Consensus of the Brazilian association of hematology, hemotherapy and cellular therapy on patient blood management.

Understanding the physiological concepts of oxygen delivery is essential to discern the mechanisms that influence its increase, reduction or maintenance in the body. This text explores the different mechanisms that help maintain oxygen delivery even in the face of reduced hemoglobin levels. Adequate oxygen delivery ensures tissue and metabolic balance, which is crucial to avoid harmful consequences such as metabolic acidosis and cellular dysoxia. The complex interaction between variables such as cardiac output, hemoglobin and heart rate (HR) plays a fundamental role in maintaining oxygen delivery, allowing the body to temporarily adjust to situations of anemia or high metabolic demand. It is important to emphasize that blood transfusions should not be based on fixed values, but rather on individual metabolic needs. Strategies to reduce myocardial consumption and monitor macro and micro hemodynamics help in making rational decisions. Individualizing treatment and considering factors such as blood viscosity in relation to the benefits of transfusion are increasingly relevant to optimize therapy and minimize risks, especially in complex clinical scenarios, such as neurocritical patients and trauma victims.

Consensus of the Brazilian association of hematology, hemotherapy and cellular therapy on patient blood management: Anemia tolerance.

Anemia is a pathological condition in which the hemoglobin and red blood cell mass decrease; it is mainly defined by the concentration of hemoglobin in the blood. The World Health Organization guidelines establish specific values to define anemia in different population groups. Early detection of anemia can also be a valuable indicator of underlying medical conditions. Clinical studies have explored the relationship between perioperative anemia and morbidity, highlighting the need for more judicious therapeutic strategies, such as the use of Patient Blood Management, which aims to prevent and treat anemia in a personalized and effective way. Patient Blood Management emerges as a promising approach to dealing with anemia, recognizing that its correction through transfusion always carries risks and that personalized prevention and treatment can offer better outcomes for patients.

Consensus of the Brazilian association of hematology, hemotherapy and cellular therapy on patient blood management: Acute normovolemic hemodilution and intraoperative autotransfusion.

Autologous blood transfusion can be achieved through different techniques, including by the patient donating blood before surgery (pre-deposit), collecting blood from the patient immediately before the operation and replacing the volume with colloids or plasma expanders (acute normovolemic hemodilution) or through the salvage of lost blood, during or immediately after surgery, and its retransfusion after washing (intraoperative or postoperative recovery). We will focus on the two methods used intraoperatively that are of fundamental importance in the management and conservation of the patient's own blood.

Consensus of the Brazilian association of hematology, hemotherapy and cellular therapy on patient blood management: Intraoperative hemostasis and volume replacement.

Hemostasis plays a critical role in surgical procedures and is essential for a successful outcome. Advances in hemostatic agents offer new approaches to controlling bleeding thereby making surgeries safer. The appropriate choice of these agents is crucial. Volume replacement, another integral part of Patient Blood Management (PBM), maintains adequate tissue perfusion, preventing cellular damage. Individualization in fluid administration is vital with the choice between crystalloids and colloids depending on each case. Colloids, unlike crystalloids, increase oncotic pressure, contributing to fluid retention in the intravascular space. Understanding these aspects is essential to ensure safe and effective surgery, minimizing complications related to blood loss and maintaining the patient's hemodynamic status.

Consensus of the Brazilian association of hematology, hemotherapy and cellular therapy on patient blood management: Antifibrinolytics.

The use of strategies to reduce blood loss and transfusions is essential in the treatment of surgical patients, including in complex cardiac surgeries and those that use cardiopulmonary bypass. Antifibrinolytics, such as epsilon-aminocaproic acid (EACA) and tranexamic acid (TXA), are widely used in these procedures, as well as in other types of surgeries. These medicines are included in the World Health Organization (WHO) list of 'essential medicines'. Scientific evidence demonstrates the effectiveness of EACA in reducing bleeding and the need for transfusions in heart surgery. EACA is highly recommended for use in heart surgery by the American Society of Anesthesiology Task Force on Perioperative Blood Management. Regarding the safety of EACA, there is no robust evidence of any significant thrombotic potential. TXA has also been shown to be effective in reducing the use of blood transfusions in cardiac and non-cardiac surgeries and is considered safer than other antifibrinolytic agents. There is no evidence of any increased risk of thromboembolic events with TXA, but doses greater than 2 g per day have been associated with an increased risk of seizures. It is also important to adjust the dose in patients with renal impairment. In conclusion, antifibrinolytics, such as EACA and TXA, are effective in reducing blood loss and transfusion use in cardiac and non-cardiac surgeries, without causing serious adverse effects.

