Evidence map›Paper›PMID 39410754›Full record

ArticleCardiology in the young2025

Pharmacoepidemiology of combination pulmonary vasodilator therapy in critically ill infants.

Karan R Kumar, Elizabeth C Ciociola, Kayla R Skinner, Gargi M Dixit, Sunshine Alvarez, Elijah K Benjamin, Jeffrey C Faulkner, Rachel G Greenberg, Reese H Clark, Daniel K Benjamin and 2 more

Abstract readMulticenter Study
In one paragraph

Article in Cardiology in the young, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Karan R KumarDepartment of Pediatrics, Duke University School of Medicine, Durham, NC, USA.ORCID https://orcid.org/0000-0001-9196-6350
Elizabeth C CiociolaUniversity of North Carolina School of Medicine, Chapel Hill, NC, USA.
Kayla R SkinnerDuke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA.
Gargi M DixitDuke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA.
Sunshine AlvarezDuke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA.
Elijah K BenjaminDuke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA.
Jeffrey C FaulknerDuke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA.
Rachel G GreenbergDepartment of Pediatrics, Duke University School of Medicine, Durham, NC, USA.
Reese H ClarkPediatrix Center for Research, Education, Quality, and Safety, Sunrise, FL, USA.
Daniel K BenjaminDepartment of Pediatrics, Duke University School of Medicine, Durham, NC, USA.
Christoph P HornikDepartment of Pediatrics, Duke University School of Medicine, Durham, NC, USA.ORCID https://orcid.org/0000-0001-7056-8759
Jan Hau LeeChildren's Intensive Care Unit, KK Women's and Children's Hospital, Singapore, Singapore.

Funding

COVID-19 Supplement - Center for Innovative TRIals in ChilDrEN and AdulTs (TRIDENT)U24TR001608 · NCATS · DUKE UNIVERSITY · PI BENJAMIN, DANIEL K., HERNANDEZ, ADRIAN · 2016 to 2022
$177.0M
NIH Summer Research Experience Programs (R25)R25HD076475 · NICHD · DUKE UNIVERSITY · PI BENJAMIN, DANIEL K. · 2013 to 2023
$1.1M
NCATS NIH HHS U24 TR001608NICHD NIH HHS R25 HD076475
6 · The paper itself

Abstract

backgroundNew drugs to target different pathways in pulmonary hypertension has resulted in increased combination therapy, but details of this use in infants are not well described. In this large multicenter database study, we describe the pharmacoepidemiology of combination pulmonary vasodilator therapy in critically ill infants.

methodsWe identified inborn infants discharged home from a Pediatrix neonatal ICU from 1997 to 2020 exposed to inhaled nitric oxide, sildenafil, epoprostenol, or bosentan for greater than two consecutive days. We compared clinical variables and drug utilisation between infants receiving simultaneous combination and monotherapy. We reported each combination's frequency, timing, and duration and graphically represented drug use over time.

resultsOf the 7681 infants that met inclusion criteria, 664 (9%) received combination therapy. These infants had a lower median gestational age and birth weight, were more likely to have cardiac and pulmonary anomalies, receive cardiorespiratory support, and had higher in-hospital mortality than those receiving monotherapy. Inhaled nitric oxide and sildenafil were most frequently used, and utilisation of combination and monotherapy for all drugs increased over time. Inhaled nitric oxide and epoprostenol were used in infants with a higher gestational age, earlier postnatal age, and shorter duration than sildenafil and bosentan. Dual therapy with inhaled nitric oxide and sildenafil was the most common combination therapy.

conclusionOur study revealed an increased use of combination pulmonary vasodilator therapy, favouring inhaled nitric oxide and sildenafil, yet with considerable practice variation. Further research is needed to determine the optimal combination, sequence, dosing, and disease-specific indications for combination therapy.

Indexed as

Critical IllnessHypertension, PulmonaryVasodilator AgentsAdministration, InhalationBosentanDrug Therapy, CombinationEpoprostenolFemaleHospital MortalityHumansInfantInfant, NewbornMaleNitric OxidePharmacoepidemiologyRetrospective StudiesBosentanEpoprostenolNitric OxideSildenafil CitrateVasodilator Agentscombination therapyinfantpharmacoepidemiologyPulmonary hypertensionpulmonary vasodilator

Identifiers

PMID39410754
PMCPMC12279383

What Socratic holds

Textmetadata
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.