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1.
Preventing postpartum hemorrhage: A network meta-analysis on routes of administration of uterotonics
Papadopoulou, A., Tournas, G., Georgiopoulos, G., Antsaklis, P., Daskalakis, G., Coomarasamy, A., Devall, A. J.
European journal of obstetrics, gynecology, and reproductive biology. 2024;295:172-180
Abstract
1. OBJECTIVE To perform a network meta-analysis to specify the route of administration that maximises the effectiveness of each of the available prophylactic uterotonics without increasing the risk for side effects. 2. DATA SOURCES Literature searches on 12th September 2022 included: CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. The reference lists of the retrieved study records were also searched. 3. STUDY ELIGIBILITY CRITERIA Population: Randomized controlled trials involving women in the third stage of labour after a vaginal or caesarean delivery in hospital or community settings. INTERVENTIONS Systemically administered prophylactic uterotonics of any route and dose for primary postpartum hemorrhage prevention. Comparison: Any other prophylactic uterotonic, or a different route or dose of a given uterotonic, or placebo, or no treatment. Outcomes (primary): postpartum hemorrhage ≥ 500 mL and ≥ 1000 mL. 4. STUDY APPRAISAL AND SYNTHESIS METHODS Risk of bias and trustworthiness assessments were performed, according to Cochrane's guidance. Direct, indirect and network meta-analyses were conducted, and results were summarized either as risk ratio or mean difference with 95% confidence intervals for dichotomous and continuous outcomes, respectively. The certainty of generated evidence was assessed according to the GRADE approach. Cumulative probabilities were calculated and the surface under the cumulative ranking curve was used to create a ranking of the available drugs. 5. RESULTS One hundred eighty-one studies involving 122,867 randomised women were included. Most studies were conducted in hospital settings in lower-middle income countries and involved women delivering vaginally. When compared with intramuscular oxytocin, carbetocin (RR 0.58, 95 % CI 0.40-0.84) and oxytocin (RR 0.75, 95 % CI 0.59-0.97) by an intravenous bolus, and intramuscular ergometrine plus oxytocin combination (RR 0.71, 95 % CI 0.56-0.91) are probably more effective in preventing primary postpartum hemorrhage. Intramuscularly administered oxytocin and carbetocin by an intravenous bolus have a favourable side effects profile. 6. CONCLUSIONS Generated evidence was generally moderate and global inconsistency was low. Carbetocin and oxytocin by an intravenous bolus, and intramuscular ergometrine plus oxytocin combination are probably the top uterotonics for primary postpartum hemorrhage prevention. Large scale studies exploring different routes of administration for available prophylactic uterotonics, and women's views should be conducted.
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2.
Efficacy and safety of rectal misoprostol versus intravenous oxytocin on reducing blood loss in cesarean section: A PRISMA-compliant systematic review and meta-analysis of randomized clinical trials
Albazee, E., Soliman, A., Albakri, K., Elbanna, M., Moussa, N. A., Faragalla, H. M.
Turkish journal of obstetrics and gynecology. 2023;20(2):142-153
Abstract
Blood loss is an inevitable complication and a major contributor to maternal morbidity and mortality at cesarean deliveries. We detected a potential preference regarding the efficacy and safety of rectal misoprostol over oxytocin as a uterotonic agent. We searched PubMed, Scopus, Web of Science, Cochrane, and other databases for the relevant trials from inception to September 2022. We included randomized clinical trials (RCTs) that compared rectal misoprostol versus intravenous oxytocin to control bleeding in women undergoing cesarean delivery. Our primary outcomes were the intra- and postoperative blood loss, and hemoglobin drop after delivery. Secondary outcomes included the need for blood transfusion, need for additional uterotonics, difference in operative time, as well as safety outcomes such as the incidence of shivering, pyrexia, nausea, and vomiting. Our search strategy revealed 1007 unique records, of them we retrieved full texts of 19 articles to check their adherence to our eligibility criteria. Seven RCTs with 1,090 participants were included. We found a significant reduction in postoperative blood loss [MD: -27.9; 95% confidence interval (CI): (-53.85, -2.10); p=0.03], and Hb drop after delivery [MD: -11; 95% CI: (-0.19, -0.03); p=0.01]. There is no significant difference regarding intraoperative blood loss, operative time, need for blood transfusion, or need for additional uterotonics. We could not find a significant difference between the two groups regarding safety outcomes, except for a higher shivering incidence in the misoprostol group [RR: 0.33; 95% CI; (0.16, 0.70); p=0.004]. We found a significant reduction in postoperative blood loss with a potentially favorable safety profile in women who administrated rectal misoprostol compared with oxytocin administration. Our findings recommend and prefer rectal misoprostol as a cheaper and effective uterotonic agent over oxytocin, which is expensive and requires an adequate cold chain for transportation and storage.
