Consensus statements on the development of out-of-hospital transfusion protocols
| Domain; statement | Rationale |
|---|---|
| 1. General oversight and clinical governance | |
| 1.1 All CCTOs shall have a protocol to guide OHT. | The panel agreed on the importance of standardization of OHT within CCTOs. For the purpose of this document, CCTOs should be viewed as organizations that provide a critical-care level of stabilization and transport of severely ill or injured patients, whether by ground or air ambulance. (16) This includes scene calls and interfacility transfers. Most Canadian local and regional emergency medical services ground ambulances will probably not be dispatched to sufficient numbers of critically ill patients to warrant the addition of OHT to such services. (17) However, some emergency medical services might create smaller units for second-tier dispatch to selected patient groups (for example, major trauma), and such units should be considered CCTOs in the context of this document. (1) |
| 1.2 The protocol shall be developed by a multidisciplinary team, be approved by the participating transfusion service, and comply with best practices and local and national transfusion guidelines. | An OHT protocol requires support from multiple organizations and individuals. This includes, but is not limited to, prehospital providers, aviation safety experts (in some cases), blood transport personnel, communication services and laboratory personnel. (18) The protocol should be reviewed and approved by the hospital transfusion committee and the CCTO’s medical advisory committee. |
| 1.3. The protocol shall incorporate principles of damage-control resuscitation, including appropriate treatment of ongoing hemorrhage and careful selection of a receiving hospital that can provide appropriate definite hemorrhage control. | Damage-control resuscitation principles in prehospital trauma care include control of external hemorrhage; application of pelvic binders (if indicated); correction of deranged physiologic measures, with particular focus on avoiding hypothermia and acidosis; and the administration of TXA. (9) Extensive crystalloid administration should be avoided if possible. (19) New technologies such as partial resuscitative endovascular balloon occlusion of the aorta (P-REBOA) might play a role in internal hemorrhage control in the future. (10) Many damage-control resuscitation principles can be applied to nontraumatic causes of hemorrhagic shock, but the panel acknowledges the lack of clear evidence. Notwithstanding the increasing number of therapeutic options outlined above, timely transfer to a receiving hospital with the resources required for definite hemorrhage control remains a key component of care for patients experiencing hemorrhagic shock. |
| 1.4 The protocol shall reflect the types and amounts of blood components and products that can be stored and transported by the CCTO, as well as additional components and products that might be available from sending facilities. | The panel anticipated that the quantity and variety of blood components and products that CCTOs will be able to access is likely going to evolve with the publication of numerous prehospital trials currently underway. (14) Optimal care for patients with major hemorrhage might require a combination of the CCTO’s stock and further blood components and products that might be available from sending facilities, and protocols should provide guidance for such situations. |
| 1.5 The protocol should be reviewed at specified regular intervals, when the CCTO adopts new relevant products or procedures, or if new, practice-changing evidence emerges. | The panel acknowledges the pace of ongoing research in this area, with a number of relevant randomized controlled trials expected over the coming years. (4), (20) In addition, changes in blood transfusion services might make new products available in the near future based on needs and logistics, for example, lyophilized plasma or whole blood. |
| 1.6 A single protocol for all patients is preferred in order to ensure compliance; there should be specific guidance provided for selected patient populations. | Previous research has demonstrated poor compliance with major hemorrhage protocols during in-hospital transfusions and a potential detrimental effect on patient outcomes. (21) To optimize compliance with OHT protocols, the panel recommended a single protocol for patients with active, major bleeding. This single protocol should include or reference considerations for specific situations such as trauma, obstetric hemorrhage, gastrointestinal bleeding, acquired coagulopathy or pediatric hemorrhage. |
| 1.7 Each CCTO shall have named lead(s) and contact person(s) for any issues related to OHT. | Owing to the inherently unpredictable nature of the critical care transport environment, situations will arise that are not directly addressed by protocols already in place. (16) It is imperative that CCTOs have a responsive and accountable system to deal with any queries and issues in a safe and timely fashion. |
