Safety and efficacy of Ninjin'yoeito along with iron supplementation therapy for preoperative anemia, fatigue, and anxiety in patients with gynecological disease: an open-label, single-center, randomized phase-II trial
BMC women's health. 2022;22(1):229
BACKGROUND Preoperative anemia affects perioperative outcomes and often causes fatigue and psychological disorders. Therefore, anemia should be treated before a patient undergoes surgery. Ninjin'yoeito (NYT), a Japanese Kampo medicine composed of ginseng and Japanese angelica root with the other 10 herbs, is administered for anemia, fatigue and anxiety; however, there are a few reports that have prospectively examined the effects of NYT before surgery for gynecological diseases. Hence, we tended to investigate its efficacy and safety. METHODS In this open-label randomized trial, women with gynecological diseases accompanied by preoperative anemia (defined as < 11.0 g/dL Hemoglobin [Hb]) were randomly assigned (1:1) into the iron supplementation and NYT groups. Patients of the iron supplementation group and the NYT group received 100 mg/day iron supplementation with and without NYT (7.5 g/day) for at least 10 days before surgery. The primary endpoint was improvement in Hb levels before and after treatment, and Cancer Fatigue Scale (CFS) and Visual Analogue Scale for Anxiety (VAS-A) scores between groups. Statistical analyses were performed with Wilcoxon signed rank test, Wilcoxon rank sum test, and Fisher's exact test as appropriate. RESULTS Forty patients were enrolled of whom 30 patients were finally analyzed after allocating 15 to each group. There was no difference in the characteristics between both groups. Hb significantly increased in both groups (iron supplementation group, 9.9 ± 0.8 g/dL vs. 11.9 ± 1.6 g/dL; NYT group, 9.8 ± 1.0 g/dL vs. 12.0 ± 1.0 g/dL); the difference in the elevations in Hb between both groups was statistically insignificant (P = 0.72). Contrarily, CFS (17.9 ± 10.2 vs. 8.1 ± 5.2) and VAS-A (56 mm (50-70) vs. 23 mm (6-48)) scores were significantly decreased only in the NYT group and these changes were greater in the NYT group (∆CFS, P = 0.015; ∆VAS-A, P = 0.014). Liver dysfunction occurred in one patient of the NYT group. CONCLUSIONS For treating preoperative anemia in women with gynecological conditions, NYT administration along with iron supplementation safely and efficiently improved the preoperative fatigue and anxiety in addition to the recovery from anemia. TRIAL REGISTRATION jRCT1051190012 (28/April/2019, retrospectively registered).
The safty profile of blood salvage applied for collected blood with amniotic fluid during cesarean section
BMC pregnancy and childbirth. 2022;22(1):160
BACKGROUND The guidelines of National Health Service(NHS, the United Kingdom) recommended for use in obstetrics at increased risk of bleeding, requiring two suction devices to reduce amniotic fluid contamination, however, when comes to massive hemorrhage, it is may difficult to operate because the complex operation may delay time. The aim of the study was to detect the effect of amniotic fluid recovery on intraoperative cell salvage in obstetrics and provide evidence for clinical applications. METHOD Thirty-four patients undergoing elective cesarean section were randomly divided into two groups. In group 1, the cumulative blood from the operation field, including the amniotic fluid, was collected using a single suction device for processing. In group 2, after suctioning away the amniotic fluid using another suction device for the cumulative blood from the operation field. From each group, four samples were taken, including maternal venous blood (sample I), blood before washing (sample II), blood after washing (sample III) and blood after filtration with a leukocyte filter (sample IV), to detect serum potassium (K +), hemoglobin (Hb), white blood cell (WBC), fetal hemoglobin (HbF), alpha fetoprotein (AFP) and squamous cell (SC) levels. RESULTS The AFP, K + and WBC levels of sample III and sample IV were significantly lower than sample I in group 1 and group 2 (P < 0.05). Significantly more SCs were found in sample III than in sample I in group 1 and group 2 (P < 0.05), but SCs of sample IV had no statistical difference compared to sample I in group 1 and group 2 (P > 0.05). There was no significant difference in the K + , Hb, WBC, AFP and SC levels of sample IV between group 1 and group 2 (P > 0.05). The HbF levels of sample III and sample IV were significantly higher in group 1 than in group 2 (P < 0.05). CONCLUSION There is little or no possibility for AF contamination to enter the re-infusion system when used in conjunction with a leucodepletion filter. For maternal with Rh-negative blood, we recommend two suction devices to reduce HbF pollution. TRIAL REGISTRATION ChiCTR1800015684 , 2018.4.15.
