Patient blood management during the COVID-19 pandemic: a narrative review.

As COVID-19 disease escalates globally, optimising patient outcome during this catastrophic healthcare crisis is the number one priority. The principles of patient blood management are fundamental strategies to improve patient outcomes and should be given high priority in this crisis situation. The aim of this expert review is to provide clinicians and healthcare authorities with information regarding how to apply established principles of patient blood management during the COVID-19 pandemic. In particular, this review considers the impact of the COVID-19 pandemic on blood supply and specifies important aspects of donor management. We discuss how preventative and control measures implemented during the COVID-19 crisis could affect the prevalence of anaemia, and highlight issues regarding the diagnosis and treatment of anaemia in patients requiring elective or emergency surgery. In addition, we review aspects related to patient blood management of critically ill patients with known or suspected COVID-19, and discuss important alterations of the coagulation system in patients hospitalised due to COVID-19. Finally, we address special considerations pertaining to supply-demand and cost-benefit issues of patient blood management during the COVID-19 pandemic.

The effect of a novel intravenous fluid (Oxsealife®) on recovery from haemorrhagic shock in pigs.

Blood transfusion is given according to haemoglobin thresholds aimed at restoration of arterial oxygen-carrying capacity. Patient survival after severe haemorrhagic shock depends on restoration of microvascular perfusion, tissue oxygen delivery, endothelial function and organ integrity. We investigated a novel crystalloid fluid designed for tissue oxygen delivery, Oxsealife® , with components that generate microvascular nitric oxide and scavenge reactive oxygen species generated during ischaemia-reperfusion injury. The amount of dissolved oxygen in blood progressively increased during step-wise in vitro haemodilution with this fluid, suggesting that the oxygen solubility coefficient of blood is dynamic, not static. We performed a pilot safety and efficacy study to compare resuscitation with this novel crystalloid vs. whole blood transfusion in a swine haemorrhagic shock model with animals bled to an arterial lactate oxygen debt target. Despite contributing no haemoglobin, viscosity nor oncotic potential, resuscitation with Oxsealife after severe haemorrhagic shock restored central haemodynamic parameters comparable to stored allogeneic blood transfusion. Tissue perfusion, oxygenation and metabolic outcomes were equivalent between treatment groups. Increased consumption of bicarbonate in animals given Oxsealife suggested greater capillary recruitment and enhanced clearance of acidic tissue metabolites. Serum markers of organ function, animal activity during recovery and histological analysis of tissue morphology and endothelial glycocalyx integrity confirmed functional recovery from haemorrhagic shock. We conclude that recovery of tissue oxygen delivery and organ function after haemorrhagic shock may not be dependent on treatments that increase haemoglobin levels. Oxsealife shows promise for treatment of severe haemorrhagic shock and may reduce the requirement for allogeneic blood products.

An international consensus statement on the management of postoperative anaemia after major surgical procedures.

Despite numerous guidelines on the management of anaemia in surgical patients, there is no pragmatic guidance for the diagnosis and management of anaemia and iron deficiency in the postoperative period. A number of experienced researchers and clinicians took part in a two-day expert workshop and developed the following consensus statement. After presentation of our own research data and local policies and procedures, appropriate relevant literature was reviewed and discussed. We developed a series of best-practice and evidence-based statements to advise on patient care with respect to anaemia and iron deficiency in the postoperative period. These statements include: a diagnostic approach to iron deficiency and anaemia in surgical patients; identification of patients appropriate for treatment; and advice on practical management and follow-up that is easy to implement. Available data allow the fulfilment of the requirements of Pillar 1 of Patient Blood Management. We urge national and international research funding bodies to take note of these recommendations, particularly in terms of funding large-scale prospective, randomised clinical trials that can most effectively address the important clinical questions and this clearly unmet medical need.

International consensus statement on the peri-operative management of anaemia and iron deficiency.

Despite current recommendations on the management of pre-operative anaemia, there is no pragmatic guidance for the diagnosis and management of anaemia and iron deficiency in surgical patients. A number of experienced researchers and clinicians took part in an expert workshop and developed the following consensus statement. After presentation of our own research data and local policies and procedures, appropriate relevant literature was reviewed and discussed. We developed a series of best-practice and evidence-based statements to advise on patient care with respect to anaemia and iron deficiency in the peri-operative period. These statements include: a diagnostic approach for anaemia and iron deficiency in surgical patients; identification of patients appropriate for treatment; and advice on practical management and follow-up. We urge anaesthetists and peri-operative physicians to embrace these recommendations, and hospital administrators to enable implementation of these concepts by allocating adequate resources.

Activity-based costs of plasma transfusions in medical and surgical inpatients at a US hospital.

