Guidelines on the management of massive blood loss

The guideline group was selected to be representative of UK-based medical experts and included the authors of previous recommendations. Preparation of the guidelines included a review of key literature, including Cochrane Database and MEDLINE and consultation with representatives of relevant specialties. Recommendations are based on appraisal of the relevant literature and expert consensus. The writing group produced the draft guideline, which was subsequently revised by consensus by members of the Transfusion Task Force of the British Committee for Standards in Haematology. The guideline was then reviewed by a sounding board of approximately 100 UK haematologists, the British Committee for Standards in Haematology (BCSH) and the British Society for Haematology Committee and comments incorporated where appropriate. Criteria used to quote levels and grades of evidence are as outlined in appendix 3 of the Procedure for Guidelines Commissioned by the BCSH (http://www.bcshguidelines.com/process1.asp#App3). The objective of this guideline is to provide healthcare professionals with clear guidance on the management of massive blood loss. They do not address the specific problems associated with major obstetric haemorrhage; these are being addressed by the Royal College of Obstetricians. In all cases individual patient circumstances may dictate an alternative approach. These guidelines summarise current opinions regarding the management of massive blood loss and update previous recommendations (Stainsby et al, 2000). These are presented as a template that can be modified to suit local circumstances, and then displayed in clinical areas. The left-hand column outlines the key steps or goals, the centre column adds procedural detail and the right-hand column provides additional advice and information (Table I). Major blood loss jeopardises the survival of patients in many clinical settings and is a challenge for haematological and blood transfusion services. Tensions may arise between those attempting to treat bleeding, those supplying blood and those providing laboratory services. Discord can waste scarce resources, or, worse, result in a bad outcome for the patient. Massive blood loss is arbitrarily defined as the loss of one blood volume within a 24 h period (Mollison et al, 1997), the normal adult blood volume being approximately 7% of ideal body weight in adults and 8–9% in children. Alternative definitions that may be more helpful in the acute situation include a 50% blood volume loss within 3 h or a rate of loss of 150 ml/min (Fakhry & Sheldon, 1994). It is imperative to recognise major blood loss early and institute effective action promptly if shock and its consequences are to be prevented. These are; Maintenance of tissue perfusion and oxygenation by restoration of blood volume and haemoglobin Arrest of bleeding by treating any traumatic, surgical or obstetric source judicious use of blood component therapy to correct coagulopathy A successful outcome requires prompt action and good communication between clinical specialties, diagnostic laboratories, hospital transfusion laboratory staff and the Blood Service. Blood component support takes time to organise and the supplying blood centre may be several hours away from the hospital. Special transfusion requirements for specific indications, e.g. components suitable for neonates, irradiated components for patients at risk of transfusion-associated graft-versus-host disease, (British Committee for Standards in Haematology Blood Transfusion Taskforce, 1996, 2004), should be taken into account if time permits, but it may be necessary to make a pragmatic decision regarding the relative risks of delaying transfusion or giving components that are not of the appropriate specification. Early consultation with senior surgical, anaesthetic and haematology colleagues is essential and the importance of good communication and co-operation in this situation cannot be over-emphasised. Appropriate surgical expertise for the area of bleeding is vital; involvement of vascular surgeons, cardiothoracic surgeons or others with specific interests is crucial to success. Consideration should be given to early referral and if necessary transfer to such expertise. In the more difficult cases, confidence to pack visceral cavities, cross clamp and tie off major vessels may be required. Radiological embolisation or stenting has an established role. An intensive care bed is likely to be required and early warning of this is advisable. A member of the clinical team should be nominated to act as co-ordinator responsible for overall organisation, liaison, communication and documentation. This is a critical role for a designated member of the permanent clinical staff. Accurate documentation of blood components given and the reason for transfusion is necessary in order to enable audit of outcome and satisfy the legal requirement for full traceability (Blood Safety and Quality Regulations, 2005). The hospital transfusion laboratory must be informed of a massive transfusion situation at the earliest possible opportunity. This will provide an opportunity to check stock, reschedule non-urgent work and call in additional staff if required out of hours. Clear local protocols for management of massive blood loss should be accessible