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3.
Desmopressin to prevent and treat bleeding in pregnant women with an inherited bleeding disorder: A systematic literature review
Al Arashi, W., Romano, L. G. R., Leebeek, F. W. G., Kruip, Mjha, van Galen, K. P. M., Turan, O., Kadir, R. A., Cnossen, M. H.
Journal of thrombosis and haemostasis : JTH. 2023
Abstract
BACKGROUND Although desmopressin (DDAVP) is an accessible and inexpensive hemostatic drug, its use in pregnancy is still debated due to safety uncertainties. OBJECTIVE We aim to review safety and effectiveness of DDAVP in women with an inherited bleeding disorder during pregnancy and delivery. METHODS Databases were searched for articles up to July 25(th) 2022, reporting maternal and/or neonatal outcomes. PRISMA methodology was followed (PROSPERO CRD42022316490). RESULTS Fifty-three studies were included, comprising 273 pregnancies. Regarding maternal outcomes, DDAVP was administered in 73 pregnancies during pregnancy and in 232 pregnancies during delivery. Safety outcome was reported in 245 pregnancies, with severe adverse event reported in two (1%; hyponatremia with neurological symptoms).Overall, DDAVP was used as monotherapy in 234 pregnancies with effectiveness reported in 153 pregnancies (82% effective; 18% ineffective). Regarding neonatal outcomes, out of 60 pregnancies with reported neonatal outcomes after DDAVP use during pregnancy, two children (3%) had a severe adverse event (preterm delivery n=1; fetal growth restriction n=1). Of the 232 deliveries, 169 neonates were exposed to DDAVP during delivery and in 114 neonates, safety outcome was reported. Two children (2%) experienced a moderate adverse event (low Apgar score n=1; transient hyperbilirubinemia not associated with DDAVP n=1). CONCLUSION DDAVP use during pregnancy and delivery seems safe for the mother with special attention to the occurrence of hyponatremia and for the child, especially during delivery. However, due to poor study designs and limited documentation of outcomes, a well-designed prospective study is warranted.
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4.
Side-effects of intravenously versus intramuscularly oxytocin for postpartum hemorrhage: a systematic review and meta-analysis of randomized controlled trials
Ai, W., Zeng, Y., Zhen, M., Lao, L., Ma, Y., Liu, L., Zhang, Y.
