Development of a national out-of-hospital transfusion protocol: a modified RAND Delphi study
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* Johannes von Vopelius-Feldt
* Joel Lockwood
* Sameer Mal
* Andrew Beckett
* Jeannie Callum
* Adam Greene
* Jeremy Grushka
* Aditi Khandelwal
* Yulia Lin
* Susan Nahirniak
* Katerina Pavenski
* Michael Peddle
* Oksana Prokopchuk-Gauk
* Julian Regehr
* Jo Schmid
* Andrew W. Shih
* Justin A. Smith
* Jan Trojanowski
* Erik Vu
* Markus Ziesmann
* Brodie Nolan

## Abstract

**Background:** Early resuscitation with blood components or products is emerging as best practice in selected patients with trauma and medical patients; as a result, out-of-hospital transfusion (OHT) programs are being developed based on limited and often conflicting evidence. This study aimed to provide guidance to Canadian critical care transport organizations on the development of OHT protocols.

**Methods:** The study period was July 2021 to June 2022. We used a modified RAND Delphi process to achieve consensus on statements created by the study team guiding various aspects of OHT in the context of critical care transport. Purposive sampling ensured representative distribution of participants in regard to geography and relevant clinical specialties. We conducted 2 written survey Delphi rounds, followed by a virtual panel discussion (round 3). Consensus was defined as a median score of at least 6 on a Likert scale ranging from 1 (“Definitely should not include”) to 7 (“Definitely should include”). Statements that did not achieve consensus in the first 2 rounds were discussed and voted on during the panel discussion.

**Results:** Seventeen subject experts participated in the study, all of whom completed the 3 Delphi rounds. After the study process was completed, a total of 39 statements were agreed on, covering the following domains: general oversight and clinical governance, storage and transport of blood components and products, initiation of OHT, types of blood components and products, delivery and monitoring of OHT, indications for and use of hemostatic adjuncts, and resuscitation targets of OHT.

**Interpretation:** This expert consensus document provides guidance on OHT best practices. The consensus statements should support efficient and safe OHT in national and international critical care transport programs.

The transfusion of blood components such as red blood cells (RBCs) and plasma is increasingly common in prehospital and transport medicine.1–3 In addition, the potential benefits of out-of-hospital administration of whole blood or blood products such as fibrinogen and prothrombin complex concentrate in selected patients are being investigated. In this report, we use the umbrella term “out-of-hospital transfusion” (OHT) to refer to the transfusion of whole blood, blood components such as RBCs and plasma, or blood products such as fibrinogen and prothrombin complex concentrate. Although the increasing practice of OHT suggests general consensus on a likely clinical benefit, evidence regarding the effect of OHT on morbidity and mortality is limited and conflicting.2,4–6 The generalizability of the limited evidence is further complicated in that the feasibility and potential benefit of OHT are dependent on multiple regional factors such as geography, patient factors and health care configuration. For example, 2 secondary analyses of the data sets from the Prehospital Air Medical Plasma (PAMPer) and the Control of Major Bleeding After Trauma (COMBAT) clinical trials suggested that OHT was beneficial if transport times were greater than 20 minutes and that a benefit present in blunt trauma does not translate to a benefit in penetrating trauma.7,8 In addition, out-of-hospital management of acute hemorrhage extends beyond OHT and includes factors such as administration of tranexamic acid, avoidance of hypothermia and physical means of hemorrhage control where possible.9,10 Efficient and effective implementation of OHT requires a combination of medical and logistic considerations that span multiple specialties. This is particularly relevant in countries like Canada, with long transport times to tertiary care centres, and remote communities that have limited or no access to physicians or blood components and products at their local health care facilities.11

We invited an expert panel to provide expert opinions on out-of-hospital hemorrhage management and, in particular, OHT to develop national consensus recommendations to guide OHT practice and to begin to optimize the effectiveness and safety of OHT.

## Methods

We used a modified RAND Delphi process to create an expert consensus document on the development of OHT protocols by Canadian critical care transport organizations (CCTOs). The study period was July 2021 to June 2022.

### Study design

We used a modified RAND Delphi process to establish recommendations for the development of local or regional OHT protocols. The Delphi technique is deemed a relevant source of evidence in health care research and is particularly important if randomized controlled trials are unavailable to set health care policies.12 It is a systematic, interactive method that relies on a panel of experts to converge on consensus statements after a series of iterative written surveys.13 Based on the study team’s experience with a recent Delphi study on in-hospital massive hemorrhage protocols,14 we modified the original technique by adding a panel discussion to the written survey rounds. This was to allow an exchange of information and opinions between participants of different backgrounds and levels of expertise. We also chose the RAND/UCLA Appropriateness Method,13 in which the participants were encouraged to edit the list of recommendations during the written survey rounds, as well as add further recommendations or comments in free-text fields.

We did not specify the number of written survey rounds a priori. Based on previous similar research,14 we estimated that 2–4 written survey rounds would be required to achieve saturation for feedback and stagnation for consensus. The study team reviewed all feedback and progress toward consensus after the second written survey round to decide whether further written rounds would be of benefit. Given the considerable geographic distance between participants, we used an online survey tool (JotForm, [https://www.jotform.com/](https://www.jotform.com/)) for the written survey rounds of the Delphi study and an online meeting platform for the panel discussion.

### Data source

At the start of the process, the study team created a list of 41 statements relating to OHT, covering the following domains:

*   General oversight and clinical governance

*   Storage and transport of blood components and products

*   Initiation of OHT

*   Types of blood components and products

*   Delivery and monitoring of OHT

*   Indications for and use of transfusion adjuncts

*   Resuscitation targets to guide transfusion.