Intravenous Tranexamic acid versus placebo during Caesarian section: A comparative study
Pakistan journal of medical sciences. 2022;38(5):1183-1187
OBJECTIVES To evaluate the effectiveness of Tranexamic Acid in preventing postpartum hemorrhage against placebo in high-risk women undergoing cesarean section. METHODS A double-blinded placebo-controlled comparative trial was conducted at the Obstetrics and Gynecology Department of Nishtar Hospital for one year, from 15(th) June 2020 to 15(th) June 2021. A total of 60 women who were at high risk of postpartum hemorrhage and had to undergo elective cesarean sections were included in the study. Among them, initial 30 patients were administered Tranexamic Acid before skin incision whereas later 30 were treated as the placebo group. These women were then observed for blood loss during surgery and within 24 hrs. after surgery and any postoperative complications such as thromboembolic events, the need for additional uterotonic agents, and blood transfusions. RESULTS Out of 60 women, 30 were placed in each group. The groups had no significant difference in terms of baseline data and post-partum hemorrhage-associated risk factors (p>0.05). However, the occurrence rate of primary post-partum hemorrhage (blood loss greater than 1000 ml) was significantly less in a tranexamic acid group than the placebo group (16.6% vs 60%, respectively, p<0.01). Similarly, the requirement of additional uterotonic agents (13.3% vs 43.3%, respectively) and the need for blood transfusion (6.0% vs 23.3%, respectively) was lower in a tranexamic group than in the placebo group. CONCLUSION The study highlighted the significance of tranexamic acid in controlling post-partum hemorrhages, the requirement of additional uterotonic agents, improving post-partum hemoglobin, and the need for blood transfusion.
Calcium chloride for the prevention of uterine atony during cesarean delivery: A pilot randomized controlled trial and pharmacokinetic study
Journal of clinical anesthesia. 2022;80:110796
STUDY OBJECTIVE To assess the feasibility, patient tolerance, pharmacokinetics, and potential effectiveness of a randomized controlled trial protocol investigating intravenous calcium chloride for the prevention of uterine atony during cesarean delivery. DESIGN Double-blind, randomized controlled pilot trial with nested population pharmacokinetic analysis. SETTING This study was performed at Lucile Packard Children's Hospital, from August 2018 to September 2019. PATIENTS Forty patients with at least two risk factors for uterine atony at the time of cesarean delivery. INTERVENTIONS One gram of intravenous calcium chloride (n = 20 patients) or a saline placebo control (n = 20 patients), in addition to standard care with oxytocin, upon umbilical cord clamping. MEASUREMENTS The primary efficacy-related outcome was the presence of uterine atony defined as the use of a second-line uterotonic medication, surgical interventions for atony, or hemorrhage with blood loss >1000 mL. Blood loss, uterine tone numerical rating scores, serial venous blood calcium levels, hemodynamics, and potential side effects were also assessed. MAIN RESULTS The study protocol proved feasible. The incidence of atony was 20% in parturients who received calcium compared to 50% in the placebo group (relative risk 0.38, P = 0.07, 95% CI 0.15-1.07, NNT 3.3). Calcium recipients tolerated the drug infusion well, with no adverse events and an equal incidence of potential side effects in the calcium and placebo groups. Ionized calcium concentration rose significantly in all patients who received calcium infusion, from baseline 1.18 mmol/L to peak levels 1.50-1.60 mmol/L. One-compartment population pharmacokinetics established clearance of 0.93 (95% CI 0.63-1.52) L/min and volume of distribution 76 (95% CI 49-94) L. CONCLUSIONS In this pilot study, investigators found that intravenous calcium chloride was well-tolerated by the 20 patients assigned to receive the study drug and may be effective in prevention of uterine atony. A 1-g dose was sufficient to substantially increase calcium levels without any critically elevated lab values or concern for adverse side effects. These encouraging findings warrant further investigation of calcium as a novel agent to prevent uterine atony with an adequately powered clinical trial. Clinical trial registry NCT03867383 https://clinicaltrials.gov/ct2/show/NCT03867383.
