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Oxytocin is widely used to prevent atonic postpartum haemorrhage after caesarean delivery. Initial treatment failure rates are high and inadequate dosing may contribute. Excessive doses, however, are associated with serious adverse effects. The pharmacokinetic data from this context are sparse and there is a lack of data in the immediate postpartum minutes after an initiating bolus. The pharmacodynamic data from this context are exclusively from dose-effect studies, with some suggesting that higher doses of oxytocin are required to provide adequate uterine tone in obese compared with non-obese women. We aimed to perform a pharmacokinetic and pharmacodynamic study that would facilitate more precise weight-based oxytocin dosing. We measured arterial oxytocin concentration, uterine tone and haemodynamic parameters in 25 women in the first 40 min after exogenous oxytocin administration at elective caesarean delivery. Serum oxytocin concentrations varied considerably between individuals. We constructed a one-compartment pharmacokinetic model of exogenous oxytocin deposition, after its administration with an initiating bolus and a maintenance infusion, at elective caesarean delivery. Body weight was evaluated as a potential covariate but was not included in the model due to lack of statistically significant reduction in the objective function. We calculated the volume of distribution and clearance (mean [coefficient of variation]) as 156.1 l [18%] and 83 ml.s -1 [32%] but found no within-individual correlation between serum oxytocin concentration and uterine tone or haemodynamic parameters. In conclusion, we observed a large variation in serum oxytocin concentrations between individuals receiving similar doses of oxytocin and were unable to establish weight-based dosing of exogenous oxytocin at caesarean delivery. Our findings suggest that future studies on oxytocin pharmacokinetics would need large sample sizes. In the absence of such data, oxytocin dosing should continue to be guided by uterine tone assessments and adjusted according to a strategy based on the best evidence from dose-effect studies., (© 2023 Association of Anaesthetists.)

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)., (Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Introduction: Postpartum depression has costly consequences for the mother, baby, and society. Numerous pharmacological and non-pharmacological interventions are available for the prevention and treatment of postpartum depression. To date, no attempt has been made to synthesize the evidence from comparisons of interventions both within and across these categories., Methods: We will perform a systematic review of the literature and perform network meta-analysis of interventions to (a) prevent and (b) treat postpartum depression. This review will include studies of primiparous or multiparous women during pregnancy or within 12 months of delivery of their baby that assess either interventions initiated during pregnancy or within 1 year of childbirth. Comparators will be other eligible interventions or control conditions. The outcome of interests will be related to the antidepressant efficacy of the interventions as well as their acceptability. The published literature will be searched in Ovid MEDLINE 1946-, Embase.com 1947-, Scopus 1823-, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. The search will use a combination of standardized terms and keywords for postpartum depression, a sensitive search filter to limit for randomized controlled trials, and a librarian-created "humans" filter. The search results will be uploaded to the Covidence online systematic review platform (Veritas Health Information Ltd., Victoria, Australia) where two review team members will independently screen articles. We will extract data to include year of publication, language, country, participants (number, demographic data, eligibility criteria, psychiatric symptoms, and co-morbidities), characteristics of the intervention and control conditions, and reported outcomes. Risk of bias for each study will be assessed independently by two review authors using the RoB 2: A revised Cochrane risk of bias tool for randomized trials. Network meta-analysis will be performed using a Bayesian hierarchical model supplemented with a Markov chain Monte Carlo approach., Discussion: Postpartum depression is a devastating disease with long-lasting consequences. Given the numerous available interventions to both prevent and treat postpartum depression and the great number of studies comparing them, it is imperative that clinicians and patients are provided with an assessment of their comparative efficacy and acceptability., Systematic Review Registration: Prospero registration (CRD42022303247)., (© 2022. The Author(s).)

Background: Evidence suggests ketamine may prevent postpartum depression (PPD) after cesarean delivery (CD) although intolerability and inconvenience of administration are problematic. We assessed the feasibility of studying ketamine (0.5 mg/kg, via subcutaneous injection or 40-min intravenous infusion) to prevent PPD after CD., Methods: Twenty-three women scheduled for cesarean delivery under neuraxial anesthesia were randomized to one of three groups: subcutaneous ketamine (SC Group, n = 8), intravenous ketamine (IV Group, n = 8) or placebo (n = 7). We measured depression (Edinburgh Postpartum Depression Scale [EPDS]) scores pre-operatively and at 1, 2, 21 and 42 days postoperatively. Anxiety, adverse effects, surgical site pain and analgesic consumption were also assessed. Feasibility was assessed based on acceptability, burden of disease, ability to collect study data and, tolerability of interventions., Results: Baseline characteristics of groups were similar, however, more women in the placebo group had pre-existing anxiety disorder (p = 0.03). 20.7% (25/121) of those approached consented to participate and 34.8% (8/23), of those assessed, screened positive for depression in the postpartum (EPDS > 12). PPD screening data was complete in 78.3% (18/23). No differences were observed for any adverse effect outcomes except for fewer incidences of intraoperative shivering with ketamine (SC: 25%, IV: 0% and Placebo: 85.7%, p = 0.01). No statistically significant difference in positive screening for PPD was observed (SC: 14.3%, IV: 50% and Placebo: 42.9%, p = 0.58)., Conclusion: An RCT was judged to be feasible and there was no evidence of intolerability of either route of ketamine administration. Dispensing with the need for intravenous access makes the subcutaneous route a particularly attractive option for use in the postpartum population. Further examination of these interventions to prevent, and possibly treat, postpartum depression is warranted., Trial Registration: NCT04227704, January 14 th , 2020., (© 2022. The Author(s).)