| 1.8 All OHT procedures should be reviewed by a designated individual (for example, the named lead for OHT [see statement 1.9]) or committee for quality assurance. | Adherence to major hemorrhage protocols in regard to safety measures, indication for transfusion and damage-control resuscitation is a critical aspect of assuring patient benefit and efficient use of blood products during in-hospital care. (21), (22) Although no direct evidence exists for protocols guiding transfusion in prehospital and retrieval settings, it is likely that the in-hospital evidence is transferrable, and many CCTOs routinely review all cases involving OHT. (23) CCTOs should have a mechanism to review all cases of OHT, including feedback to care providers and shared learning across the CCTO. |
| 1.9 In addition to the minimal regional and national training requirements for competence in blood product transfusion, prehospital care providers shall have formal training specific to blood transfusion in the prehospital or transport medicine setting. | Standards of training exist for all health care providers performing transfusion of blood products, and CCTOs must assure their clinicians have received initial training and are compliant with ongoing standard requirements. (24) Provision of multimodal training has been shown to improve relevant knowledge of and adherence to best practice in blood product transfusion in hospital settings. (25) Transfusion in the critical care transport setting poses additional logistical and clinical challenges. Additional training that takes these aspects into account is important to ensure safe and efficient practice. (18) |
| 1.10 Any clinical or administrative adverse events, errors or near-misses shall be documented and reported through the CCTO’s incident report system. This shall trigger a notification of the named lead(s) of the CCTO and the participating transfusion service. | A timely information cascade after errors or near-misses will allow for the preservation of information and materials required for a thorough investigation. (26) Importantly, errors or near-misses with a high probability of recurrence can be addressed quickly and further harm avoided. A transparent and just culture in regard to errors is paramount to support such a reporting system. (27) Adverse event reporting systems will also be required to comply with regulatory safety requirements. |
| 1.11 The quality metrics in Box 1 should be tracked on all OHTs and the data reviewed quarterly at the CCTO’s medical advisory committee, with representation from the participating transfusion service. | Safety, efficiency and clinical effectiveness in OHT requires cooperation and procedural compliance, from the blood transfusion service to the blood delivery and storage system, to the transfusion at the patient’s side, and to posttransfusion documentation and tracing. (18) Audit of quality indicators is an important tool for measuring and improving compliance with protocols and must be undertaken regularly. (28) The panel agreed that some flexibility should be included in the choice of quality metrics. Box 1 contains a list of (strongly) recommended metrics. |
| 1.12 If the patient (or a substitute decision-maker) is unable to consent to OHT, this should be documented in the CCTO’s patient records. If consent can be obtained, documentation of consent should include an explanation of the risks and alternatives to OHT. | Obtaining consent is a crucial step before commencing transfusion of blood products. (29) The panel anticipated that many patients requiring OHT will not be able to consent owing to the severity of their underlying illness or injury. (18), (30) Nevertheless, in such cases, there should be documentation of the reason why consent could not be obtained. The panel strongly recommended a structured and standardized documentation approach for consent, or refusal or inability to obtain consent. (31), (32) |
| 1.13 CCTOs shall comply with all Health Canada Blood Regulations, and applicable Canadian Standards Association and provincial standards that govern OHT. | Although storage and transfusion of blood components and products will occur outside of traditional hospital settings, the same standards as for in-hospital practice apply. (33) |
| 2. Storage and transport of blood components and products | |
| 2.1 Blood components and products shall be stored in validated storage containers in accordance with national and regional accreditation standards of the participating transfusion service. | One of the main logistical challenges of OHT is the storage of blood components and products outside of blood transfusion services’ laboratories. As per many transfusion standards, the use of validated containers is required to reduce the risk of transfusion complications and wastage. (18), (32) |
| 2.2 Containers shall be closely inspected/monitored for any compromise or defects at defined times (i.e., start and end of shift, before initiation of OHT, on return to participating transfusion service). | Containers will be frequently moved between different storage areas at CCTO bases, aircraft and vehicles, and will also be transported to the patient’s side at scene or sending facility. The frequent movement and storage in compartments shared with other equipment in aircrafts or vehicles introduces a risk of damage to containers, with the subsequent risk of wastage of blood components and products if not recognized and mitigated. |