Efficacy of oxytocics on reducing intraoperative blood loss during abdominal myomectomy: a systematic review and meta-analysis of randomized placebo-controlled trials
Journal of gynecology obstetrics and human reproduction. 2022;:102358
OBJECTIVE To conduct a systematic review and meta-analysis on the efficacy of oxytocics administration (oxytocin and carbetocin) on reducing intraoperative bleeding during abdominal myomectomy. METHODS PubMed, Scopus, Web of Science, Cochrane Library, and Google Scholar databases were searched from inception until March 2021. Only randomized placebo-controlled trials (RCTs) were considered. The included RCTs were evaluated for risk of bias. The main outcome measures were mean intraoperative blood loss (ml), mean duration of hospital stay (day), mean operation time (min), mean difference of postoperative hemoglobin (g/dl), mean difference of postoperative hematocrit (%), and rate of blood transfusion (%). Pooled outcomes were summarized as risk ratio (RR) or mean difference (MD) with their 95% confidence interval (CI) in a random-effects model. RESULTS Seven RCTs met the inclusion criteria (n=758 patients; 329 patients per group). Compared with control group, oxytocin and carbetocin resulted in a significantly lower intraoperative blood loss (MD=-281.08 ml, 95% CI [-400.63, -161.53], p<0.001), hospital stay (MD=-0.21 days, 95% CI [-0.31, -0.10], p<0.001), and need for blood transfusion (RR=0.32, 95% CI [0.22, 0.46], p<0.001). Subgroup analysis revealed that oxytocin, but not carbetocin, correlated with a reduced mean difference of postoperative hemoglobin (MD=0.60 g/dl, 95% CI [0.24 to 0.96], p=0.001), postoperative hematocrit (MD=2.29%, 95% CI [1.06, 3.52], p<0.001), and operation time (MD=-14.66 min, 95% CI [-21.04, -8.25], p<0.001) compared with control group. CONCLUSION Among women undergoing abdominal myomectomy, administration of oxytocin and carbetocin correlated with several beneficial clinical outcomes, such as reduced intraoperative blood loss, hospital stay, and blood transfusion requirement.
Impact of "natural" cesarean delivery on peripartum blood loss: A randomized controlled trial
American journal of obstetrics & gynecology MFM. 2022;:100642
BACKGROUND Early skin to skin contact after vaginal delivery increases milk production and may increase oxytocin release, leading to reduction in postpartum hemorrhage (PPH) rate. OBJECTIVE To examine the impact of "natural" cesarean deliveries (NCD) on perioperative maternal blood loss. STUDY DESIGN This is a randomized controlled trial conducted at a single university affiliated medical center, between August 2016 and February 2018. Term singleton gestations scheduled for a planned CD under spinal anesthesia were included. Women were randomized at a ratio of 1:1 to NCD (study group) or traditional CD (control group) during the routine preoperative assessment. Women in the study group watched fetal extraction, had early skin to skin contact, and breastfed until the end of surgery. Neonates in the control group were presented to the mother for few minutes. Blood samples were drawn from all women, during fascia closure, to determine oxytocin levels using an ELISA kit. The Laboratory component was performed after recruitment completion and was accomplished in February 2019. The primary outcome was postpartum hemoglobin (Hb) levels. To detect a difference of 0.5 g/dL between the groups with α = .05 and β = 80%, 214 women were needed. RESULTS Of 214 women that were randomized, 23 were excluded. There were no significant differences in demographic and obstetric variables between the groups. Postpartum Hb levels were 10.1±1.1 and 10.3±1.3 g/dL in the study and control groups, respectively (P = .19). There were no significant differences in rates of PPH and blood transfusion. Maternal pain scores, satisfaction, and exclusive breastfeeding, were comparable. Maternal oxytocin blood levels were 389.5±183.7 and 408.5±233.6 pg/mL in the study and control groups, respectively (P = .96). Incidence of neonatal hypothermia was comparable between the groups (P=.13). CONCLUSIONS NCD does not affect perioperative Hb level or maternal oxytocin blood concentration. CLINICAL TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT02768142.
