Effect of transdermal nitroglycerin patch on severe preeclamptic women with abnormal Doppler indices


  • El-Sayed S. El-Ebshehy Department of Obstetrics and Gynecology, Tanta University, Tanta, Egypt
  • Ahmed M. Hagras Department of Obstetrics and Gynecology, Tanta University, Tanta, Egypt
  • Amr T. Elbadry Department of Obstetrics and Gynecology, Tanta University, Tanta, Egypt
  • Ahmed M. Awara Department of Obstetrics and Gynecology, Tanta University, Tanta, Egypt




Doppler ultrasound, Severe preeclampsia, Nitric oxide, Nitroderm patch


Background: The aim is to evaluate the effect of maternal transdermal nitro-glycerine patch administration on blood flow resistance on maternal uterine artery, fetal umbilical and middle cerebral arteries in patients with severe pre-eclampsia in early gestational age (24 weeks to 33 weeks) associated with abnormal Doppler indices (placental insufficiency) and also its effect on maternal mean arterial blood pressure.

Methods: This is a prospective interventional clinical trial conducted on (50) pregnant women with singleton pregnancy diagnosed with severe pre-eclampsia admitted in high-risk pregnancy unit at the Department of Obstetrics  in Tanta University Hospitals, A 50-mg transdermal GTN patch (Novartis Pharma) was applied to the abdominal skin, releasing nitroglycerin at a rate of 0.4 mg/h. Doppler ultrasonography and measurement of maternal blood pressure were performed before application of transdermal GTN patch, after 4 hours of application, after 24 hours and after 48 hours.

Results: the application of a 50-mg transdermal GTN patch to the maternal abdomen was associated with a significant decline in the PI of the uteroplacental and fetoplacental blood flow. No change was observed in the PI of the cerebral circulation. And also, there was a significant decrease in maternal blood pressure (MAP).

Conclusions: Nitroderm patch (nitric oxide donors) may be used as initial therapy in cases of severe preeclampsia complicated by placental insufficiency in the form of abnormal Doppler indices.


Abalos E, Cuesta C, Grosso AL, Chou D, Say L. Global and regional estimates of preeclampsia and eclampsia: a systematic review. Eur J Obstet Gynecol Reprod Biol. 2013; 170(1): 1–7. .

Ducat A, Doridot L, Calicchio R, Méhats C, Vilotte JL, Castille J, Barbaux S, et al: Endothelial cell dysfunction in the STOX1 model of preeclampsia. Sci Rep. 2016;6:19196.

Tuzcu ZB, Asicioglu E, Sunbul M, Ozben B, Arikan H, Koc M. Circulating endothelial cell number and markers of endothelial dysfunction in previously preeclamptic women. Am J Obstet Gynecol. 2015; 213(4):533.

Orabona R, Sciatti E, Vizzardi E, Bonadei I, Valcamonico A, Metra M et al: Endothelial dysfunction and vascular stiffness in women with a previous pregnancy complicated by early or late pre-eclampsia. Ultrasound Obstet Gynecol. 2017;49(1): 116-23.

Sakar MN, Atay AE, Demir S, Bakir VL, Demir B, Balsak D, et al: Association of endothelial nitric oxide synthase gene G894T polymorphism and serum nitric oxide levels in patients with preeclampsia and gestational hypertension. J Matern Fetal Neonatal Med. 2015;28(16):1907-11.

Zawiejska A, Wender-Ozegowska E, Iciek R, Brazert J. Concentrations of endothelial nitric oxide synthase, angiotensin-converting enzyme, vascular endothelial growth factor and placental growth factor in maternal blood and maternal metabolic status in pregnancy complicated by hypertensive disorders. J Hum Hypertens. 2014;28(11):670-6.

Du L, He F, Kuang L, Tang W, Li Y, Chen D. eNOS/iNOS and endoplasmic reticulum stress-induced apoptosis in the placentas of patients with preeclampsia. J Hum Hypertens. 2017;31(1):49.

