Essential Role of Patient Blood Management in a Pandemic: A Call for Action.

The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a pandemic. Global health care now faces unprecedented challenges with widespread and rapid human-to-human transmission of SARS-CoV-2 and high morbidity and mortality with COVID-19 worldwide. Across the world, medical care is hampered by a critical shortage of not only hand sanitizers, personal protective equipment, ventilators, and hospital beds, but also impediments to the blood supply. Blood donation centers in many areas around the globe have mostly closed. Donors, practicing social distancing, some either with illness or undergoing self-quarantine, are quickly diminishing. Drastic public health initiatives have focused on containment and "flattening the curve" while invaluable resources are being depleted. In some countries, the point has been reached at which the demand for such resources, including donor blood, outstrips the supply. Questions as to the safety of blood persist. Although it does not appear very likely that the virus can be transmitted through allogeneic blood transfusion, this still remains to be fully determined. As options dwindle, we must enact regional and national shortage plans worldwide and more vitally disseminate the knowledge of and immediately implement patient blood management (PBM). PBM is an evidence-based bundle of care to optimize medical and surgical patient outcomes by clinically managing and preserving a patient's own blood. This multinational and diverse group of authors issue this "Call to Action" underscoring "The Essential Role of Patient Blood Management in the Management of Pandemics" and urging all stakeholders and providers to implement the practical and commonsense principles of PBM and its multiprofessional and multimodality approaches.

Open Heart Surgery in Jehovah's Witnesses: A Propensity Score Analysis.

BACKGROUND: Jehovah's Witnesses (JW) refuse allogeneic blood transfusions and therefore pose a unique challenge in case of major surgery. This retrospective study reviewed an experience with JW patients who were undergoing open heart surgery. METHODS: By using patient blood management strategies, 35 adult JW patients underwent cardiac surgery at Kepler University Hospital in Linz, Austria between 2008 and 2017. Outcomes were compared with patients who accepted blood transfusions (non-JW patients) by using propensity score matching. RESULTS: There were no significant differences in clinical and operative data between the groups. Twelve JW patients (34.3%) were pretreated with erythropoietin and iron, with a preoperative increase in mean hemoglobin of 2.0 g/dL. On admission, hemoglobin was 14.1 ± 1.1 g/dL in JW patients, compared with 13.2 ± 2.0 g/dL in non-JW patients (P = .022). The hematocrit in JW patients was higher throughout the hospital stay, even though 51.4% of non-JW patients received allogeneic red blood cell transfusions. The perioperative red blood cell loss was significantly lower in JW patients than in non-JW patients (619 ± 420 mL vs 929 ± 520 mL; P = .010). Major complication rates were not different between the groups. The hemoglobin at discharge was 11.5 ± 1.5 g/dL in JW patients compared with 10.3 ± 1.3 g/dL in non-JW patients (P < .001). In-hospital mortality was 2.9% in each group, and long-term survival was comparable. CONCLUSIONS: By implementing patient blood management, open heart surgery in JW patients can be performed with low morbidity and mortality. Preoperative optimization of hemoglobin and minimization of perioperative blood loss are cornerstones in the prevention of blood loss, anemia, and transfusions.

The efficacy of pre-operative preparation with intravenous iron and/or erythropoietin in anaemic patients undergoing orthopaedic surgery: An observational study.

BACKGROUND: Pre-operative anaemia and transfusion are common among patients undergoing elective orthopaedic surgery. Application of 'patient blood management' might be the most effective way to reduce both anaemia and transfusion. Pre-operative administration of iron and/or erythropoietin (EPO) is one of the cornerstones of the first pillar of patient blood management, but in a daily clinical setting, efficacy and long-term safety of this measure have not been analysed thoroughly to date. OBJECTIVE: To investigate the influence of pre-operative preparation (PREP) of patients with iron and/or EPO on peri-operative transfusion needs and long-term survival. DESIGN: Single-centre, retrospective study. SETTING: Anaesthesia department, University hospital. INTERVENTIONS: Pre-operative preparation with iron and/or EPO versus no preparation. METHODS: After approval of our local ethics committee, data of 5518 patients who received total hip or total knee replacement between 2008 and 2014 were included. Patients receiving iron and/or EPO were included in the PREP group, whereas patients without iron and/or EPO were included in the no preparation group. From the full data set, a bias-reduced subset of 662 patients was obtained by means of propensity score-matching to compare peri-operative red blood cell utilisation and long-term survival of patients between groups. RESULTS: Patients in the PREP group needed a lower number of units of red blood cells than patients in the no preparation group (0.2 ±â€Š0.8 vs. 0.5 ±â€Š1.3, P < 0.001), had a lower transfusion rate (12 vs. 24%, P < 0.05) and had a similar haemoglobin concentration (10.7 ±â€Š1.3 vs. 10.6 ±â€Š1.1 g dl, not significant) at discharge. No differences in long-term survival were observed between the two study groups. CONCLUSION: PREP of patients with iron and/or EPO in orthopaedic patients can be considered highly effective in terms of transfusion reduction, without influencing long-term survival.