Perioperative prophylactic internal iliac artery balloon occlusion for prevention of postpartum haemorrhage in placenta praevia: a randomised controlled trial (abridged secondary publication)
Hong Kong medical journal = Xianggang yi xue za zhi. 2022;28 Suppl 1(1):23-26
Prophylactic tranexamic acid during myomectomy: A systematic review and meta-analysis of randomized controlled trials
European journal of obstetrics, gynecology, and reproductive biology. 2022;276:82-91
OBJECTIVE To conduct a systematic review and meta-analysis of randomized controlled trials on the clinical efficacy and safety of prophylactic tranexamic acid (TXA) versus control (normal saline/no treatment) during myomectomy. METHODS Six databases were screened from inception until 21-February-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. RESULTS Seven studies, comprising eight arms and 571 patients (TXA = 304 patients, control = 267 patients) were analyzed. The included studies had an overall low risk of bias. The mean intraoperative blood loss (MD = -224.34 ml, 95% CI [-303.06, -145.61], p < 0.001), mean postoperative blood loss, and mean total blood loss were significantly reduced in favor of the prophylactic TXA group. Additionally, the mean postoperative hemoglobin (MD = 0.4 mg/dl, 95% CI [0.11, 0.68], p = 0.006) and mean postoperative hematocrit levels were significantly higher in favor of the prophylactic TXA group. While the mean hospital stay was significantly reduced in favor of the prophylactic TXA group (MD = -0.39 d, 95% [-0.74, -0.04], p = 0.03), there was no significant difference between both groups regarding the mean operation time and rate of blood transfusion. None of the participants in both groups developed any incidence of thromboembolic events. The rate of nausea was significantly higher in disfavor of the prophylactic TXA group (RR = 2.68, 95% CI [1.11, 6.43], p = 0.03). CONCLUSION Among patients undergoing myomectomy, prophylactic TXA was largely safe and linked to substantial reductions in perioperative blood loss and related morbidities.
Tranexamic Acid for Prevention of Hemorrhage in Elective Repeat Cesarean Delivery - A Randomized Study
American journal of obstetrics & gynecology MFM. 2022;:100573
BACKGROUND The American College of Obstetricians and Gynecologists states that data is insufficient to recommend Tranexamic acid (TXA) prophylaxis for postpartum hemorrhage. OBJECTIVE This study's objective was to evaluate if prophylactic TXA reduces calculated blood loss versus placebo in women undergoing elective repeat cesarean delivery. STUDY DESIGN A double-blind, randomized, placebo-controlled trial, examining calculated blood loss with prophylactic doses of 1-gram of TXA given before skin incision and after placental delivery and standard uterotonics in women with singleton pregnancies at least 37 weeks' gestation, presenting for their second or third cesarean delivery under neuraxial anesthesia. The primary outcome was calculated blood loss at 24 hours. The calculation was based on the participant's height, weight, and the difference in hematocrit before the start of surgery and 24 hours after delivery. Prespecified secondary outcomes were quantification of maternal coagulation activity during the perioperative course. A sample size of 50 women per group was planned (N=100), based on a meta-analysis of mean reduction in blood loss after TXA. RESULTS 723 women were screened, and 110 women were randomized as follows: 55 to TXA and 55 to placebo. The primary outcome of mean calculated blood for TXA (2274 ± 469 mL) and the placebo group (2407 ± 388 mL), p > 0.05. In the secondary outcomes, D-dimer levels were lower in the TXA group than the placebo group 24 hours after delivery (2.1 ± 1.2 µg/mL versus 4.3 ± 2.4 µg/mL), p < 0.001. CONCLUSIONS Prophylactic tranexamic acid did not decrease mean calculated blood loss. Significantly less participants had calculated blood loss greater than 2000 mL in the tranexamic acid group compared to the placebo group with lower levels of D-dimer at 24 hours.
Women undergoing elective repeat caesarean delivery (n= 110).
Prophylactic doses of tranexamic acid (TXA) before skin incision and after placental delivery (n= 55).
Standard uterotonics (n= 55).
The mean calculated blood loss for TXA was 2,274 ± 469 mL, and for standard uterotonics was 2407 ± 388 mL. D-dimer levels were lower in the TXA group than the placebo group 24 hours after delivery (2.1 ± 1.2 µg/mL vs. 4.3 ± 2.4 µg/mL).
Epidural anaesthesia and myomectomy-associated blood loss: - a prospective randomised controlled study
Ginekologia polska. 2022
OBJECTIVES The management of anaesthesia for patients with large myomas is particularly important due to disruption of hemodynamic as a result of massive haemorrhage, the prolonged duration of surgery and requirement for additional interventions. This study evaluated the effect of anaesthetic technique on blood loss in patients undergoing myomectomy due to large fibroid uterus. MATERIAL AND METHODS A total of 156 patients that underwent myomectomy were randomized into two equal groups according to the type of anaesthesia: Epidural anaesthesia group and General anaesthesia group. The volume of blood loss and blood products transfusion was reviewed for each patient. RESULTS The intraoperative blood loss and need for blood transfusion were significantly higher in general anaesthesia group (p < 0.001). The mean hematocrit change was 2.5 ± 1.5 vs 3.7 ± 2.9 % (p = 0.001) for both groups. CONCLUSIONS In the myomectomy planning of women with a large fibroid uterus, the team of gynecologists and anaesthesiologists should take care to choose the most optimal technique for anaesthesia.