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Published on: August 19, 2020
Topical nitroglycerin ointment as salvage therapy for peripheral tissue ischemia in newborns: a systematic review
Katelyn Sushko1, Catherine Litalien2, Lauren Ferruccio2
1School of Nursing (Sushko), Faculty of Health Sciences, McMaster University, Hamilton, Ont.; Division of General Pediatrics (Litalien), Department of Pediatrics, and the Rosalind & Morris Goodman Family Pediatric Formulations Centre, Centre hospitalier universitaire Sainte-Justine, Université de Montréal, Montréal, Que.; Department of Pharmacy (Ferruccio), Hamilton Health Sciences, Hamilton, Ont.; Rosalind & Morris Goodman Family Pediatric Formulations Centre (Gilpin), Centre hospitalier universitaire Sainte-Justine, Université de Montréal, Montréal, Que.; Department of Emergency Medicine (Mazer-Amirshahi), MedStar Washington Hospital Center, Georgetown University School of Medicine, Washington, DC; Division of Pediatric Hematology/Oncology (Chan), McMaster Children's Hospital, McMaster University, Hamilton, Ont.; Division of Clinical Pharmacology (van den Anker), Department of Pediatrics, Children's National Hospital, Washington, DC; Division of Paediatric Pharmacology and Pharmacometrics (van den Anker), University Children's Hospital, University of Basel, Basel, Switzerland; Division of Neonatology (Lacaze-Masmonteil), Department of Pediatrics, University of Calgary, Alberta Children's Hospital, Calgary, Alta.; Division of Neonatology (Samiee-Zafarghandy), Department of Pediatrics, McMaster Children's Hospital, McMaster University, Hamilton, Ont. sushkokj@mcmaster.ca.
Background:
Topical nitroglycerin (TNG) ointment has been used for almost 3 decades to treat neonatal peripheral tissue ischemia, but this product is now no longer being produced by its Canadian manufacturer. Our aim was to investigate the efficacy and safety of TNG products in newborns in neonatal intensive care units.
Methods:
In this systematic review we searched Embase, CINAHL, MEDLINE, PubMed and Web of Science from inception to April 2020 for studies on the use of TNG products (TNG ointment, TNG spray, glyceryl trinitrate [GTN] patch) for the treatment of neonatal tissue ischemia. We did not apply language or study design limitations. Animal studies and duplicate records were excluded. Two reviewers screened and extracted data. The Tool for Evaluating the Methodological Quality of Case Reports and Case Series was used to assess the risk of bias of individual studies.
Results:
We included 23 articles (20 case reports, 2 case series and 1 retrospective audit) describing the use of TNG ointment, TNG spray or GTN patch in the treatment of 39 tissue ischemia events in 37 newborns. Twenty-three (62.2%), 12 (32.4%), 1 (2.7%) and 1 (2.7%) infants received TNG ointment, GTN patch, both TNG ointment and GTN patch, and TNG spray, respectively. Nineteen (76.0%) and 7 (53.8%) injuries treated with TNG ointment and GTN patch showed complete recovery, respectively. Two (16.7%) infants treated with GTN patch experienced adverse events (i.e., methemoglobinemia) requiring treatment discontinuation.
Interpretation:
TNG ointment presents a safe therapeutic modality for salvage therapy of neonatal tissue ischemia. Engagement of stakeholders is essential to address its recent commercial inaccessibility in Canada.
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