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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 outcomes 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., Competing Interests: Declaration of Competing Interest The authors declare that they do not have any conflicts of interest., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

Purpose: In labour, neuraxial analgesia is the standard in the provision of pain relief. However, the optimal mode of delivering epidural solution has not been determined, and some parturients may need an alternative to epidural analgesia. We sought to conduct a systematic review and network meta-analysis to compare continuous epidural infusion (CEI), programmed intermittent epidural bolus (PIEB), computer-integrated CEI, computer-integrated PIEB, patient-controlled epidural bolus (PCEA), fentanyl patient-controlled analgesia (PCA), and remifentanil PCA, either alone or in combination., Methods: We searched CENTRAL, CINAHL, Ovid Embase, Ovid Medline, and Web of Science for randomized controlled trials that included nulliparous and/or multiparous parturients in spontaneous or induced labour. The maintenance epidural solution had to include a low concentration local anesthetic and an opioid. Specific subgroups in the obstetric population such as preeclampsia were excluded. Network meta-analysis was performed with a frequentist method, and continuous and dichotomous outcomes are presented as mean differences and odds ratios, respectively, with 95% confidence intervals., Results: Overall, 73 trials were included. For the first coprimary outcome, the need for rescue analgesia, CEI was inferior to PIEB and PIEB + PCEA was superior to PCEA alone, with a low certainty of evidence given the presence of serious limitations and imprecision. The second coprimary outcome, the maternal satisfaction, was improved by PIEB + PCEA compared with CEI + PCEA and PCEA alone, with a low quality of evidence in view of the presence of serious limitations and imprecision. Fentanyl PCA increased the requirement for rescue analgesia and decreased maternal satisfaction relative to many methods of delivering epidural solution. In terms of secondary outcomes, PIEB increased analgesic efficacy compared with CEI, and PCEA reduced local anesthetic consumption at the expense of inferior analgesia relative to CEI and PIEB. PIEB + PCEA was superior to CEI + PCEA in regard to the pain score at 2 h and 4 h, consumption of local anesthetic, incidence of lower lower limb motor blockade and the rate of spontaneous vaginal delivery. Fentanyl and remifentanil PCA did not provide the same level of analgesia as all epidural methods, resulted in increasing analgesic ineffectiveness with time spent in labour, and predisposed to a higher incidence of side effects such as nausea and/or vomiting and sedation. Remifentanil PCA was superior to fentanyl PCA for analgesia at an early time point, and it increased the incidence of oxygen desaturation relative to other strategies of delivering epidural solution., Conclusions: Opioid PCA did not provide the same level of analgesia as epidural methods with a higher incidence of side effects. We interpret the findings of our systematic review and network meta-analysis as suggesting PIEB + PCEA to be the optimal delivery mode of epidural solution. Nevertheless, the potential differing importance of the various maternal, fetal, and neonatal outcomes in determining which is optimal has not, to our knowledge, been elucidated yet., Study Registration: PROSPERO (CRD42021254978); registered 27 May 2021., (© 2023. Canadian Anesthesiologists' Society.)

Purpose: Carbetocin has been shown to reduce the requirement for additional uterotonics in women exclusively undergoing elective Cesarean delivery (CD). The aim of this review was to determine whether this effect could also be demonstrated in the setting of non-elective CD., Methods: Medline, Embase, CINAHL, Web of Science and Cochrane databases were searched for randomized-controlled trials (RCTs) in any language comparing carbetocin to oxytocin. Studies with data on women undergoing non-elective CD, where carbetocin was compared with oxytocin, were included. The primary outcome was the need for additional uterotonics. Secondary outcomes included incidence of blood transfusion, estimated blood loss (mL), incidence of postpartum hemorrhage (PPH; > 1000 mL) and mean hemoglobin drop (g·dL -1 RESULTS: Five RCTs were included, with a total of 1,214 patients. The need for additional uterotonics was reduced with carbetocin compared with oxytocin (odds ratio, 0.30; 95% CI, 0.11 to 0.86; I 2 , 90.60%). Trial sequential analysis (TSA) confirmed that the information size needed to show a significant reduction in the need for additional uterotonics had been exceeded. No significant differences were shown with respect to any of the secondary outcomes, but there was significant heterogeneity between the studies., Conclusions: Carbetocin reduces the need for additional uterotonics in non-elective CD compared with oxytocin. TSA confirmed that this analysis was appropriately powered to detect the pooled estimated effect. Further trials utilizing consistent core outcomes are needed to determine an effect on PPH., Trial Registration: PROSPERO CRD42019147256, registered 13 September 2019.