| 2.3 If a temperature-monitoring device is included in the storage container, it shall be inspected for temperature range violations before initiation of OHT. | Depending on local practices, such as choice of storage containers and frequency of exchange of blood components and products, temperature-monitoring devices will be included in the storage containers. (18) Identifying any temperature violations before initiation of OHT is a critical step in avoiding transfusion complications. |
| 2.4 All prehospital providers handling blood components and products shall receive training regarding the safe storage and handling of the containers, as well as the procedures for receiving blood components and products from the transfusion service, and returning blood components and products to the transfusion service. | Training in the clinical aspects of OHT is addressed in statement 1.12. However, the panel agreed that specific training and instructions regarding the storage, handling and exchange procedures for blood products and components were important to reduce the risk of wastage. |
| 3. Initiation of out-of-hospital transfusion | |
3.1 The indication for OHT is confirmed or suspected hemorrhagic shock secondary to traumatic or nontraumatic hemorrhage AND 2 or more of:
| Although the panel expected that trauma would be the main cause for OHT, it is important to also consider OHT in nontraumatic causes of hemorrhagic shock such as obstetric, gastrointestinal, peri-or postoperative, or aneurysmal hemorrhage. (18), (30) Previous research in patients with trauma has shown that clinician gestalt alone is a poor predictor of the need for massive transfusion, which suggests the need for standardized transfusion protocol triggers. (34) The combination of clinical and laboratory parameters to trigger OHT in this statement aims to provide guidance but also some flexibility to the health care provider. For patients whose condition is unstable in need of urgent transfusion (at least 2 of hypotension, tachycardia or end-organ dysfunction), OHT can be commenced without the need for laboratory testing. (35) In patients with none or only 1 of these clinical signs of hemorrhagic shock, OHT might still be beneficial, and the decision can be augmented by obtaining point-of-care laboratory values, if possible. (36), (37) In patients with trauma, additional factors such as injury patterns (amputation, pelvic fracture, penetrating trauma) or positive findings of Focused Assessment with Sonography in Trauma (FAST) scanning can be used to determine the indication for transfusion. (36), (38) |
| 3.2 In addition to acute hemorrhagic shock, OHT may be initiated in other cases in which a transport physician considers the benefits to outweigh the risks. | Although statement 3.1 aims to provide a comprehensive trigger for OHT, there might be situations that do not fulfil the above criteria in which OHT might be considered. As these cases are likely to have a less time-sensitive nature and more marginal benefit–risk ratios, the panel agreed that this decision should be made by a CCTO transport physician. (36) |
| 3.3 OHT may be commenced without physician authorization within the boundaries of a clearly defined medical directive, or if the anticipated delay would result in major harm to the patient (e.g., severe hemodynamic compromise). | Transfusion of blood products typically requires physician orders. However, the panel agreed that critically ill or injured patients might come to harm if initiation of OHT is delayed owing to the need to obtain remote physician authorization. (39) Protocols should therefore include mechanisms for autonomous initiation of OHT within clearly defined boundaries (see statement 3.2, for example). |
| 3.4 The indication for commencing OHT should be clearly documented in the patient’s records. | Blood components and products are scarce resources. (40) In addition, the risk–benefit ratio of OHT needs to be carefully considered for individual patients. (41) Documentation of indications for OHT is necessary to demonstrate the consideration of risk to benefit and for auditing protocol adherence. |
| 3.5 If feasible, a pretransfusion blood sample should be obtained by the prehospital provider to be used by the hospital transfusion service for ABO and Rh investigations. | Pretransfusion samples, although not immediately beneficial in the context of OHT, can be valuable for blood transfusion services when further transfusions are required, reduce downstream use of group O RBC and support eligibility for organ donation if indicated. (42) The panel had concerns regarding the increased workload for prehospital providers and accurate sample labelling. Nevertheless, a number of CCTOs currently obtain pretransfusion samples when feasible, and this option should be considered in the development of OHT protocols. (23), (43) |
| 4. Types of blood components and products | |
