Preoperative Erythropoietin Research Articles

Spinal deformity surgery in patients for whom blood transfusion is not an option: a single-center experience.

Spinal deformity surgery is associated with significant blood loss, often requiring the transfusion of blood and/or blood products. For patients declining blood or blood products, even in the face of life-threatening blood loss, spinal deformity surgery has been associated with high rates of morbidity and mortality. For these reasons, patients for whom blood transfusion is not an option have historically been denied spinal deformity surgery. The authors retrospectively reviewed a prospectively collected data set. All patients declining blood transfusion who underwent spinal deformity surgery at a single institution between January 2002 and September 2021 were identified. Demographics collected included age, sex, diagnosis, details of any prior surgery, and medical comorbidities. Perioperative variables included levels decompressed and instrumented, estimated blood loss, blood conservation techniques used, length of surgery, length of hospital stay, and complications from surgery. Radiographic measurements included, where appropriate, sagittal vertical axis correction, Cobb angle correction, and regional angular correction. Spinal deformity surgery was performed in 31 patients (18 male, 13 female) over 37 admissions. The median age at surgery was 41.2 years (range 10.9-70.1 years), and 64.5% had significant medical comorbidities. A median of 9 levels (range 5-16 levels) were instrumented per surgery, and the median estimated blood loss was 800 mL (range 200-3000 mL). Posterior column osteotomies were performed in all surgeries, and pedicle subtraction osteotomies in 6 cases. Multiple blood conservation techniques were used in all patients. Preoperative erythropoietin was administered prior to 23 surgeries, intraoperative cell salvage was used in all, acute normovolemic hemodilution was performed in 20, and perioperative administration of antifibrinolytic agents was performed in 28 surgeries. No allogenic blood transfusions were administered. Surgery was staged intentionally in 5 cases, and there was 1 unintended staging due to intraoperative blood loss from a vascular injury. There was 1 readmission for a pulmonary embolus. There were 2 minor postoperative complications. The median length of stay was 6 days (range 3-28 days). Deformity correction and the goals of surgery were achieved in all patients. Two patients underwent revision surgery during the follow-up period: one for pseudarthrosis and the other for proximal junctional kyphosis. With proper preoperative planning and judicious use of blood conservation techniques, spinal deformity surgery may be performed safely in patients for whom blood transfusion is not an option. The same techniques can be applied widely to the general population in order to minimize blood loss and the need for allogeneic blood transfusion.

The Effects of Preoperative Administration of Erythropoietin in Pediatric Patients Undergoing Cranial Vault Remodeling for Craniosynostosis.

Over 90% of patients undergoing cranial vault remodeling for craniosynostosis receive blood transfusions to compensate for intraoperative blood loss. However, transfusions are not without risk and can lead to allergic and immune transfusion reactions as well as rare cases of infectious transmissions. Preoperative use of erythropoietin in cranial vault remodeling has been demonstrated to be safe and to reduce transfusion requirements in prior studies. This study's purpose is to add to the body of data supporting the safe use of a protocolized erythropoietin alfa regimen before cranial vault remodeling and strip craniectomy procedures with decreased blood transfusion requirements and other favorable outcomes. A retrospective chart review was performed on patients who underwent cranial vault remodeling between 2006 and 2021 at our tertiary care center. Two groups were identified: in the first, preoperative erythropoietin was administered under protocol; and in the second, preoperative erythropoietin was not administered. The groups were compared with respect to age, perioperative hemoglobin levels, estimated blood loss during surgery, packed red blood cell transfusion volume, length of hospital stay, and length of surgery. Demographics were not significantly different in terms of age, weight, diagnosis, gender, and type of procedure. Patients who were administered preoperative erythropoietin were found to have significantly increased preoperative hemoglobin levels (13.6 versus 12.3 g/dL), as well as decreased estimated intraoperative blood loss (376 versus 1099 mL), the volume of packed red blood cells transfused (316 versus 897 mL), length of hospital stay, and length of surgery. Postoperative hemoglobin levels were not found to be significantly different. In this study, preoperative administration of erythropoietin with elemental iron was beneficial for patients undergoing cranial vault remodeling for craniosynostosis. Specifically, it decreased the need for red blood cell transfusion, intraoperative blood loss, and length of hospital stay. No adverse events were recorded in the treatment arm. Further studies may include a separate group administered iron alone.

Effects of perioperative erythropoietin administration on acute kidney injury and red blood cell transfusion in patients undergoing cardiac surgery: A systematic review and meta-analysis.