Background: Postpartum hemorrhage causes a quarter of global maternal deaths. The World Health Organization recommends oxytocin as the first line agent to prevent hemorrhage during cesarean delivery. However, some randomized controlled trials suggest that other uterotonics are superior., Objective: We conducted a network meta-analysis comparing the ability of pharmacologic agents to reduce blood loss and minimize the need for additional uterotonics during cesarean delivery., Data Sources: We searched the Cochrane Central Register of Controlled Trials, Embase, and MEDLINE databases from inception to May 2020., Study Eligibility Criteria: We included randomized controlled trials that compared oxytocin, carbetocin, misoprostol, ergometrine, carboprost, or combinations of these in the prevention of postpartum hemorrhage during cesarean delivery., Methods: We performed a systematic review followed by an NMA in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Quality of the evidence was assessed with the Confidence in Network Meta-Analysis approach and Grading of Recommendations, Assessment, Development and Evaluations tool within the summary of findings table. Our primary outcomes were the estimated blood loss and need for additional uterotonics. Secondary outcomes included nausea and postpartum hemorrhage of >1000 mL. We performed sensitivity analyses to explore the influence of surgical context and oxytocin administration strategy., Results: A total of 46 studies with 7368 participants were included. Of those, 21 trials (6 agents and 3665 participants) formed the "estimated blood loss" network and, considering the treatment effects, certainty in the evidence, and surface under the cumulative ranking curve scores, carbetocin was assessed to probably be superior to oxytocin, but only in reducing the estimated blood loss by a clinically insignificant volume (54.83 mL; 95% confidence interval, 26.48-143.78). Misoprostol, ergometrine, and the combination of oxytocin and ergometrine were assessed to probably be inferior, whereas the combination of oxytocin and misoprostol was assessed to definitely be inferior to oxytocin. A total of 37 trials (8 agents and 6193 participants) formed the "additional uterotonic" network and, again, carbetocin was assessed to probably be superior to oxytocin, requiring additional uterotonics 185 (95% confidence interval, 130-218) fewer times per 1000 cases. Oxytocin plus misoprostol, oxytocin plus ergometrine, and misoprostol were assessed to probably be inferior, whereas carboprost, ergometrine, and the placebo were definitely inferior to oxytocin. For both primary outcomes, oxytocin administration strategies had a higher probability of being the best uterotonic, if initiated as a bolus., Conclusion: Carbetocin is probably the most effective agent in reducing blood loss and the need for additional uterotonics. Oxytocin appears to be more effective when initiated as a bolus., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Oxytocin is one of the most commonly used medications during labour and delivery. Recent insights from basic neuroscience research suggest that the uterotonic effects of oxytocin may arguably be trivial when compared with its profound effects on higher-order human behaviour. The purpose of this review is to highlight the potential consequences of manipulating oxytocinergic signalling during the peripartum period and its long-term impact on the maternal-infant dyad. We identified four domains where modulation of oxytocinergic signalling might be consequential: postpartum depression; breastfeeding; neurodevelopment; and chronic pain, and performed a literature search to address the impact of peripartum oxytocin administration. We have shown modest, but inconsistent, evidence linking peripartum oxytocin administration with postpartum depression. Breastfeeding success appeared to be negatively correlated with peripartum oxytocin exposure, perhaps secondary to impaired primitive neonatal reflexes and maternal-infant bonding. The association between perinatal oxytocin exposure and subsequent development of neurodevelopmental disorders such as autism in the offspring was weak, but these studies were limited by the lack of information on the cumulative dose. Finally, we identified substantial evidence for analgesic and anti-hypersensitivity effects of oxytocin which might partly explain the low incidence of chronic pain after caesarean birth. Although most data presented here are observational, our review points to a compelling need for robust clinical studies to better dissect the impact of peripartum oxytocin administration, and as stewards of its use, increase the precision with which we administer oxytocin to prevent overuse of the drug., (© 2021 Association of Anaesthetists.)

