Maximum Oxytocin Dose and Uterine Rupture During Trial of Labor After Cesarean

To evaluate the association between maximum oxytocin dose and uterine rupture among individuals undertaking a trial of labor after cesarean (TOLAC). Secondarily, to evaluate the association between total time on oxytocin and time at maximum oxytocin dose and uterine rupture.

We conducted a secondary analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network Assessment of Perinatal Excellence study, an observational cohort of deliveries after 23 weeks of gestation across 25 U.S. hospitals from 2008 to 2011. Individuals with a singleton, cephalic, live fetus who had one prior cesarean delivery and were undertaking TOLAC, including those undergoing spontaneous, augmented, or induced labor, were included. Those with a contraindication to TOLAC or a fetus with an anomaly or known genetic abnormality were excluded. The exposure was intrapartum oxytocin dose in milli-international units per minute (milli-international units/min), assessed both categorically (0, 1-20, more than 20 milli-international units/min) and continuously. The primary outcome was uterine rupture. Secondary outcomes were vaginal birth after cesarean (VBAC), blood transfusion, and intensive care unit (ICU) admission. Trends in outcomes by oxytocin were assessed using the Cochran-Armitage trend test. Multivariable modeling estimated the association between maximum oxytocin dose (both as a categorical and continuous variable) and outcomes. The duration of any oxytocin, the duration at the maximum dose of oxytocin, and outcomes were assessed.

Of 5,201 individuals undergoing TOLAC, 3,406 (65.5%) received 0 milli-international units/min of oxytocin, 1,659 (31.9%) received 1-20 milli-international units/min, and 136 (2.6%) received more than 20 milli-international units/min. The majority of the cohort (n=3,391) entered spontaneous labor; 1,076 patients received augmentation and 733 were induced. The range of maximum oxytocin doses was 0-60 milli-international units/min. There were 37 cases of uterine rupture (0.7%, 95% CI, 0.5-0.9%). The frequency of uterine rupture by maximum oxytocin dose category was 0.2% (n=7) with no oxytocin (0 milli-international units/min), 1.6% (n=27) with an oxytocin dose of 1-20 milli-international units/min, and 2.2% (n=3) with oxytocin doses greater than 20 milli-international units/min. Higher maximum oxytocin doses were associated with a trend of an increase in uterine rupture (P<.001 Cochran-Armitage test of trend). In adjusted modeling, maximum oxytocin doses of 1-20 milli-international units/min and doses greater than 20 milli-international units/min were associated with uterine rupture (adjusted odds ratio [aOR] 8.82, 95% CI, 3.61-21.6; and aOR 11.0, 95% CI, 2.67-45.3, respectively), compared with 0 milli-international units/min; however, a higher maximum dose (more than 20 milli-international units/min) was not associated with uterine rupture (aOR 1.25, 95% CI, 0.37-4.22) when compared with a lower maximum dose of oxytocin (1-20 milli-international units/min). When analyzed as a continuous variable, a higher maximum oxytocin dose was associated with higher odds of uterine rupture (aOR 1.40 for each 5 milli-international units/min higher dose of oxytocin, 95% CI, 1.21-1.62) but also was associated with successful VBAC. Maximum oxytocin dose was not associated with blood transfusion or ICU admission. Longer duration of any intrapartum oxytocin and longer duration at maximum oxytocin dose also were associated with higher odds of uterine rupture.

Receipt of oxytocin at both lower and higher doses was associated with higher odds of uterine rupture across the full cohort when compared with no oxytocin exposure and also was associated with successful VBAC. Although a trend of increasing rupture with higher doses was observed, a maximum intrapartum higher dose (greater than 20 milli-international units/min) of oxytocin was not associated with uterine rupture when compared with lower dose. Thus, an upper safety threshold for maximum dose of oxytocin could not be identified.