COVID-19-associated coagulopathy and acute kidney injury in critically ill patients.

OBJECTIVE: The incidence of thrombotic events and acute kidney injury is high in critically ill patients with COVID-19. We aimed to evaluate and compare the coagulation profiles of patients with COVID-19 developing acute kidney injury versus those who did not, during their intensive care unit stay. METHODS: Conventional coagulation and platelet function tests, fibrinolysis, endogenous inhibitors of coagulation tests, and rotational thromboelastometry were conducted on days 0, 1, 3, 7, and 14 following intensive care unit admission. RESULTS: Out of 30 patients included, 13 (43.4%) met the criteria for acute kidney injury. Comparing both groups, patients with acute kidney injury were older: 73 (60-84) versus 54 (47-64) years, p=0.027, and had a lower baseline glomerular filtration rate: 70 (51-81) versus 93 (83-106) mL/min/1.73m2, p=0.004. On day 1, D-dimer and fibrinogen levels were elevated but similar between groups: 1780 (1319-5517) versus 1794 (726-2324) ng/mL, p=0.145 and 608 (550-700) versus 642 (469-722) g/dL, p=0.95, respectively. Rotational thromboelastometry data were also similar between groups. However, antithrombin activity and protein C levels were lower in patients who developed acute kidney injury: 82 (75-92) versus 98 (90-116), p=0.028 and 70 (52-82) versus 88 (78-101) µ/mL, p=0.038, respectively. Mean protein C levels were lower in the group with acute kidney injury across multiple time points during their stay in the intensive care unit. CONCLUSION: Critically ill patients experiencing acute kidney injury exhibited lower endogenous anticoagulant levels. Further studies are needed to understand the role of natural anticoagulants in the pathophysiology of acute kidney injury within this population.

COVID-19-associated coagulopathy and acute kidney injury in critically ill patients

ABSTRACT Objective The incidence of thrombotic events and acute kidney injury is high in critically ill patients with COVID-19. We aimed to evaluate and compare the coagulation profiles of patients with COVID-19 developing acute kidney injury versus those who did not, during their intensive care unit stay. Methods Conventional coagulation and platelet function tests, fibrinolysis, endogenous inhibitors of coagulation tests, and rotational thromboelastometry were conducted on days 0, 1, 3, 7, and 14 following intensive care unit admission. Results Out of 30 patients included, 13 (43.4%) met the criteria for acute kidney injury. Comparing both groups, patients with acute kidney injury were older: 73 (60-84) versus 54 (47-64) years, p=0.027, and had a lower baseline glomerular filtration rate: 70 (51-81) versus 93 (83-106) mL/min/1.73m2, p=0.004. On day 1, D-dimer and fibrinogen levels were elevated but similar between groups: 1780 (1319-5517) versus 1794 (726-2324) ng/mL, p=0.145 and 608 (550-700) versus 642 (469-722) g/dL, p=0.95, respectively. Rotational thromboelastometry data were also similar between groups. However, antithrombin activity and protein C levels were lower in patients who developed acute kidney injury: 82 (75-92) versus 98 (90-116), p=0.028 and 70 (52-82) versus 88 (78-101) µ/mL, p=0.038, respectively. Mean protein C levels were lower in the group with acute kidney injury across multiple time points during their stay in the intensive care unit. Conclusion Critically ill patients experiencing acute kidney injury exhibited lower endogenous anticoagulant levels. Further studies are needed to understand the role of natural anticoagulants in the pathophysiology of acute kidney injury within this population.

Early administration of fibrinogen concentrate in patients with polytrauma with thromboelastometry suggestive of hypofibrinogenemia: A randomized feasibility trial.