Development of Multivariable Models to Predict and Benchmark Transfusion in Elective Surgery Supporting Patient Blood Management.

BACKGROUND: Blood transfusion is a highly prevalent procedure in hospitalized patients and in some clinical scenarios it has lifesaving potential. However, in most cases transfusion is administered to hemodynamically stable patients with no benefit, but increased odds of adverse patient outcomes and substantial direct and indirect cost. Therefore, the concept of Patient Blood Management has increasingly gained importance to pre-empt and reduce transfusion and to identify the optimal transfusion volume for an individual patient when transfusion is indicated. OBJECTIVES: It was our aim to describe, how predictive modeling and machine learning tools applied on pre-operative data can be used to predict the amount of red blood cells to be transfused during surgery and to prospectively optimize blood ordering schedules. In addition, the data derived from the predictive models should be used to benchmark different hospitals concerning their blood transfusion patterns. METHODS: 6,530 case records obtained for elective surgeries from 16 centers taking part in two studies conducted in 2004-2005 and 2009-2010 were analyzed. Transfused red blood cell volume was predicted using random forests. Separate models were trained for overall data, for each center and for each of the two studies. Important characteristics of different models were compared with one another. RESULTS: Our results indicate that predictive modeling applied prior surgery can predict the transfused volume of red blood cells more accurately (correlation coefficient cc = 0.61) than state of the art algorithms (cc = 0.39). We found significantly different patterns of feature importance a) in different hospitals and b) between study 1 and study 2. CONCLUSION: We conclude that predictive modeling can be used to benchmark the importance of different features on the models derived with data from different hospitals. This might help to optimize crucial processes in a specific hospital, even in other scenarios beyond Patient Blood Management.

Patient Blood Management Bundles to Facilitate Implementation.

More than 30% of the world's population are anemic with serious economic consequences including reduced work capacity and other obstacles to national welfare and development. Red blood cell transfusion is the mainstay to correct anemia, but it is also 1 of the top 5 overused procedures. Patient blood management (PBM) is a proactive, patient-centered, and multidisciplinary approach to manage anemia, optimize hemostasis, minimize iatrogenic blood loss, and harness tolerance to anemia. Although the World Health Organization has endorsed PBM in 2010, many hospitals still seek guidance with the implementation of PBM in clinical routine. Given the use of proven change management principles, we propose simple, cost-effective measures enabling any hospital to reduce both anemia and red blood cell transfusions in surgical and medical patients. This article provides comprehensive bundles of PBM components encompassing 107 different PBM measures, divided into 6 bundle blocks acting as a working template to develop institutions' individual PBM practices for hospitals beginning a program or trying to improve an already existing program. A stepwise selection of the most feasible measures will facilitate the implementation of PBM. In this manner, PBM represents a new quality and safety standard.

Gender disparities in red blood cell transfusion in elective surgery: a post hoc multicentre cohort study.

OBJECTIVES: A post hoc gender comparison of transfusion-related modifiable risk factors among patients undergoing elective surgery. SETTINGS: 23 Austrian centres randomly selected and stratified by region and level of care. PARTICIPANTS: We consecutively enrolled in total 6530 patients (3465 women and 3065 men); 1491 underwent coronary artery bypass graft (CABG) surgery, 2570 primary unilateral total hip replacement (THR) and 2469 primary unilateral total knee replacement (TKR). MAIN OUTCOME MEASURES: Primary outcome measures were the number of allogeneic and autologous red blood cell (RBC) units transfused (postoperative day 5 included) and differences in intraoperative and postoperative transfusion rate between men and women. Secondary outcomes included perioperative blood loss in transfused and non-transfused patients, volume of RBCs transfused, perioperative haemoglobin values and circulating red blood volume on postoperative day 5. RESULTS: In all surgical groups, the transfusion rate was significantly higher in women than in men (CABG 81 vs 49%, THR 46 vs 24% and TKR 37 vs 23%). In transfused patients, the absolute blood loss was higher among men in all surgical categories while the relative blood loss was higher among women in the CABG group (52.8 vs 47.8%) but comparable in orthopaedic surgery. The relative RBC volume transfused was significantly higher among women in all categories (CABG 40.0 vs 22.3; TKR 25.2 vs 20.2; THR 26.4 vs 20.8%). On postoperative day 5, the relative haemoglobin values and the relative circulating RBC volume were higher in women in all surgical categories. CONCLUSIONS: The higher transfusion rate and volume in women when compared with men in elective surgery can be explained by clinicians applying the same absolute transfusion thresholds irrespective of a patient's gender. This, together with the common use of a liberal transfusion strategy, leads to further overtransfusion in women.

