Influence of different volumes and frequency of programmed intermittent epidural bolus in labor on maternal and neonatal outcomes: A systematic review and network meta-analysis

Study objective: In labor, programmed intermittent epidural bolus (PIEB) can be defined as the bolus administration of epidural solution at scheduled time intervals. Compared to continuous epidural infusion (CEI) with or without patient controlled epidural analgesia (PCEA), PIEB has been associated with decreased pain scores and need for rescue analgesia and increased maternal satisfaction. The optimal volume and dosing interval of PIEB, however, has still not been determined. Design: Systematic review and network meta-analysis registered with PROSPERO (CRD42022362708). Settings: Labor. Patients: Pregnant patients. Interventions: Central, CINAHL, Global Health, Ovid Embase, Ovid Medline and Web of Science were searched for randomized controlled trials that examined pregnant patients in labor who received CEI or PIEB with or without a PCEA component. Network meta-analysis was performed with a frequentist method, facilitating the indirect comparison of PIEB with different volumes and dosing intervals through the common comparator of CEI and substituting or supplementing direct comparisons with these indirect ones. Continuous and dichotomous out-comes were presented as mean differences and odds ratios, respectively, with 95% confidence intervals. The risk of bias was evaluated using the Cochrane risk of bias 2 tool. Main results: Overall, 30 trials were included. For the first primary endpoint, need for rescue analgesia, PIEB delivered at a volume of 4 ml and frequency of 45 min (4/45) was inferior to PIEB 8/45 (OR 3.55; 95% CI 1.12-11.33), PIEB 10/60 was superior to PIEB 2.5/15 (OR 0.36; 95% CI 0.16-0.82), PIEB 4/45 (OR 0.14; 95% CI 0.03-0.71) and PIEB 5/60 (OR 0.23; 95% CI 0.08-0.70), and PIEB 5/30 was not inferior to PIEB 10/60 (OR 0.61; 95% CI 0.31-1.19). For the second primary endpoint, maternal satisfaction, no differences were present between the various PIEB regimens. The quality of evidence for these multiple primary endpoints was low owing to the presence of serious limitations and imprecision. Importantly, PIEB 5/30 decreased the pain score at 4 h compared to PIEB 2.5/15 (MD 2.45; 95% CI 0.13-4.76), PIEB 5/60 (MD-2.28; 95% CI-4.18--0.38) and PIEB 10/60 (MD 1.73; 95% CI 0.31-3.16). Mean ranking of interventions demonstrated PIEB 10/60 followed by PIEB 5/30 to be best placed to reduce the cumulative dose of local anesthetic, and this resulted in an improved incidence of lower limb motor blockade for PIEB 10/60 in comparison to CEI (OR 0.30; 95% CI 0.14-0.67). No differences in neonatal outcomes were found. Some concerns were present for the risk of bias in two thirds of trials and the risk of bias was shown to be high in the remaining one third of trials. Conclusions: Future research should focus on PIEB 5/30 and PIEB 10/60 and how the method of analgesia initiation, nature and concentration of local anesthetic, design of epidural catheter and rate of administration might influence outcomes related to the mother and neonate.