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• W2072112773 abstract "The management of acute massive blood loss is considered and a template guideline is formulated, supported by a review of the key literature and current evidence. It is emphasized that, if avoidable deaths are to be prevented, surgeons, anaesthetists, haematologists and blood-bank staff need to communicate closely in order to achieve the goals of secure haemostasis, restoration of circulating volume, and effective management of blood component replacement. The management of acute massive blood loss is considered and a template guideline is formulated, supported by a review of the key literature and current evidence. It is emphasized that, if avoidable deaths are to be prevented, surgeons, anaesthetists, haematologists and blood-bank staff need to communicate closely in order to achieve the goals of secure haemostasis, restoration of circulating volume, and effective management of blood component replacement. Complications of major blood loss and massive transfusion may jeopardize the survival of patients from many specialties, and challenge haematological and blood transfusion resources. Avoidable deaths of patients with major haemorrhage are well recognized,1Why Mothers Die: Report on Confidential Enquiries into Maternal Deaths in the United Kingdom 1994–1996. The Stationery Office, London1998: 48-55Google Scholar 2Report of the National Confidential Enquiry into Perioperative Deaths 1994/1995. The Stationery Office, London1997Google Scholar and locally agreed and/or speciality-specific guidelines3Management of Postpartum Haemorrhage—A Clinical Practice Guideline for Professionals involved in Maternity Care in Scotland. Scottish Programme for Clinical Effectiveness in Reproductive Health, Aberdeen1998Google Scholar are needed to ensure effective management. Current UK published guidelines4British Committee for Standards in Haematology Guidelines for transfusion for massive blood loss.Clin Lab Haematol. 1988; 10: 265-273Crossref PubMed Scopus (30) Google Scholar 5British Committee for Standards in Haematology Guidelines for the use of fresh frozen plasma.Transfusion Med. 1992; 2: 57-63Crossref PubMed Scopus (154) Google Scholar 6British Committee for Standards in Haematology Guidelines for platelet transfusions.Transfusion Med. 1992; 2: 311-318Crossref PubMed Scopus (97) Google Scholar are based on historical transfusion practice and are not easily referred to in an emergency situation. A symposium on massive transfusion was organized by the National Blood Service Northern Zone in December 1998 and was attended by anaesthetists, traumatologists, haematologists, nurses and blood-bank personnel. At the conclusion of the meeting, a number of key principles were agreed and, in consultation with delegates, a guideline document was produced and is now available in hospitals served by the Leeds, Liverpool, Manchester, Newcastle and Trent Blood Centres as a basis for local protocols. The guideline is presented in this article (Table 1) as a simple template which may be modified to take into account local circumstances and displayed in clinical areas. The left-hand column of the template outlines the key steps or goals, the centre column adds procedural detail and the right-hand column provides additional advice and information.Table 1Acute massive blood loss: template guidelineGoalProcedureCommentsRestore circulating volumeInsert wide-bore peripheral cannulae14 G or largerGive adequate volumes of warmed crystalloid, ?colloid,Monitor central venous pressurebloodBlood loss is often underestimatedAim to maintain normal blood pressure and urine outputRefer to Advanced Trauma Life Support guidelines>30 ml h−1Keep patient warmContact key personnelClinician in chargeNominated coordinator should take responsibility forDuty anaesthetistcommunication and documentationBlood bankDuty haematologistArrest bleedingEarly surgical or obstetric interventionInterventional radiologyRequest laboratory investigationsFBC, PT, APTT, fibrinogen; blood-bank sample, biochemical profile, blood gases or pulse oximetryTake samples at earliest opportunity as results may be affected by colloid infusionEnsure correct sample identityMisidentification is commonest transfusion riskRepeat FBC, PT, APTT, fibrinogen every 4 h or after 1/3 blood volume replacementMay need to give components before results availableRepeat after blood component infusionRequest suitable red cellsUn-crossmatched group O Rh negativeRh positive is acceptable if patient is male or In extreme emergencypostmenopausal female No more