Background:The renoprotective effects of erythropoietin (EPO) are well-known; however, the optimal timing of EPO administration remains controversial. Red blood cell (RBC) transfusion is an independent risk factor for cardiac surgery-associated acute kidney injury (CSA-AKI). We aimed to evaluate the efficacy of EPO on CSA-AKI and RBC transfusion according to the timing of administration.Methods:We searched the Cochrane Library, EMBASE, and MEDLINE databases for randomized controlled trials. The primary outcome was the incidence of CSA-AKI following perioperative EPO administration, and the secondary outcomes were changes in serum creatinine, S-cystatin C, S-neutrophil gelatinase-associated lipocalin, urinary neutrophil gelatinase-associated lipocalin, length of hospital and intensive care unit (ICU) stay, volume of RBC transfusion, and mortality. The subgroup analysis was stratified according to the timing of EPO administration in relation to surgery.Results:Eight randomized controlled trials with 610 patients were included in the study. EPO administration significantly decreased the incidence of CSA-AKI (odds ratio: 0.60, 95% confidence interval [CI]: 0.43–0.85, P = .004; I 2 = 52%; P for heterogeneity = .04), intra-operative RBC transfusion (standardized mean difference: −0.30, 95% CI: −0.55 to −0.05, P = .02; I 2 = 15%, P for heterogeneity = .31), and hospital length of stay (mean difference: −1.54 days, 95% CI: −2.70 to −0.39, P = .009; I 2 = 75%, P for heterogeneity = .001) compared with control groups. Subgroup analyses revealed that pre-operative EPO treatment significantly reduced the incidence of CSA-AKI, intra-operative RBC transfusion, serum creatinine, and length of hospital and ICU stay.Conclusion:Pre-operative administration of EPO may reduce the incidence of CSA-AKI and RBC transfusion, but not in patients administered EPO during the intra-operative or postoperative period. Therefore, pre-operative EPO treatment can be considered to improve postoperative outcomes by decreasing the length of hospital and ICU stay in patients undergoing cardiac surgery.

Preoperative Administration of Erythropoietin for Craniosynostosis Patients Undergoing Cranial Vault Remodeling: Is There a Benefit?

Pediatric patients undergoing corrective surgery for craniosynostosis frequently require intraoperative and postoperative blood transfusions because of low baseline circulating blood volume and significant surgical blood loss.1 Allogenic blood transfusion can have high morbidity associated with its use, including acute hemolytic reactions, immunosuppression, and infection spread.2 Administration of preoperative erythropoietin has been briefly evaluated in the literature as an option for reducing the need for allogenic blood transfusion.1 We believe that this process should be considered for craniosynostosis patients undergoing cranial vault remodeling. Preoperative erythropoietin has demonstrated appreciable success in mitigating the requirement for administering allogenic blood transfusions and should be more embraced by craniofacial surgeons. In a recent meta-analysis, Aljaaly et al. reported that among all studies examining preoperative erythropoietin use in children undergoing craniosynostosis surgery, the proportion of patients and the volume of allogenic blood transfused were reduced.1 Hemoglobin measurements immediately before surgery and following completion of the preoperative erythropoietin protocol have also been demonstrably higher than in controls who do not receive treatment before operative intervention. These collective outcomes result in lower morbidity and significantly reduced hospital stays. Erythropoietin administration in children undergoing calvarial remodeling has also been proven to be safe.3 Naran et al. evaluated 369 patients and concluded that preoperative administration of erythropoietin does not increase the risk of thrombotic events or any other major complication, such as blindness or death, during and after treatment.4 Initiating preoperative erythropoietin in combination with other blood-salvaging techniques such as a cell salvage system has similarly resulted in decreased blood transfusions rates.4 Although the physiologic benefits of administering erythropoietin before surgery appear to be evident despite the paucity of robust clinical data, controversy regarding its cost-effectiveness has prevented universal acceptance of this preoperative protocol (Table 1).1,4 We believe that the costs associated with using preoperative erythropoietin may be comparable to undergoing surgery with no preoperative management, given that the administration of erythropoietin reduces intraoperative and postoperative blood transfusion requirements.5 In addition, preoperative erythropoietin decreases morbidity and reduces hospital length of stay.2 These indirect cost savings may serve to counteract the associated costs of undergoing preoperative erythropoietin management and should be considered within the greater context when deciding which blood salvaging technique to perform. Table 1. - Benefits and Disadvantages of Administering Preoperative Erythropoietin for Craniosynostosis Patients Undergoing Corrective Surgery Pros Reduced proportion of patients requiring blood transfusion Decreased volume of blood transfusion required High safety profile with low risk of complications Indirect cost savings Cons Cost of administering EPO Inconvenience of commuting for management EPO, erythropoietin. Administration of preoperative erythropoietin is a safe and effective technique that deserves recognition as a reputable option for pediatric craniosynostosis patients undergoing cranial vault remodeling. Its associated reduced morbidity, coupled with potential cost savings, provides craniofacial surgeons with another option for blood salvaging. Although studies have reported enhanced outcomes with preoperative erythropoietin, there is significant variation in transfusion protocols between institutions. This lack of uniformity should be addressed in future head-to-head studies to standardize the technique better. Higher quality prospective clinical studies on the use of erythropoietin before craniosynostosis surgery and studies geared toward this technique’s cost-effectiveness are also needed to elucidate its impact on comprehensive patient outcomes further. DISCLOSURE The authors have no financial interest in relation to the content of this article. No funding was received for this work. Rami P. Dibbs, B.A.Division of Plastic SurgeryMichael E. DeBakey Department of SurgeryBaylor College of MedicineDivision of Plastic SurgeryTexas Children’s Hospital João Matheus Bombardelli, M.D.Department of SurgeryHouston Methodist Hospital Andrew M. Ferry, B.S.Renata S. Maricevich, M.D.Division of Plastic SurgeryMichael E. DeBakey Department of SurgeryBaylor College of MedicineDivision of Plastic SurgeryTexas Children’s HospitalHouston, Texas