| 4.1 At a minimum, OHT stocks of CCTOs shall include 2 units of O Rh(D)-negative RBCs. | The panel agreed that, pending availability of whole blood and further evidence for other blood components and products, RBCs are the central component of OHT. (2), (18), (43) The panel considered that a large number of patients could safely receive O Rh(D)-positive RBCs. (44), (45) However, for patients truly requiring O Rh(D)-negative RBCs, the CCTO’s stock of RBCs might be the only blood component or product available, and, as such, CCTOs should stock O Rh(D)-negative RBCs whenever possible. In addition, logistical considerations favour CCTOs’ carrying 1 type of RBCs consistently rather than a mix of RBC Rh types. (18) Finally, administration of Rh(D)-positive blood without a pretransfusion sample can delay Rh-group determination considerably after OHT. (46) |
| 4.2 If blood group is unknown, O Rh(D)-negative RBCs shall be the preferred RBC for patients of child-bearing potential. CCTOs may consider the use of O Rh(D)-positive RBCs for all other patients. | In addition to the CCTO’s O Rh(D)-negative RBCs (statement 4.1), further blood products might be available through the CCTO or sending health care facility. (14) The Ontario Massive Hemorrhage Protocol guideline suggests the use of O Rh(D)-positive RBCs for all patients with the exception of patients of child-bearing potential, in order to maintain sufficient O Rh(D)-negative stocks. (14) Group O Rh(D)-positive RBCs should be used in these circumstances, if this is possible without delay. (47) |
| 4.3 Depending on local availability, feasibility and clinical requirements, CCTOs may consider including plasma in addition to RBCs. | Correction or prevention of coagulopathy is an important aspect of damage-control resuscitation for hemorrhagic shock. Many CCTOs internationally stock plasma in addition to or instead of RBCs. (5)– (7), (48) The Ontario Massive Hemorrhage Protocol guidelines suggest a ratio of RBCs to plasma of 2:1 in massive transfusion, (14) and there is evidence that prehospital administration of plasma might improve survival in patients with trauma with longer transfer times. (7) Although availability of group AB plasma is limited in Canada, (40), (49) CCTOs should consider including plasma if availability and logistics allow this. |
| 4.4 CCTOs may consider storing and transporting 2000 IU of PCC and 4 g of fibrinogen concentrate as an alternative to thawed plasma. | The Ontario Massive Hemorrhage Protocol guidelines recommend PCC and fibrinogen as an alternative to plasma for health care facilities where plasma is not immediately available for logistic reasons. (14) CCTOs are similar to such facilities in their limited storage capabilities of blood components and products, and therefore could consider the addition of PCC and fibrinogen to their OHT stocks as an alternative to plasma. |
| 4.5 Additional blood components and products, such as larger volumes of RBCs or thawed plasma, platelets or specific clotting factor concentrates may be requested from the sending health care facility as required. The benefits of obtaining these additional products need to be balanced against the risks of delaying transfer of the patient. | Frequently in hemorrhagic shock, and particularly with longer transport times to definitive care, the CCTO’s stock of blood components and products will be insufficient to meet the patient’s needs. (18), (30), (43) The option of obtaining further blood products from a sending health care facility or a health care facility on route to definitive care should be explored. The potential benefits of releasing these limited stocks from the sending facility need to be weighed against the risk of depleting local resources, to the potential detriment of other patients requiring care at the sending facility. Importantly, this process should occur with no or minimal delay in transport to definitive care, and thus should be initiated early on, if appropriate. |
| 5. Delivery and monitoring of out-of-hospital transfusion | |
| 5.1 Prehospital providers should have access to a standard operating procedure that includes the indication for and administration and monitoring of OHT, and the management of adverse reactions. | OHT might be an infrequent event for prehospital providers working in Canadian CCTOs. (18), (30) Access to relevant standard operating procedures, electronically or in print, is essential to ensure protocol adherence, (23) and their use has been shown to improve quality of care in other aspects of prehospital or retrieval medicine. (50) |
| 5.2 RBCs and plasma shall be given through a commercial, portable and approved warming device. | Avoidance of hypothermia is an important aspect of damage-control resuscitation. (51) Blood components and products that are stored at low temperatures (RBCs and plasma) should therefore be given through a warming device. Multiple portable devices for use in the critical care transport environment are commercially available. (18), (23) |
| 5.3 All patients receiving OHT should have their temperature measured within 30 minutes of provider assessment, and then at a minimum of every 30 minutes (or continuously where available) until arrival at the receiving hospital. | In both traumatic injury and postpartum hemorrhage, temperature monitoring is infrequently performed, and, when the temperature is measured, hypothermia is common. (51), (52) Hypothermia in traumatic injury is associated with worse outcomes, (51) although prospective trials have not confirmed whether aggressive warming protocols would alter outcomes. (52) Warming of patients improves their comfort, and, therefore, even in the absence of a confirmed survival benefit, it should be a core part of every OHT. |