BACKGROUND AND OBJECTIVES: Fresh frozen plasma (FFP) usage has significantly increased over the last decade leading to elevated healthcare costs. Although FFP is used in several clinical settings, it is often inappropriately transfused and evidence for its clinical efficacy is poor. Here, we describe plasma usage and transfusion costs in a real-world US inpatient setting to determine the cost-effectiveness of FFP transfusion and for comparison to various patient blood management (PBM) options to treat coagulopathies. MATERIALS AND METHODS: All activities related to plasma transfusion recorded at a single US hospital over one calendar year were collected in a stepwise manner using an activity-based costing (ABC) methodology. This model maps all technical, administrative and clinical processes inherent to the cost of plasma. RESULTS: Of 18 200 inpatients recorded, 849 were charged for blood products. In total, 136 medical and surgical inpatients were charged for 577 units of FFP, receiving a total of 534 units; 43 units were charged but not transfused. The total cost per unit of FFP transfused was $409·62 and $1,608·37 per patient transfused with FFP. Wasted products, in-hospital processes and overhead costs were found to account for 89·8% of the total cost of FFP transfusions. CONCLUSION: This study is the first to use ABC methodology to determine the full cost of plasma transfusion in a US inpatient setting. These data reveal the true cost of plasma, providing a useful reference point to compare with the cost of other PBM options to manage coagulation disorders.

'Fit to fly': overcoming barriers to preoperative haemoglobin optimization in surgical patients.

In major surgery, the implementation of multidisciplinary, multimodal and individualized strategies, collectively termed Patient Blood Management, aims to identify modifiable risks and optimise patients' own physiology with the ultimate goal of improving outcomes. Among the various strategies utilized in Patient Blood Management, timely detection and management of preoperative anaemia is most important, as it is in itself a risk factor for worse clinical outcome, but also one of the strongest predisposing factors for perioperative allogeneic blood transfusion, which in turn increases postoperative morbidity, mortality and costs. However, preoperative anaemia is still frequently ignored, with indiscriminate allogeneic blood transfusion used as a 'quick fix'. Consistent with reported evidence from other medical specialties, this imprudent practice continues to be endorsed by non-evidence based misconceptions, which constitute serious barriers for a wider implementation of preoperative haemoglobin optimisation. We have reviewed a number of these misconceptions, which we unanimously consider should be promptly abandoned by health care providers and replaced by evidence-based strategies such as detection, diagnosis and proper treatment of preoperative anaemia. We believe that this approach to preoperative anaemia management may be a viable, cost-effective strategy that is beneficial both for patients, with improved clinical outcomes, and for health systems, with more efficient use of finite health care resources.

Patient blood management in Europe.

Preoperative anaemia is common in patients undergoing orthopaedic and other major surgery. Anaemia is associated with increased risks of postoperative mortality and morbidity, infectious complications, prolonged hospitalization, and a greater likelihood of allogeneic red blood cell (RBC) transfusion. Evidence of the clinical and economic disadvantages of RBC transfusion in treating perioperative anaemia has prompted recommendations for its restriction and a growing interest in approaches that rely on patients' own (rather than donor) blood. These approaches are collectively termed 'patient blood management' (PBM). PBM involves the use of multidisciplinary, multimodal, individualized strategies to minimize RBC transfusion with the ultimate goal of improving patient outcomes. PBM relies on approaches (pillars) that detect and treat perioperative anaemia and reduce surgical blood loss and perioperative coagulopathy to harness and optimize physiological tolerance of anaemia. After the recent resolution 63.12 of the World Health Assembly, the implementation of PBM is encouraged in all WHO member states. This new standard of care is now established in some centres in the USA and Austria, in Western Australia, and nationally in the Netherlands. However, there is a pressing need for European healthcare providers to integrate PBM strategies into routine care for patients undergoing orthopaedic and other types of surgery in order to reduce the use of unnecessary transfusions and improve the quality of care. After reviewing current PBM practices in Europe, this article offers recommendations supporting its wider implementation, focusing on anaemia management, the first of the three pillars of PBM.

What is really dangerous: anaemia or transfusion?

Summary While complex physiological mechanisms exist to regulate and optimize tissue oxygenation under various conditions, clinical and experimental evidence indicates that anaemia, unchecked, is associated with organ injury and unfavourable outcomes. More data (especially from human studies) are needed to answer questions regarding the optimal approaches to the treatment of acute and chronic anaemia. Meantime, allogeneic blood transfusions remain the most common treatment, particularly in surgical/trauma patients and those with moderate-to-severe anaemia. Clinical studies emphasize the paradox that both anaemia and transfusion are associated with organ injury and increased morbidity and mortality across a wide span of disease states and surgical interventions. Further characterization of the mechanisms of injury is needed to appropriately balance these risks and to develop novel treatment strategies that will improve patient outcomes. Here, we present the current understanding of the physiological mechanisms of tissue oxygen delivery, utilization, adaptation, and survival in the face of anaemia and current evidence on the independent (and often, synergistic) deleterious impact of anaemia and transfusion on patient outcomes. The risks of anaemia and transfusion in the light of substantial variations in transfusion practices, increasing costs, shrinking pool of donated resources, and ambiguity about actual clinical benefits of banked allogeneic blood demand better management strategies targeted at improving patient outcomes.