Pancreatic resections in patients who refuse blood transfusions. The application of a perioperative protocol for a true bloodless surgery

BackgroundThe refusal of blood transfusions compels surgeons to face ethical and clinical issues. A single-institution experience with a dedicated perioperative blood management protocol was reviewed to assess feasibility and short-term outcomes of true bloodless pancreatic surgery. MethodsThe institutional database was reviewed to identify patients who refused transfusion and were scheduled for elective pancreatic surgery from 2010 through 2018. A protocol to optimize the hemoglobin values by administration of drugs stimulating erythropoiesis was systematically used. ResultsPerioperative outcomes of 32 Jehovah’s Witnesses patients were included. Median age was 67 years (range, 31–77). Nineteen (59.4%) patients were treated with preoperative erythropoietin. Twenty-four (75%) patients underwent pylorus-preserving pancreaticoduodenectomy, 4 (12.5%) distal pancreatectomy (DP) with splenectomy, 3 (9.4%) spleen-preserving DP, and 1 (3.1%) total pancreatectomy. Median estimated blood loss and surgical duration were 400 mL (range, 100–1000) and 470 min (range, 290–595), respectively. Median preoperative hemoglobin was 13.9 g/dL (range, 11.7–15.8) while median postoperative nadir hemoglobin was 10.5 g/dL (range, 7.1–14.1). The most common histological diagnosis (n = 15, 46.9%) was pancreatic ductal adenocarcinoma. Clavien-Dindo grade I-II complications occurred in fourteen (43.8%) patients while one (3.1%) patient had a Clavien-Dindo grade IIIa complication wich was an abdominal collection that required percutaneous drainage. Six (18.8%) patients presented biochemical leak or postoperative pancreatic fistula grade B. Median hospital stay was 16 days (range, 8–54) with no patient requiring transfusion or re-operation and no 90-day mortality. ConclusionsA multidisciplinary approach and specific perioperative management allowed performing pancreatic resections in patients who refused transfusion with good short-term outcomes.

Impact of multidisciplinary engagement in a quality improvement blood conservation protocol for craniosynostosis.