Frontiers in pharmacology. 2023;14:1273771
Abstract
Background: Oxytocin is the gold standard uterotonic agent for prevention of postpartum hemorrhage. However, there is no consensus with clear evidence about the side-effects of oxytocin administered intravenously or intramuscularly for management of the third stage of labor. We conducted a systematic review and meta-analysis of randomized controlled trials to evaluate the side-effects of intravenously or intramuscularly oxytocin for preventing postpartum hemorrhage in the third stage of labor. Methods: Six representative databases were searched from the inception to July 2023. Randomized controlled trials which explored the intravenously and intramuscularly oxytocin and provided at least one side-effect were included. Statistical analysis included random or fixed-effect meta-analyses using relative risk. Results: Nine studies included, involving 8,295 participants. Ten types of side-effects were reported. There was no statistical difference in hypotension (RR = 1.01, 95%CI = 0.88-1.15), anemia (0.98, 0.83-1.15), tachycardia (0.90, 0.69-1.17), shivering (0.90, 0.69-1.17), headache (0.86, 0.31-2.37), nausea (0.70, 0.20-2.42), vomiting (0.97, 0.26-3.58), uvular edema (0.82, 0.23-2.91), diarrhea (0.97, 0.26-3.58), and fever (0.97, 0.26-3.58) between intravenously or intramuscularly groups. Conclusion: There are no significant differences of side-effects between intravenously and intramuscularly administration of oxytocin for preventing postpartum hemorrhage in the third labor. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=407571.
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5.
The use of a short course of Ulipristal Acetate for acute abnormal uterine bleeding in women without uterine fibroids
Lambrecht, I., Van den Bosch, T.
Facts, views & vision in ObGyn. 2023;15(2):99-105
Abstract
BACKGROUND Ulipristal Acetate (UPA) is a synthetic selective progesterone receptor modulator. It is used as emergency contraception and to reduce pain and blood loss in women of reproductive age with uterine fibroids. The first mechanism of action is myometrial apoptosis, the second is on the hypo-thalamic-pituitary-ovarian axis and the third action, is an anti-proliferative effect on the endometrium. Mainly based on the latter two, UPA is increasingly used off-label in women with abnormal uterine bleeding (AUB) without fibroids. OBJECTIVES The aim of this paper is to find evidence for a short course of UPA to treat acute AUB without fibroids, performing a systematic review as well as scrutinising literature data on the pharmacokinetics and on short term bleeding control in women with fibroids. MATERIALS AND METHODS A systematic electronic literature review was performed in February 2022. Inclusion criteria were UPA administered to women without myomas in a setting of acute uterine bleeding. Further criteria included papers describing early bleeding control using UPA, deemed independent of the presence of fibroids, with specific attention to the median time to amenorrhoea. MAIN OUTCOME MEASURES The main outcome measured was the bleeding control within 10 days. RESULTS One case report was identified. The data on symptomatic women with fibroids using 5 mg or 10 mg daily revealed bleeding control was reported within 10 days in 81% and 89% respectively, with amenorrhoea in 57% and in 78% respectively. CONCLUSION A short-term administration may prove effective in abnormal uterine bleeding irrespective of the presence of uterine fibroids. However, more randomised controlled trials are needed and should be performed before implementation in general clinical practice. WHAT IS NEW? A short course of Ulipristal acetate as promising treatment for acute uterine bleeding without fibroids.
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6.
The efficacy of misoprostol in reducing intraoperative blood loss in women undergoing elective cesarean section. A systematic review and meta-analysis
Maged AM, Wali AA, Metwally AA, Salah N
The journal of obstetrics and gynaecology research. 2022
Abstract
OBJECTIVES To evaluate the efficacy of misoprostol to minimized blood loss during and after cesarean delivery (CD). SEARCH STRATEGY Screening of MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials from inception to February 2021 using the keywords related to misoprostol, CD, postpartum hemorrhage, and intraoperative blood loss and their MeSH terms. SELECTION CRITERIA Only RCTs were included. Participants included women undergoing CD whether elective or selective. Thirty studies including 6593 women, 26 in English, 2 in Thai, 1 in French, and 1 in Chinese. DATA COLLECTION AND ANALYSIS Data from all selected studies were extracted independently by two authors. Data extracted included location of the trial, sample size, inclusion and exclusion criteria, participants characteristics, intervention details including timing, dose, and route of drug administration. Outcomes assessed included estimated intraoperative and postoperative blood loss, occurrence of postpartum hemorrhage, the need for additional uterotonics, and hemoglobin difference. MAIN RESULTS Four studies (968 women) compared preoperative to postoperative misoprostol and found a mean difference in intraoperative blood loss of -205.00 (-339.22, -70.77), p = 0.003 and in postoperative blood loss -216.27 (-347.08, -85.46), p < 0.001 and a significantly lower need for additional uterotonics with a risk ratio of 0.54 (0.46, 0.64), p < 0.00001. Twenty-two studies (4701 participants) compared misoprostol to oxytocin. There was a mean difference in intraoperative blood loss of -108.43 (-156.04, -60.82), p < 0.0001. Nine of these trials with 1978 participants evaluated postoperative blood loss. These found a mean difference of -64.12 (-116.19, -12.04) with a p = 0.02. Fourteen trials with 3166 participants measured the difference between preoperative and postoperative hemoglobin. These found a mean difference of -0.25 (-0.35, -0.15) with a p < 0.001. Twenty trials with 4416 participants measured the need for administration of additional uterotonics. These found a risk ratio of 0.62 (0.49, 0.78) with a p value of <0.001. CONCLUSION The combined use of misoprostol and oxytocin during CD is effective in reducing blood loss during and after CD.