than 2 unitsUn-crossmatched ABO group-specificLaboratory will complete cross-match after issue When blood group knownFully cross-matchedFurther cross-match not required after replacement of 1 blood volume (8–10 units) If irregular antibodies present When time permitsUse blood warmer and/or rapid infusion device.Blood-warmer indicated if flow rate >50 ml kg−1 h−1 in adultEmploy blood salvage if available and appropriateSalvage contraindicated if wound heavily contaminatedRequest plateletsAllow for delivery time from blood centreTarget platelet count:Anticipate platelet count <50×109 litre−1 after 2 × blood volume replacement >100×109 litre−1 for multiple/CNS trauma or if platelet function abnormal >50×109 litre−1 for other situationsRequest FFPAim for PT and APTT <1.5× control meanPT and APTT >1.5× control mean correlates with(12–15 ml kg−1 body weight=1 litre or 4 units for an adult)Allow for 30 min thawing timeincreased surgical bleedingRequest cryoprecipitateReplace fibrinogen and factor VIIIFibrinogen <0.5 strongly associated with microvascular(1–1.5 packs/10 kg body weight)bleedingAim for fibrinogen >1.0 g litre−1 Allow for delivery time plus 30 min thawing timeFibrinogen deficiency develops early when plasma-poor red blood cells used for replacementSuspect DICTreat underlying cause if possibleShock, hypothermia, acidosis leading to risk of DICMortality from DIC is high Open table in a new tab The accompanying commentary is not intended to be an exhaustive review, but provides key references on which the recommendations are based. The Hospital Transfusion Committee has a central role in ensuring the optimum and safe use of blood components. The development of protocols for the management of massive transfusion is an important part of the remit of such committees and it is hoped that this article will facilitate this process. Massive blood loss is usually defined as the loss of one blood volume within a 24 h period,7Hewitt PE Machin SJ Massive blood transfusion.in: Contreras M ABC of Transfusion. BMJ Publishing, London1992Google Scholar normal blood volume being approximately 7% of ideal body weight in adults and 8–9% in children. Alternative definitions include 50% blood volume loss within 3 h or a rate of loss of 150 ml min−1.8Fakhry SM Sheldon GF Massive transfusion in the surgical patient.in: Jeffries LC Brecher ME Massive Transfusion. American Association of Blood Banks, Bethesda, Maryland1994Google Scholar Such definitions emphasize the importance of the early recognition of major blood loss and the need for effective action to prevent shock and its consequences. Priorities for treatment are: • restoration of blood volume to maintain tissue perfusion and oxygenation; • achieving haemostasis by: • treating any surgical source of bleeding; • correcting coagulopathy by the judicious use of blood component therapy. A successful outcome requires prompt action and good communication between clinical specialties, diagnostic laboratories, blood-bank staff and the local blood centre. Blood component support takes time to organize and the blood centre may be up to 2 h away from the hospital. Early consultation with surgical, anaesthetic and haematology colleagues is advisable, and the importance of good communication and cooperation in this situation cannot be overemphasized. A member of the clinical team should be nominated to act as the coordinator responsible for overall organization, liaison, communication and documentation. This is a critical role for a designated member of the permanent clinical staff. The Hospital Transfusion Committee should provide a forum in which a rapid communication cascade can be agreed and massive transfusion episodes reviewed. Prolonged oligaemic shock carries a high mortality rate because of organ failure and disseminated intravascular coagulation. Restoration of circulating volume is initially achieved by rapid infusion of crystalloid or colloid through large-bore (14 gauge or larger) peripheral cannulae.9Donaldson MDJ Seaman MJ Park GR Massive blood transfusion.Br J Anaesth. 