in all relevant clinical and laboratory areas and understood by all involved staff. Regular ‘drills’ can improve awareness and confidence and ensure that the blood transfusion chain works efficiently. It is good practice to review such cases after the event, to assess what went well and what did not, and to update protocols accordingly. The Hospital Transfusion Committee (HTC) has a central role in ensuring the optimum and safe use of blood components. The development of protocols for management of massive transfusion is an important part of its remit. The HTC also provides a forum in which a rapid communication cascade can be agreed and massive transfusion episodes critically reviewed. As part of contingency planning for national blood shortage situations, every hospital should have an Emergency Blood Management Plan in place that provides guidance on clinical priorities for the use of large volumes of blood components. In exceptional circumstances it may be necessary to make a decision to cease energetic transfusion support when the chances of the patient's survival are low, determined on a case-by-case basis. The HTC should establish a mechanism for making such difficult decisions on an individual basis, taking into account such factors as co-morbidity, potential for control of bleeding, reversal of the underlying cause and competing demands for available blood components. The over-riding first requirement is maintenance of tissue perfusion and oxygenation, which is critical in preventing the development of hypovolaemic shock and consequent high mortality from multi-organ failure. Restoration of circulating volume is initially achieved by rapid infusion of crystalloid or colloid through large bore (up to 14 gauge) peripheral cannulae (Donaldson et al, 1992). Alternatively, larger bore central access devices can be used dependent on local skills and availability The use of albumin and non-albumin colloids versus crystalloids for volume replacement has been the subject of debate following controversial meta-analyses (Cochrane Injuries Group Albumin Reviewers, 1998; Schierhout & Roberts, 1998). A controlled trial of normal saline versus 4% human albumin for fluid resuscitation involving over 7000 patients in 16 intensive Care Units in Australia and New Zealand (Finfer et al, 2004) found no difference in outcome at 28 d and concluded that they were clinically equivalent (Grade A recommendation, Level 1b evidence). Hypothermia increases the risk of end organ failure and coagulopathy (Iserson & Huestis, 1991; American College of Surgeons, 1997) and may be prevented by pre-warming of resuscitation fluids, patient warming devices such as warm air blankets and the use of temperature controlled blood warmers (Grade C recommendation, Level IV evidence). 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 screen (including fibrinogen estimation and thrombin time) and biochemistry investigations. Accurate patient identification is of paramount importance in all aspects of healthcare, and particularly in emergency situations. Every patient must wear an identification wristband, and there must be a robust and tested system in place for identification of unknown unconscious patients, including subsequent merging of clinical and laboratory records. When dealing with an evolving process it is important to check parameters frequently, (and after each therapeutic intervention) to monitor the need for and the efficacy of component therapy. Appropriate use of near-patient testing devices, which can include thromboelastography (TEG), can offer rapid data to guide component therapy (Samama & Ozier, 2003) but requires expert interpretation. Advice should be sought from a consultant with transfusion expertise regarding appropriate investigations, their interpretation and optimum corrective therapy. Allogeneic blood from volunteer donors is a limited and valuable resource that must be used carefully, appropriately and safely. There is a lack of good evidence from randomised controlled trials to support recommendations for the use of blood components in massive transfusions, although the design of such trials in the emergency setting is problematic. The target platelet count and the efficacy of fresh frozen plasma are key areas where further research is needed. All blood components supplied by the UK transfusion services are now leucodepleted as a precaution against transfusion transmission of variant Creutzfeldt-Jakob disease (vCJD), in addition to mandatory testing for viral markers (human immunodeficiency virus [HIV], hepatitis B virus [HBV], hepatitis C virus [HCV] and Human T lymphotropic virus type 1 [HTLV 1]). Benefits of leucodepletion also include reduced non-haemolytic febrile transfusion reactions, reduced transmission of leucocyte-associated viruses, such as cytomegalovirus, reduced immunosuppressive effects of transfusion (Blajchman et al, 2001) and reduced cytokine-mediated organ damage. (Erber, 2002) Transfusion giving sets, which should be changed at least 12-hourly during red cell infusion and prior to platelet infusion, include a screen filter. Any additional filter is unnecessary and may impede blood flow. (McClelland, 2001) The function of red cells is oxygen delivery to tissues; they should not be used as a volume expander. In the UK, the blood services will routinely provide