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7.
Efficacy and Safety of Carbetocin Versus Misoprostol in Cesarean Section: A Systematic Review and Meta-Analysis
Albazee, E., Sadan, M., Alenezi, A. M., Almutairi, A. N., Alenezi, M. M., Almonayea, L. E.
Cureus. 2022;14(12):e32901
Abstract
In the absence of comprehensive data investigating carbetocin versus misoprostol for reducing postpartum hemorrhage (PPH) during cesarean section (CS), we performed this investigation to compare the efficiency and side events of carbetocin versus misoprostol in the protection and reduction of PPH for women who underwent CS. From inception to September 2022, we depended on searching through various databases for eligible trials involving Cochrane, Web of Science, PubMed, Scopus, and Google Scholar. From the efficacy prospect, we found that carbetocin substantially decreased intraoperative blood loss (p<0.001), hemoglobin/hematocrit levels (p<0.001), and the need for blood transfusion (p=0.002)/additional surgical interventions (p=0.003) than misoprostol. However, we revealed no substantial variation between both drugs for the need for additional uterotonic agents (p=0.08). From the safety prospect, we found that incidences of fever (p=0.002), heat sensation (p=0.007), metallic taste (p=0.01), and shivering (p=0.0002) were lower in carbetocin administration than in misoprostol. However, headache (p=0.34) and palpitation (p=0.11) incidences revealed no substantial variation between both drugs. In conclusion, from the efficacy and safety prospect, for women who underwent CS, carbetocin is more effective and safer in preventing and reducing PPH than misoprostol.
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8.
Preventing postpartum hemorrhage after cesarean delivery: a network meta-analysis of available pharmacologic agents
Jaffer, D., Singh, P. M., Aslam, A., Cahill, A. G., Palanisamy, A., Monks, D. T.
American Journal of Obstetrics and Gynecology. 2022;226(3):347-365
Abstract
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.
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9.