The lead author (J.V.-F.) drafted the initial statements and domains based on clinical experience using OHT in CCTOs in the United Kingdom and Canada, after which B.N., J.L. and S.M. each provided written comments and revisions, resulting in a second draft. The third and final draft was agreed on during a meeting of the entire study team (B.N., J.V.-F., J.L., S.M.).

### Participants

The study team created a list of subject experts for study participation from personal contacts, with the following inclusion criteria: senior clinician in a CCTO, or in-hospital trauma care with an interest in transfusion or in a transfusion service involved in OHT, and current clinical practice in Canada. In addition, potential participants on this list were given the option to nominate further experts for potential participation in the study. During this selection process of potential study participants, we use purposive sampling based on professional background, clinical specialty, and location of practice. Given the relatively small pool of eligible experts in Canada, we sought a sample size of 15–20 participants to achieve good representation. 15 Potential participants were contacted via email, with 2 further follow-up emails in 2-week intervals. The recruitment email contained a short summary of the study objective and design (Appendix 1, available at [www.cmajopen.ca/content/11/3/E546/suppl/DC1](http://www.cmajopen.ca/content/11/3/E546/suppl/DC1)), and participants completed a written consent form for participation. There was no financial remuneration. The study team did not participate in the written survey rounds; B.N. and J.V.-F. moderated the panel discussion but did not express opinions on statements discussed.

### Delphi process and statistical analysis

In each written survey round, participants were asked to score each of the recommendation statements on a Likert scale ranging from 1 (“Definitely should not include”) to 7 (“Definitely should include”). Participants were also asked to propose wording changes to existing statements, add comments or add additional statements they considered important. Participants were blinded to the other participants’ identities and responses during the written survey rounds. Once all participants had submitted their ratings and comments, the research team calculated median Likert scores for each statement and reviewed all comments. The research team was blinded to the identity of the participants during this phase of the Delphi process. The following outcomes were possible after each written survey round:

*   Median score 6–7: consensus achieved. Statement included as written, or with minor adjustments based on participants’ comments if these changes did not alter the meaning of the statement. These statements were excluded from further rounds.

*   Median score 6–7 with critical commentary: if 1 or more participants suggested relevant changes to a statement that changed some or all of the original meaning, these changes were incorporated, and the revised statement was included in the next round.

*   Median score 3–5: the research team reviewed the participants’ comments and updated the relevant statements accordingly. All statements were included in the next round.

*   Median score 1–2: unless there were participants’ comments clearly in favour of these statements, they were considered as rejected by the panel and removed from the process.

*   Merging of 1 or more existing statements: if participants’ comments suggested a substantial improvement of statements by merging them into 1 item, the resulting merged statement was then included in the next round.

*   New statements: new statements suggested by participants were added in their respective domain and included in the next round.

This process was repeated until the study team determined that there was stagnation of consensus and saturation of information from the free-text feedback. Only statements requiring further review to achieve consensus (median Likert scale score 6–7 with critical commentary or median score 3–5) were reviewed in an online meeting of participants (round 3), which allowed discussion and clarification of statements. For technical reasons, participants’ identities and responses were not blinded during the panel discussion. The meeting was recorded and transcribed by an automatic transcription service, and the recording and transcription were made available to all participants. If participants preferred to remain anonymous, they were given the option to not actively participate in the panel discussion but, rather, to review the recording and transcription and provide written feedback to the study team. All participants (including those who were unable to attend the virtual meeting) were then asked via email to review the recording or transcription and indicate whether the statements crafted during the meeting should be included in the document. Consensus in the online meeting was defined as agreement by all participants to include a given statement.

### Presentation of results

The final agreed-on statements were included in a table with domains and order of statements updated based on participants’ feedback. In addition, the study team drafted a rationale for each statement, based on current literature and participants’ comments during the Delphi rounds. All participants were given the opportunity to review the recommendation statements and the corresponding rationales in their final form before completion of the study.

### Authorship

After reviewing the participants’ contributions to the research project, the study team decided to offer coauthorship to all participants during the final Delphi round. All participants consented to authorship and reviewed the final manuscript.

### Ethics approval

Research ethics board review and approval was provided by the Research Ethics Office, Unity Health Toronto (REB 21-155).

## Results

We invited 29 subject experts, of whom 17 (7 females [41%] and 10 males [59%]) agreed to participate in the study. All participants held senior positions within their respective organizations. Table 1 provides an overview of the participants’ backgrounds.

View this table:
[Table 1:](http://www.cmajopen.ca/content/11/3/E546/T1)

Table 1: 
Characteristics of study participants

Of the 12 subject experts who did not participate, 1 declined and 11 did not respond. As part of the purposive sampling strategy, the study team attempted to recruit additional participants from provinces that were underrepresented, but these efforts were ultimately unsuccessful. Overall, the study team identified 21 subject experts, and a further 8 were nominated by potential participants.

After reviewing the results of the written survey rounds 1 and 2, the study team concluded that no further progress on consensus could be achieved through further written rounds, and we proceeded to the online panel discussion. The final modified RAND Delphi structure used in this study therefore consisted of 3 rounds: 2 written surveys of recommendation statements, followed by a panel discussion. All participants completed rounds 1 and 2 of the modified Delphi process, and 13 participants (76%) attended the virtual panel meeting (round 3). All participants who were unable or wished not to attend the virtual meeting reviewed the recording or transcription, or both, and provided further commentary if required. All 17 participants reviewed the final list of statements. Table 2 shows the progression toward consensus for all the statements.