Tranexamic acid and obstetric hemorrhage: give empirically or selectively?

Antifibrinolytic agents such as tranexamic acid (TXA) inhibit the fibrinolytic pathway and protect blood clots from being degraded, thereby promoting hemostasis. They have been used to reduce blood loss in various settings including obstetrics. Based on current evidence, TXA can be considered as a therapeutic adjunct to control postpartum hemorrhage (PPH) after vaginal and cesarean deliveries, with earlier administration preferred. This strategy has been demonstrated to reduce mortality due to bleeding (but not the incidence of transfusion) in developing countries. On the other hand, the benefit-risk ratio of TXA has not been fully assessed in developed countries which have much lower PPH-related mortality rates and better access to other management modalities. As a proposed prophylactic agent to prevent PPH, the level of evidence is currently insufficient to recommend the routine use of TXA to prevent blood loss after vaginal and cesarean deliveries. The results of large new multicenter studies assessing the impact of TXA on maternal blood loss-related outcomes after cesarean delivery are awaited. While most studies to date have focused on empirical and one-size-fit-all dosing of TXA, more selective and individualized treatment protocols (possibly guided by functional coagulation assays) are needed to pave the way for safer and more effective use of this inexpensive and widely used medication.

Iron overload and toxicity: the hidden risk of multiple blood transfusions.

BACKGROUND: The quantity of iron in body is carefully regulated, primarily by control of iron absorption, and excess total body iron can be extremely toxic. Since humans have no mechanism for elimination of excess iron, multiple transfusions of red blood cells, which are required for the management of a number of disorders, inevitably result in iron overload. Cumulative iron overload, in turn, leads to iron toxicity with organ dysfunction and damage. MATERIALS: This review examines the relationship between iron metabolism and hematologic disorders treated with multiple transfusions, with emphasis on the diagnosis and current methods of management of iron overload and toxicity in transfusion-dependent patients. Primarily using key words, we identified and reviewed more than 100 pertinent articles in English and other languages in the Medline database plus an additional number of abstracts of presentations at recent meetings of relevant scientific associations. RESULTS: Transfusion-dependent disorders include those characterized by decreased red blood cell production, increased red blood cell destruction, or chronic blood loss. Patients receiving chronic transfusion therapy should be screened and monitored for iron overload, yet in our opinion, this is not always done routinely. Once iron overload has been identified, it should be treated to reduce the risk of morbidity and mortality from iron toxicity, which particularly affects the liver and heart. CONCLUSION: Increased awareness of the risks of iron overload from chronic transfusion therapy should result in greater use of interventions such as iron chelation to reduce total body iron and the risk of long-term sequelae.

Fatigue of isolated rat diaphragm: role of impaired neuromuscular transmission.

We compared the contributions of impaired neuromuscular transmission (transmission fatigue) and impaired muscle contractility (contractile fatigue) to fatigue of the isolated rat diaphragm. To make this comparison, we measured the differences in active tension elicited by direct muscle stimulation and by indirect (phrenic nerve) stimulation before and after fatigue induced by indirect supramaximal stimulation at varying frequencies and durations. Transmission fatigue was observed after all experimental protocols. Although significant contractile fatigue was not demonstrated after brief periods of low-frequency stimulation (6 min, 15 Hz, 25% duty cycle), it was present after longer or higher frequency stimulation. We repeated the direct stimulation in the presence of neuromuscular blockade with 6 microM d-tubocurarine to demonstrate that a reduced response to stimulation of intramuscular branches of the phrenic nerve during direct stimulation was not responsible for the apparent contractile fatigue. Since we found significant decreases in the response to direct stimulation even after neuromuscular blockade, we could verify the presence of contractile fatigue. We conclude that both contractile and transmission fatigue can occur in the isolated rat diaphragm and that transmission fatigue is a much more important factor after brief periods of fatiguing contractions.

Bioartificial organ support for hepatic, renal, and hematologic failure.

The current strategy to the treatment of SIRS and MODS uses a multidisciplinary approach that emphasizes supportive therapy. Herein, we have presented a futuristic approach that focuses on replacing the function of failed organs using bioartificial technology (Table 1). Bioartificial organ technology may allow the intensivist to provide physiologic organ replacement either as a bridge to transplantation or as a "time-buying" element until native organs that have become acutely dysfunctional or nonfunctional in a variety of clinical settings, can recover their function or regenerate their mass. As bioartificial organ technology matures, it is conceivable as an ultimate goal that non-immunogenic bioartificial organs would be miniaturized or redesigned and acutely placed within the intracorporeal space as replacement organs.

A practical approach to achieving bloodless surgery.

The term bloodless surgery refers to the practice of performing surgical procedures without the use of allogenic blood and avoiding the use of stored blood, including autologous blood, entirely. This article reviews the scientific and clinical literature regarding bloodless surgery and describes the application of a full-service, bloodless program within a community hospital.