leucodepleted red cells in optimal additive solution, which has low viscosity (Hogman et al, 1983) and contains minimal plasma. Red cells also contribute to haemostasis by their effect on platelet margination and function. The optimal haematocrit to prevent coagulopathy is unknown, but experimental evidence suggests that a relatively high haematocrit, possibly 0·35 l/l, may be required to sustain haemostasis in patients with massive blood loss (Reiss, 2000; Hardy et al, 2004). Red cell transfusion is likely to be required when 30–40% blood volume is lost; over 40% blood volume loss is immediately life-threatening (American College of Surgeons, 1997). Blood loss may be underestimated particularly if concealed and in young fit people, such as in the obstetric setting. Blood replacement should be guided by clinical estimation of blood loss in conjunction with the patient's response to volume replacement. Haemoglobin and haematocrit levels should be measured frequently, but in the knowledge that the haemoglobin level is a poor indicator of blood loss in the acute situation. Red cells are rarely indicated when the haemoglobin concentration is >10 g/dl but almost always indicated when it is <6 g/dl. (British Committee for Standards in Haematology Blood Transfusion Task Force, 2001) (Grade C recommendation, Level IV evidence). Decisions on red cell transfusion at intermediate haemoglobin concentrations should be based on the patient's risk factors for complications of inadequate oxygenation, such as rate of blood loss, cardiorespiratory reserve, oxygen consumption and atherosclerotic disease. Measured physiological variables, such as heart rate, arterial pressure, pulmonary capillary wedge pressure and cardiac output may assist the decision-making process, but it should be emphasised that silent tissue or organ ischaemia may occur in the presence of stable vital signs. The clinician who communicates with the transfusion laboratory should indicate the timescale within which blood is needed at the bedside, (i.e. immediately, within 20 min, within an hour) in order that the laboratory scientist knows how much time is available for ABO and D grouping and pre-transfusion testing. In an extreme situation where blood is required immediately and the patient's blood group is unknown, it may be necessary to issue Group O un-crossmatched red cells. Females of reproductive age (i.e. under 50 years) whose blood group is unknown must be given group O Rh D negative red cells in order to avoid sensitisation and the risk of haemolytic disease of the newborn in subsequent pregnancy. It is acceptable to give O Rh D positive cells to males and older females of unknown blood group (Schwab et al, 1986), as group O Rh D negative blood is a scarce resource. ABO group-specific red cells should be given at the earliest possible opportunity. Blood group determination takes less than 10 min and so it should not be necessary to give large volumes of group O blood. In a patient with known red cell antibodies, the risk of a haemolytic transfusion reaction will need to be assessed against the risk of withholding transfusion until compatible blood can be provided. Red cells undergo changes during 4°C storage (the ‘storage lesion’) including increase of extracellular potassium, decrease in ATP and 2,3-diphosphoglycerate (2,3 DPG) content and lowering of pH. Although 2,3 DPG is after d has been within 24 h of transfusion et al, and have not any clinically on oxygen when older components are et al, blood may be of in requirements for blood and can be in where it is in et al, are an alternative to blood but there is no available in the UK 2004). consensus that the platelet count should not be to the critical level of 50 in the bleeding patient (Grade C recommendation, level IV and this is by the BCSH guidelines for the use of platelet (British Committee for Standards in Haematology Blood Transfusion Task Force, 2003) A platelet count of 50 may be when approximately blood volumes have been by fluid or red cell components et al, but there is individual A platelet transfusion of in a patient with bleeding is so as to provide a of to ensure that the level not that critical for A target level of 100 10 has been for those with or central system Task Force of the College of American 1997) (Grade C recommendation, level IV evidence). platelet transfusion may be required when platelet function is as after in patients with or to therapy. In the requirement for are and it may be necessary to from the blood centre at levels the target in order to ensure their availability when needed. can be given an blood giving although a platelet giving it has less Transfusion of through a giving used for red cells is not is the cause of coagulopathy in massive transfusion of of coagulation factors following volume replacement with crystalloid or colloid and transfusion of red cell components. The level of fibrinogen the critical level of is likely to be after blood volume loss, by the of coagulation factors to after blood loss. 1998; 2000). of the time and time to the normal is with an risk of clinical coagulopathy et al, It is essential that laboratory of coagulation are these may need interpretation by a should be the and not from the as this is should have in place to ensure that clinical staff are laboratory should be to issue blood components in the first