1992; 69: 621-630Crossref PubMed Scopus (57) Google Scholar The use of albumin and non-albumin colloids versus crystalloids for volume replacement has recently been the subject of debate after two controversial meta-analyses,10Schierhout G Roberts I Fluid resuscitation with colloid or crystalloid solutions in critically ill patients: a systematic review of randomised trials.Br Med J. 1998; 316: 961-964Crossref PubMed Scopus (536) Google Scholar 11Cochrane Injuries Group Albumin Reviewers Human albumin administration in critically ill patients: systematic review of randomised trials.Br Med J. 1998; 317: 235-240Crossref PubMed Scopus (37) Google Scholar and the use of colloid is not recommended in the latest American College of Surgeons Advanced Trauma Life Support Guidelines.12American College of Surgeons Advanced Trauma Life Support Course Manual. American College of Surgeons, Chicago, Illinois1997: 103-112Google Scholar Further trials are required before firm recommendations can be made. Red cell transfusion is likely to be required when 30–40% of blood volume is lost; the loss of over 40% of blood volume is immediately life-threatening.12American College of Surgeons Advanced Trauma Life Support Course Manual. American College of Surgeons, Chicago, Illinois1997: 103-112Google Scholar Hypothermia increases the risk of disseminated intravascular coagulation and other complications12American College of Surgeons Advanced Trauma Life Support Course Manual. American College of Surgeons, Chicago, Illinois1997: 103-112Google Scholar 13Iserson KV Huestis DW Blood warming: current applications and techniques.Transfusion. 1991; 31: 558-571Crossref PubMed Scopus (45) Google Scholar and may be prevented by prewarming the resuscitation fluids, patient-warming devices such as warm air blankets, and the use of temperature-controlled blood warmers. Blood loss is usually underestimated, and it must be remembered that haemoglobin and haematocrit values do not fall for several hours after acute haemorrhage.9Donaldson MDJ Seaman MJ Park GR Massive blood transfusion.Br J Anaesth. 1992; 69: 621-630Crossref PubMed Scopus (57) Google Scholar For acutely anaemic patients, the American Society of Anesthesiologists Task Force on Blood Component Therapy has concluded, on the basis of the available evidence, that transfusion is rarely indicated when the haemoglobin concentration is >10 g dl−1 but is almost always indicated when it is <6 g dl−1.14American Society of Anesthesiologists Task Force Practice guidelines for blood component therapy.Anesthesiology. 1996; 84: 732-747Crossref PubMed Scopus (861) Google Scholar Determination of whether intermediate haemoglobin concentrations justify red cell transfusion should be based on the patient's risk factors for complications of inadequate oxygenation, such as the rate of blood loss, cardiorespiratory reserve, oxygen consumption and atherosclerotic disease. Measured cardiological variables, such as heart rate, arterial pressure, pulmonary capillary wedge pressure and cardiac output, may assist the decision-making process, but it should be emphasized that silent ischaemia may occur in the presence of stable vital signs. Intraoperative blood salvage may be of great value in reducing the requirement for allogeneic blood, but bacterial contamination of the wound is a relative contraindication.15British Committee for Standards in Haematology Guidelines for autologous transfusion. II. Perioperative haemodilution and cell salvage.Br J Anaesth. 1997; 78: 768-771Crossref PubMed Scopus (114) Google Scholar Blood samples should be sent to the laboratory at the earliest possible opportunity for blood grouping, antibody screening and compatibility testing, as well as for baseline haematology, coagulation screening, including fibrinogen estimation and biochemistry investigations. When dealing with an evolving process, it is important to check the parameters frequently (at least four-hourly and after each therapeutic intervention) to monitor the need for and the efficacy of component therapy. Expert advice should be sought from a haematologist regarding appropriate investigations, their interpretation and the optimum corrective therapy. In an extreme situation it may be necessary to use group O un-crossmatched red cells if the blood group is unknown. In an emergency, premenopausal females whose blood group is unknown should be given ORh(D) negative red cells in order to avoid sensitization and the risk of haemolytic disease of the newborn in subsequent pregnancy. It is acceptable to give ORh(D) positive cells to males and postmenopausal females of unknown blood group.16Schwab CW Shayne JP Turner J Immediate trauma resuscitation with type O uncrossmatched blood: a two year prospective experience.J Trauma. 