Does the severity of preoperative anemia or blood transfusion have a stronger impact on long-term survival after cardiac surgery?

BACKGROUND: Preoperative anemia and transfusion are associated with increased morbidity and mortality in cardiac surgery patients. It is unclear which of these factors plays the leading role in poor outcomes after cardiac surgery. The goal of this study was to analyze the influence of anemias of varying severity and intraoperative transfusion on long-term survival, and to characterize their interaction in cardiac surgery patients. METHODS: This was an observational cohort study conducted at a German university hospital. All patients undergoing cardiac surgery between 2006 and 2011 were screened for eligibility; duration of follow-up was 3 years. A total of 4494 patients were suitable for analysis; data on long-term survival were available for 3131 of these patients. The main outcome measure was survival at the 3-year follow-up. Length of stay and in-hospital mortality were assessed as secondary outcomes. RESULTS: Multivariate Cox regression analyses indicated that both the severity of preoperative anemia (mild anemia: hazard ratio [HR], 1.441; 95% confidence interval [CI], 1.201-1.728; severe anemia: HR, 1.805; 95% CI, 1.336-2.440) and intraoperative transfusion (HR, 1.340; 95% CI, 1.109-1.620) were associated with decreased long-term survival. Long-term survival was worse in anemic patients who received an intraoperative transfusion compared with those who did not receive an intraoperative transfusion. CONCLUSIONS: Both preoperative anemia and transfusion are by themselves and in combination associated with decreased long-term survival. When anemic patients require transfusion, our results provide evidence that the risk of death after cardiac surgery may depend to a considerable extent on the severity of preoperative anemia.

Data Driven Methods for Predicting Blood Transfusion Needs in Elective Surgery.

Research in blood transfusions mainly focuses on Donor Blood Management, including donation, screening, storage and transport. However, the last years saw an increasing interest in recipient related optimizations, i.e. Patient Blood Management (PBM). Although PBM already aims at reducing transfusion rates by pre- and intra-surgical optimization, there is still a high potential of improvement on an individual level. The present paper investigates the feasibility of predicting blood transfusions needs based on datasets from various treatment phases, using data which have been collected in two previous studies. Results indicate that prediction of blood transfusions can be further improved by predictive modelling including individual pre-surgical parameters. This also allows to identify the main predictors influencing transfusion practice. If confirmed in a prospective dataset, these or similar predictive methods could be a valuable tool to support PBM with the ultimate goal to reduce costs and improve patient outcomes.

Implementation and validation of a conceptual benchmarking framework for patient blood management.

BACKGROUND: Public health authorities and healthcare professionals are obliged to ensure high quality health service. Because of the high variability of the utilisation of blood and blood components, benchmarking is indicated in transfusion medicine. OBJECTIVES: Implementation and validation of a benchmarking framework for Patient Blood Management (PBM) based on the report from the second Austrian Benchmark trial. METHODS: Core modules for automatic report generation have been implemented with KNIME (Konstanz Information Miner) and validated by comparing the output with the results of the second Austrian benchmark trial. RESULTS: Delta analysis shows a deviation <0.1% for 95% (max. 1.4%). CONCLUSION: The framework provides a reliable tool for PBM benchmarking. The next step is technical integration with hospital information systems.

The second Austrian benchmark study for blood use in elective surgery: results and practice change.

