A randomized controlled trial comparing isosorbide dinitrate-oxytocin versus misoprostol-oxytocin at management of foetal intrauterine death

Autoři: Gabriel Arteaga-Troncoso aff001;  Aide E. Chacon-Calderon aff002;  Francisco J. Martinez-Herrera aff002;  Sylvia G. Cruz-Nuñez aff003;  Marcela Lopez-Hurtado aff004;  Aurora Belmont-Gomez aff005;  Alberto M. Guzman-Grenfell aff006;  Blanca E. Farfan-Labonne aff007;  Carlos J. Neri-Méndez aff003;  Francisco Zea-Prado aff003;  Fernando M. Guerra-Infante aff004
Působiště autorů: Department of Cellular Biology and Development, National Institute of Perinatology, Mexico City, Mexico aff001;  Department of Obstetrics and Gynecology, Women’s Clinic and Neonatology, Secretariat for National Defense, Mexico City, Mexico aff002;  Department of Obstetric and Gynecology, National Institute of Perinatology, Mexico City, Mexico aff003;  Department of Infectology and Immunology, National Institute of Perinatology, Mexico City, Mexico aff004;  Department of Clinical Pharmacology, National Institute of Perinatology, Mexico City, Mexico aff005;  Department of Immunobiochemistry, National Institute of Perinatology, Mexico City, Mexico aff006;  Department of Neurosciences, National Institute of Perinatology, Mexico City, Mexico aff007
Vyšlo v časopise: PLoS ONE 14(11)
Kategorie: Research Article
doi: 10.1371/journal.pone.0215718



The metabolic activity of endogenous nitric oxide (NO) and the medical use of nitrovasodilatory drugs like isosorbide dinitrate have been shown to be potential inducers inducers of cervical ripening prior to surgical evacuation of the uterus.


To assess the therapeutic efficacy and safety of combined isosorbide dinitrate-oxytocin in the management of intrauterine foetal death (IUFD).


Sixty women with IUFD after 20 weeks of gestation requesting uterine evacuation were randomly selected to receive isosorbide dinitrate gel solution (80 mg/1.5 mL; n = 30) or misoprostol gel solution (100 mcg/1.5 mL; n = 30) every 3 h with a maximum of four doses or until a Bishop score >7 was reached. Subsequently, patients received a high dose of intravenous oxytocin until complete uterus evacuation was achieved. Therapeutic efficacy was evaluated by mean the relative risk of the foetal expulsion based on comparison of event rates, and the proportion of women induced to labor at 7, 10 and 15 h after the administration of isosorbide dinitrate or misoprostol. Safety was assessed on the basis of woman´s vital signs and evaluation of adverse effects, including headache, abdominal pain, pelvic pain, lower back pain, nausea, dizziness and vomiting.


The foetal expulsion rate using the isosorbide dinitrate-oxytocin combination was approximately 4.4 times, and at least 2.1 times, the foetal expulsion rate with the misoprostol-oxytocin regimen at any given point in time. The proportion of women achieved vaginal delivery at 15 hours was 100% for the isosorbide dinitrate-oxytocin group and 86.7% for the misoprostol-oxytocin group. The average delivery induction interval was significantly lower when isosorbide dinitrate-oxytocin was used (8.7 ± 3.1 h) than when misoprostol-oxytocin (11.9 ± 3.1 h) was used. A total of 20% of patients in the isosorbide dinitrate-oxytocin group recorded headache, and no cases of uterine tachysystole, haemorrhage or coagulopathy were recorded.


This study indicates that intravaginal isosorbide dinitrate followed by intravenous oxytocin was more effective than the conventional method used to induce labour in the medical management of foetal death in pregnancies after 20 weeks of gestation.

Trial registration

Clinicaltrials.gov NCT02488642.

Klíčová slova:

Abdominal pain – Blood pressure – Fetal death – Headaches – Heart rate – Nitric oxide – Oxytocin – Pregnancy


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2019 Číslo 11