| 5.4 All patients should receive interventions to prevent hypothermia and achieve normothermia (≥ 36°C) | See rationale for statement 5.3. |
| 5.5 Point-of-care hemoglobin level, lactate level and/or base excess may be used to guide OHT (see statements 3.1 and 7.2) but should not delay initiation of transfusion in critically ill or injured patients. | During in-hospital massive hemorrhage protocols, regular laboratory testing is used to direct management. (14) A number of commercially available point-of-care testing devices are now small and light enough that they have been successfully incorporated into the critical care transport environment. (16), (53) The panel encourages the use of point-of-care testing, with the caveat that it should not impede or delay OHT in critically ill or injured patients. |
| 5.6 Monitoring for and clinical management of transfusion reactions should follow the same standards as for in-hospital blood transfusions. | Transfusion reactions range from relatively common and benign febrile nonhemolytic reactions to rare and severe hemolytic transfusion reactions. (54) The monitoring for and management of such transfusion reactions should be clearly outlined in standard operation procedures and should closely mirror established protocols of in-hospital practice. Since the vast majority of RBCs administered during OHT will be uncrossmatched, patients should be closely monitored for signs and symptoms of delayed hemolytic transfusion reactions. |
| 6. Indications for and use of transfusion adjuncts | |
| 6.1 TXA should be given as soon as possible with any OHT for hemorrhagic shock due to trauma within the previous 3 hours. | Early administration of TXA has been shown to reduce mortality from traumatic hemorrhage, with the effect gradually decreasing over time. (55) Administration of TXA later than 3 hours after the initial injury is associated with increased mortality. (56) Current recommendations include a 1-g bolus followed by either a further 1 g of TXA as bolus or infusion, or a single 2-g bolus. (57), (58) |
| 6.2 TXA should be given as soon as possible with any OHT for hypovolemic shock due to postpartum hemorrhage. | Early administration of TXA has been shown to reduce mortality from postpartum hemorrhage, with earlier administration more beneficial than later administration. (56), (59) |
| 6.3 Consideration of calcium gluconate or calcium chloride administration should be prompted by OHT protocols at defined intervals (e.g., after 2 units and after every 4 units thereafter). | Hypocalcemia is common in patients with trauma and is associated with increased mortality. (60) RBCs are preserved with citrate, which could cause or exacerbate hypocalcemia, particularly during OHT with large volumes of RBCs. Calcium plays an important role in the clotting cascade and as an inotrope. (60) The panel considers there to be insufficient evidence for routine calcium administration during OHT; however, a prompt to consider empirical administration or point-of-care testing (if feasible) is considered beneficial. |
| 6.4 PCC, 2000 IU, should be given empirically for adult patients requiring OHT because of hemorrhage and taking warfarin or a direct factor Xa inhibitor (e.g., rivaroxaban, apixaban, edoxaban). | The Canadian National Advisory Committee on Blood and Blood Products recommends the empirical administration of 2000 IU of PCC in patients taking warfarin with major bleeding and an unknown International Normalized Ratio. (61) The same dosage is recommended for the management of severe bleeding in patients taking a direct factor Xa inhibitor. |
| 7. Resuscitation targets to halt ongoing transfusion | |
7.1 OHT should be re-evaluated if the following SBP has been achieved in acute traumatic hemorrhagic shock:
| Permissive hypotension has become an established concept in early damage-control resuscitation for trauma. However, much uncertainty remains as to what the ideal blood pressure targets are and after what time more aggressive restoration of perfusion might be beneficial. (62) This statement reflects commonly used SBP targets. (63), (64) These values should be seen as a trigger to review the current situation and OHT, rather than an automatic stop of an ongoing transfusion. The factors outlined in statement 7.2 can be used to supplement decision-making. |
7.2 For longer transfers, particularly interfacility transfers, or in patients in whom active bleeding has stopped, the following factors, in addition to SBP, can be used to guide the amount and speed of OHT:
| There is considerable uncertainty regarding when to stop or reduce an ongoing OHT. (14) The decision should be supported by multiple data points, in addition to factors such as the volume of remaining blood components and products and length of transport to definite care. See also rationale for statement 7.1. |
Note: CCTP = critical care transport organization, OHT = out-of-hospital transfusion, PCC = prothrombin complex concentrate, RBC = red blood cell, SBP = systolic blood pressure, TXA = tranexamic acid.