BACKGROUND: Five years after the first Austrian benchmark study demonstrated relatively high transfusion rate and an abundance of nonindicated transfusions in elective surgeries, this study was conducted to investigate the effects of the first benchmark study. STUDY DESIGN AND METHODS: Data from 3164 patients undergoing primary unilateral total hip replacement (THR), primary unilateral noncemented total knee replacement (TKR), or coronary artery bypass graft (CABG) surgery at 15 orthopedic and six cardiac centers were collected and compared with the first study. RESULTS: Transfusion rates decreased in THR (41% to 30%) and TKR (41% to 25%), but remained unchanged in CABG surgery (57% vs. 55%) compared with the first study. More than 80% of all transfusions involved at least 2 units of red blood cells (RBCs). Marked variations were observed in transfusion rates among the centers. The prevalence of anemia was three times higher in patients who received transfusions versus those who did not. However, preoperative anemia was left untreated in the majority of patients. A considerable intercenter variability of RBC loss ranging from 26% to 43% in THR, from 24% to 40% in TKR, and from 30% to 49% in CABG procedures was observed. CONCLUSION: The second benchmark study demonstrates substantial intercenter variability and small but significant reductions in RBC transfusions and RBC loss. Even though the main independent predictors of transfusion were the relative lost RBC volume followed by the relative preoperative and the lowest relative postoperative hemoglobin, preoperative anemia was not adequately treated in many patients, underscoring the importance of patient blood management in these patients.

Six percent hydroxyethyl starch 130/0.4 (Voluven®) versus 5% human serum albumin for volume replacement therapy during elective open-heart surgery in pediatric patients.

BACKGROUND: Although 5% albumin (human serum albumin [HSA]) is widely used in cardiac surgery children, synthetic colloids may provide a valuable alternative. This study compared 6% hydroxyethyl starch (HES) 130/0.4 with HSA for volume replacement in this population. METHODS: The study was a two-center, randomized, controlled, parallel-group, double-blind trial performed in children aged 2-12 yr undergoing elective surgery for congenital heart disease under extracorporeal circulation. The primary objective was to demonstrate equivalence between HES and HSA with regard to the total volume of colloid infusion for intraoperative volume replacement including priming of the extracorporeal circuitery. RESULTS: In the per-protocol population, mean volume of colloid required until end of surgery was (mean ± SD) 36.6 ± 11.8 ml/kg body weight in the HES group (N = 29) and 37.0 ± 11.9 ml/kg body weight in the HSA group (N = 26; ratio of means HES/HSA = 0.98 [95% CI, 0.84-1.16]). Intraoperative fluid balance was less positive in the HES group (P = 0.047). No difference was found regarding hemodynamics, the use of vasoactive and inotropic drugs. Blood loss, erythrocytes transfusion, and renal function were not different between groups. The incidence of adverse events up to postoperative day 28 did not differ between the groups. CONCLUSIONS: In pediatric cardiac surgery, HES showed equivalence to HSA with regard to volume replacement therapy in children aged from 2 to 12 yr. Although there was no suggestion of an imbalance of safety measures between HES and HSA, the study was not powered to provide any firm conclusions about safety of tetrastarch in this population.

Re-evaluating currently available data and suggestions for planning randomised controlled studies regarding the use of hydroxyethyl starch in critically ill patients - a multidisciplinary statement.

INTRODUCTION: Hydroxyethyl starch (HES) is a commonly used colloid in critically ill patients. However, its safety has been questioned in recent studies and meta-analyses. METHODS: We re-evaluated prospective randomised controlled trials (RCT) from four meta-analyses published in 2013 that compared the effect of HES with crystalloids in critically ill patients, focusing on the adherence to 'presumably correct indication'. Regarding the definition of 'presumably correct indication', studies were checked for the following six criteria (maximum six points): short time interval from shock to randomisation (<6 h), restricted use for initial volume resuscitation, use of any consistent algorithm for haemodynamic stabilisation, reproducible indicators of hypovolaemia, maximum dose of HES, and exclusion of patients with pre-existing renal failure or renal replacement therapy. RESULTS: Duration of fluid administration ranged from 90 min up to a maximum of 90 days. Four studies considered follow-up until 90-day mortality, three studies 28-/30-day mortality, whereas four studies reported only early mortality. Included studies showed a large heterogeneity of the indication score ranging between 1 and 4 points with a median (25%; 75% quartile) of 4 (2; 4). CONCLUSIONS: The most important question, whether or not HES may be harmful when it is limited to immediate haemodynamic stabilisation, cannot be answered yet in the absence of any study sufficiently addressing this question. In order to overcome the limitations of most of the previous studies, we now suggest an algorithm emphasising the strict indication of HES. Additionally, we give a list of suggestions that should be adequately considered in any prospective RCT in the field of acute volume resuscitation in critically ill patients.

Pillar III--optimisation of anaemia tolerance.

