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 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.

Comparison of different delivery modalities of epidural analgesia and intravenous analgesia in labour: a systematic review and network meta-analysis.

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.

RéSUMé: OBJECTIF: Pendant le travail obstétrical, l'analgésie neuraxiale constitue la norme de soins pour soulager la douleur. Néanmoins, le mode optimal d'administration de la solution péridurale n'a pas été déterminé et certaines parturientes pourraient avoir besoin d'une alternative à l'analgésie péridurale. Nous avons cherché à réaliser une revue systématique et une méta-analyse en réseau pour comparer l'analgésie péridurale par perfusion continue (APPC), l'administration programmée de bolus périduraux (PIEB), l'APPC intégrée par ordinateur, l'analgésie péridurale contrôlée par la patiente (l'APCP), l'analgésie contrôlée par la patiente (ACP) de fentanyl et l'ACP de rémifentanil, soit seules ou en combinaison. MéTHODE: Nous avons effectué des recherches dans les bases de données CENTRAL, CINAHL, Ovid Embase, Ovid Medline et Web of Science pour en tirer les études randomisées contrôlées incluant des parturientes nullipares et/ou multipares en travail spontané ou induit. La solution péridurale de maintien devait inclure un anesthésique local à faible concentration et un opioïde. Des sous-groupes spécifiques dans la population obstétricale, comme par exemple les parturientes atteintes de prééclampsie, ont été exclus. Une méta-analyse en réseau a été réalisée à l'aide d'une méthode fréquentiste, et les résultats continus et dichotomiques sont présentés sous forme de différences moyennes et de rapports de cotes, respectivement, avec des intervalles de confiance à 95 %. RéSULTATS: Au total, 73 études ont été incluses. Concernant le premier critère d'évaluation coprincipal, soit le besoin d'analgésie de secours, l'APPC était inférieure à la PIEB, et la PIEB + APCP était supérieure à l'APCP seule, avec un faible niveau de fiabilité des données probantes compte tenu de la présence de limitations et d'imprécisions importantes. Le deuxième critère d'évaluation coprincipal, soit la satisfaction maternelle, a été amélioré avec la PIEB + APCP comparativement à l'APPC + APCP et à l'APCP seule, avec une faible qualité de données probantes compte tenu de la présence de limitations et d'imprécisions importantes. L'ACP à base de fentanyl a augmenté le besoin d'analgésie de secours et diminué la satisfaction maternelle par rapport à de nombreuses méthodes d'administration de la solution péridurale. En termes de critères d'évaluation secondaires, la PIEB a amélioré l'efficacité analgésique par rapport à l'APPC, et l'APCP a diminué la consommation d'anesthésiques locaux au détriment d'une analgésie inférieure par rapport à l'APPC et à la PIEB. La PIEB + APCP était supérieure à l'APPC + APCP en ce qui a trait aux scores de douleur à 2 h et 4 h, à la consommation d'anesthésiques locaux, à l'incidence de bloc moteur des membres inférieurs et au taux d'accouchement vaginal spontané. Les ACP de fentanyl et de rémifentanil n'ont pas fourni le même niveau d'analgésie que toutes les méthodes péridurales et ont entraîné une augmentation de l'inefficacité analgésique avec le temps passé en travail actif, en plus de prédisposer les parturientes à une incidence plus élevée d'effets secondaires tels que les nausées et/ou vomissements et la sédation. L'ACP de rémifentanil était supérieure à l'ACP de fentanyl en début d'analgésie mais a augmenté l'incidence de désaturation en oxygène par rapport aux stratégies de livraison de la solution péridurale. CONCLUSION: L'ACP à base d'opioïdes n'a pas fourni le même niveau d'analgésie que les méthodes péridurales, avec une incidence plus élevée d'effets secondaires. Nous interprétons les résultats de notre revue systématique et de notre méta-analyse en réseau comme suggérant que la PIEB + APCP constitue le mode d'administration optimal de la solution péridurale. Néanmoins, la différence potentielle en importance des divers devenirs maternels, fœtaux et néonataux pour déterminer la modalité optimale n'a pas encore été élucidée, à notre connaissance. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42021254978); enregistrée le 27 mai 2021.