View this table:
[Table 2:](http://www.cmajopen.ca/content/11/3/E546/T2)

Table 2: 
Statements and progress over the 3 Delphi rounds toward consensus on out-of-hospital transfusion protocols

Of the 41 initial statements, 21 were accepted with no or only minor changes after round 1, and 5 were merged with others. The remaining 15 statements were modified according to participants’ comments and included in round 2, together with 7 additional new statements suggested by participants. In round 2, a further 9 statements were accepted, and 2 statements were merged with another. No statements received median scores of 1 or 2 in either of the first 2 rounds. The remaining 11 statements were discussed in the virtual panel meeting. During the panel meeting (including feedback from participants who were unable to attend), consensus was achieved on all but 2 statements. Table 3 contains a comprehensive list of the 39 final consensus statements and their rationales, Box 1 lists the 9 quality metrics, and Table 4 shows the 2 statements for which no consensus was achieved.

View this table:
[Table 3:](http://www.cmajopen.ca/content/11/3/E546/T3)

Table 3: 
Consensus statements on the development of out-of-hospital transfusion protocols

View this table:
[Table 4:](http://www.cmajopen.ca/content/11/3/E546/T4)

Table 4: 
Statements for which consensus was not achieved

Box 1: 
### **Suggested quality metrics for quarterly review by the critical care transport organization’s medical advisory committee**

Strongly recommended

*   Number of wasted blood components and products (absolute number and proportion of total blood components and products)

*   Transfusion-related errors (i.e., ABO/Rh incompatibility, compromised blood products)

*   Independent double checks of blood components and products

*   Proportion of patients receiving OHT who met protocol indications

*   Proportion of blood components and products successfully traced to final disposition (i.e., transfused, returned to transfusion services, wasted)

Recommended

*   Proportion of patients with OHT where receiving facilities were notified of need for further in-hospital transfusion, before arrival (pre-alert).

*   Proportion of patients who received tranexamic acid within 1 h of first contact with CCTO (if within 3 h of injury or acute postpartum hemorrhage)

*   Proportion of patients who had temperature of > 35°C by time of arrival at receiving hospital

*   Proportion of patients of child-bearing potential who received O Rh(D)-negative RBCs


*   Note: CCTO = critical care transport organization, OHT = out-of-hospital transfusion, RBC = red blood cell.

## Interpretation

Through a modified RAND Delphi process, we developed 39 expert consensus statements and 9 quality metrics on the transfusion of blood components and products in the prehospital and retrieval setting. This guidance document specifically addresses OHT and the CCTOs responsible for implementing and assuring the quality of OHT. Although some of the guidance in this document is specific to the Canadian setting, to the best of our knowledge, this is one of the very few documents providing guidance on OHT internationally.66 We hope it will prove useful to CCTOs in Canada and other countries around the world. The consensus statements cover various aspects of OHT, from logistics to clinical aspects and quality-assurance measures. As such, we consider the multidisciplinary makeup of the expert panel participating in the study to be an important strength of this research.

The 2 domains for which gaining consensus was more challenging were domains 3 (initiation of OHT) and 4 (types of blood components or products). This slower, and, in the case of 2 statements, failed progress toward consensus in these domains likely reflects the lack of clear evidence and considerable variation in practice in these areas.67 From our experience during this modified RAND Delphi process, we stress the benefit of an exchange of information among the subject experts, particularly between patient-facing clinicians and transfusion specialists, as well as the importance of striking a balance between specific and flexible guidance statements.

The importance of dialogue among subject experts is reflected in several statements that found consensus only after the panel discussion. In particular, statements in domain 4 did not achieve consensus (or, in 1 case, rejection) until round 3. Transfusion medicine experts were able to outline the current estimates of the risk of Rh(D) sensitization, which was considerably lower than many patient-facing clinicians had assumed.44 On the other hand, logistical considerations, the higher proportion of patients of child-bearing potential receiving OHT in some participants’ CCTOs, and the higher risk of errors in the critical care transport setting compared to in-hospital practice resulted in agreement to primarily recommend O Rh(D)-negative RBCs for CCTOs. Other important discussion points during the panel meeting were the limited availability of plasma49 — which contrasted with a desire by many patient-facing clinicians to stock blood components and products that could provide clotting factors and volume7 — and the consideration of alternatives to plasma, such as prothrombin complex concentrate and fibrinogen.14

Statement 3.1, regarding the indication to commence OHT, can be seen as an example of the panel’s attempt to balance specific guidance with flexibility. Although there are multiple scores and algorithms to predict the requirement for massive transfusion for patients with trauma in the emergency department, none of the current methods to decide on which patients benefit from early transfusion in trauma achieve particularly high specificity or sensitivity.38 In addition, most of these scores have not been validated in the prehospital setting or in nontraumatic causes of major hemorrhage. The authors of a recent systematic review on the topic concluded that the process to trigger major hemorrhage protocols should be “individualized to hospital resources and skill set to aid clinical judgment.”38 This conclusion holds particular truth in the context of OHT in the setting of the unique geographic challenges faced by CCTOs in Canada. The patient population requiring OHT might be as diverse as a patient with trauma transported via a 30-minute flight from the scene of an accident to the nearest trauma centre, a patient with a perioperative major hemorrhage in a smaller hospital requiring a 90-minute interfacility transfer to the nearest tertiary care centre, or a patient with postpartum hemorrhage in a remote nursing station with no access to blood products or laboratory testing, and transport time exceeding 2 hours.11,30 We believe that this expert consensus document can help to overcome such challenges through a nationwide approach to OHT protocols that provides specific guidance while taking into account the variability in geography, patient factors, in-hospital and prehospital blood product availability, and other available resources.

Regarding the statements of domain 4 (types of blood components and products), currently there is a lack of solid evidence to support strong recommendations. However, research in this field is developing at a steady pace.68–70 Although we attempted to incorporate a level of flexibility to accommodate this limitation, this guidance document will need to be reviewed and updated in the future, in keeping with statement 1.5. For example, the Prehospital Lyophilized Plasma (PREHOP-PLYO) trial,68 comparing OHT of lyophilized plasma to normal saline in patients with trauma, was published shortly after we completed our Delphi rounds. However, given the small sample (150 patients) and the current unavailability of lyophilized plasma in Canada, the results of that trial have no immediate impact on this guidance document. Appendix 2 (available at [www.cmajopen.ca/content/11/3/E546/suppl/DC1](http://www.cmajopen.ca/content/11/3/E546/suppl/DC1)) provides an overview of ongoing trials that will provide relevant results over the coming years.