Preoperative Misoprostol to Reduce Blood Loss and Related Morbidities During Abdominal Hysterectomy: a Systematic Review and Meta-analysis of 10 Randomized Placebo-Controlled Trials
Abu-Zaid A, Mohammed YA, Baradwan S, Sayad R, Faraag E, Mohammed ER, Mohammed SM, Ashour AS
Reproductive sciences (Thousand Oaks, Calif.). 2022
Abstract
The objective of this study is to perform a meta-analysis of all randomized controlled trials (RCTs) that surveyed the efficacy and safety of preoperative misoprostol versus placebo during abdominal hysterectomy. Six databases were screened from inception until 3 August 2022. The eligible studies were assessed for risk of bias. The outcomes were summarized as mean difference (MD) and risk ratio (RR) with 95% confidence intervals (CI) in a random-effects model. Ten RCTs with 1076 patients (misoprostol = 537, placebo = 539 patients) were analyzed. Six and four RCTs had an overall low and high risk of bias (single-blinded), respectively. The mean intraoperative blood loss (n = 10 RCTs, MD = - 78.97 ml, 95% [- 130.89, - 27.06], p = 0.003), mean difference in hemoglobin drop (n = 10 RCTs, MD = - 0.42 g/dl, 95% CI [- 0.69, - 0.14], p = 0.003), and mean length of hospital stay (n = 5 RCTs, MD = - 0.2 d, 95% CI [- 0.24, - 0.16], p < 0.001) were significantly reduced in favor of the misoprostol group compared with the placebo group. However, there were no significant differences between both groups regarding the mean operative time (n = 8 RCTs, MD = - 0.63 min, 95% CI [- 5.07, 3.81], p = 0.78), rate of perioperative blood transfusion (n = 7 RCTs, RR = 0.83, 95% CI [0.53, 1.3], p = 0.42), and rate of drug-related adverse events (i.e., nausea, vomiting, diarrhea, headache, chills, and fever). Leave-one-out sensitivity analyses revealed stability for all endpoints, except hospitalization stay. There was no publication bias for all endpoints, except perioperative blood transfusion. Among patients undergoing abdominal hysterectomy, preoperative administration of misoprostol was largely safe and linked to substantial decrease in blood loss-related morbidities.
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10.
Ascorbic Acid for Prevention of Intraoperative Blood Loss and Related Complications During Myomectomy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Abu-Zaid A, Alrashidi H, Almouh A, Abualsaud ZM, Saleh AM, Aldawsari SB, Alajmi MM, Alomar O
Cureus. 2022;14(11):e31571
Abstract
Leiomyomas are inherently well-vascularized neoplasms; thus, they are very vulnerable to bleeding-associated complications during myomectomy. Ascorbic acid has well-established functions in tissue healing and the prevention of bleeding tendencies. Several randomized controlled trials (RCTs) have explored the antihemorrhagic utility of ascorbic acid administration during myomectomy. This research aimed to systematically and meta-analytically summarize the clinical antihemorrhagic efficacy of ascorbic acid (i.e., the intervention arm) versus placebo/no treatment (i.e., the control arm) during myomectomy. We electronically searched six sources, i.e., PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, and Google Scholar. Our search was from inception until October 2022. We used the Cochrane Risk of Bias Scale (version 2) to assess the quality of the included studies. We summarized the effect sizes as the mean difference (MD) or risk ratio (RR) with a 95% confidence interval (CI) in a fixed-effects or random-effects model. Overall, three RCTs met the inclusion criteria, comprising a total of 193 patients: 99 patients were allocated to the ascorbic acid arm, whereas 94 patients were allocated to the control arm. The overall study quality was "low" and "some concerns" risk of bias in two and one RCT(s), respectively. There was no significant difference between the ascorbic acid and control arms regarding the mean intraoperative blood loss (n=2 RCTs, MD = -190.29 ml, 95% CI [-626.62, 246.05], p=0.39) and mean change in hemoglobin level (n=3 RCTs, MD = -0.26 mg/dl, 95% CI [-0.56, 0.04], p=0.09), respectively. Conversely, the ascorbic acid arm had statistically significant reductions in the mean operative time (n=3 RCTs, MD = -24.10 min, 95% CI [-30.67, -17.53], p<0.001) and the rate of blood transfusion (n=3 RCTs, RR=0.36, 95% CI [0.15, 0.87], p=0.02) compared with the control arm. No serious adverse events related to ascorbic acid were identified. In conclusion, ascorbic acid administration was associated with several beneficial effects, including reductions in mean operative time and rate of blood transfusion, but without affecting the mean intraoperative blood loss and mean change in hemoglobin level. In view of the limitations of the present meta-analysis, the use of ascorbic acid as an antihemorrhagic additive among patients undergoing myomectomy is not strongly recommended.