Patients undergoing open cranial vault remodeling for craniosynostosis frequently experience substantial blood loss requiring blood transfusion. Multiple reports in the literature have evaluated the impact of individual blood conservation techniques on blood transfusion rates during craniosynostosis surgery. The authors engaged a multidisciplinary team and assessed the impact of input from multiple stakeholders on the evolution of a comprehensive quality improvement protocol aimed at reducing or eliminating blood transfusion in patients undergoing open surgery for craniosynostosis. Over a 4-year period from 2012 to 2016, 39 nonsyndromic patients were operated on by a single craniofacial plastic surgeon. Initially, no clear blood conservation protocol existed, and specific interventions were individually driven. In 2014, a new pediatric neurosurgeon joined the craniofacial team, and additional stakeholders in anesthesiology, transfusion medicine, critical care, and hematology were brought together to evaluate opportunities for developing a comprehensive blood conservation protocol. The initial version of the protocol involved the standardized administration of intraoperative aminocaproic acid (ACA) and the use of a cell saver. In the second version of the protocol, the team implemented the preoperative use of erythropoietin (EPO). In addition, intraoperative and postoperative resuscitation and transfusion guidelines were more clearly defined. The primary outcomes of estimated blood loss (EBL), transfusion rate, and intraoperative transfusion volume were analyzed. The secondary impact of multidisciplinary stakeholder input was inferred by trends in the data obtained with the implementation of the partial and full protocols. Implementing the full quality improvement protocol resulted in a 66% transfusion-free rate at the time of discharge compared to 0% without any conservation protocol and 27% with the intermediate protocol. The administration of EPO significantly increased starting hemoglobin/hematocrit (11.1 g/dl/31.8% to 14.7 g/dl/45.6%, p < 0.05). The group of patients receiving ACA had lower intraoperative EBL than those not receiving ACA, and trends in the final-protocol cohort, which had received both preoperative EPO and intraoperative ACA, demonstrated decreasing transfusion volumes, though the decrease did not reach statistical significance. Patients undergoing open calvarial vault remodeling procedures benefit from the input of a multidisciplinary stakeholder group in blood conservation protocols. Further research into comprehensive protocols for blood conservation may benefit from input from the full surgical team (plastic surgery, neurosurgery, anesthesiology) as well as additional pediatric subspecialty stakeholders including transfusion medicine, critical care, and hematology.

A protocol of situation-dependent transfusion, erythropoietin and tranexamic acid reduces transfusion in fronto-orbital advancement for metopic and coronal craniosynostosis.

Assess the effect of a protocol of preoperative erythropoietin (EPO) and ferrous sulfate in addition to perioperative tranexamic acid (TXA) on blood transfusions in patients with coronal or metopic craniosynostosis undergoing cranial vault remodeling (CVR) with fronto-orbital advancement (FOA). Retrospective review of all coronal and metopic craniosynostosis patients undergoing CVR and FOA from March 2010 to June 2019 was performed. Before 2014 ("Control group"), all patients received blood transfusion at the start of surgery. In 2014, a protocol of preoperative EPO and ferrous sulfate with perioperative TXA and non-automatic transfusion was instituted ("Study group"). Patient demographics and anthropometrics, perioperative hemoglobin (Hb) levels, and transfusion details were collected and compared. Thirty-six patients met inclusion criteria. Twenty-one patients were in the control group, and 15 in the Study group. Nineteen patients had metopic synostosis, 11 had unicoronal synostosis, and 6 had bicoronal synostosis. There were no significant differences between groups in demographics, operative time, intraoperative crystalloid volume, craniofacial syndromes, or sutures affected. The Study group had higher preoperative Hb (13.9 ± 1.0 vs. 12.6 ± 0.8g/dL, p < 0.001), lower intraoperative Hb nadir (7.4 ± 1.8 vs. 9.2 ± 1.2g/dL) lower intraoperative transfusion rate (66.7% vs. 100%, p = 0.008), lower postoperative transfusion rate (0% vs 28.6%, p = 0.03), and exposure to fewer unique units of packed red blood cells (0.7 ± 0.6 vs. 1.5 ± 0.9units). Our protocol resulted in decreased transfusion needs. These results add valuable information to the growing body of work on transfusion reduction in craniosynostosis surgery.

Use of preoperative erythropoietin therapy to facilitate autologous blood donation in orthopedic surgery: A meta-analysis.

Autologous blood transfusion helps to avoid or reduce the need for allogenic blood transfusion in patients undergoing major surgery. We examined the value of erythropoietin therapy to support preoperative autologous blood donation (PABD) in patients undergoing orthopedic surgery. For this systematic review and meta-analysis, Medline, Cochrane, EMBASE, and Google Scholar databases were searched from October 26th, 1989 until September 30th, 2017. Primary outcomes were percentages of patients able to donate ≥4 units of blood for autologous transfusion, amount of allogeneic blood transfused, changes in hematocrit and hemoglobin levels from before PABD to immediately before surgery, and adverse events. Of 256 studies identified, 18 studies met the inclusion criteria with a total of 1914 patients (mean age 51-69 years), of whom 1153 were treated with erythropoietin. Erythropoietin was associated with a greater percentage of patients able to donate ≥4 units of blood for autologous use compared to controls (OR = 6.00, 95% CI = 3.97 to 9.09, P < .001). Patients receiving preoperative erythropoietin had significantly less of a reduction in hematocrit and hemoglobin levels from before PABD to immediately before surgery compared with controls (hematocrit: mean differences = -1.438, 95% CI = -2.14 to -0.73, P < .001; hemoglobin: mean differences = -1.426, 95% CI = -1.78 to -1.07, P < .001). No significant differences were observed in the amount of allogenic blood transfused between patients receiving erythropoietin and controls (difference in means = -0.220, 95% CI = -0.536 to 0.097, P = .174). Patients who received erythropoietin were less likely to experience dizziness than controls, but the incidence of nausea or fatigue were similar between groups. Erythropoietin therapy during the PABD period results in less of a reduction in hematocrit and hemoglobin levels and an increase in the percentage of patients able to donate blood preoperatively.