Importantly, we consider this document a starting point rather than an end product in the process of ensuring consistent and equitable access to blood components and products for all patients, irrespective of geographic location. Although outside the scope of this project, we have created a national collaboration and OHT working group with all Canadian CCTOs to assure that processes are aligned as much as possible across the Canadian provinces, that emerging evidence and new technology are reviewed in a timely and efficient manner, and that quality-improvement measures are shared across organizations. This collaboration will also ideally include a pan-Canadian OHT registry with consistent data entry from all participating CCTOs for quality assurance and future research projects. This registry will allow us to measure adherence to these recommendations by Canadian CCTOs over the coming years.

### Limitations

Our modified RAND Delphi study achieved representation from major relevant clinical specialties and a wide geographic distribution. However, we were not able to recruit clinicians from every Canadian province, and there was a lack of representation from obstetricians and patient representatives. As with any self-selecting group of experts, there is the risk of recruiting only participants with similar opinions. Based on participants’ comments during the survey rounds and panel discussion, the study team was reassured that a wide range of opinion was captured during the study process. Although direct participation of patient representatives would have been challenging given the very specific focus of the study, we could have involved patient and public representatives in the planning stages of the research. Finally, no pediatric specialists participated in this research, and we did not provide any specific guidance on the pediatric population. Although many of the principles in the document can be applied to pediatric patients, we recommend involving local pediatric specialists when creating OHT guidelines for this population.

### Conclusion

This nationwide consensus document covers a wide range of important domains in the development of OHT protocols. It should support CCTOs in establishing and standardizing OHT, to ensure efficient and equitable use of this valuable resource.

## Acknowledgements

The authors thank Melissa McGowan, Emma O’Neil and Richard Wu for their administrative support during the course of this research.

## Footnotes

*   **Competing interests:** Brodie Nolan reports research funding from Canadian Blood Services and Physicians’ Services Incorporated Foundation. Andrew Shih reports payments for consulting on educational materials in relation to bleeding management from Octapharma Canada and payments for advisory board participation in relation to clotting factor concentrates from CSL Behring. He has received speaker honoraria from Octapharma Canada and CSL Behring. Octapharma Canada reimbursed travel expenses for attending a meeting for the FARES-II trial comparing clotting factor concentrates to plasma in cardiac surgery. He is vice-chair of the National Advisory Committee on Blood and Blood Products. No other competing interests were declared.

*   This article has been peer reviewed.

*   **Contributors:** Johannes von Vopelius-Feldt, Joel Lockwood, Sameer Mal and Brodie Nolan contributed to the study conception and design, and analyzed the data. Johannes von Vopelius-Feldt and Brodie Nolan drafted the manuscript, with contribution from Adam Greene. Andrew Beckett, Jeannie Callum, Adam Greene, Jeremy Grushka, Aditi Khandelwal, Yulia Lin, Susan Nahirniak, Katerina Pavenski, Michael Peddle, Oksana Prokopchuk-Gauk, Julian Regehr, Jo Schmid, Andrew Shih, Justin Smith, Jan Trojanowski, Erik Vu and Markus Ziesmann contributed to data collection and interpretation. All of the authors revised the manuscript critically for important intellectual content, approved the final version to be published and agreed to be accountable for all aspects of the work.

*   **Funding:** Brodie Nolan received funding for this study from the St. Michael’s Hospital Medical Services Association Innovation Fund (no. SMH-22-013).

*   **Data sharing:** Anonymized data can be shared on reasonable request by contacting the corresponding author.

*   **Supplemental information:** For reviewer comments and the original submission of this manuscript, please see [www.cmajopen.ca/content/11/3/E546/suppl/DC1](http://www.cmajopen.ca/content/11/3/E546/suppl/DC1).

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY-NC-ND 4.0) licence, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is noncommercial (i.e., research or educational use), and no modifications or adaptations are made. See: [https://creativecommons.org/licenses/by-nc-nd/4.0/](https://creativecommons.org/licenses/by-nc-nd/4.0/)

## References

1.  Rehn M, Weaver A, Brohi K, et al. (2019) Effect of prehospital red blood cell transfusion on mortality and time of death in civilian trauma patients. Shock 51:284–8.
    
    [PubMed](http://www.cmajopen.ca/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fcmajo%2F11%2F3%2FE546.atom) 

2.  van Turenhout EC, Bossers SM, Loer SA, et al. (2020) Pre-hospital transfusion of red blood cells. Part 2: A systematic review of treatment effects on outcomes. Transfus Med 30:106–33.
    
    

3.  Shand S, Curtis K, Dinh M, et al. (2019) What is the impact of prehospital blood product administration for patients with catastrophic haemorrhage: an integrative review. Injury 50:226–34.
    
    

4.  Crombie N, Doughty HA, Bishop JRB, et al., RePHILL collaborative group (2022) Resuscitation with blood products in patients with trauma-related haemorrhagic shock receiving prehospital care (RePHILL): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet Haematol 9:e250–61.
    
    [CrossRef](http://www.cmajopen.ca/lookup/external-ref?access_num=10.1016/S2352-3026(22)00040-0&link_type=DOI) 
    
    [PubMed](http://www.cmajopen.ca/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fcmajo%2F11%2F3%2FE546.atom) 

5.  Sperry JL, Guyette FX, Brown JB, et al., PAMPer Study Group (2018) Prehospital plasma during air medical transport in trauma patients at risk for hemorrhagic shock. N Engl J Med 379:315–26.
    
