Association of Placebo, Indomethacin, Ibuprofen, and Acetaminophen With Closure of Hemodynamically Significant Patent Ductus Arteriosus in Preterm Infants

Mitra, Souvik; Flórez, Iván D.; Tamayo, María; Mbuagbaw, Lawrence; Vanniyasingam, Thuva; Veroniki, Areti Angeliki; Zea, Adriana M.; Zhang, Yuan; Sadeghirad, Behnam; Thabane, Lehana

doi:10.1001/jama.2018.1896

Cited by 265 publications

(262 citation statements)

References 103 publications

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“…Paracetamol can also promote successful ductal closure perhaps with fewer renal side effects than ibuprofen [179]. Meta-analyses of all available studies suggest high-dose oral ibuprofen gives better PDA closure rates than intravenous ibuprofen or indomethacin, although no particular regimen compared with placebo influenced any important long-term outcome [180]. Routine indomethacin or ibuprofen treatment of all infants to promote PDA closure is not considered good practice [181].…”

Section: Managing Blood Pressure and Perfusionmentioning

confidence: 99%

European Consensus Guidelines on the Management of Respiratory Distress Syndrome – 2019 Update

et al. 2019

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As management of respiratory distress syndrome (RDS) advances, clinicians must continually revise their current practice. We report the fourth update of “European Guidelines for the Management of RDS” by a European panel of experienced neonatologists and an expert perinatal obstetrician based on available literature up to the end of 2018. Optimising outcome for babies with RDS includes prediction of risk of preterm delivery, need for appropriate maternal transfer to a perinatal centre and timely use of antenatal steroids. Delivery room management has become more evidence-based, and protocols for lung protection including initiation of CPAP and titration of oxygen should be implemented immediately after birth. Surfactant replacement therapy is a crucial part of management of RDS, and newer protocols for its use recommend early administration and avoidance of mechanical ventilation. Methods of maintaining babies on non-invasive respiratory support have been further developed and may cause less distress and reduce chronic lung disease. As technology for delivering mechanical ventilation improves, the risk of causing lung injury should decrease, although minimising time spent on mechanical ventilation using caffeine and, if necessary, postnatal steroids are also important considerations. Protocols for optimising general care of infants with RDS are also essential with good temperature control, careful fluid and nutritional management, maintenance of perfusion and judicious use of antibiotics all being important determinants of best outcome.

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Section: Managing Blood Pressure and Perfusionmentioning

confidence: 99%

European Consensus Guidelines on the Management of Respiratory Distress Syndrome – 2019 Update

et al. 2019

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“…The most effective intravenous ibuprofen-dosing regimen determined in meta-analyses by Mitra et al consisted of a 20 mg kg −1 first dose, followed by additional 10 mg kg −1 doses after 24 and 48 h, all with 15 min infusion rates [19]. Simulation of concentration-time profiles of both ibuprofen enantiomers in a typical neonate with PDA at PNA of 24 h and a body weight of 840 g following this dosage regimen, predicted a corresponding (S)-ibuprofen trough concentration at 48 h after ibuprofen start of 43 mg l −1 (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The risk of developing side effects and toxicity of nonsteroidal anti-inflammatory drugs seems related to peak concentrations. The meta-analyses by Mitra et al reported less side effects with a continuous administration than an intermittent regimen, although the odds ratio for oliguria of 0.07 was not found significant (0.00–1.84) [19]. Gournay et al reported a placebo controlled trial with major side effects of ibuprofen concerning gastrointestinal adverse effects, severe intraventricular hemorrhages caused by thrombocytopathy, necrotizing enterocolitis, and renal dysfunction [18].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, three randomized controlled trials have shown more effectiveness for ibuprofen treatment compared with placebo [18], and for high versus low ibuprofen dosage [10, 15]. Recently, a state-of-the-art meta-analyses of randomized controlled trials comparing pharmacotherapeutic interventions by Mitra et al in the JAMA came to the same conclusions, and besides found higher effectiveness for oral compared to intravenous administration [19]. In current practice, local interpretation of available evidence has led to a large variety of dosing regimens in clinical practice [20].…”

Section: Introductionmentioning

confidence: 94%

“…Namely, the risk of developing side effects and toxicity of nonsteroidal anti-inflammatory drugs seems related to peak concentrations, as continuous administration of indomethacin showed less side effects than an intermittent regimen [29]. In addition, the meta-analyses by Mitra et al 2018 found that a continuous infusion of intravenous ibuprofen was associated with the lowest incidence of oliguria compared to all included intermittent dosing regimens [19]. …”

Section: Introductionmentioning

confidence: 99%

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Simulation-based suggestions to improve ibuprofen dosing for patent ductus arteriosus in preterm newborns

Flint

Heine

Spaans

et al. 2018

Eur J Clin Pharmacol

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PurposeIbuprofen is the drug of choice for treatment of patent ductus arteriosus (PDA). There is accumulating evidence that current ibuprofen-dosing regimens for PDA treatment are inadequate. We aimed to propose an improved dosing regimen, based on all current knowledge.MethodsWe performed a literature search on the clinical pharmacology and effectiveness of ibuprofen. (R)- and (S)-ibuprofen plasma concentration-time profiles of different dosing regimens were simulated using a population pharmacokinetic model and evaluated to obtain a safe, yet likely more efficacious ibuprofen exposure.ResultsThe most effective intravenous ibuprofen dosing in previous clinical trials included a first dose of 20 mg kg−1 followed by 10 mg kg−1 every 24 h. Simulations of this dosing regimen show an (S)-ibuprofen trough concentration of 43 mg L−1 is reached at 48 h, which we assumed the target through concentration. We show that this target can be reached with a first dose of 18 mg kg−1, followed by 4 mg kg−1 every 12 h. After 96 h postnatal age, the dose should be increased to 5 mg kg−1 every 12 h due to maturation of clearance. This twice-daily dosing has the advantage over once-daily dosing that an effective trough level may be maintained, while peak concentrations are substantially (22%) lower.ConclusionsWe propose to improve intermittent ibuprofen-dosing regimens by starting with a high first dose followed by a twice-daily maintenance dosing regimen that requires increase over time and should be continued until sufficient effect has been achieved.Electronic supplementary materialThe online version of this article (10.1007/s00228-018-2529-y) contains supplementary material, which is available to authorized users.

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2019 Update on Pediatric Medical Overuse

et al. 2020

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Association of Placebo, Indomethacin, Ibuprofen, and Acetaminophen With Closure of Hemodynamically Significant Patent Ductus Arteriosus in Preterm Infants

Abstract: PROSPERO Identifier: CRD42015015797.

Cited by 265 publications

References 103 publications

European Consensus Guidelines on the Management of Respiratory Distress Syndrome – 2019 Update

European Consensus Guidelines on the Management of Respiratory Distress Syndrome – 2019 Update

Simulation-based suggestions to improve ibuprofen dosing for patent ductus arteriosus in preterm newborns

2019 Update on Pediatric Medical Overuse

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