Bhavina K, Radhika J, Pandian SS. VEGF and eNOS expression in umbilical cord from pregnancy complicated by hypertensive disorder with different severity. BioMed research international. 2014;2014.

Johal T, Lees CC, Everett TR, Wilkinson IB. The nitric oxide pathway and possible therapeutic options in pre-eclampsia. Br J Clin Pharmacol. 2014;78(2):244–57.

Hashimoto S, Kobayashi A: Clinical pharmacokinetics and pharmacodynamics of glyceryl trinitrate and its metabolites Clin Pharmacokinetics 2003;42(3):205-21.

Abdel Razik M, El-Berry S, Abosereah M, Edris Y, Sharafeldeen A. Prophylactic treatment for preeclampsia in high-risk teenage primigravidae with nitric oxide donors. J Matern Fetal Neonatal Med 2015; 16: 2617-2620.

Coleman MA, McCowan LM, North RA: Mid-trimester artery Doppler screening as a predictor of adverse pregnancy outcome in high-risk women. Ultrasound Obstet Gynecol. 2000;15(1):7-12.

Arduini D, Rizzo G, Normal values of pulsatility index from fetal vessels: a cross-sectional study on 1556 healthy fetuses. J Perinat Med.1990;18(3):165-72.

Dawoud MF, Salm, Said AF. Maternal and fetal evaluation in patients with preeclampsia managed by nitroglycerine transdermal patch. Tanta Med Sci J. 2007;2:240-53.

Kähler C, Schleußner E, Möller A, Seewald HJ. Nitric oxide donors: effects on fetoplacental blood flow. Europe J bstet Gynecol Reproduct Biol. 2004;115(1):10-4.

Trapani A, Gonçalves LF, Pires MD. Transdermal nitroglycerin in patients with severe pre‐eclampsia with placental insufficiency: effect on uterine, umbilical and fetal middle cerebral artery resistance indices. Ultrasound Obstet Gynecol. 2011;38(4):389-94.

Schleussner E, Lehmann T, Kähler C, Schneider U, Schlembach D, Groten T. Impact of nitric oxide donors pentaerythrityl-tetranitrate on perinatal outcome in risk pregnancies: a prospective randomised double blinded trial. J Perinat Med 2014.;42(4):507-14.

Grunewald C, Kublickas M, Carlström K, Lunell NO, Nisell H. Effects of nitroglycerin on the uterine and umbilical circulation in severe preeclampsia. Obstet Gynecol. 1995;86(4):600-4.

Chaudhuri G, Buga GM, Gold ME, Wood KS, Ignarro JL. Characterization and actions of human umbilical endotheliumderived relaxing factor. Br J Pharmacol. 1991;102(2):331-6.

Baschat AA, Gembruch U. The cerebroplacental Doppler ratio revisited. Ultrasound Obstet Gynecol 2003;21(2):124-7.

Cetin A, Yurtcu N, Guvenal T, Imir AG, Duran B, Cetin M. The effect of glyceryl trinitrate on hypertension in women with severe preeclampsia, HELLP syndrome, and eclampsia. Hypertens Pregnancy. 2004;23(1):37-46.

Manzur‐Verástegui S, Mandeville PB, Gordillo‐Moscoso A, Hernández‐Sierra JF, Rodríguez‐Martínez M. Efficacy of nitroglycerine infusion versus sublingual nifedipine in severe preeclampsia: a randomized, triple-blind, controlled trial. Clin Exp Pharmacol Physiol. 2008;35(5-6):580-5.

Cacciatore B, Halmesmäki E, Kaaja R, Teramo K, Ylikorkala O. Effects of transdermal nitroglycerin on impedance to flow in the uterine, umbilical, and fetal middle cerebral arteries in pregnancies complicated by preeclampsia and intrauterine growth retardation. Am J Obstet Gynecol. 1998;179(1):140-5.






Original Research Articles