    [PubMed](http://www.cmajopen.ca/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fcmajo%2F11%2F3%2FE546.atom) 

6.  Moore HB, Moore EE, Chapman MP, et al. (2018) Plasma-first resuscitation to treat haemorrhagic shock during emergency ground transportation in an urban area: a randomised trial. Lancet 392:283–91.
    
    [PubMed](http://www.cmajopen.ca/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fcmajo%2F11%2F3%2FE546.atom) 

7.  Pusateri AE, Moore EE, Moore HB, et al. (2020) Association of prehospital plasma transfusion with survival in trauma patients with hemorrhagic shock when transport times are longer than 20 minutes: a post hoc analysis of the PAMPer and COMBAT clinical trials. JAMA Surg 155:e195085.
    
    

8.  Reitz KM, Moore HB, Guyette FX, et al. (2020) Prehospital plasma in injured patients is associated with survival principally in blunt injury: results from two randomized prehospital plasma trials. J Trauma Acute Care Surg 88:33–41.
    
    

9.  Duchesne J, Taghavi S, Houghton A, et al., Damage Control Resuscitation Committee (2021) Prehospital mortality due to hemorrhagic shock remains high and unchanged: a summary of current civilian EMS practices and new military changes. Shock 56:3–8.
    
    

10. Jamal L, Saini A, Quencer K, et al. (2021) Emerging approaches to pre-hospital hemorrhage control: a narrative review. Ann Transl Med 9:1192.
    
    

11. Nolan B, Ackery A, Mamakwa S, et al. (2018) Care of the injured patients at nursing stations and during air medical transport. Air Med J 37:161–4.
    
    

12. Jünger S, Payne SA, Brine J, et al. (2017) Guidance on Conducting and Reporting DElphi Studies (CREDES) in palliative care: recommendations based on a methodological systematic review. Palliat Med 31:684–706.
    
    [CrossRef](http://www.cmajopen.ca/lookup/external-ref?access_num=10.1177/0269216317690685&link_type=DOI) 
    
    [PubMed](http://www.cmajopen.ca/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fcmajo%2F11%2F3%2FE546.atom) 

13. Boulkedid R, Abdoul H, Loustau M, et al. (2011) Using and reporting the Delphi method for selecting healthcare quality indicators: a systematic review. PLoS One 6:e20476.
    
    [CrossRef](http://www.cmajopen.ca/lookup/external-ref?access_num=10.1371/journal.pone.0020476&link_type=DOI) 
    
    [PubMed](http://www.cmajopen.ca/lookup/external-ref?access_num=21694759&link_type=MED&atom=%2Fcmajo%2F11%2F3%2FE546.atom) 

14. Callum JL, Yeh CH, Petrosoniak A, et al. (2019) A regional massive hemorrhage protocol developed through a modified Delphi technique. CMAJ Open 7:E546–61.
    
    [Abstract/FREE Full Text](http://www.cmajopen.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NToiY21ham8iO3M6NToicmVzaWQiO3M6ODoiNy8zL0U1NDYiO3M6NDoiYXRvbSI7czoyMToiL2NtYWpvLzExLzMvRTU0Ni5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

15. Akins RB, Tolson H, Cole BR (2005) Stability of response characteristics of a Delphi panel: application of bootstrap data expansion. BMC Med Res Methodol 5:37.
    
    [CrossRef](http://www.cmajopen.ca/lookup/external-ref?access_num=10.1186/1471-2288-5-37&link_type=DOI) 
    
    [PubMed](http://www.cmajopen.ca/lookup/external-ref?access_num=16321161&link_type=MED&atom=%2Fcmajo%2F11%2F3%2FE546.atom) 

16. 1.  Low A, 
    2.  Hulme J
    
    , eds (2014) ABC of transfer and retrieval medicine (John Wiley and Sons, Oxford (UK)), pp 103–25.
    
    

17. Rouse C, Hayre J, French J, et al. (2018) A traumatic tale of two cities: Does EMS level of care and transportation model affect survival in patients with trauma at level 1 trauma centres in two neighbouring Canadian provinces? Emerg Med J 35:83–8.
    
    [Abstract/FREE Full Text](http://www.cmajopen.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NzoiZW1lcm1lZCI7czo1OiJyZXNpZCI7czo3OiIzNS8yLzgzIjtzOjQ6ImF0b20iO3M6MjE6Ii9jbWFqby8xMS8zL0U1NDYuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

18. Krook C, O’Dochartaigh D, Martin D, et al. (2019) Blood on board: the development of a prehospital blood transfusion program in a Canadian helicopter emergency medical service. CJEM 21:365–73.
    
    

19. Sung CW, Sun JT, Huang EPC, et al., PATOS Clinical Research Network (2022) Association between prehospital fluid resuscitation with crystalloids and outcome of trauma patients in Asia by a cross-national multicenter cohort study. Sci Rep 12:4100.
    
    

20. Martinaud C, Tiberghien P, Bégué S, et al. (2019) Rational and design of the T-STORHM Study: a prospective randomized trial comparing fresh whole blood to blood components for acutely bleeding trauma patients. Transfus Clin Biol 26:198–201.
    
    

21. Bawazeer M, Ahmed N, Izadi H, et al. (2015) Compliance with a massive transfusion protocol (MTP) impacts patient outcome. Injury 46:21–8.
    
    [CrossRef](http://www.cmajopen.ca/lookup/external-ref?access_num=10.1016/j.injury.2014.09.020&link_type=DOI) 
    
    [PubMed](http://www.cmajopen.ca/lookup/external-ref?access_num=25452004&link_type=MED&atom=%2Fcmajo%2F11%2F3%2FE546.atom) 

22. Cotton BA, Gunter OL, Isbell J, et al. (2008) Damage control hematology: the impact of a trauma exsanguination protocol on survival and blood product utilization. J Trauma 64:1177–82, discussion 1182–3.
    
