Erythropoietin plus iron versus control treatment including placebo or iron for preoperative anaemic adults undergoing non-cardiac surgery.

BACKGROUND: Approximately 30% of adults undergoing non-cardiac surgery suffer from preoperative anaemia. Preoperative anaemia is a risk factor for mortality and adverse outcomes in different surgical specialties and is frequently the reason for blood transfusion. The most common causes are renal, chronic diseases, and iron deficiency. International guidelines recommend that the cause of anaemia guide preoperative anaemia treatment. Recombinant human erythropoietin (rHuEPO) with iron supplementation has frequently been used to increase preoperative haemoglobin concentrations in patients in order to avoid the need for perioperative allogeneic red blood cell (RBC) transfusion. OBJECTIVES: To evaluate the efficacy of preoperative rHuEPO therapy (subcutaneous or parenteral) with iron (enteral or parenteral) in reducing the need for allogeneic RBC transfusions in preoperatively anaemic adults undergoing non-cardiac surgery. SEARCH METHODS: We searched CENTRAL, Ovid MEDLINE(R), Ovid Embase, ISI Web of Science: SCI-EXPANDED and CPCI-S, and clinical trial registries WHO ICTRP and ClinicalTrials.gov on 29 August 2019. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) that compared preoperative rHuEPO + iron therapy to control treatment (placebo, no treatment, or standard of care with or without iron) for preoperatively anaemic adults undergoing non-cardiac surgery. We used the World Health Organization (WHO) definition of anaemia: haemoglobin concentration (g/dL) less than 13 g/dL for males, and 12 g/dL for non-pregnant females (decision of inclusion based on mean haemoglobin concentration). We defined two subgroups of rHuEPO dosage: 'low' for 150 to 300 international units (IU)/kg body weight, and 'high' for 500 to 600 IU/kg body weight. DATA COLLECTION AND ANALYSIS: Two review authors collected data from the included studies. Our primary outcome was the need for RBC transfusion (no autologous transfusion, fresh frozen plasma or platelets), measured in transfused participants during surgery (intraoperative) and up to five days after surgery. Secondary outcomes of interest were: haemoglobin concentration (directly before surgery), number of RBC units (where one unit contains 250 to 450 mL) transfused per participant (intraoperative and up to five days after surgery), mortality (within 30 days after surgery), length of hospital stay, and adverse events (e.g. renal dysfunction, thromboembolism, hypertension, allergic reaction, headache, fever, constipation). MAIN RESULTS: Most of the included trials were in orthopaedic, gastrointestinal, and gynaecological surgery and included participants with mild and moderate preoperative anaemia (haemoglobin from 10 to 12 g/dL). The duration of preoperative rHuEPO treatment varied across the trials, ranging from once a week to daily or a 5-to-10-day period, and in one trial preoperative rHuEPO was given on the morning of surgery and for five days postoperatively. We included 12 trials (participants = 1880) in the quantitative analysis of the need for RBC transfusion following preoperative treatment with rHuEPO + iron to correct preoperative anaemia in non-cardiac surgery; two studies were multiarmed trials with two different dose regimens. Preoperative rHuEPO + iron given to anaemic adults reduced the need RBC transfusion (risk ratio (RR) 0.55, 95% confidence interval (CI) 0.38 to 0.80; participants = 1880; studies = 12; I2 = 84%; moderate-quality evidence due to inconsistency). This analysis suggests that on average, the combined administration of rHuEPO + iron will mean 231 fewer individuals will need transfusion for every 1000 individuals compared to the control group. Preoperative high-dose rHuEPO + iron given to anaemic adults increased the haemoglobin concentration (mean difference (MD) 1.87 g/dL, 95% CI 1.26 to 2.49; participants = 852; studies = 3; I2 = 89%; low-quality evidence due to inconsistency and risk of bias) but not low-dose rHuEPO + iron (MD 0.11 g/dL, 95% CI -0.46 to 0.69; participants = 334; studies = 4; I2 = 69%; low-quality evidence due to inconsistency and risk of bias). There was probably little or no difference in the number of RBC units when rHuEPO + iron was given preoperatively (MD -0.09, 95% CI -0.23 to 0.05; participants = 1420; studies = 6; I2 = 2%; moderate-quality evidence due to imprecision).  There was probably little or no difference in the risk of mortality within 30 days of surgery (RR 1.19, 95% CI 0.39 to 3.63; participants = 230; studies = 2; I2 = 0%; moderate-quality evidence due to imprecision) or of adverse events including local rash, fever, constipation, or transient hypertension (RR 0.93, 95% CI 0.68 to 1.28; participants = 1722; studies = 10; I2 = 0%; moderate-quality evidence due to imprecision). The administration of rHuEPO + iron before non-cardiac surgery did not clearly reduce the length of hospital stay of preoperative anaemic adults (MD -1.07, 95% CI -4.12 to 1.98; participants = 293; studies = 3; I2 = 87%; low-quality evidence due to inconsistency and imprecision). AUTHORS' CONCLUSIONS: Moderate-quality evidence suggests that preoperative rHuEPO + iron therapy for anaemic adults prior to non-cardiac surgery reduces the need for RBC transfusion and, when given at higher doses, increases the haemoglobin concentration preoperatively. The administration of rHuEPO + iron treatment did not decrease the mean number of units of RBC transfused per patient. There were no important differences in the risk of adverse events or mortality within 30 days, nor in length of hospital stay. Further, well-designed, adequately powered RCTs are required to estimate the impact of this combined treatment more precisely.