1986; 26: 897-902Crossref PubMed Scopus (51) Google Scholar Group-specific red cells should be given at the earliest possible opportunity as group O blood is a scarce resource. It is important to bear in mind that most transfusion-related morbidity is due to incorrect blood being transfused.17Williamson LM Lowe S Love E et al.Serious Hazards of Transfusion. Annual Report 1997–1998. SHOT Steering Group, Manchester1999Google Scholar It is therefore essential that protocols are in place for the administration of blood and blood components18British Committee for Standards in Haematology Guidelines. The administration of blood and blood components and the management of transfused patients.Transfusion Med. 1999; 9: 227-238Crossref PubMed Scopus (105) Google Scholar and that these are adhered to even in an emergency situation. All blood components supplied by the UK transfusion services are now leucodepleted and the blood bank will provide red cells in optimal additive solution, containing virtually no plasma, platelets or leucocytes. The benefits of leucodepletion include reduced non-haemolytic febrile transfusion reactions, reduced transmission of leucocyte-associated viruses, such as cytomegalovirus, and reduced immunosuppressive effects of transfusion.19Dzik WH Leucoreduced blood components: laboratory and clinical aspects.in: Rossi EC Simon TL Moss GS Gould SA Principles of Transfusion Medicine. Williams & Wilkins, Baltimore, Maryland1996: 353-373Google Scholar An additional microaggregate filter is not necessary. Expert consensus argues that platelets should not be allowed to fall below the critical level of 50×109 litre−1 in acutely bleeding patients.20Contreras M Consensus Conference on Platelet Transfusion. Final statement.Blood Rev. 1998; 12: 239-241Abstract Full Text PDF PubMed Scopus (10) Google Scholar A higher target level of 100×109 litre−1 has been recommended for those with multiple high-energy trauma or central nervous system injury.21Development Task Force of the College of American Pathologists Practice parameter for the use of fresh frozen plasma, cryoprecipitate and platelets.J Am Med Assoc. 1994; 271: 777-781Crossref PubMed Scopus (276) Google Scholar 22Horsey PJ Multiple trauma and massive transfusion [editorial].Anaesthesia. 1997; 52: 1027-1029Crossref PubMed Scopus (24) Google Scholar Empirical platelet transfusion may be required when platelet function is abnormal, as is found after cardiopulmonary bypass. A platelet count of 50×109 litre−1 is to be anticipated when approximately two blood volumes have been replaced by plasma-poor red cells,23Hiippala ST Myllyla GJ Vahtera EM Hemostatic factors and replacement of major blood loss with plasma-poor red cell concentrates.Anesth Analg. 1995; 81: 360-365PubMed Google Scholar but there is marked individual variation. In assessing the requirement for platelets, frequent measurements are needed, and it may be necessary to request platelets from the blood centre at levels above the desired target in order to ensure their availability when needed. Most clinical studies and guidelines have been based on the use of whole blood or plasma-reduced red cells, which contain some residual coagulation factor activity. Nowadays, red cell replacement is likely to be in the form of plasma-poor red cells suspended in optimal additive solution, in which coagulation factor activity is negligible. Under these circumstances, coagulation factor deficiency is the primary cause of coagulopathy. The level of fibrinogen falls first; the critical level of 1.0 g litre−1 is likely to be reached after 150% blood loss, followed by decreases in other labile coagulation factors to 25% activity after 200% blood loss.23Hiippala ST Myllyla GJ Vahtera EM Hemostatic factors and replacement of major blood loss with plasma-poor red cell concentrates.Anesth Analg. 1995; 81: 360-365PubMed Google Scholar Prolongation of activated partial thromboplastin time (APTT) and prothrombin time (PT) to 1.5 times the mean normal value is correlated with an increased risk of clinical coagulopathy24Ciavarella D Reed RL Counts RB et al.Clotting factor levels and the risk of diffuse microvascular bleeding in the massively transfused patient.Br J Haematol. 1987; 67: 365-368Crossref PubMed Scopus (240) Google Scholar and requires correction. Laboratory tests of coagulation should be monitored frequently and interpreted with advice from a clinical haematologist; laboratories should have in place standard operating procedures to ensure that clinical staff are contacted appropriately. Experienced laboratory staff should be empowered to issue blood components in the first instance using a locally agreed algorithm. It may be necessary to request components before results are available, depending on the rate of bleeding and the laboratory turnaround time. Although ‘formula replacement’ with fresh plasma is not recommended, it has been suggested that infusion of FFP should be considered after one blood volume has been lost.25Hiippala S Replacement of massive blood loss.Vox Sang. 1998; 74: 399-407Crossref PubMed Scopus (131) Google Scholar The dose should be large enough to maintain coagulation factors well above the critical level, bearing in mind that the efficacy may be reduced because of rapid consumption.21Development Task Force of the College of American Pathologists Practice parameter for the use of fresh frozen plasma, cryoprecipitate and platelets.J Am Med Assoc. 