OBJECTIVE: To evaluate the clinical effects of early administration of fibrinogen concentrate in patients with severe trauma and hypofibrinogenemia. METHODS: We conducted an open randomized feasibility trial between December 2015 and January 2017 in patients with severe trauma admitted to the emergency department of a large trauma center. Patients presented with hypotension, tachycardia, and FIBTEM findings suggestive of hypofibrinogenemia. The intervention group received fibrinogen concentrate (50 mg/kg), and the control group did not receive early fibrinogen replacement. The primary outcome was feasibility assessed as the proportion of patients receiving the allocated treatment within 60 min after randomization. The secondary outcomes were transfusion requirements and other exploratory outcomes. Randomization was performed using sequentially numbered and sealed opaque envelopes. ClinicalTrials.gov: NCT02864875. RESULTS: Thirty-two patients were randomized (16 in each group). All patients received the allocated treatment within 60 min after randomization (100%, 95% confidence interval, 86.7%-100%). The median length of intensive care unit stay was shorter in the intervention group (8 days, interquartile range [IQR] 5.75-10.0 vs. 11 days, IQR 8.5-16.0; p=0.02). There was no difference between the groups in other clinical outcomes. No adverse effects related to treatment were recorded in either group. CONCLUSION: Early fibrinogen replacement with fibrinogen concentrate was feasible. Larger trials are required to properly evaluate clinical outcomes.

Early administration of fibrinogen concentrate in patients with polytrauma with thromboelastometry suggestive of hypofibrinogenemia: A randomized feasibility trial

OBJECTIVE: To evaluate the clinical effects of early administration of fibrinogen concentrate in patients with severe trauma and hypofibrinogenemia. METHODS: We conducted an open randomized feasibility trial between December 2015 and January 2017 in patients with severe trauma admitted to the emergency department of a large trauma center. Patients presented with hypotension, tachycardia, and FIBTEM findings suggestive of hypofibrinogenemia. The intervention group received fibrinogen concentrate (50 mg/kg), and the control group did not receive early fibrinogen replacement. The primary outcome was feasibility assessed as the proportion of patients receiving the allocated treatment within 60 min after randomization. The secondary outcomes were transfusion requirements and other exploratory outcomes. Randomization was performed using sequentially numbered and sealed opaque envelopes. ClinicalTrials.gov: NCT02864875. RESULTS: Thirty-two patients were randomized (16 in each group). All patients received the allocated treatment within 60 min after randomization (100%, 95% confidence interval, 86.7%-100%). The median length of intensive care unit stay was shorter in the intervention group (8 days, interquartile range [IQR] 5.75-10.0 vs. 11 days, IQR 8.5-16.0; p=0.02). There was no difference between the groups in other clinical outcomes. No adverse effects related to treatment were recorded in either group. CONCLUSION: Early fibrinogen replacement with fibrinogen concentrate was feasible. Larger trials are required to properly evaluate clinical outcomes.

Bleeding management after implementation of the Hemorrhage Code (Code H) at the Hospital Israelita Albert Einstein, São Paulo, Brazil.

Objective To describe the implementation of a care protocol based on rapid response teams, for management and resolution of bleeding. Methods A hospital protocol called Hemorrhage Code (Code H) was devised and developed. In a flow line, a multidisciplinary team provides comprehensive, fast and effective care to the patient with a severe hemorrhagic condition. In another flow line, professionals based at the hospital pharmacy focus on identifying patients at risk of bleeding, to avoid this event. Several hospital professionals and sectors were trained, each with specific roles, ensuring full support to the medical and nursing staffs. Results After implementing this protocol, we were able to significantly reduce the number of catastrophic events related to failure in bleeding management. Conclusion Code H is an example of a value-based medicine and precision medicine project by delivering comprehensive and multidisciplinary care, in addition to point-of-care testing introduced in clinical practice, optimizing patient safety and care practices at the hospital. Furthermore, it will be possible to minimize the risk of lawsuits for the hospital and physicians, as well as rationalizing resources with benefits for administrators and payers.