The impact of antenatal factor XIII levels on postpartum haemorrhage: a prospective observational study.

PURPOSE: Postpartum haemorrhage (PPH) is a leading cause of maternal mortality and morbidity. Our aim was to investigate the relationships between antenatal factor XIII (FXIII), fibrinogen levels, and blood loss at childbirth. METHODS: This prospective observational study evaluated an unselected cohort of pregnant women admitted for intended vaginal deliveries of singletons at term. To determine clotting factor levels, we obtained blood samples at a maximum of three days prior to vaginal delivery. A calibrated collecting drape was used to quantify blood loss in the third stage of labour. Moderate and severe PPH were diagnosed as blood losses ≥ 500 mL and ≥ 1000 mL, respectively. In a multiple logistic regression analysis, we determined whether coagulation factors and their interactions could independently predict (severe) PPH. RESULTS: We analysed 548 vaginal deliveries that occurred during the study period. Of those, 78 (14.2%) lost ≥ 500 mL and 18 (3.3%) lost ≥ 1000 mL of blood. The mean pre-delivery FXIII activity in women with PPH (79.33% ± 15.5) was significantly (p < 0.001) lower than in women without PPH (86.45% ± 14.6). A receiver operating characteristic curve analysis detected antenatal FXIII cutoff levels of 83.5% and 75.5% for PPH and severe PPH, respectively. The multiple logistic regression analysis showed that FXIII alone (p < 0.001) and its interaction with fibrinogen (p = 0.03) significantly predicted PPH. FXIII was not significantly correlated with blood loss among patients with severe PPH. CONCLUSION: Our results suggested that antenatal FXIII levels may have a significant influence on PPH. The interaction between FXIII and fibrinogen might also provide slight advantages in forecasting PPH.

Can prepartum thromboelastometry-derived parameters and fibrinogen levels really predict postpartum hemorrhage?

BACKGROUND: Decreased postpartum rotational thromboelastometric parameters of coagulation (ROTEM®) and fibrinogen levels have been associated with postpartum hemorrhage (PPH). However, the predictive power of prepartum ROTEM® parameters and fibrinogen levels (Fbgpre) for PPH remains unknown. METHODS: This prospective observational pilot study included 217 healthy pregnant women. Maximum clot firmness (FIBTEM-MCF), fibrinogen levels and standard coagulation parameters were measured upon admission to the delivery room for labor and within 1 h after vaginal delivery. Blood loss was measured with a calibrated collecting drape during the third stage of labor. PPH was defined as blood loss ≥500 mL. Predictors for bleeding were identified via receiver operating characteristic analyses and bivariate and multivariate regression analyses. RESULTS: Women with and without PPH did not differ in median FIBTEM-MCF [23 mm (25th percentile 20 mm, 75th percentile 26 mm) vs. 23 mm (19 mm, 26 mm), respectively; P=0.710] or mean Fbgpre (4.57±0.77 g/L vs. 4.45±0.86 g/L, respectively; P=0.431). Blood loss and prepartum coagulation parameters were not correlated (FIBTEM-MCF, rs=-0.055, P=0.431; Fbgpre, rs=-0.017, P=0.810). The areas under the curves (predictive power for PPH) for FIBTEM-MCF and Fbgpre and were 0.52 (0.41-0.64, P=0.699) and 0.53 [95% confidence interval (95% CI) 0.40-0.65, P=0.644], respectively. Neither FIBTEM-MCF nor Fbgpre was associated with PPH. However, primiparity [odds ratio (OR) 4.27, 95% CI 1.32-13.80, P=0.015) and urgent cesarean section (2.77, 1.00-7.67, P=0.050) were independent predictors of PPH. CONCLUSIONS: ROTEM® parameters, Fbgpre and postpartum blood loss were not associated, nor did these factors predict PPH. Sufficiently powered prospective studies are needed to confirm these results.

Predelivery maternal fibrinogen as a predictor of blood loss after vaginal delivery.