a agreed It may be necessary to components are on the rate of bleeding and the laboratory Although with fresh plasma is not it may be required in where rapid of coagulation cannot be of should be after one blood volume is 1998). The should be large to coagulation factors well the critical in that the efficacy may be reduced of rapid consumption Task Force of the College of American (Grade C recommendation, level IV evidence). It should be in although is (British Committee for Standards in Haematology Blood Transfusion Taskforce, 2004) and used in of massive blood loss, there is evidence of its clinical efficacy from randomised et al, 2004) frozen plasma if given in will correct fibrinogen and coagulation but large volumes may be required. fibrinogen levels critically low therapy should be Task Force of the College of American (Grade C recommendation, level IV evidence). contains fibrinogen Blood Quality data that contains approximately the is 1 of be to provide an adult therapeutic of provides fibrinogen in a volume of also contains and It should be that transfusion of the patient to fibrinogen is used in but is not in the frozen may be at 4°C for to 24 h (British Committee for Standards in Haematology Blood Transfusion Taskforce, 2004). It is for the laboratory to a therapeutic of as as they of a massive transfusion in order to British Committee for Standards in Haematology Guidelines on as an alternative to when major bleeding (British Committee for Standards in 1998). such as and have been used to established in the setting of massive blood & 2003) concluded that there is evidence from randomised controlled trials of in to support or a clinically important effect et al, et al, 2004) and evidence is et al, This is for use in with to treat bleeding or as for use has been off as a in settings of massive blood transfusion and there are many of its successful The of these is a in blood loss following of the with subsequent patient survival from situations. The is but may effective through transfusion in this setting. The use of as for patients with massive has been to be et al, 2004). A review concluded that the of in patients with bleeding is and relatively safe of evidence from controlled trials is not available so trials are likely to provide more for its use et al, 2005). such evidence available it is to the use of in where there is blood loss of with no evidence of or where surgical control of bleeding is not possible and there has been replacement of coagulation factors with and and of There should be a local in place and the decision should be at consultant coagulation is a in the bleeding patient but is obstetric The clinical of is in vessels can result in damage. A can result from the of the coagulation cascade to tissue in consumption of and coagulation at risk are those with tissue to or and those with massive or et al, 2004). This a high and is difficult to of the and in of that by with and fibrinogen of are of a and estimation of platelet fibrinogen and is of may also be in providing an early evidence of a consumption coagulopathy should be sought bleeding so that appropriate and action can be taken to address the underlying of the coagulation of and given than in but The associated with blood transfusion is the giving of the blood to the which can at result in a haemolytic reaction (Stainsby et al, 2005). of such to the of Transfusion that the risk of may be particularly high in an emergency situation. must be in place for the of blood and blood components (British Committee for Standards in Haematology Blood Transfusion Taskforce, and these must be to the of acute and acute are but occur more following of and than red cells (Stainsby et al, 2005). The Blood now from donors to the risk of changes may occur to and the infusion of large volumes of red cells and blood plasma. The is to & This may occur as a result of large volume plasma infusion, particularly in the presence of where is It should be by infusion of as this requires to A of 10 of has been & to can be given in over 10 min, when the should be and further bleeding and is the of and blood this may to the high extracellular concentration in red cell This may be by and the associated with it should be with with to correct Early is likely to be required after the of bleeding in the of massive on prompt good communication and involvement of senior with the necessary expertise. has to of the associated physiological This has in more with effective blood component therapy guided by testing, and effective warming et al, age and co-morbidity, and of and development of the (Erber, 2002) for audit resuscitation with crystalloids should be by blood for full blood coagulation blood and blood a designated and member of the resuscitation should of a that must type of blood component or replacement time for of the traceability of blood components protocols and must be available and displayed in e.g. and care and blood Regular of emergency management of massive transfusion should be and to Regular audit of management of massive review by Transfusion and Hospital Transfusion Committee against the guidelines with to the advice and information in these guidelines is to be and at the time of to the the British Society for Haematology the any legal for the content of these of the authors has a of Task at time of writing this guideline