Recommendations for Cardiopulmonary Resuscitation (CPR) of patients with suspected or confirmed COVID-19.

The care for patients suffering from cardiopulmonary arrest in a context of a COVID-19 pandemic has particularities that should be highlighted. The following recommendations from the Brazilian Association of Emergency Medicine (ABRAMEDE), the Brazilian Society of Cardiology (SBC) and the Brazilian Association of Intensive Medicine (AMIB) and the Brazilian Society of Anesthesiology (SBA), associations and societies official representatives of specialties affiliated to the Brazilian Medical Association (AMB), aim to guide the various assistant teams, in a context of little solid evidence, maximizing the protection of teams and patients. It is essential to wear full Personal Protective Equipment (PPE) for aerosols during the care of Cardiopulmonary Resuscitation (CPR) and it is imperative to consider and treat the potential causes in these patients, especially hypoxia and arrhythmias caused by changes in the QT interval or myocarditis. The installation of an advanced invasive airway must be obtained early and the use of High Efficiency Particulate Arrestance (HEPA) filters at the interface with the valve bag is mandatory; situations of occurrence of CPR during mechanical ventilation and in a prone position demand peculiarities that are different from the conventional CPR pattern. Faced with the care of a patient diagnosed or suspected of COVID-19, the care follows the national and international protocols and guidelines 2015 ILCOR (International Alliance of Resuscitation Committees), AHA 2019 Guidelines (American Heart Association) and the Update of the Cardiopulmonary Resuscitation and Emergency Care Directive of the Brazilian Society of Cardiology 2019.

A atenção ao paciente vítima de parada cardiorrespiratória em um contexto de pandemia de COVID-19 possui particularidades que devem ser ressaltadas. As seguintes recomendações da Associação Brasileira de Medicina de Emergência (ABRAMEDE), Sociedade Brasileira de Cardiologia (SBC), Associação de Medicina Intensiva Brasileira (AMIB) e Sociedade Brasileira de Anestesiologia (SBA), associações e sociedades representantes oficiais de especialidades afiliadas a Associação Medica Brasileira (AMB), têm por objetivo orientar as diversas equipes assistentes, em um contexto de poucas evidências sólidas, maximizando a proteção das equipes e dos pacientes.É fundamental a paramentação completa com Equipamentos de Proteção Individual (EPIs) para aerossóis durante o atendimento de Parada Cardiorrespiratória (PCR), e imperativo que se considerem e tratem os potenciais causas nesses pacientes, principalmente hipóxia e arritmias causadas por alterações no intervalo QT ou miocardites. A instalação de via aérea invasiva avançada deve ser obtida precocemente e o uso de filtros High Efficiency Particulate Arrestance (HEPA) na interface com a bolsa-válvula é obrigatório; situações de ocorrência de PCR durante a ventilação mecânica e em posição pronada demandam peculiaridades distintas do padrão convencional de PCR. Frente ao atendimento de um paciente com diagnóstico ou suspeito de COVID-19, o atendimento segue em acordo com os protocolos e diretrizes nacionais e internacionais 2015 ILCOR (Aliança Internacional dos Comitês de Ressuscitação), Diretrizes AHA 2019 (American Heart Association) e a Atualização da Diretriz de Ressuscitação Cardiopulmonar e Cuidados de Emergência da Sociedade Brasileira de Cardiologia 2019.

Position Statement: Cardiopulmonary Resuscitation of Patients with Confirmed or Suspected COVID-19 - 2020. / Posicionamento para Ressuscitação Cardiopulmonar de Pacientes com Diagnóstico ou Suspeita de COVID-19 ­ 2020.