PURPOSE: The present study investigated whether fibrinogen level during the first stage of labor is associated with bleeding severity in the third stage of labor. METHODS: We prospectively enrolled 1019 pregnant women with planned vaginal delivery. Upon admission to delivery, maternal fibrinogen levels, hemoglobin content, and coagulation parameters were evaluated. Blood loss in the third stage of labor was systematically measured using a calibrated collecting drape. Univariate and multivariate analyses were performed to identify predictors of PPH (blood loss ≥500 mL) and S-PPH (blood loss ≥1000 mL). RESULTS: Among 809 vaginal deliveries, mean maternal predelivery fibrinogen was 4.65 ± 0.77 g/L, PPH incidence was 12 %, S-PPH incidence was 3.5 %, and median blood loss was 250 mL. Fibrinogen levels were significantly lower in women with S-PPH (4.22 ± 0.82 g/L) than without S-PPH (4.67 ± 0.75 g/L; p = 0.004), but did not significantly differ between women with PPH (4.67 ± 0.84 g/L) and those without PPH (4.67 ± 0.75 g/L; p = 0.985). Instrumental delivery and predelivery fibrinogen levels were independent predictors of S-PPH. Primiparous status, birth weight >4000 g, genital tract laceration, episiotomy and instrumental delivery were independent predictors of PPH. CONCLUSION: For each 1 g/L increase of predelivery fibrinogen level, the risk of S-PPH after vaginal delivery decreases by a factor of 0.405 (95 % CI 0.219-0.750; p = 0.004).

Evaluation of measured postpartum blood loss after vaginal delivery using a collector bag in relation to postpartum hemorrhage management strategies: a prospective observational study.

AIM: To evaluate the incidence of postpartum hemorrhage (PPH) and severe PPH via routine use of a pelvic drape to objectively measure blood loss after vaginal delivery in connection with PPH management. METHODS: This prospective observational study was undertaken at the obstetrical department of the Charité University Hospital from December 2011 to May 2013 and evaluated an unselected cohort of planned vaginal deliveries (n=1019 live singletons at term). A calibrated collecting drape was used to meassure blood loss in the third stage of labor. PPH and severe PPH were defined as blood loss ≥500 mL and ≥1000 mL, respectively. Maternal hemoglobin content was evaluated at admission to delivery and at the first day after childbirth. RESULTS: During the study period, 809 vaginal deliveries were analysed. Direct measurement revealed a median blood loss of 250 mL. The incidences of PPH and severe PPH were 15% and 3%, respectively. Mean maternal hemoglobin content at admission was 11.9±1.1 g/dL, with a mean decrease of 1.0±1.1 g/dL. Blood loss measured after vaginal delivery correlated significantly with maternal hemoglobin decrease. CONCLUSIONS: This study suggests that PPH incidence may be higher than indicated by population-based data. Underbuttocks drapes are simple, objective bedside tools to diagnose PPH. Blood loss should be quantified systematically if PPH is suspected.

Neuraxial anesthesia for pain control after cesarean section: a prospective randomized trial comparing three different neuraxial techniques in clinical practice.

BACKGROUND: Cesarean section (CS) is associated with a moderate-high intensity of postoperative pain. We investigate whether continuous local anesthetic/opioid administration using patient controlled epidural anesthesia (PCEA) is superior in controlling pain after CS than epidural (ED) or intrathecal (IT) opioid bolus administration. METHODS: One hundred ninety-nine women undergoing elective CS were randomized into 3 groups: PCEA: Combined spinal-epidural anesthesia (CSE) with a PCEA of ropivacaine 0.1% + sufentanil 0.5 µg/mL for 24 hours after CS. ED: CSE with an ED bolus of 3 mg morphine after CS. IT: spinal anesthesia with an IT bolus of 0.1 mg morphine before CS. Primary objectives were pain (VAS/Visual Analogue Scale 0-100) at 9 h, VAS at 1, 2, 6, 24 and 48 hours, side effects and additional analgesic requirements as secondary endpoints. RESULTS: VAS (rest/mobilization) 10(0-23)/40(20-56) at 9 hours for IT was lower (P=0.11/P=0.003) than VAS 20(0-30)/50(30-60) for ED and 20(0-40)/50(30-70) for PCEA (P=0.005/P=0.01). VAS 10(0-29)/40(20-60) at 6 hours for IT was significantly lower than VAS 20(4-40)/50(30-70) for ED (P=0.02/P=0.02). During mobilization at 24/48 hours VAS 40(20-58)/30(20-40) between IT and PCEA with VAS 50(40-70)/40(20-63) differed significantly (P=0.04/P=0.001). With exception of pruritus, which was less in the PCEA group at 9 hours, side effects were similar in all groups. Ibuprofen consumption in the first 24 hours was significantly lower for IT and PCEA compared to ED. CONCLUSIONS: PCEA is less effective then IT and ED opioid bolus administration for post cesarean pain relief. IT provides better analgesia than ED or PCEA, as pointed out by lower ibuprofen consumption.