Oxytocin dosing during trial of labor after cesarean to minimize the risk of uterine rupture: a systematic review and meta-analysis

OBJECTIVE: Oxytocin remains the mainstay for induction and for the management of labor arrest during trial of labor after cesarean (TOLAC). Therefore, the clinical question should be not whether to use oxytocin, but how to optimize its administration. This meta-analysis aimed to assess which oxytocin protocol, in terms of initial dose, amount of increase, timing to next increase, and maximum dose, may minimize the risk of uterine rupture (UR) during TOLAC. DATA SOURCES: PubMed, Embase and Clinicaltrials.gov were searched up to September 21, 2024. STUDY ELIGIBILITY CRITERIA: Randomized and nonrandomized studies evaluating the association between induction and/or augmentation with oxytocin and UR during TOLAC versus spontaneous TOLAC were eligible. To be included, studies had to report at least one parameter of the oxytocin protocol used (ie, initial dose, amount of increase, timing to next increase, or maximum dose). The primary outcome was UR. METHODS: Effect measures were expressed as odds ratios (ORs) with 95% confidence intervals (CIs) and pooled using the Mantel-Haenszel method under a random-effects model. Oxytocin exposure was categorized to perform three separate meta-analyses, ie, any use (for induction and/or augmentation), for induction only, and for augmentation only. In all three comparisons, subgroup analyses assessed differences based on oxytocin initial dose (<= 2 vs >2 mU/min), amount of increase (<= 2 vs >2 mU/min), timing to next increase (<30 vs >= 30 minutes), and maximum dose (<= 20 vs >20 mU/min). RESULTS: Twenty-one observational studies with 51,511 patients undergoing TOLAC were included. Oxytocin use during TOLAC was consistently associated with a significantly higher risk of UR across all analyses (any use: OR 1.94, 95% CI 1.36-2.77, P=.0003; induction only: OR 2.07, 95% CI, 1.28-3.36, P=.003; augmentation only: OR 2.03, 95% CI 1.22-3.38; P=.007). Among oxytocin protocol parameters, the initial oxytocin dose showed no relationship with UR risk. A significant association was found in some analyses only for increments <= 2 mU/min, though the >2 mU/min subgroup was consistently underpowered. A higher risk of UR was uniformly observed when dose escalations were performed at intervals <30 minutes. Both moderate (<= 20 mU/min) and high (>20 mU/min) maximum doses were significantly associated with increased odds, with a greater risk at higher doses. CONCLUSIONS: These findings showed an association between oxytocin dosing during TOLAC and an increased risk of UR. Specifically, they suggest that both the timing and cumulative exposure of oxytocin, rather than the initial or incremental dose alone, may critically influence UR risk during TOLAC. Protocols adopting longer escalation intervals (>= 30 minutes) and limiting maximum doses (<= 20 mU/min) may enhance safety during TOLAC. Reliable evidence, such as that from randomized trials, is required to confirm these results and define the optimal oxytocin regimen in TOLAC management.