Consensus of the Brazilian association of hematology, hemotherapy and cellular therapy on patient blood management: Management of critical bleeding

Abstract The management of major bleeding is a critical aspect of modern healthcare and it is imperative to emphasize the importance of applying Patient Blood Management (PBM) principles. Although transfusion support remains a vital component of bleeding control, treating severe bleeding goes beyond simply replacing lost blood. A more comprehensive, multidisciplinary approach is essential to optimize patient outcomes and minimize the risks associated with excessive transfusions.

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

Abstract 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: Anemia tolerance mechanisms

Abstract 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: Antifibrinolytics

Abstract 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.

Consensus of the Brazilian association of hematology, hemotherapy and cellular therapy on patient blood management: Inadvertent intraoperative hypothermia

Abstract 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: Intraoperative hemostasis and volume replacement

Abstract 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.

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.

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.

Avaliação da aeração e edema pulmonar por meio de tomografia computadorizada em pacientes submetidos a revascularização do miocárdio / Evaluation of the aeration and edema pulmonary by means of computed tomography in patients undergoing coronary artery bypass graft

Introdução: A disfunção respiratória é uma das complicações de maior prevalência no período pós-operatório de pacientes submetidos à cirurgia de revascularização do miocárdio (RM) com circulação extracorpórea (CEC), mesmo na ausência de doença pulmonar prévia1. Por meio de tomografia computadorizada, foram investigadas as alterações pulmonares pósoperatórias e o seu impacto na oxigenação. Métodos: vinte pacientes não hipoxêmicos em programação de cirurgia eletiva de revascularização do miocárdio com CEC foram estudados. Medidas hemodinâmicas, e amostras sanguíneas seriadas foram obtidas antes da cirurgia, após a intubação orotraqueal, após a CEC, na UTI, 12h, 24h e 48h após a cirurgia. Tomografias volumétricas pré e pós-operatórias foram adquiridas em condições de apneia após uma expiração espontânea. Os dados foram analisados usando teste de t Student; o comportamento temporal dos dados hemodinâmicos e outras variáveis fisiológicas foi analisado ao longo do tempo, usando análise de variância de uma via para repetidas medidas, seguido pelo teste de Student-Neumann-Keuls, quando necessário.Resultados: a relação PaO2/FiO2 diminuiu de forma significativa após a indução da anestesia, atingindo o seu nadir após a saída de CEC. Comparando-se com a TC pré-operatória, foi observada uma redução de 31% no volume de gás pulmonar (p<0,001), ao passo que foi observado um aumento do volume de tecido de 19% (p<0,001). A área não aerada dos pulmões aumentou de 253 97 g(p < 0.001), de 3 % a 27 %, após a cirurgia; e a área pobremente aerada pulmonar apresentou aumento de 72 68 g (p < 0.001), de 24 % to 27 %, enquanto a área normalmente aerada pulmonar reduziu de 147 119 g (p < 0.001), que representa 72 % to 46%. Não foram observadas correlações entre a relação PO2/FIO2 ou na fração de shunt nas primeiras 24 horas pós-operatórias Conclusões: A estrutura pulmonar está profundamente modificada após a cirurgia de RM com CEC. Associadas a outros fatores, essas alterações são...

Introduction: Hypoxemia is a frequent complication after coronary artery bypass graft (CABG) with cardiopulmonary bypass (CPB), usually attributed to atelectasis. Using computed tomography (CT), we investigated pulmonary alterations postoperatively and its impact on oxygenation. Methods: Twenty non-hypoxemic patients with normal cardiac function scheduled to CABG under CPB were studied. Hemodynamic measurements and blood samples were obtained before surgery, after intubation, after CPB, at ICU admission, 12h, 24h and 48h after surgery. Pre and postoperative volumetric thoracic CT scans were acquired in apnea conditions after a spontaneous expiration. Data was analyzed using paired Student t test and two-way repeated measures analysis of variance followed by SNK test when indicated. Results: PaO2/FiO2 ratio was significantly reduced after anesthesia induction, reaching its nadir after CPB and partially ameliorating 12h after surgery. Compared to preoperative CT, there was a postoperative 31 % reduction in pulmonary gas volume (p < 0.001) while tissue volume increased by 19 % (p < 0.001). Non-aerated lung increased by 253 97 g(p < 0.001), from 3 % to 27 %, after surgery and poorly-aerated lung by 72 68 g (p < 0.001), from 24 % to 27 % while normally-aerated lung was reduced by 147 119 g (p < 0.001), from 72 % to 46 %. No correlations were observed between PaO2/FiO2 ratio or shunt fraction at 24 h postoperatively and postoperative lung alterations. Conclusions: Lung structure is profoundly modified after CABG with CPB. Taken together, these multiple alterations occurring in the lungs are responsible for postoperative hypoxemia instead of atelectasis alone.