    [CrossRef](http://www.cmajopen.ca/lookup/external-ref?access_num=10.1097/TA.0b013e31816c5c80&link_type=DOI) 
    
    [PubMed](http://www.cmajopen.ca/lookup/external-ref?access_num=18469638&link_type=MED&atom=%2Fcmajo%2F11%2F3%2FE546.atom) 
    
    [Web of Science](http://www.cmajopen.ca/lookup/external-ref?access_num=000255915400006&link_type=ISI) 

23. (2013) Pre-hospital Care Standard Operating Procedure: pre-hospital blood transfusion (London’s Air Ambulance, London (UK)) Available: [https://cdn-links.lww.com/permalink/sla/a/sla\_2015\_03\_13\_torrance\_1301890\_sdc1.pdf](https://cdn-links.lww.com/permalink/sla/a/sla\_2015\_03\_13_torrance_1301890_sdc1.pdf). accessed 2022 June 26.
    
    

24. (2018) Qmentum Standards Transfusion Services. Version 12 (Accreditation Canada, Ottawa) Available: [https://store.accreditation.ca/products/transfusion-services#:~:text=Accreditation%20Canada%27s%20Transfusion%20Services%20Standards%20are%20based%20on%20CSA%20Standards,the%20demand%20for%20transfusion%20services](https://store.accreditation.ca/products/transfusion-services#:~:text=Accreditation%20Canada%27s%20Transfusion%20Services%20Standards%20are%20based%20on%20CSA%20Standards,the%20demand%20for%20transfusion%20services). accessed 2022 Feb. 15.
    
    

25. Lee TC, Murray J, McDonald EG (2019) An online educational module on transfusion safety and appropriateness for resident physicians: a controlled before–after quality-improvement study. CMAJ Open 7:E492–6.
    
    [Abstract/FREE Full Text](http://www.cmajopen.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NToiY21ham8iO3M6NToicmVzaWQiO3M6ODoiNy8zL0U0OTIiO3M6NDoiYXRvbSI7czoyMToiL2NtYWpvLzExLzMvRTU0Ni5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=) 

26. Bartlett G (2019) Reporting adverse transfusion events. NLBCP-037. St. John’s: Provincial Blood Coordinating Program (Department of Health and Community Services, Government of Newfoundland and Labrador), Available: [https://www.gov.nl.ca/hcs/files/bloodservices-pdf-reporting-adverse-events.pdf](https://www.gov.nl.ca/hcs/files/bloodservices-pdf-reporting-adverse-events.pdf). accessed 2022 Feb. 15.
    
    

27. Flott K, Nelson D, Moorcroft T, et al. (2018) Enhancing safety culture through improved incident reporting: a case study in translational research. Health Aff (Millwood) 37:1797–804.
    
    

28. Nel TJ (2008) Clinical guidelines, audits and hemovigilance in managing blood transfusion needs. Transfus Altern Transfus Med 10:61–9.
    
    [CrossRef](http://www.cmajopen.ca/lookup/external-ref?access_num=10.1111/j.1778-428X.2008.00104.x&link_type=DOI) 

29. Bartlett G (2019) Consent or refusal to administration of blood components and blood products. NLBCP-023. St. John’s: Provincial Blood Coordinating Program (Department of Health and Community Services, Government of Newfoundland and Labrador), Available: [https://www.gov.nl.ca/hcs/files/bloodservices-pdf-informed-consent-blood-comp.pdf](https://www.gov.nl.ca/hcs/files/bloodservices-pdf-informed-consent-blood-comp.pdf). accessed 2022 Feb. 15.
    
    

30. MacDonald RD, Ramjaun A (2020) Blood product transfusion during air medical transport: a needs assessment. CJEM 22:S67–73.
    
    

31. Jorgenson T, Golbaba B, Guinn N, et al. (2017) When blood is not an option: the case for a standardized blood transfusion consent form. ASA Monitor 81:48–50.
    
    

32. (2014) Guidance document: blood regulations (Health Canada, Ottawa) modified 2022 Nov. 7. Available: [https://www.canada.ca/en/health-canada/services/drugs-health-products/biologics-radiopharmaceuticals-genetic-therapies/applications-submissions/guidance-documents/blood-regulations/guidance-document-blood-regulations.html](https://www.canada.ca/en/health-canada/services/drugs-health-products/biologics-radiopharmaceuticals-genetic-therapies/applications-submissions/guidance-documents/blood-regulations/guidance-document-blood-regulations.html). accessed 2022 Feb. 15.
    
    

33. (2020) CAN/CSA-Z902:20: blood and blood components (Canadian Standards Association, Toronto), 4th ed, pp 1–18.
    
    

34. Pommerening MJ, Goodman MD, Holcomb JB, et al., MPH on behalf of the PROMMTT Study Group (2015) Clinical gestalt and the prediction of massive transfusion after trauma. Injury 46:807–13.
    
    

35. Schroll R, Swift D, Tatum D, et al. (2018) Accuracy of shock index versus ABC score to predict need for massive transfusion in trauma patients. Injury 49:15–9.
    
    

36. Trudeau J, Dawe P, Shih A (2021) Clinical guide to transfusion, Chapter 11: Massive hemorrhage and emergency transfusion (Canadian Blood Services, Ottawa) Available: [https://professionaleducation.blood.ca/en/print/pdf/node/172](https://professionaleducation.blood.ca/en/print/pdf/node/172). accessed 2022 June 26.
    
    

37. Sohn CH, Kim YJ, Seo DW, et al. (2018) Blood lactate concentration and shock index associated with massive transfusion in emergency department patients with primary postpartum haemorrhage. Br J Anaesth 121:378–83.
    