Care for patients with cardiac arrest in the context of the coronavirus disease 2019 (COVID-19) pandemic has several unique aspects that warrant particular attention. This joint position statement by the Brazilian Association of Emergency Medicine (ABRAMEDE), Brazilian Society of Cardiology (SBC), Brazilian Association of Intensive Care Medicine (AMIB), and Brazilian Society of Anesthesiology (SBA), all official societies representing the corresponding medical specialties affiliated with the Brazilian Medical Association (AMB), provides recommendations to guide health care workers in the current context of limited robust evidence, aiming to maximize the protection of staff and patients alike. It is essential that full aerosol precautions, which include wearing appropriate personal protective equipment, be followed during resuscitation. It is also imperative that potential causes of cardiac arrest of particular interest in this patient population, especially hypoxia, cardiac arrhythmias associated with QT prolongation, and myocarditis, be considered and addressed. An advanced invasive airway device should be placed early. Use of HEPA filters at the bag-valve interface is mandatory. Management of cardiac arrest occurring during mechanical ventilation or during prone positioning demands particular ventilator settings and rescuer positioning for chest compressions which deviate from standard cardiopulmonary resuscitation techniques. Apart from these logistical issues, care should otherwise follow national and international protocols and guidelines, namely the 2015 International Liaison Committee on Resuscitation (ILCOR) and 2019 American Heart Association (AHA) guidelines and the 2019 Update to the Brazilian Society of Cardiology Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Guideline.

Intensive support recommendations for critically-ill patients with suspected or confirmed COVID-19 infection.

In December 2019, a series of patients with severe pneumonia were identified in Wuhan, Hubei province, China, who progressed to severe acute respiratory syndrome and acute respiratory distress syndrome. Subsequently, COVID-19 was attributed to a new betacoronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Approximately 20% of patients diagnosed as COVID-19 develop severe forms of the disease, including acute hypoxemic respiratory failure, severe acute respiratory syndrome, acute respiratory distress syndrome and acute renal failure and require intensive care. There is no randomized controlled clinical trial addressing potential therapies for patients with confirmed COVID-19 infection at the time of publishing these treatment recommendations. Therefore, these recommendations are based predominantly on the opinion of experts (level C of recommendation).

Intensive support recommendations for critically-ill patients with suspected or confirmed COVID-19 infection / Recomendações de suporte intensivo para pacientes graves com infecção suspeita ou confirmada pela COVID-19

ABSTRACT In December 2019, a series of patients with severe pneumonia were identified in Wuhan, Hubei province, China, who progressed to severe acute respiratory syndrome and acute respiratory distress syndrome. Subsequently, COVID-19 was attributed to a new betacoronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Approximately 20% of patients diagnosed as COVID-19 develop severe forms of the disease, including acute hypoxemic respiratory failure, severe acute respiratory syndrome, acute respiratory distress syndrome and acute renal failure and require intensive care. There is no randomized controlled clinical trial addressing potential therapies for patients with confirmed COVID-19 infection at the time of publishing these treatment recommendations. Therefore, these recommendations are based predominantly on the opinion of experts (level C of recommendation).

RESUMO Em dezembro de 2019, uma série de pacientes com pneumonia grave foi identificada em Wuhan, província de Hubei, na China. Esses pacientes evoluíram para síndrome respiratória aguda grave e síndrome do desconforto respiratório agudo. Posteriormente, a COVID-19 foi atribuída a um novo betacoronavírus, o coronavírus da síndrome respiratória aguda grave 2 (SARS-CoV-2). Cerca de 20% dos pacientes com diagnóstico de COVID-19 desenvolvem formas graves da doença, incluindo insuficiência respiratória aguda hipoxêmica, síndrome respiratória aguda grave, síndrome do desconforto respiratório agudo e insuficiência renal aguda e requerem admissão em unidade de terapia intensiva. Não há nenhum ensaio clínico randomizado controlado que avalie potenciais tratamentos para pacientes com infecção confirmada pela COVID-19 no momento da publicação destas recomendações de tratamento. Dessa forma, essas recomendações são baseadas predominantemente na opinião de especialistas (grau de recomendação de nível C).