Transfusion-Free Cranial Vault Remodeling: A Novel, Multifaceted Approach.

Approximately one in 2000 babies are born with craniosynostosis, and primary open repair is typically performed before 1 year of age. Historically, the procedure has been associated with nearly 100 percent transfusion rates. To decrease the rates of transfusion, the authors' center has developed a novel multimodal blood conservation protocol. The authors administered their standard of care to children aged 1 year or younger undergoing primary repair of craniosynostosis between 2008 and 2014. In 2014, the authors implemented the following protocol: (1) preoperative erythropoietin and ferrous sulfate, (2) local anesthetic with epinephrine infiltration of the incision, (3) PlasmaBlade incision and subgaleal dissection, (4) hypervolemic hemodilution, and (5) intravenous tranexamic acid. Procedures performed before the protocol implementation served as controls. The authors performed classic fronto-orbital advancement with anterior cranial vault remodeling for coronal and metopic craniosynostosis. For lambdoid and sagittal craniosynostosis, barrel stave osteotomies, cranial base outfracture, and interposition bone grafting were performed. A total of 279 children with a mean age of 6 months who had craniosynostosis repairs were included. One hundred forty-five underwent repair before the authors' protocol, and 134 had repairs during the authors' blood conservation protocol. Both groups were similar in demographics. Overall blood loss and operative times were significantly reduced by 73 percent and 11 percent, respectively. Blood transfusion rate decreased 92 percent (p < 0.001). These results show a strong association between the authors' blood conservation protocol and significantly reduced transfusion rates. The authors believe this is a significant step forward and can be safely applied in the great majority of children undergoing craniosynostosis repairs. Therapeutic, III.

Effect of preoperative recombinant human erythropoietin administration on inflammatory lung injury due to cardiopulmonary bypass

Objective To discuss the effects of preoperative use of recombinant human erythropoietin (rHuEPO) on inflammatory lung injury patients after cardiopulmonary bypass (CPB) under extracorporeal circulation. Methods A total of 54 patients who were scheduled to receive elective open cardiac operations under CPB were enrolled. They were divided into two groups(n=27). rHuEPO group: patients were titrated intravenously with rHuEPO (100 IU/kg, diluted into 50 ml normal saline) for consecutive three days at the same time period before operation. Control group: equivalent normal saline in place of rHuEPO was given to patients via venous injection. Peak airway pressure (Ppeak), plateau pressure (Pplat), and pulmonary dynamic compliance (Cdyn) were well monitored and recorded before CPB (T1), immediately after chest closure (T2), and 2, 4 h and 6 h after surgery (T3, T4, and T5). At T1, T2, T5, and 12, 24, 48 h, and 72 h after surgery (T6, T7, T8, and T9), arterial oxygenation indices (OI) were also recorded. Furthermore, at pre-rHuEPO treatment (T0), T1, T2, T5, T6, T7, T8, and T9, the plasma levels of the tumor necrosis factor (TNF)-α and interleukin (IL)-1β and IL-10 were measured. The time of mechanical ventilation and stay in intense care unit (ICU), discharge time and hospitalization stay were also recorded. Results Compared with the control group, Cdyn in the rHuEPO group at T2-T5 were significantly increased (P<0.05), whereas Ppeak and Pplat were decreased (P<0.05). OI values of rHuEPO group at T2 and T5-T9 were significantly higher than that of control group(P<0.05). It was demonstrated that at any time point after closing chest, the plasma concentrations of TNF-α, IL-1β, and IL-10 in both groups were relatively elevated compared with those before, while the concentrations of TNF-α and IL-1β in the rHuEPO group were lower than those in control group (P<0.05). Compared with the control group, patients receiving rHuEPO treatment underwent an apparent reduction in both mechanical ventilation and staying time in ICU (P<0.05). Conclusions Preoperative rHuEPO administration can attenuate the inflammatory lung injury after CPB via the anti-inflammation pathway and ameliorate pulmonary functions. Key words: Recombinant human erythropoietin; Cardiopulmonary bypass; Lung injury; Inflammatory response

Minimizing transfusion in sagittal craniosynostosis surgery: the Children's Hospital of Minnesota Protocol.