    

38. Shih AW, Al Khan S, Wang AYH, et al. (2019) Systematic reviews of scores and predictors to trigger activation of massive transfusion protocols. J Trauma Acute Care Surg 87:717–29.
    
    

39. Meyer DE, Vincent LE, Fox EE, et al. (2017) Every minute counts: time to delivery of initial massive transfusion cooler and its impact on mortality. J Trauma Acute Care Surg 83:19–24.
    
    [PubMed](http://www.cmajopen.ca/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fcmajo%2F11%2F3%2FE546.atom) 

40. Prokopchuk-Gauk O, Petraszko T, Nahirniak S, et al. (2021) Blood shortages planning in Canada: the National Emergency Blood Management Committee experience during the first 6 months of the COVID-19 pandemic. Transfusion 61:3258–66.
    
    

41. Jackson BP, Sperry JL, Yazer MH (2021) Prehospital plasma transfusion: What does the literature show? Transfus Med Hemother 48:358–65.
    
    

42. Yazer MH (2006) The blood bank “black box” debunked: pretransfusion testing explained. CMAJ 174:29–32.
    
    [FREE Full Text](http://www.cmajopen.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiRlVMTCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiY21haiI7czo1OiJyZXNpZCI7czo4OiIxNzQvMS8yOSI7czo0OiJhdG9tIjtzOjIxOiIvY21ham8vMTEvMy9FNTQ2LmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

43. Greene A, Vu EN, Archer T, et al. (2021) A service evaluation of prehospital blood transfusion by critical care paramedics in British Columbia, Canada. Air Med J 40:441–5.
    
    

44. Frohn C, Dümbgen L, Brand JM, et al. (2003) Probability of anti-D development in D–patients receiving D+ RBCs. Transfusion 43:893–8.
    
    

45. Meyer E, Uhl L (2015) A case for stocking O D+ red blood cells in emergency room trauma bays. Transfusion 55:791–5.
    
    

46. Yazer MH, Spinella PC, Doyle L, et al., Biomedical Excellence for Safer Transfusion Collaborative (2020) Transfusion of uncrossmatched group O erythrocyte-containing products does not interfere with most ABO typings. Anesthesiology 132:525–34.
    
    

47. (2022) Utilization and inventory management of group O RHD-negative red cells (National Advisory Committee on Blood and Blood Products), Available: [https://nacblood.ca/sites/default/files/2022-05/Utilization%20and%20Inventory%20Management%20of%20Group%20O%20RhD%20Negative%20Red%20Blood%20Cells.pdf](https://nacblood.ca/sites/default/files/2022-05/Utilization%20and%20Inventory%20Management%20of%20Group%20O%20RhD%20Negative%20Red%20Blood%20Cells.pdf). accessed 2022 Feb. 15.
    
    

48. Michalsen KS, Rognås L, Vandborg M, et al. (2021) Prehospital transfusion of red blood cells and plasma by an urban ground-based critical care team. Prehosp Disaster Med 36:170–4.
    
    

49. (2020) Our commitment to increasing plasma sufficiency in Canada (Canadian Blood Services, Ottawa) Available: [https://blood.ca/en/about-us/media/plasma/plasma-sufficiency](https://blood.ca/en/about-us/media/plasma/plasma-sufficiency). accessed 2022 June 26.
    
    

50. Chen C, Kan T, Li S, et al. (2016) Use and implementation of standard operating procedures and checklists in prehospital emergency medicine: a literature review. Am J Emerg Med 34:2432–9.
    
    [PubMed](http://www.cmajopen.ca/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fcmajo%2F11%2F3%2FE546.atom) 

51. Rösli D, Schnüriger B, Candinas D, et al. (2020) The impact of accidental hypothermia on mortality in trauma patients overall and patients with traumatic brain injury specifically: a systematic review and meta-analysis. World J Surg 44:4106–17.
    
    

52. Perlman R, Callum J, Laflamme C, et al. (2016) A recommended early goal-directed management guideline for the prevention of hypothermia-related transfusion, morbidity, and mortality in severely injured trauma patients. Crit Care 20:107.
    
    

53. (2016) Critical Care Transport Standards Version 1.0 (Association of Critical Care Transport, Platte City (MO)) Available: [https://nasemso.org/wp-content/uploads/ACCT-Standards-Version1-Oct2016.pdf](https://nasemso.org/wp-content/uploads/ACCT-Standards-Version1-Oct2016.pdf). accessed 2022 Feb. 15.
    
    

54. Callum J, Pinkerton P, Lima A, et al. (2021) Clinical guide to transfusion, Adverse reactions (Canadian Blood Services, Ottawa) Available: [https://anesthesiology.queensu.ca/sites/anesthesiology/files/inline-files/CBS\_Clinical\_Guide\_to\_Transfusion.pdf](https://anesthesiology.queensu.ca/sites/anesthesiology/files/inline-files/CBS\_Clinical_Guide_to_Transfusion.pdf). accessed 2023 Jan. 6.
    
    

55. Roberts I, Shakur H, Coats T, et al. (2013) The CRASH-2 trial: a randomised controlled trial and economic evaluation of the effects of tranexamic acid on death, vascular occlusive events and transfusion requirement in bleeding trauma patients. Health Technol Assess 17:1–79.
    
    [CrossRef](http://www.cmajopen.ca/lookup/external-ref?access_num=10.3310/hta17370&link_type=DOI) 
    
    [PubMed](http://www.cmajopen.ca/lookup/external-ref?access_num=23972041&link_type=MED&atom=%2Fcmajo%2F11%2F3%2FE546.atom) 
    
    [Web of Science](http://www.cmajopen.ca/lookup/external-ref?access_num=000317180500001&link_type=ISI) 

56. Gayet-Ageron A, Prieto-Merino D, Ker K, et al., Antifibrinolytic Trials Collaboration (2018) Effect of treatment delay on the effectiveness and safety of antifibrinolytics in acute severe haemorrhage: a meta-analysis of individual patient-level data from 40 138 bleeding patients. Lancet 391:125–32.
    
