Pharmacological agents for prevention of pruritus in women undergoing Caesarean delivery with neuraxial morphine: a systematic review and Bayesian network meta-analysis.

BACKGROUND: Neuraxial opioids provide effective analgesia for Caesarean delivery, however, pruritus can be a troubling side-effect. Effective agents to prevent pruritus are needed. Our objective was to perform an updated systematic review and network meta-analysis to provide clinicians with a comparison of relative efficacy of available interventions to reduce the incidence of pruritus, induced by either intrathecal or epidural single-shot morphine, in women undergoing Caesarean delivery. METHODS: Databases systematically searched (up to January 2022) included PubMed MEDLINE, Web of Science, EBSCO CINAHL, Embase, LILACS, and two Cochrane databases. We included randomised, controlled trials involving adult female patients undergoing Caesarean delivery. We pooled trials comparing interventions used for preventing pruritus after Caesarean delivery and performed a Bayesian model network meta-analysis. RESULTS: The final primary network included data from comparisons of 14 distinct interventions (including placebo) used to reduce the incidence of pruritus in 6185 participants. We judged five interventions to be 'definitely superior' to placebo: propofol, opioid agonist-antagonists (neuraxial), opioid antagonists, opioid agonist-antagonists (systemic), and serotonin antagonists. For the network evaluating the incidence of severe pruritus (warranting additional therapeutic treatment of pruritus), data were available for 14 interventions (including placebo) in 4489 patients. For this outcome, we judged three interventions to be 'definitely superior' to placebo: dopamine antagonists (neuraxial) and systemic and neuraxial opioid agonist-antagonists. CONCLUSION: Our analysis found several interventions to be effective in reducing the incidence of pruritus. Although sub-hypnotic doses of propofol appear to have an antipruritic effect, replication of this finding and further investigation of optimal dosing are warranted. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42022367058).

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.

Vasopressor drugs for the prevention and treatment of hypotension during neuraxial anaesthesia for Caesarean delivery: a Bayesian network meta-analysis of fetal and maternal outcomes.

BACKGROUND: The optimal choice of vasopressor drugs for managing hypotension during neuraxial anaesthesia for Caesarean delivery is unclear. Although phenylephrine was recently recommended as a consensus choice, direct comparison of phenylephrine with vasopressors used in other healthcare settings is largely lacking. Therefore, we assessed this indirectly by collating data from relevant studies in this comprehensive network meta-analysis. Here, we provide the possible rank orders for these vasopressor agents in relation to clinically important fetal and maternal outcomes. METHODS: RCTs were independently searched in MEDLINE, Web of Science, Embase, The Cochrane Central Register of Controlled Trials, and clinicaltrials.gov (updated January 31, 2019). The primary outcome assessed was umbilical arterial base excess. Secondary fetal outcomes were umbilical arterial pH and Pco2. Maternal outcomes were incidences of nausea, vomiting, and bradycardia. RESULTS: We included 52 RCTs with a total of 4126 patients. Our Bayesian network meta-analysis showed the likelihood that norepinephrine, metaraminol, and mephentermine had the lowest probability of adversely affecting the fetal acid-base status as assessed by their effect on umbilical arterial base excess (probability rank order: norepinephrine > mephentermine > metaraminol > phenylephrine > ephedrine). This rank order largely held true for umbilical arterial pH and Pco2. With the exception of maternal bradycardia, ephedrine had the highest probability of being the worst agent for all assessed outcomes. Because of the inherent imprecision when collating direct/indirect comparisons, the rank orders suggested are possibilities rather than absolute ranks. CONCLUSION: Our analysis suggests the possibility that norepinephrine and metaraminol are less likely than phenylephrine to be associated with adverse fetal acid-base status during Caesarean delivery. Our results, therefore, lay the scientific foundation for focused trials to enable direct comparisons between these agents and phenylephrine.

Perioperative gabapentin and post cesarean pain control: A systematic review and meta-analysis of randomized controlled trials.

