July 2000

Nitroglycerin application during cesarean delivery: Plasma levels, fetal/maternal ratio of nitroglycerin, and effects in newborns.
David M, Walka MM, Schmid B, Sinha P, Veit S, Lichtenegger W. American Journal of Obstetrics & Gynecology. 182(4):955-961, 2000 Apr.

[see abstract below]

Commentary by Peter Dwane, M.D.

This paper quantifies the amount of drug to which the fetal circulation is exposed after a 250-500 mg bolus of nitroglycerin (GTN) is given intravenously to its mother, and corroborates the clinical impression that the human fetus tolerates this drug exposure well. However, the study sheds no light on the effect of GTN on the maternal circulation, and does not examine how the maternal consequences that this dose of drug, if used for any length of time, eventually effects the fetus

GTN is commonly used by anesthesiologists to produce acute uterine relaxation anti-, intra-, and postpartum. It is rapidly hydrolyzed by the adult liver. In fetuses, metabolism occurs primarily in the placenta. In sheep, GTN has been shown to inhibit spontaneous contractions, while causing mild maternal hypotension, without adverse fetal cardiovascular or acid-base changes. However, there are no large blinded, controlled studies of the effectiveness of GTN for acute uterine relaxation. And until this present study, there are no human studies of placental transfer/metabolism of GTN.

This randomized, controlled, double-blinded study of 97 patients in three groups: control (normal saline); 250 mg I.V. GTN; 500 mg I.V. GTN, was carried out on normal parturients having elective cesarean sections. At the time of uterine incision, an injection of 5cc of normal saline containing the study drug was made through an intravenous line placed in the patient's hand, which was then flushed with 100 cc of normal saline. One and five minutes after the injection of drug, maternal venous samples were drawn from a proximal venous site on the same extremity. The blood sample was separated, and the plasma was immediately frozen at -80 C0 for further gas-chromatography-mass spectroscopic analysis. In addition, arterial and venous blood samples were collected from the umbilical cord immediately after it was clamped and cut at delivery, and saved for the same analysis.

Unfortunately, there is no mention of either the anesthetic technique (general vs. regional), nor of the maternal cardiovascular effects of these doses of GTN, which are in the higher range of doses commonly used for the treatment of retained placenta and for external cephalic versions. However, the effects of the GTN on the newborn were clinically and statistically insignificant, in that the Apgar score, umbilical pH, newborn: heart rate and blood pressures were similar for all three study groups. And in none of the three newborns transferred to the neonatal department was there a casual relationship with the administration of GTN.

The F/M ratios of GTN were of the order of 0.002 - 0.005; i.e. the fetal levels were 1/400th to 1/200th those of the maternal venous GTN levels. This suggests that with GTN transfer, and/or placental uptake and metabolism, only a very small amount of GTN reaches the fetal central circulation. And as we have extrapolated from sheep studies and anecdotal clinical practice GTN has little or no effect on the newborn, in the absence of maternal hypotension.

ABSTRACTS