    [CrossRef](http://www.cmajopen.ca/lookup/external-ref?access_num=10.1016/S0140-6736(17)32455-8&link_type=DOI) 
    
    [PubMed](http://www.cmajopen.ca/lookup/external-ref?access_num=29126600&link_type=MED&atom=%2Fcmajo%2F11%2F3%2FE546.atom) 

57. Rowell SE, Meier EN, McKnight B, et al. (2020) Effect of out-of-hospital tranexamic acid vs placebo on 6-month functional neurologic outcomes in patients with moderate or severe traumatic brain injury. JAMA 324:961–74.
    
    [CrossRef](http://www.cmajopen.ca/lookup/external-ref?access_num=10.1001/jama.2020.8958&link_type=DOI) 
    
    [PubMed](http://www.cmajopen.ca/lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fcmajo%2F11%2F3%2FE546.atom) 

58. Guyette FX, Brown JB, Zenati MS, et al., STAAMP Study Group (2020) Tranexamic acid during prehospital transport in patients at risk for hemorrhage after injury: a double-blind, placebo-controlled, randomized clinical trial. JAMA Surg 156:11–20.
    
    

59. WOMAN Trial Collaborators (2017) Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial [erratum in *Lancet* 2017;389:2104]. Lancet 389:2105–16.
    
    [CrossRef](http://www.cmajopen.ca/lookup/external-ref?access_num=10.1016/S0140-6736(17)30638-4&link_type=DOI) 
    
    [PubMed](http://www.cmajopen.ca/lookup/external-ref?access_num=28456509&link_type=MED&atom=%2Fcmajo%2F11%2F3%2FE546.atom) 

60. Wray JP, Bridwell RE, Schauer SG, et al. (2021) The diamond of death: hypocalcemia in trauma and resuscitation. Am J Emerg Med 41:104–9.
    
    

61. (2022) Recommendations for the use of prothrombin complex concentrates in Canada (National Advisory Committee on Blood and Blood Products), Available: [https://nacblood.ca/sites/default/files/2022-04/PCC-Recommendations%20\_Revision%20Feb%202022%20_Posted%20April%202022.pdf](https://nacblood.ca/sites/default/files/2022-04/PCC-Recommendations%20_Revision%20Feb%202022%20_Posted%20April%202022.pdf). accessed 2022 Feb. 15.
    
    

62. Tran A, Yates J, Lau A, et al. (2018) Permissive hypotension versus conventional resuscitation strategies in adult trauma patients with hemorrhagic shock: asystematic review and meta-analysis of randomized controlled trials. J Trauma Acute Care Surg 84:802–8.
    
    

63. Kudo D, Yoshida Y, Kushimoto S (2017) Permissive hypotension/hypotensive resuscitation and restricted/controlled resuscitation in patients with severe trauma. J Intensive Care 5:11.
    
    

64. Carney N, Totten AM, O’Reilly C, et al. (2017) Guidelines for the management of severe traumatic brain injury, fourth edition. Neurosurgery 80:6–15.
    
    [CrossRef](http://www.cmajopen.ca/lookup/external-ref?access_num=10.1227/NEU.0000000000001432&link_type=DOI) 
    
    [PubMed](http://www.cmajopen.ca/lookup/external-ref?access_num=27654000&link_type=MED&atom=%2Fcmajo%2F11%2F3%2FE546.atom) 

65. Holcomb JB, Tilley BC, Baraniuk S, et al., PROPPR Study Group (2015) Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial. JAMA 313:471–82.
    
    [CrossRef](http://www.cmajopen.ca/lookup/external-ref?access_num=10.1001/jama.2015.12&link_type=DOI) 
    
    [PubMed](http://www.cmajopen.ca/lookup/external-ref?access_num=25647203&link_type=MED&atom=%2Fcmajo%2F11%2F3%2FE546.atom) 

66. Yazer MH, Spinella PC, Bank EA, et al. (2022) THOR-AABB working party recommendations for a prehospital blood product transfusion program. Prehosp Emerg Care 26:863–75.
    
    

67. Thies KC, Truhlár A, Keene D, et al. (2020) Pre-hospital blood transfusion: an ESA survey of European practice. Scand J Trauma Resusc Emerg Med 28:79.
    
    

68. Jost D, Lemoine S, Lemoine F, et al., Prehospital Lyophilized Plasma (PREHO-PLYO) Study Group (2022) Prehospital lyophilized plasma transfusion for trauma-induced coagulopathy in patients at risk for hemorrhagic shock. JAMA Netw Open 5:e2223619.
    
    

69. (2021) ClinicalTrials.gov: [NCT05081063](http://www.cmajopen.ca/lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT05081063&atom=%2Fcmajo%2F11%2F3%2FE546.atom), Low-titer O positive whole blood versus component therapy for emergent transfusion in trauma patients. updated 2022 Aug. 12. Available: [https://clinicaltrials.gov/ct2/show/NCT05081063](https://clinicaltrials.gov/ct2/show/NCT05081063). accessed 2022 Feb. 15.
    
    

70. (2020) ClinicalTrial.gov: [NCT04684719](http://www.cmajopen.ca/lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04684719&atom=%2Fcmajo%2F11%2F3%2FE546.atom), Type O whole blood and assessment of age during prehospital resuscitation trial (TOWARA TRIAL). updated 2022 Sept. 28. Available: [https://clinicaltrials.gov/ct2/show/NCT04684719](https://clinicaltrials.gov/ct2/show/NCT04684719). accessed 2022 Feb. 15.
    
    

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