To assess the success of a protocol using preoperative erythropoietin (EPO) and iron with perioperative tranexamic acid (TXA) in reducing blood transfusion in sagittal craniosynostosis surgery. A retrospective chart review of all sagittal craniosynostosis patients undergoing open repair at our institution since 2010 was conducted. A novel protocol of preoperative EPO with iron and perioperative TXA, along with a shift away from automatic transfusion, was initiated in 2014. Perioperative hemoglobin levels, length of stay, and transfusion rates were compared between the historical control and the study group receiving the protocol. A total of 36 patients met inclusion criteria. Twenty-eight patients were male and 8 were female. Twenty-two patients were in the control group receiving neither TXA nor EPO and automatically received a transfusion, while 14 were in the study group and received the full protocol. There were no significant demographic differences between groups. Within the control group, 100% of patients were transfused compared with 14.3% of the study group (p < 0.0001). The study group also had a shorter postoperative length of stay in the hospital (mean, 3.4days; range, 3-6) than the control (mean, 4days; range, 2-5.5, p = 0.038). The study group had a higher preoperative hemoglobin than the control (13.6 vs. 11.8g/dL, p = 0.0001). Our protocol of preoperative EPO and iron with perioperative TXA increased the preoperative hemoglobin and was associated with a low transfusion rate without negatively impacting postoperative course.

Impact of Preoperative Erythropoietin on Allogeneic Blood Transfusions in Surgical Patients: Results From a Systematic Review and Meta-analysis.

Erythropoietic-stimulating agents such as erythropoietin have been used as part of patient blood management programs to reduce or even avoid the use of allogeneic blood transfusions. We review the literature to evaluate the effect of preoperative erythropoietin use on the risk of exposure to perioperative allogeneic blood transfusions. The study involved a systematic review and meta-analysis of randomized controlled trials evaluating the use of preoperative erythropoietin. The primary outcome was the reported incidence of allogeneic red blood cell transfusions during inpatient hospitalizations. Secondary outcomes included phase-specific allogeneic red blood cell transfusions (ie, intraoperative, postoperative), intraoperative estimated blood loss, perioperative hemoglobin levels, length of stay, and thromboembolic events. A total of 32 randomized controlled trials (n = 4750 patients) were included, comparing preoperative erythropoietin (n = 2482 patients) to placebo (n = 2268 patients). Preoperative erythropoietin is associated with a significant decrease in incidence of allogeneic blood transfusions among all patients (n = 28 studies; risk ratio, 0.59; 95% CI, 0.47-0.73; P < .001) as well as patients undergoing cardiac (n = 9 studies; risk ratio, 0.55; 95% CI, 0.37-0.81; P = .003) and elective orthopedic (n = 5 studies; risk ratio, 0.36; 95% CI, 0.28-0.46; P < .001) surgery compared to placebo, respectively. Preoperative erythropoietin was also associated with fewer phase-specific red blood cell transfusions. There was no difference between groups in incidence of thromboembolic events (n = 28 studies; risk ratio, 1.02; 95% CI, 0.78-1.33; P = .68). Preoperative erythropoietin is associated with a significant reduction in perioperative allogeneic blood transfusions. This finding is also confirmed among the subset of patients undergoing cardiac and orthopedic surgery. Furthermore, our study demonstrates no significant increase in risk of thromboembolic complications with preoperative erythropoietin administration.

Preoperative erythropoietin treatment improves survival following major hepatic resection in a cirrhotic rat model

Preoperative erythropoietin treatment improves survival following major hepatic resection in a cirrhotic rat model

Safety and feasibility of elective liver resection in adult Jehovah's Witnesses: the Henri Mondor Hospital experience

BackgroundElective liver resection (LR) in Jehovah’s Witness (JW) patients, for whom transfusion is not an option, involves complex ethical and medical issues and surgical difficulties. MethodsConsecutive data from a LR program for liver tumors in JWs performed between 2014 and 2017 were retrospectively reviewed. A systematic review of the literature with a pooled analysis was performed. ResultsTen patients were included (median age = 61 years). None needed preoperative erythropoietin. Tumor biopsy was not performed. Major hepatectomy was performed in 4 patients. The median estimated blood loss was 200 mL. A cell-saver was installed in 2 patients, none received saved blood. The median hemoglobin values before and at the end of surgery were 13.4 g/dL and 12.6 g/dL, respectively (p = 0.04). Nine complications occurred in 4 patients, but no postoperative hemorrhage occurred. In-hospital mortality was nil. Nine studies including 35 patients were identified in the literature; there was reported no mortality and low morbidity. None of the patients were transfused. ConclusionsBy using a variety of blood conservation techniques, the risk/benefit ratio of elective liver resection for liver was maintained in selected adult JW patients. JW faith should not constitute an absolute exclusion from hepatectomy.