1994; 271: 777-781Crossref PubMed Scopus (276) Google Scholar 25Hiippala S Replacement of massive blood loss.Vox Sang. 1998; 74: 399-407Crossref PubMed Scopus (131) Google Scholar FFP alone, if given in sufficient quantity, will correct fibrinogen and most coagulation factor deficiencies, but large volumes may be required. If fibrinogen levels remain critically low (<1.0 g litre−1), cryoprecipitate therapy should be considered.21Development Task Force of the College of American Pathologists Practice parameter for the use of fresh frozen plasma, cryoprecipitate and platelets.J Am Med Assoc. 1994; 271: 777-781Crossref PubMed Scopus (276) Google Scholar 25Hiippala S Replacement of massive blood loss.Vox Sang. 1998; 74: 399-407Crossref PubMed Scopus (131) Google Scholar The Guidelines on Oral Anticoagulation of the British Committee for Standards in Haematology recommend prothrombin complex concentrate as an alternative to FFP when major bleeding complicates anticoagulant overdose.26British Committee for Standards in Haematology Guidelines on oral anticoagulation (third edition).Br J Haematol. 1998; 101: 374-387Crossref PubMed Scopus (393) Google Scholar It should be remembered, however, that these preparations are potentially thrombogenic and the role of specific coagulation factor concentrate outwith hereditary bleeding disorders is unproven. DIC is a feared complication in the acutely bleeding patient. It carries a considerable mortality rate, and once established it is difficult to reverse. At particular risk are: patients with prolonged hypoxia or hypovolaemia; patients with cerebral or extensive muscle damage; and patients who become hypothermic after infusion of cold resuscitation fluids. Laboratory evidence of DIC should be sought before microvascular bleeding becomes evident so that appropriate and aggressive action can be taken to address the underlying cause. Frequent estimation of platelet count, fibrinogen, PT and APTT is strongly recommended; measurement of fibrinogen degradation products or d-dimers may be useful. Prolongation of PT and APTT beyond that expected by dilution, together with significant thrombocytopenia and fibrinogen of <1.0 g litre−1, are highly suggestive of DIC. Treatment consists of platelets, FFP and cryoprecipitate, given sooner rather than later, in sufficient dosage but avoiding circulatory overload. A guideline has been defined as ‘a systematically developed statement that assists in decision-making about appropriate health care for specific clinical situations’.27Field MJ Lohr KN Clinical Practice Guidelines: Direction of a New Agency. Institute of Medicine, Washington, DC1990Google Scholar Successful implementation will depend on local ownership by adaptation to local circumstances and accessibility at the point of clinical activity. In developing this template guideline, we have examined such sound scientific evidence as is available, reviewed the relevant literature and professional consensus statements, and taken into account discussion and comment from contributors and delegates at the National Blood Service Northern Zone Symposium on Massive Transfusion. The recommendations contained in these guidelines must be regarded as Grade C, based as they are on uncontrolled observational studies and a consensus of expert opinion (Level 3 evidence). Well-designed case–control studies and randomized clinical trials are lacking in this important area of transfusion medicine. A recent cohort study28Cinat ME Wallace WC Nastanske F et al.Improved survival following massive transfusion in patients who have undergone trauma.Arch Surg. 1999; 134: 964-970Crossref PubMed Scopus (163) Google Scholar shows a significantly improved survival rate in massively transfused patients over a 10-yr period and associates this with more effective and efficient rewarming techniques, aggressive resuscitation and component therapy, and improved blood-banking. There is a need for further studies to clarify these issues and provide firm evidence on which future recommendations can be based." @default.
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