Papaverine administration during labor induction in nulliparous patients: a retrospective cohort study

To evaluate the association between papaverine administration during labor induction and maternal and neonatal outcomes among nulliparous patients, with particular emphasis on cesarean delivery, labor duration, and timing of administration relative to rupture of membranes.

Retrospective cohort study. Participants/Materials: The study included 1,889 nulliparous patients with singleton pregnancies who underwent medically indicated labor induction with intravenous oxytocin between January 2020 and December 2024. Patients were categorized according to papaverine exposure: no papaverine (n=1,185), one 80-mg intramuscular dose (n=618), or two 80-mg intramuscular doses (n=86).

A tertiary university-affiliated medical center in northern Israel.

Maternal, intrapartum, postpartum, and neonatal data were extracted from electronic medical records. The primary outcome was mode of delivery. Secondary outcomes included cesarean delivery due to non-progressive labor, delivery within 24 hours, postpartum hemorrhage, puerperal endometritis, 5-minute Apgar score <7, umbilical cord pH <7.2 and <7.1, and neonatal intensive care unit admission. Pairwise comparisons were performed between each papaverine group and the no-papaverine group using the independent-samples t test, Mann-Whitney U test, Pearson's chi-square test, or Fisher's exact test, as appropriate. A multivariable logistic regression model was used to evaluate factors associated with cesarean delivery. Mode of delivery was also evaluated according to the timing of papaverine administration relative to rupture of membranes.

Compared with no papaverine, one-dose papaverine administration was associated with a lower cesarean delivery rate (24.4% vs. 33.9%; RR 0.72, 95% CI 0.61-0.85; P<0.001), whereas the cesarean delivery rate did not differ significantly between the two-dose and no-papaverine groups (30.2% vs. 33.9%; P=0.484). Cesarean delivery due to non-progressive labor was less frequent with one dose compared with no papaverine (11.5% vs. 17.1%; RR 0.67, 95% CI 0.52-0.86; P=0.002), whereas no significant difference was observed between the two-dose and no-papaverine groups (20.9% vs. 17.1%; P=0.369). Delivery within 24 hours was more frequent with one dose than with no papaverine (65.0% vs. 53.9%; RR 1.21, 95% CI 1.12-1.30; P<0.001) and less frequent with two doses than with no papaverine (37.2% vs. 53.9%; RR 0.69, 95% CI 0.52-0.91; P=0.003). Vaginal delivery rates were highest when papaverine was administered before rupture of membranes (77.0%), followed by administration after rupture of membranes (73.0%) and no papaverine exposure (66.1%; P<0.001). In multivariable analysis, papaverine administration was independently associated with lower odds of cesarean delivery (adjusted OR 0.64, 95% CI 0.50-0.81; P<0.001). Maternal postpartum complications and neonatal outcomes were generally similar between groups.

The retrospective, single-center design may introduce selection bias and residual confounding. Papaverine administration was based on clinician discretion, and the relatively small two-dose group limited evaluation of dose-dependent effects. Long-term maternal and neonatal outcomes were not assessed.

Papaverine administration during labor induction, particularly as a single dose, was associated with a lower cesarean delivery rate and a greater likelihood of delivery within 24 hours, without an observed increase in adverse maternal or neonatal outcomes. Vaginal delivery was most frequent among patients who received papaverine before rupture of membranes; however, this exploratory finding requires prospective confirmation.