Preoperative erythropoietin treatment improves survival following major hepatic resection in a cirrhotic rat model

Major hepatic resection of a cirrhotic liver may result in a fatal clinical course. Preoperative erythropoietin (EPO) treatment has been shown to have protective properties and to stimulate liver regeneration. This study aims to investigate the effect of preoperative EPO on survival following major hepatic resection in a cirrhotic rat model. Cirrhotic liver was induced by intraperitoneal injection of thioacetamide (200mg/kg/mL) in 72 Lewis rats. Each 36 rats received EPO (1IU/g, every second day, 5 times preoperatively) or saline (control) and major hepatectomy (removal of the left and half of the median lobe) was performed. Biochemical and immunohistochemical parameters, cytokines and overall survival were compared following surgery. Rats that received preoperative EPO had decreased hepatic aspartate aminotransferase, alanine aminotransferase and interleukin (IL)-1β expression, 48hours following surgery. They had increased hepatocyte growth factor and vascular endothelial growth factor expression at 1hour, increased IL-6 expression at 24, 48 and 120hours and increased Ki-67, 120hours following surgery. Overall, survival was significantly improved among EPO-treated rats (P=0.034). Preoperative EPO treatment has a protective effect and stimulates liver regeneration, leading to improved overall survival following major hepatectomy in a cirrhotic rat model.

Effect of Erythropoietin on Transfusion Requirements for Craniosynostosis Surgery in Children.

Pediatric craniosynostosis surgery is associated with significant blood loss often requiring allogenic blood transfusion (ABT). This study explores the clinical effectiveness of preoperative erythropoietin (EPO) administration in pediatric craniosynostosis surgery in reducing transfusion requirements. A systematic review and meta-analysis of the literature was performed for studies published in English language between 1946 and 2015. Inclusion criteria included original studies in the pediatric population (0-8 years of age) involving preoperative use of EPO in craniofacial procedures with quantitative reporting of perioperative blood transfusion. Extracted data included demographics, hematocrit, hemoglobin, estimated blood loss, number of patients transfused, and amount of ABT. Four studies met the inclusion criteria with a total of 117 patients. Patients were divided into 2 groups: EPO versus control. No statistical differences were found in the demographics between the 2 groups. Mean preoperative hematocrit level was higher in the EPO group compared with control (43% vs 35%). The percentage of patients who required ABT and the volume of transfused blood were less in the EPO group (54% vs 98% and 84 vs 283 mL, respectively). Meta-analysis of 3 comparable studies showed a lower proportion of patients who needed blood transfusion in the EPO group. The present meta-analysis demonstrated that preoperative administration of EPO in pediatric craniosynostosis surgery decreased the proportion of patients requiring ABT. In addition, the volume of transfusion was reduced in patients who received EPO. Future randomized studies are needed to establish the cost-effectiveness of routine preoperative EPO administration in craniosynostosis surgery.

The effectiveness of a de-implementation strategy to reduce low-value blood management techniques in primary hip and knee arthroplasty: a pragmatic cluster-randomized controlled trial

BackgroundPerioperative autologous blood salvage and preoperative erythropoietin are not (cost) effective to reduce allogeneic transfusion in primary hip and knee arthroplasty, but are still used. This study aimed to evaluate the effectiveness of a theoretically informed multifaceted strategy to de-implement these low-value blood management techniques.MethodsTwenty-one Dutch hospitals participated in this pragmatic cluster-randomized trial. At baseline, data were gathered for 924 patients from 10 intervention and 1040 patients from 11 control hospitals undergoing hip or knee arthroplasty. The intervention included a multifaceted de-implementation strategy which consisted of interactive education, feedback on blood management performance, and a comparison with benchmark hospitals, aimed at orthopedic surgeons and anesthesiologists. After the intervention, data were gathered for 997 patients from the intervention and 1096 patients from the control hospitals. The randomization outcome was revealed after the baseline measurement. Primary outcomes were use of blood salvage and erythropoietin. Secondary outcomes included postoperative hemoglobin, length of stay, allogeneic transfusions, and use of local infiltration analgesia (LIA) and tranexamic acid (TXA).ResultsThe use of blood salvage (OR 0.08, 95% CI 0.02 to 0.30) and erythropoietin (OR 0.30, 95% CI 0.09 to 0.97) reduced significantly over time, but did not differ between intervention and control hospitals (blood salvage OR 1.74 95% CI 0.27 to 11.39, erythropoietin OR 1.33, 95% CI 0.26 to 6.84). Postoperative hemoglobin levels were significantly higher (β 0.21, 95% CI 0.08 to 0.34) and length of stay shorter (β −0.36, 95% CI −0.64 to −0.09) in hospitals receiving the multifaceted strategy, compared with control hospitals and after adjustment for baseline. Transfusions did not differ between the intervention and control hospitals (OR 1.06, 95% CI 0.63 to 1.78). Both LIA (OR 0.0, 95% CI 0.0 to 0.0) and TXA (OR 0.3, 95% CI 0.2 to 0.5) were significantly associated with the reduction in blood salvage over time.ConclusionsBlood salvage and erythropoietin use reduced over time, but not differently between intervention and control hospitals. The reduction in blood salvage was associated with increased use of local infiltration analgesia and tranexamic acid, suggesting that de-implementation is assisted by the substitution of techniques. The reduction in blood salvage and erythropoietin did not lead to a deterioration in patient-related secondary outcomes.Trial registrationwww.trialregister.nl, NTR4044