Comparison of local and regional anesthesia modalities in breast surgery: A systematic review and network meta-analysis.

STUDY OBJECTIVE: Moderate to severe postoperative pain occurs in up to 60% of women following breast operations. Our aim was to perform a network meta-analysis and systematic review to compare the efficacy and side effects of different analgesic strategies in breast surgery. DESIGN: Systematic review and network meta-analysis. SETTING: Operating room, postoperative recovery room and ward. PATIENTS: Patients scheduled for breast surgery under general anesthesia. INTERVENTIONS: Following an extensive search of electronic databases, those who received any of the following interventions, control, local anesthetic (LA) infiltration, erector spinae plane (ESP) block, pectoralis nerve (PECS) block, paravertebral block (PVB) or serratus plane block (SPB), were included. Exclusion criteria were met if the regional anesthesia modality was not ultrasound-guided. Network plots were constructed and network league tables were produced. MEASUREMENTS: Co-primary outcomes were the pain at rest at 0-2 h and 8-12 h. Secondary outcomes were those related to analgesia, side effects and functional status. MAIN RESULTS: In all, 66 trials met our inclusion criteria. No differences were demonstrated between control and LA infiltration in regard to the co-primary outcomes, pain at rest at 0-2 and 8-12 h. The quality of evidence was moderate in view of the serious imprecision. With respect to pain at rest at 8-12 h, ESP block, PECS block and PVB were found to be superior to control or LA infiltration. No differences were revealed between control and LA infiltration for outcomes related to analgesia and side effects, and few differences were shown between the various regional anesthesia techniques. CONCLUSIONS: In breast surgery, regional anesthesia modalities were preferable from an analgesic perspective to control or LA infiltration, with a clinically significant decrease in pain score and cumulative opioid consumption, and limited differences were present between regional anesthetic techniques themselves.

Carbetocin compared with oxytocin in non-elective Cesarean delivery: a systematic review, meta-analysis, and trial sequential analysis of randomized-controlled trials.

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; I2, 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.

RéSUMé: OBJECTIF: Il a été démontré que la carbétocine réduisait les besoins en utérotoniques supplémentaires exclusivement chez les femmes subissant un accouchement par césarienne planifié. L'objectif de ce compte rendu était de déterminer si cela pouvait également être démontré dans le cas d'un accouchement par césarienne non planifié. MéTHODE: Les bases de données Medline, Embase, CINAHL, Web of Science et Cochrane ont été passées en revue pour en extraire les études randomisées contrôlées (ERC), toutes langues confondues, comparant la carbétocine à l'ocytocine. Les études comportant des données concernant des femmes subissant un accouchement par césarienne non planifié et comparant la carbétocine à l'ocytocine ont été incluses. Le critère d'évaluation principal était le besoin d'utérotoniques supplémentaires. Les critères secondaires comprenaient l'incidence de transfusion sanguine, la perte de sang estimée (mL), l'incidence d'hémorragie postpartum (HPP; > 1000 mL) et la baisse moyenne du taux d'hémoglobine (g·dL−1). RéSULTATS: Cinq ERC ont été retenues, incluant 1214 patientes au total. Les besoins en utérotoniques supplémentaires étaient plus faibles lors de l'utilisation de carbétocine par rapport à l'ocytocine (rapport de cotes, 0,30; IC 95 %, 0,11 à 0,86; I2, 90,60 %). L'analyse séquentielle des essais a confirmé que la taille des informations démontrant une réduction significative du besoin d'utérotoniques supplémentaires avait été dépassée. Aucune différence significative n'a été démontrée en ce qui touchait nos critères d'évaluation secondaires, mais l'hétérogénéité des études était considérable. CONCLUSION: La carbétocine réduit le besoin d'utérotoniques supplémentaires lors d'un accouchement par césarienne non planifié comparativement à l'ocytocine. L'analyse séquentielle des essais a confirmé que cette analyse disposait de suffisamment de puissance pour détecter l'effet estimé pondéré. Des études supplémentaires portant sur des critères constants sont nécessaires afin de déterminer un effet sur l'HPP. ENREGISTREMENT DE L'éTUDE: PROSPERO CRD42019147256, enregistrée le 13 septembre 2019.