Preventing postpartum hemorrhage after cesarean delivery: a network meta-analysis of available pharmacologic agents.

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.

A randomized feasibility pilot-study of intravenous and subcutaneous administration of ketamine to prevent postpartum depression after planned cesarean delivery under neuraxial anesthesia.

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 14th, 2020.

Interventions to treat and prevent postpartum depression: a protocol for systematic review of the literature and parallel network meta-analyses.

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).

Did you hear the one about the policeman, the doctor and the pharmacist at 30000 feet?

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.