Donat R. Spahn

Management of bleeding and coagulopathy following major trauma: an updated European guideline

IntroductionEvidence-based recommendations are needed to guide the acute management of the bleeding trauma patient. When these recommendations are implemented patient outcomes may be improved.MethodsThe multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing a guideline for the management of bleeding following severe injury. This document represents an updated version of the guideline published by the group in 2007 and updated in 2010. Recommendations were formulated using a nominal group process, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence and based on a systematic review of published literature.ResultsKey changes encompassed in this version of the guideline include new recommendations on the appropriate use of vasopressors and inotropic agents, and reflect an awareness of the growing number of patients in the population at large treated with antiplatelet agents and/or oral anticoagulants. The current guideline also includes recommendations and a discussion of thromboprophylactic strategies for all patients following traumatic injury. The most significant addition is a new section that discusses the need for every institution to develop, implement and adhere to an evidence-based clinical protocol to manage traumatically injured patients. The remaining recommendations have been re-evaluated and graded based on literature published since the last edition of the guideline. Consideration was also given to changes in clinical practice that have taken place during this time period as a result of both new evidence and changes in the general availability of relevant agents and technologies.ConclusionsA comprehensive, multidisciplinary approach to trauma care and mechanisms with which to ensure that established protocols are consistently implemented will ensure a uniform and high standard of care across Europe and beyond.http://ccforum.com/content/17/4/442

Management of bleeding following major trauma: an updated European guideline

IntroductionEvidence-based recommendations are needed to guide the acute management of the bleeding trauma patient, which when implemented may improve patient outcomes.MethodsThe multidisciplinary Task Force for Advanced Bleeding Care in Trauma was formed in 2005 with the aim of developing a guideline for the management of bleeding following severe injury. This document presents an updated version of the guideline published by the group in 2007. Recommendations were formulated using a nominal group process, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) hierarchy of evidence and based on a systematic review of published literature.ResultsKey changes encompassed in this version of the guideline include new recommendations on coagulation support and monitoring and the appropriate use of local haemostatic measures, tourniquets, calcium and desmopressin in the bleeding trauma patient. The remaining recommendations have been reevaluated and graded based on literature published since the last edition of the guideline. Consideration was also given to changes in clinical practice that have taken place during this time period as a result of both new evidence and changes in the general availability of relevant agents and technologies.ConclusionsThis guideline provides an evidence-based multidisciplinary approach to the management of critically injured bleeding trauma patients.

Activity-based costs of blood transfusions in surgical patients at four hospitals

BACKGROUND: Blood utilization has long been suspected to consume more health care resources than previously reported. Incomplete accounting for blood costs has the potential to misdirect programmatic decision making by health care systems. Determining the cost of supplying patients with blood transfusions requires an in‐depth examination of the complex array of activities surrounding the decision to transfuse.

Preconditioning by Sevoflurane Decreases Biochemical Markers for Myocardial and Renal Dysfunction in Coronary Artery Bypass Graft Surgery: A Double-blinded, Placebo-controlled, Multicenter Study

Background Preconditioning by volatile anesthetics is a promising therapeutic strategy to render myocardial tissue resistant to perioperative ischemia. It was hypothesized that sevoflurane preconditioning would decrease postoperative release of brain natriuretic peptide, a biochemical marker for myocardial dysfunction. In addition, several variables associated with the protective effects of preconditioning were evaluated. Methods Seventy-two patients scheduled for coronary artery bypass graft surgery under cardioplegic arrest were randomly assigned to preconditioning during the first 10 min of complete cardiopulmonary bypass with either placebo (oxygen–air mixture only) or sevoflurane 4 vol% (2 minimum alveolar concentration). No other volatile anesthetics were administered at any time during the study. Treatment was strictly blinded to anesthesiologists, perfusionists, and surgeons. Biochemical markers of myocardial dysfunction and injury (brain natriuretic peptide, creatine kinase–MB activity, and cardiac troponin T), and renal dysfunction (cystatin C) were determined. Results of Holter electrocardiography were recorded perioperatively. Translocation of protein kinase C was assessed by immunohistochemical analysis of atrial samples. Results Sevoflurane preconditioning significantly decreased postoperative release of brain natriuretic peptide, a sensitive biochemical marker of myocardial contractile dysfunction. Pronounced protein kinase C &dgr; and &egr; translocation was observed in sevoflurane-preconditioned myocardium. In addition, postoperative plasma cystatin C concentrations increased significantly less in sevoflurane-preconditioned patients. No differences between groups were found for perioperative ST-segment changes, arrhythmias, or creatine kinase–MB and cardiac troponin T release. Conclusions Sevoflurane preconditioning preserves myocardial and renal function as assessed by biochemical markers in patients undergoing coronary artery bypass graft surgery under cardioplegic arrest. This study demonstrated for the first time translocation of protein kinase C isoforms &dgr; and &egr; in human myocardium in response to sevoflurane.

