six preterm infants were prospectively enrolled. Five infants with PDA were successfully treated with oral paracetamol. Only one patient did not respond to paracetamol treatment whereas another one received a second cure due to reopening of the ductus. Conclusion: Paracetamol may be a useful treatment option for the primer treatment of PDA in preterm infants. If paracetamol is shown to be effective in a large series, because of low risk of side effects, low cost and preparation is available in enteral form, it may be an advantageous alternative at PDA treatment.

An alternative drug (paracetamol) in the management of patent ductus arteriosus in ibuprofen-resistant or contraindicated preterm infants

The most commonly used drugs for closure of a haemodynamically significant patent ductus arteriosus (hsPDA) are cyclooxygenase inhibitors, mainly indomethacin and intravenous/oral ibuprofen. In contrast to high closure rates, several adverse effects have been reported with such medications, including gastrointestinal bleeding and perforation, weakened platelet aggregation, hyperbilirubinaemia and renal failure.1 ,2 The role of paracetamol as an …

Oral versus intravenous ibuprofen for patent ductus arteriosus closure: a randomised controlled trial in extremely low birthweight infants

Objective To compare the efficacy and safety of oral versus intravenous ibuprofen for the pharmacological closure of patent ductus arteriosus (PDA) in less mature preterm infants. Design Prospective, randomised controlled study. Setting Tertiary neonatal intensive care unit. Patients and interventions The study enrolled 80 preterm infants with gestational age ≤28 weeks, birth weight <1000 g, postnatal age 48 to 96 h, and had echocardiographically confirmed significant PDA. Seventy extremely low birthweight (ELBW) 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. Main outcome measures The success rate and the safety of the drugs in ELBW preterm infants were the major outcomes. Results PDA closure rate was significantly higher with oral ibuprofen (83.3% vs 61.7%) after the first course of the treatment (p=0.04). Although the primary closure rate was marginally higher in the oral ibuprofen group, the need for a second course of ibuprofen during the whole hospitalisation was similar between groups: 11 of 36 in oral versus 15 of 34 in intravenous groups (p=0.24) because of a higher reopening rate in the oral group. In addition to no increase in side effects with oral ibuprofen use, the need for postnatal steroid use for chronic lung disease was significantly lower in oral ibuprofen group (p=0.001). Conclusions Oral ibuprofen is as effective as intravenous ibuprofen for PDA closure even in ELBW infants.

Oral versus intravenous ibuprofen: which is better in closure of patent ductus arteriosus?

To the Editor. — We read with great interest the article by Cherif et al,1 in which the authors compared the efficacy and tolerance between oral and intravenous ibuprofen in early closure of patent ductus arteriosus (PDA) in very low birth weight (VLBW) infants. They concluded that the rate of early ductal closure with oral ibuprofen was at least as good as with the intravenous route in VLBW infants and was associated with fewer adverse effects. In Turkey, we have been using oral ibuprofen in closure of PDA successfully for many years because of the unavailability of intravenous …

The role of plasma N-terminal pro-B-type natriuretic peptide in predicting the severity of transient tachypnea of the newborn

BACKGROUND/AIM Transient tachypnea of the newborn (TTN) is a consequence of inadequate neonatal lung fluid clearance. Natriuretic peptides play an important role in the regulation of extracellular fluid volume. The aim of the study was to investigate the relation between plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and TTN, and to find out its role in predicting disease severity. METHODS A prospective controlled study involving 67 infants with TTN and 33 controls ≥34 weeks gestational age was conducted. Study and control groups were compared for plasma NT-proBNP levels measured on the 6th, 24th, 72nd and 120th hours of life. Cardiac systolic functions were evaluated by echocardiography. RESULTS NT-proBNP levels were significantly higher in neonates with TTN compared to controls at 6th, 24th, 72nd and 120th hours (p<0.001). NT-proBNP levels at 24th and 72nd hours were significantly higher in infants with prolonged tachypnea (p=0.007 and p=0.03) and in those who required respiratory support (p=0.006 and p<0.001). Tachypnea duration was correlated with NT-proBNP levels at 24h (r=0.41, p=0.001). At a cut-off value of 6575 pg/ml, NT-proBNP had a sensitivity of 85% and specificity of 64% to predict mechanical ventilation requirement. Cardiac systolic functions were normal in all TTN patients. CONCLUSION Plasma NT-proBNP levels are increased in neonates with TTN. Measurement of plasma NT-proBNP can be useful for predicting infants who will have prolonged tachypnea and mechanical ventilation requirement.

Evaluation and treatment of neonatal thrombus formation in 17 patients.

Introduction: Thrombosis is a rare but serious event in neonates. Perinatal risk factors associated with the developing hemostatic system increase the risk of thromboembolism. Treatment protocols vary between different centers. In this study, thrombosis and subsequent treatment were evaluated in 17 neonates hospitalized in a neonatal intensive care unit. This is the largest series reported to date. Method: From January 2007 to December 2009, thrombosis was diagnosed in 17 newborns hospitalized in a neonatal intensive care unit. Most were treated with recombinant tissue plasminogen activator (r-tPA) and enoxaparin as anticoagulant therapy. Results: Eleven courses of r-tPA therapy were administered to 10 patients. Sixteen patients received low-molecular-weight heparin (LMWH) treatment. None of the patients had hemorrhagic complications due to therapy. Recurrence was observed in 1 patient 1.5 months after the first course of r-tPA and retreatment was performed. A complete decrease in thrombus size was achieved in 9 patients and a partial decrease in 5 patients. One patient died before treatment was initiated; another died at the end of the first day of treatment and thus could not be evaluated. One patient who had a homozygous mutation for factor V Leiden did not respond to treatment and the extremity involved was amputated. Conclusions: Thrombosis in neonates is a multifactorial disorder. Treatment consisting of r-tPA and an anticoagulant was shown to be a safe and effective approach to clot dissolution in neonates.

Renal and mesenteric tissue oxygenation in preterm infants treated with oral ibuprofen

Abstract Background: Hemodynamically significant patent ductus arteriosus (PDA) is a common problem in preterm infants which often causes significant morbidities. Although PDA induces alterations in various tissue perfusion, there is scarce information about the effect of oral ibuprofen on hemodynamics of regional tissues. Objective: To investigate, using near-infrared spectroscopy, the effect of oral ibuprofen on renal and mesenteric tissue oxygenation and oxygen extraction in preterm infants with a diagnosis of hemodynamically significant PDA. Patients and methods: Fifteen infants (gestational age <32 weeks) with the diagnosis of hemodynamically significant PDA treated with oral ibuprofen were monitored for near-infrared spectroscopy – determined renal and mesenteric oxygenation. The infants with PDA were matched for gestational age, postnatal age with infants without PDA, who served as control subjects. Results: In infants with PDA, mean arterial blood pressure was significantly lower compared with the control infants [39.3 (range:36–54) versus 51 (range:43–66) mmHg, respectively; p < 0.001)]. There were no significant differences in regional oxygen saturation and fractional oxygen extraction of renal and mesenteric tissues in PDA and control infants (p > 0.05). And ibuprofen treatment did not negatively influence renal and mesenteric oxygenation and extraction in infants with PDA (p > 0.05). Conclusion: Renal and mesenteric tissue oxygenation and oxygen extraction were preserved in preterm infants with a diagnosis of hemodynamically significant PDA treated with oral ibuprofen.