Atelectasias durante anestesia: fisiopatologia e tratamento: [revisão] / Atelectasis during anesthesia: pathophysiology and treatment: [review]

JUSTIFICATIVA E OBJETIVOS: O colapso pulmonar intra-operatório é uma complicação de elevada incidência em pacientes submetidos à intervenção cirúrgica sob anestesia geral com relaxamento/paralisia da musculatura. Essa complicação está associada à piora das trocas gasosas no intra-operatório e, em alguns casos, necessidade de suporte respiratório prolongado no período pós-operatório. Os objetivos deste estudo foram revisar os aspectos fisiopatológicos da formação de atelectasias durante anestesia geral e as possíveis manobras terapêuticas para prevenir e tratar essa complicação. CONTEÚDO: Nesta revisão, os conceitos sobre a incidência de atelectasias intra-operatórias, os fatores relacionados com o seu desenvolvimento, tanto mecânicos quanto associados ao ajuste do respirador durante procedimento cirúrgico, os aspectos do diagnóstico e as estratégias de prevenção e tratamento foram abordados de maneira sistemática. CONCLUSÕES: A compreensão dos mecanismos relacionados com o desenvolvimento do colapso pulmonar durante o período intra-operatório, assim como o seu tratamento, pode contribuir para a redução da incidência de complicações pulmonares pós-operatórias, o tempo de recuperação e os custos hospitalares.

BACKGROUND AND METHODS: The incidence of intraoperative pulmonary collapse is elevated in patients undergoing surgery under general anesthesia with muscle relaxation/paralysis. This complication is associated with worsening intraoperative gas exchange and, in some cases, the need for prolonged postoperative respiratory support. The objective of this report was to review the pathophysiological aspects of atelectasis during general anesthesia and possible therapeutic maneuvers that could prevent and treat this complication. CONTENTS: This review discusses the concepts about the incidence of intraoperative atelectasis, factors that influence their development, both mechanical and those related to mechanical ventilator settings during the surgery, diagnostic criteria, and strategies to prevent and treat this complication. CONCLUSIONS: Understanding of the mechanisms related with the development of intraoperative pulmonary collapse, as well as its treatment, can contribute to reduce the incidence of postoperative pulmonary complications, the length of recovery and hospital costs.

JUSTIFICATIVA Y OBJETIVOS: El colapso pulmonar intraoperatorio es una complicación de elevada incidencia en pacientes sometidos a la intervención quirúrgica bajo anestesia general con relajamiento/parálisis de la musculatura. Esta complicación está asociada al empeoramiento de los cambios de gas en el intraoperatorio y en algunos casos, necesidad de soporte respiratorio prolongado en el período postoperatorio. Los objetivos de este estudio fueron los de revisar los aspectos fisiopatológicos de la formación de atelectasias durante anestesia general y las posibles maniobras terapéuticas para prevenir y tratar esa complicación. CONTENIDO: En esta revisión, los conceptos sobre la incidencia de atelectasias intraoperatorias, los factores relacionados a su desarrollo, tanto mecánicos como los relacionados al ajuste del respirador durante el procedimiento quirúrgico, los aspectos del diagnóstico y las estrategias de prevención y tratamiento fueron abordados de manera sistemática. CONCLUSIONES: La comprensión de los mecanismos relacionados al desarrollo del colapso pulmonar durante el período intraoperatorio, como también su tratamiento, pueden contribuir para la reducción de la incidencia de complicaciones pulmonares postoperatorias, el tiempo de recuperación y los costes de las internaciones en los hospitales.