Anemia and patient blood management in hip and knee surgery: a systematic review of the literature

A systematic search was conducted to determine the characteristics of perioperative anemia, its association with clinical outcomes, and the effects of patient blood management interventions on these outcomes in patients undergoing major orthopedic surgery. In patients undergoing total hip or knee arthroplasty and hip fracture surgery, preoperative anemia was highly prevalent, ranging from 24 ± 9% to 44 ± 9%, respectively. Postoperative anemia was even more prevalent (51% and 87 ± 10%, respectively). Perioperative anemia was associated with a blood transfusion rate of 45 ± 25% and 44 ± 15%, postoperative infections, poorer physical functioning and recovery, and increased length of hospital stay and mortality. Treatment of preoperative anemia with iron, with or without erythropoietin, and perioperative cell salvage decreased the need for blood transfusion and may contribute to improved patient outcomes. High-impact prospective studies are necessary to confirm these findings and establish firm clinical guidelines.

Red blood cell transfusion in clinical practice

Every year, about 75 million units of blood are collected worldwide. Red blood cell (RBC) transfusion is one of the few treatments that adequately restore tissue oxygenation when oxygen demand exceeds supply. Although the respiratory function of blood has been studied intensively, the trigger for RBC transfusion remains controversial, and doctors rely primarily on clinical experience. Laboratory assays that indicate failing tissue oxygenation would be ideal to guide the need for transfusion, but none has proved easy, reproducible, and sensitive to regional tissue hypoxia. The clinical importance of the RBCs storage lesion (ie, the time-dependent metabolic, biochemical, and molecular changes that stored blood cells undergo) is poorly understood. RBCs can be filtered, washed, frozen, or irradiated for specific indications. Donor screening and testing have dramatically reduced infectious risks in the developed world, but infection remains a major hazard in developing countries, where 13 million units of blood are not tested for HIV or hepatitis viruses. Pathogen inactivation techniques are in clinical trials for RBCs, but none is available for use. Despite serious immunological and non-immunological complications, RBC transfusion holds a therapeutic index that exceeds that of many common medications.

The European guideline on management of major bleeding and coagulopathy following trauma: Fourth edition

BackgroundSevere trauma continues to represent a global public health issue and mortality and morbidity in trauma patients remains substantial. A number of initiatives have aimed to provide guidance on the management of trauma patients. This document focuses on the management of major bleeding and coagulopathy following trauma and encourages adaptation of the guiding principles to each local situation and implementation within each institution.MethodsThe pan-European, multidisciplinary Task Force for Advanced Bleeding Care in Trauma was founded in 2004 and included representatives of six relevant European professional societies. The group used a structured, evidence-based consensus approach to address scientific queries that served as the basis for each recommendation and supporting rationale. Expert opinion and current clinical practice were also considered, particularly in areas in which randomised clinical trials have not or cannot be performed. Existing recommendations were reconsidered and revised based on new scientific evidence and observed shifts in clinical practice; new recommendations were formulated to reflect current clinical concerns and areas in which new research data have been generated. This guideline represents the fourth edition of a document first published in 2007 and updated in 2010 and 2013.ResultsThe guideline now recommends that patients be transferred directly to an appropriate trauma treatment centre and encourages use of a restricted volume replacement strategy during initial resuscitation. Best-practice use of blood products during further resuscitation continues to evolve and should be guided by a goal-directed strategy. The identification and management of patients pre-treated with anticoagulant agents continues to pose a real challenge, despite accumulating experience and awareness. The present guideline should be viewed as an educational aid to improve and standardise the care of the bleeding trauma patients across Europe and beyond. This document may also serve as a basis for local implementation. Furthermore, local quality and safety management systems need to be established to specifically assess key measures of bleeding control and outcome.ConclusionsA multidisciplinary approach and adherence to evidence-based guidance are key to improving patient outcomes. The implementation of locally adapted treatment algorithms should strive to achieve measureable improvements in patient outcome.

Volatile anesthetics mimic cardiac preconditioning by priming the activation of mitochondrial KATP channels via multiple signaling pathways