Bleeding management after implementation of the Hemorrhage Code (Code H) at the Hospital Israelita Albert Einstein, São Paulo, Brazil / Manejo de sangramento após implantação do Código Hemorrágico (Código H) no Hospital Israelita Albert Einstein, São Paulo, Brasil

ABSTRACT Objective To describe the implementation of a care protocol based on rapid response teams, for management and resolution of bleeding. Methods A hospital protocol called Hemorrhage Code (Code H) was devised and developed. In a flow line, a multidisciplinary team provides comprehensive, fast and effective care to the patient with a severe hemorrhagic condition. In another flow line, professionals based at the hospital pharmacy focus on identifying patients at risk of bleeding, to avoid this event. Several hospital professionals and sectors were trained, each with specific roles, ensuring full support to the medical and nursing staffs. Results After implementing this protocol, we were able to significantly reduce the number of catastrophic events related to failure in bleeding management. Conclusion Code H is an example of a value-based medicine and precision medicine project by delivering comprehensive and multidisciplinary care, in addition to point-of-care testing introduced in clinical practice, optimizing patient safety and care practices at the hospital. Furthermore, it will be possible to minimize the risk of lawsuits for the hospital and physicians, as well as rationalizing resources with benefits for administrators and payers.

RESUMO Objetivo Descrever a implantação de um protocolo de atendimento nos moldes de times de resposta rápida, para manejo e resolução do sangramento. Métodos Foi idealizado e desenvolvido um protocolo institucional, chamado Código Hemorrágico, ou Código H, no qual, em um fluxo, um time multiprofissional e multidisciplinar foi constituído para atendimento integral, rápido e eficaz do paciente com doença hemorrágica grave. Em um outro fluxo, os profissionais, centralizados na farmácia do hospital, focavam na identificação do paciente com risco de hemorragia, no sentido de evitar o evento. Vários profissionais e setores do hospital foram treinados, e cada um, com funções específicas, deveria oferecer garantia total de apoio e suporte às equipes médica e de enfermagem. Resultados Após a implementação do protocolo, o número de eventos catastróficos relacionados à falha no manejo do sangramento reduziu significativamente. Conclusão O Código H é um exemplo de projeto de medicina baseada em valor e de medicina de precisão, por meio de atendimento integral e multidisciplinar, além de testes point of care introduzidos na prática clínica, com otimização da segurança do paciente e da prática assistencial na instituição. Ainda, por meio dele, deve ser possível minimizar o risco de ações judiciais para o hospital e os médicos, além de racionalizar recursos, com benefícios para administradores e fontes pagadoras.

A new era of thromboelastometry / A nova era da tromboelastometria

ABSTRACT Severe hemorrhage with necessity of allogeneic blood transfusion is common complication in intensive care unit and is associated with increased morbidity and mortality. Prompt recognition and treatment of bleeding causes becomes essential for the effective control of hemorrhage, rationalizing the use of allogeneic blood components, and in this way, preventing an occurrence of their potential adverse effects. Conventional coagulation tests such as prothrombin time and activated partial thromboplastin time present limitations in predicting bleeding and guiding transfusion therapy in critically ill patients. Viscoelastic tests such as thromboelastography and rotational thromboelastometry allow rapid detection of coagulopathy and goal-directed therapy with specific hemostatic drugs. The new era of thromboelastometry relies on its efficacy, practicality, reproducibility and cost-effectiveness to establish itself as the main diagnostic tool and transfusion guide in patients with severe active bleeding.

RESUMO A hemorragia grave com necessidade de transfusão de sangue e componentes é uma complicação frequente na unidade de terapia intensiva e está associada ao aumento da morbidade e da mortalidade. A identificação adequada e o tratamento precoce da causa específica da coagulopatia tornam-se fundamentais para o controle efetivo da hemorragia, racionalizando a utilização de sangue e componentes, e desta forma, prevenindo a ocorrência de efeitos adversos. Testes convencionais da coagulação (tempo de ativação de protrombina e tempo de tromboplastina parcial ativada) apresentam limitações para prever sangramento e guiar a terapia transfusional em pacientes graves. Testes viscoelásticos como a tromboelastografia e tromboelastometria rotacional permitem a rápida detecção da coagulopatia e orientam a terapia de forma individualizada, alvo dirigida com drogas hemostáticas específicas. A nova era da tromboelastometria confia na sua eficácia, praticidade, reprodutibilidade e custo-eficácia para se firmar como a principal ferramenta diagnóstica e guia transfusional em pacientes com sangramento ativo grave.