In the case of acute bleeding, the use of the anaemia tolerance of a patient enables the physician to either avoid blood transfusions or delay them after bleeding has ceased. This concept is the cornerstone of the third pillar of modern patient blood management programmes. Its efficacy depends on the degree of utilisation of anaemia tolerance, which is not constant but depends on the compensatory capacity of the individual patient in a given situation. Fortunately, the specifications of anaemia tolerance can be influenced by the anaesthesiologist. This article presents the concept of anaemia tolerance and highlights the options for how anaemia tolerance can be optimised in the pre-, intra-, and postoperative periods.

Preoperative identification of patients with increased risk for perioperative bleeding.

PURPOSE OF REVIEW: Although the overall complication rate in cardiac surgery has been decreased, perioperative bleeding increasing morbidity and mortality is still frequent. Furthermore, the widespread use of new antithrombotic and antiplatelet agents presents an additional challenge in daily practice. Therefore, identifying patients with increased bleeding risk would be advantageous to optimize perioperative management. RECENT FINDINGS: Bleeding classifications are frequently discussed, but are of little relevance for the perioperative setting. In the nonsurgical setting the most relevant risk factors in bleeding prediction are age, renal disease, sex, pre-existing anemia, and the administration of antithrombotic/antiplatelet drugs. In cardiac surgery, the Papworth Bleeding Risk Stratification Score identifies mainly procedure-linked risk factors and might be one of the most suitable scores to be used. Routine laboratory screening appears to have limited utility. SUMMARY: Apart from precise bleeding history only insufficient data exist in cardiac surgery to exactly predict bleeding complications. Therefore, there is urgent need for further studies to improve perioperative bleeding management.

Patient Blood Management: A Patient-Orientated Approach to Blood Replacement with the Goal of Reducing Anemia, Blood Loss and the Need for Blood Transfusion in Elective Surgery.

Patient Blood Management (PBM) describes an evidence-based, multidisciplinary therapeutic approach. Its focus is on the treatment of the individual patient and as such comprises transfusion therapy and pharmacotherapy. Furthermore, the applicability of PBM is not limited to the perioperative setting but is applicable also to other therapeutic measures and disciplines where significant blood loss is known to occur and where transfusion of blood products is part of the established treatment. PBM is fundamentally based on 3 pillars: (1) optimization of the (preoperative) erythrocyte volume, (2) reduction of diagnostic, therapeutic, or intraoperative blood loss, and (3) increasing individual tolerance towards anemia and accurate blood transfusion triggers. PBM primarily identifies patients at risk of transfusion and provides a management plan aimed at reducing or eliminating the risk of anemia and the need for allogeneic transfusion, thus reducing the inherent risks, inventory pressures, and the escalating costs associated with transfusion.

Levosimendan versus milrinone in neonates and infants after corrective open-heart surgery: a pilot study.

OBJECTIVE: Low cardiac output syndrome commonly complicates the postoperative course after open-heart surgery in children. To prevent low cardiac output syndrome, prophylactic administration of milrinone after cardiopulmonary bypass is commonly used in small children. The aim of this study was to compare the effect of prophylactically administered levosimendan and milrinone on cardiac index in neonates and infants after corrective open-heart surgery. DESIGN: Prospective, single-center, double-blind, randomized pilot study. SETTING: Tertiary care center, postoperative pediatric cardiac intensive care unit. PATIENTS: After written informed consent, 40 infants undergoing corrective open-heart surgery were included. INTERVENTIONS: At weaning from cardiopulmonary bypass, either a 24-hr infusion of 0.1 µg/kg/min levosimendan or of 0.5 µg/kg/min milrinone were administered. Cardiac output was evaluated at 2, 6, 9, 12, 18, 24, and 48 hrs after cardiopulmonary bypass using a transesophageal Doppler technique (Cardio-QP, Deltex Medical, Chichester, UK). Cardiac index was calculated from cardiac output and the patients' respective body surface area. RESULTS: Intention-to-treat data of 39 patients (19 in the levosimendan and 20 in the milrinone group) were analyzed using analysis of variance for repeated measurements for statistics. Analysis of variance revealed for both, cardiac index and cardiac output, similar results with no significant differences of the factors group and time. A significant interaction for cardiac output (p = .005) and cardiac index (p = .007) was found, which indicates different time courses of cardiac index in the two groups. Both drugs were well tolerated; no death or serious adverse event occurred. CONCLUSIONS: In our small study, postoperative cardiac index over time was similar in patients with prophylactically administered levosimendan and patients with prophylactically given milrinone. We observed an increase in cardiac output and cardiac index over time in the levosimendan group, whereas cardiac output and cardiac index remained stable in the milrinone group. This pilot study has primarily served to obtain experience using the new drug levosimendan in neonates and infants and to initiate further multicenter trials in pediatric patients.