Post-dural puncture headache is one of the most undesirable complications of spinal anaesthesia. Previous pairwise meta-analyses have either compared groups of needles or ranked individual needles based on the pooled incidence of post-dural puncture headache. These analyses have suggested both the gauge and needle tip design as risk-factors, but failed to provide an unbiased comparison of individual needles. This network meta-analysis compared the odds of post-dural puncture headache with needles of varying gauge and tip design. We searched randomised controlled trials in medical databases. The primary outcome measure of the network meta-analysis was the incidence of post-dural puncture headache. Secondary outcomes were procedural failure, backache and non-specific headache. Overall, we compared 11 different needles in 61 randomised controlled trials including a total of 14,961 participants. The probability of post-dural puncture headache and procedural failure was lowest with 26-G atraumatic needles. The 29-G cutting needle was more likely than three atraumatic needles to have the lowest odds of post-dural puncture headache, although with increased risk of procedural failure. The probability rankings were: 26 atraumatic > 27 atraumatic > 29 cutting > 24 atraumatic > 22 atraumatic > 25 atraumatic > 23 cutting > 22 cutting > 25 cutting > 27 cutting = 26 cutting for post-dural puncture headache; and 26 atraumatic > 25 cutting > 22 cutting > 24 atraumatic > 22 atraumatic > 25 atraumatic > 26 cutting > 29 cutting > 27 atraumatic = 27 cutting for procedural success. Meta-regression by type of surgical population (obstetric/non-obstetric) and participant position (sitting/lateral) did not alter these rank orders. This analysis provides an unbiased comparison of individual needles that does not support the use of simple rules when selecting the optimal needle. The 26-G atraumatic needle is most likely to enable successful insertion while avoiding post-dural puncture headache but, where this is not available, our probability rankings can help clinicians select the best of available options., (© 2020 Association of Anaesthetists.)

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.

Rapid-onset epidural local anaesthesia can avoid general anaesthesia for caesarean delivery. We performed a Bayesian network meta-analysis of direct and indirect comparisons to rank speed of onset of the six local anaesthetics most often used epidurally for surgical anaesthesia for caesarean delivery. We searched Google Scholar, PubMed, EMBASE, Ovid, CINAHL and CENTRAL to June 2019. We analysed 24 randomised controlled trials with 1280 women. The mean (95%CrI) onset after bupivacaine 0.5% was 19.8 (17.3-22.4) min, compared with which the mean (95%CrI) speed of onset after lidocaine 2% with bicarbonate, 2-chloroprocaine 3% and lidocaine 2% was 6.4 (3.3-9.6) min faster, 5.7 (3.0-8.3) min faster and 3.9 (1.8-6.0) min faster, respectively. Speed of onset was similar to bupivacaine 0.5% after ropivacaine 0.75% and l-bupivacaine 0.5%: 1.6 (-1.4 to 4.8) min faster and 0.4 (-2.2 to 3.0) min faster, respectively. The rate (95%CrI) of intra-operative hypotension was least after l-bupivacaine 0.5%, 315 (236-407) per 1000, and highest after 2-chloroprocaine 3%, 516 (438-594) per 1000. The rate (CrI) of intra-operative supplementation of analgesia was least after ropivacaine 0.75% 48 (19-118) per 1000 and highest after 2-chloroprocaine 3%, 250 (112-569) per 1000., (© 2019 Association of Anaesthetists.)

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 Pco 2 . 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 Pco 2 . 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., (Copyright © 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Carbetocin has been found to be superior to oxytocin in terms of need for additional uterotonics and prevention of postpartum haemorrhage at caesarean delivery. However, this is based on combined data from labouring and non-labouring parturients and it remains unclear how effective carbetocin is in the purely elective setting. The aim of this review was to compare carbetocin to oxytocin in elective caesarean delivery., Methods: Medline, Embase, CINAHL, Web of Science, and the Cochrane databases were searched for randomised controlled trials in any language. The primary outcome was need for additional uterotonics. Secondary outcomes were mean blood loss, need for blood transfusion and incidence of postpartum haemorrhage >1000 mL., Results: Nine studies with a total of 1962 patients were included. Trial sequential analysis confirmed that the information size (n=1692) had surpassed that required (n=1166) in order to demonstrate a statistically significant reduction in the use of additional uterotonics. Need for additional uterotonics was reduced by 53% with carbetocin compared to oxytocin (OR 0.47, 95% CI 0.34 to 0.64; P <0.001, I 2 =63.5). The number needed-to-treat was 11. The risk of bias, data heterogeneity and inconsistency in reporting bleeding outcomes made it difficult to reach definite conclusions about prevention of PPH., Conclusions: Carbetocin is associated with a reduced need for additional uterotonics when compared with oxytocin at elective caesarean delivery. Standardisation of bleeding-related outcomes in studies is necessary to facilitate synthesis of data in future analyses., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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.

This is the remarkable story of survival against all the odds. A passenger had a myocardial infarction complicated by a witnessed cardiac arrest while on a commercial flight through some of the most remote airspace on the planet. Immediate cardiopulmonary resuscitation and use of an automatic external defibrillator achieved rapid return of spontaneous circulation. Passengers and crew worked effectively together, under the guidance of a physician, to provide critical care to the patient while the flight diverted so he could be transferred to an emergency hospital in Beijing for eventual thrombolysis and postresuscitation care. He made a rapid and full recovery to be discharged from hospital, neurologically intact, 10 days later., (2014 BMJ Publishing Group Ltd.)