Background Volatile anesthetics induce pharmacological preconditioning in cardiac tissue. The purpose of this study was to test whether volatile anesthetics mediate this effect by activation of the mitochondrial adenosine triphosphate–sensitive potassium (mitoKATP) or sarcolemmal KATP (sarcKATP) channel in rat ventricular myocytes and to evaluate the signaling pathways involved. Methods A cellular model of ischemia with subsequent hypoosmolar trypan blue staining served to determine the effects of 5-hydroxydecanoate, a selective mitoKATP channel blocker, HMR-1098, a selective sarcKATP channel blocker, diazoxide, a preconditioning mimicking agent, and various modulators of putative signaling pathways on cardioprotection elicited by sevoflurane and isoflurane. Microscopy was used to visualize and measure autofluorescence of flavoproteins, a direct index of mitoKATP channel activity. Results Volatile anesthetics significantly enhanced diazoxide-mediated activation of mitoKATP channels as assessed by autofluorescence of myocytes. Conversely, volatile anesthetics alone did not alter mitoKATP channel activity, implying a priming effect of volatile anesthetics on mitoKATP channels. Administration of the protein kinase C inhibitor chelerythrine completely blocked this effect. Also, pretreatment with volatile anesthetics potentiated diazoxide-mediated protection against ischemia, as indicated by a reduction in trypan blue–positive myocytes. Importantly, cardioprotection afforded by volatile anesthetics was unaffected by the sarcKATP channel blocker HMR-1098 but sensitive to modulations of nitric oxide and adenosine–Gi signaling pathways. Conclusions Using autofluorescence in live cell imaging microscopy and a simulated model of ischemia, the authors present evidence that volatile anesthetics mediate their protection in cardiomyocytes by selectively priming mitoKATP channels through multiple triggering protein kinase C–coupled signaling pathways. These observations provide important new insight into the mechanisms of anesthetic-induced preconditioning.

Cardiovascular and coronary physiology of acute isovolemic hemodilution : a review of nonoxygen-carrying and oxygen-carrying solutions

Acute isovolemic hemodilution is used increasingly to avoid the potentially serious side effects of homologous blood transfusions. Cardiovascular physiology during hemodilution is characterized by a marked increase in cardiac output and organ blood flow to compensate for the decrease in arterial oxygen-carrying capacity. During advanced hemodilution an increased oxygen extraction is also observed, such that oxygen consumption generally is maintained even during advanced hemodilution. The increase in cardiac output is related mainly to a decrease in blood viscosity and an enhanced sympathetic tone resulting in stimulation of the heart. The magnitude and the mechanisms involved in the increase depend upon species, state of awareness (awake versus anesthetized), type of anesthesia, type of exchange solution, and condition of the heart prior to hemodilution. Recent laboratory findings, as well as clinical practice in cardiac surgery, suggest that moderate hemodilution to hematocrit values of approximately 25% is well tolerated in single vessel coronary artery disease which should thus not be regarded as an absolute contraindication for moderate hemodilution. An integral concept to minimize homologous blood transfusions consists of preoperative autologous blood donation, preoperative isovolemic hemodilution, meticulous (asanguineous) surgical technique, and acceptance of minimum hemoglobin levels during the entire hospitalization. The incidence of homologous blood transfusions will be reduced using acute isovolemic hemodilution. This incidence will be further reduced once hemoglobin solutions become clinically available for specific indications. At present, research activities are concentrated on defining the critical level of hemodilution in various pathologic conditions and to investigate pharmacology and physiology of the new hemoglobin solutions. Finally, several chemically modified hemoglobin-based oxygen-carrying solutions devoid of renal toxicity will be available in the future. The cardiovascular physiology and pharmacology of these hemoglobin solutions have been studied. Cardiac output is generally constant and oxygen extraction is increased to maintain oxygen consumption during hemodilution with hemoglobin solutions. In most studies, some vasoconstriction was observed also, which might result from interaction of the hemoglobin molecule with the EDRF/NO system. However, with enhanced purification, chemical modification or microencapsulation of the hemoglobin molecule, vasoconstriction can be limited.

Recommendations on the use of recombinant activated factor VII as an adjunctive treatment for massive bleeding – a European perspective

IntroductionOur aim was to develop consensus guidelines for use of recombinant activated factor VII (rFVIIa) in massive hemorrhage.MethodsA guidelines committee derived the recommendations using clinical trial and case series data identified through searches of available databases. Guidelines were graded on a scale of A to E (with A being the highest) according to the strength of evidence available. Consensus was sought among the committee members for each recommendation.ResultsA recommendation for the use of rFVIIa in blunt trauma was made (grade B). rFVIIa might also be beneficial in post-partum hemorrhage (grade E), uncontrolled bleeding in surgical patients (grade E), and bleeding after cardiac surgery (grade D). rFVIIa could not be recommended for use in the following: in penetrating trauma (grade B); prophylactically in elective surgery (grade A) or liver surgery (grade B); or in bleeding episodes in patients with Child–Pugh A cirrhosis (grade B). Efficacy of rFVIIa was considered uncertain in bleeding episodes in patients with Child–Pugh B and C cirrhosis (grade C). Monitoring of rFVIIa efficacy should be performed visually and by assessment of transfusion requirements (grade E), while thromboembolic adverse events are a cause for concern. rFVIIa should not be administered to patients considered unsalvageable by the treating medical team.ConclusionThere is a rationale for using rFVIIa to treat massive bleeding in certain indications, but only adjunctively to the surgical control of bleeding once conventional therapies have failed. Lack of data from randomized, controlled clinical trials, and possible publication bias of the case series data, limits the strength of the recommendations that can be made.