Cesarean delivery occurs in roughly one third of pregnancies. Effective postoperative pain control is a goal for patients and physicians. Limiting opioid use in this period is important as some percentage of opioid naïve individuals will develop persistent use. Gabapentin is a non-opioid medication that has been used perioperatively to improve postoperative pain and limit opioid requirements. The goal of this study is to determine the efficacy of perioperative gabapentin in improving post cesarean delivery pain control. The following data sources were searched from their inception through October 2018: MEDLINE, Ovid, ClinicalTrials.gov, Sciencedirect, and the Cochrane Library at the CENTRAL Register of Controlled Trials. A systematic review of the literature was performed to include all randomized trials examining the effect of perioperative gabapentin on post cesarean delivery pain control and other postoperative outcomes. The primary outcome was the analgesic effect of gabapentin on post cesarean delivery pain, measured by visual analog scale (VAS; 0-100) or Numerical Rating Scale (NRS; 0-10) on movement 24 hours (h) postoperative. These scores were directly compared by multiplying all NRS scores by a factor of 10. Meta-analysis was performed using the random effects model of DerSimonian and Laird, to produce summary treatment effects in terms of mean difference (MD) with 95% confidence interval (CI). Six placebo controlled trials (n = 645) were identified as relevant and included in the meta-analysis. All studies included only healthy pregnant women (American Society of Anesthesiologist (ASA) physical status I or II) undergoing spinal anesthesia for cesarean delivery at term. Participants were randomized to either 600 mg oral gabapentin or placebo preoperatively and in one study the medications were also continued postoperatively. Pooled data showed that women who received gabapentin prior to cesarean delivery had significantly lower VAS pain scores at 24 h on movement (MD -11.58, 95% CI -23.04 to -0.12). VAS pain scores at other time points at rest or on movement were not significantly different for those who received gabapentin and placebo although there was a general trend toward lower pain scores for women receiving gabapentin. There was no significant between-group difference in use of additional pain medications, supplemental opioids, and maternal or neonatal side effects. There was higher pain control satisfaction at 12 and 24 h in the gabapentin versus placebo groups.

A Perioperative Course of Gabapentin Does Not Produce a Clinically Meaningful Improvement in Analgesia after Cesarean Delivery: A Randomized Controlled Trial.

BACKGROUND: Studies examining the efficacy of a single preoperative dose of gabapentin for analgesia after cesarean delivery (CD) have been inconclusive. The authors hypothesized that a perioperative course of gabapentin would improve analgesia after CD. METHODS: This single-center, randomized, double-blind, placebo-controlled, parallel-group, superiority trial was designed to determine the analgesic efficacy of a perioperative course of gabapentin when added to a multimodal analgesic regimen. Women scheduled for elective CD during spinal anesthesia were randomized to receive a perioperative oral course of either gabapentin (600 mg preoperatively followed by 200 mg every 8 h for 2 days) or placebo. Postoperative pain was measured at 24 and 48 h, at rest and on movement, on a visual analogue scale (VAS, 0 to 100 mm). The primary outcome was pain on movement at 24 h. Neonatal outcomes, opiate consumption, VAS satisfaction (0 to 100 mm), adverse effects, and persistent pain were also assessed. RESULTS: Baseline characteristics were similar between groups. There was a statistically significant but small reduction in VAS pain score (mean [95% CI]) on "movement" (40 mm [36 to 45] vs. 47 mm [42 to 51]; difference, -7 mm [-13 to 0]; P = 0.047) at 24 h in the gabapentin (n = 100) compared with control group (n = 97). There was more sedation in the gabapentin group at 24 h (55 vs. 39%, P = 0.026) but greater patient VAS satisfaction (87 vs. 77 mm, P = 0.003). CONCLUSIONS: A perioperative course of gabapentin produces a clinically insignificant improvement in analgesia after CD and is associated with a higher incidence of sedation.