Endogenic erythropoietin secretion in patients undergoing off-pump coronary artery bypass grafting.

Erythropoietin (EPO) deficiency or inadequate EPO secretion in response to bleeding may result in profound or prolonged anaemia after cardiac surgery. The aim of the study was to evaluate the changes in EPO secretion in patients undergoing off-pump coronary artery bypass grafting (OPCAB). Blood samples from 43 patients (mean age 65.1 ± 7.6 years) were obtained before surgery and on the 1st, 2nd, and 6th day post isolated OPCAB. EPO levels ≥ 4.3 mIU/mL were considered normal. Thirteen (30%) patients had the preoperative EPO level below normal range even though their preoperative haemoglobin was ≥ 13 g/dL. In patients with basal EPO deficiency lower peak EPO levels were observed compared to the group with normal basal EPO levels, even though reduction in haemoglobin concentrations was comparable in both groups. Moreover, lower reticulocytosis was noted on day 1 (8.5 ± 4.0‰ vs. 11.7 ± 4.4‰; p = 0.04) and a tendency toward lower values was seen on day 2 (9.6 ± 4.3‰ vs. 13.0 ± 5.8‰; p = 0.07) among patients with preoperative EPO deficiency. Erythropoietin deficiency is common in patients scheduled for OPCAB, and it results in diminished increase in EPO secretion in response to bleeding. Consequently, in patients with EPO deficiency, reticulocytosis is lower than it could be predicted based on the observation of patients with normal EPO levels and similar blood loss.

Erythropoietin with iron supplementation for preoperative anaemia in non-cardiac surgery

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: We aim to evaluate the efficacy and safety of preoperative erythropoietin (rHuEPO) with supplemental iron (parenteral or oral) in reducing perioperative allogeneic red blood cell transfusions in preoperatively anaemic people undergoing non-cardiac surgery.

Implementing a blood management protocol during the entire perioperative period allows a reduction in transfusion rate in major orthopedic surgery: a before-after study.

Patient blood management (PBM) must be promoted in orthopedic surgery and relies on different strategies implemented during the entire perioperative period. Our aim was to assess whether the introduction of a pre-, intra-, and postoperative PBM protocol combining erythropoietin (EPO), ferric carboxymaltose (FCM), and tranexamic acid was effective in reducing perioperative transfusion and postoperative anemia. In a two-phase prospective observational study, all patients admitted for total hip or knee arthroplasty were included the day before surgery. In Phase 1, use of EPO, iron, and tranexamic acid was left to the discretion of the anesthesiologists. In Phase 2, a protocol combining these treatments was implemented in the perioperative period. Perioperative hemoglobin levels and transfusion rates were recorded. A total of 367 patients were included (184 and 183 in Phase 1 and 2, respectively). During Phase 2, implementing a PBM protocol allowed an increase in preoperative EPO prescription in targeted patients (i.e., with Hb < 13 g/dL; 18 [38%] vs. 34 [62%], p = 0.03) and in postoperative use of intravenous iron (12 [6%] vs. 32 [18%], p = 0.001) and tranexamic acid (157 [86%] vs. 171 [94%] patients, p = 0.02). In Phase 2, the number of patients who received transfusions (24 [13%] vs. 5 [3%], p = 0.0003) and of patients with a Hb level of less than 10 g/dL at discharge (46 [25%] vs. 26 [14%], p = 0.01) were reduced. Introduction of a PBM protocol, using EPO, FCM, and tranexamic acid, reduces the number of perioperative transfusions and of patients with a Hb level of less than 10 g/dL at discharge.