Prehospital Blood Product Resuscitation for Trauma: A Systematic Review

Iain M Smith, Robert H James, Janine Dretzke, Mark J Midwinter, Iain M Smith, Robert H James, Janine Dretzke, Mark J Midwinter

Abstract

Introduction: Administration of high ratios of plasma to packed red blood cells is a routine practice for in-hospital trauma resuscitation. Military and civilian emergency teams are increasingly carrying prehospital blood products (PHBP) for trauma resuscitation. This study systematically reviewed the clinical literature to determine the extent to which the available evidence supports this practice.

Methods: Bibliographic databases and other sources were searched to July 2015 using keywords and index terms related to the intervention, setting, and condition. Standard systematic review methodology aimed at minimizing bias was used for study selection, data extraction, and quality assessment (protocol registration

Prospero: CRD42014013794). Synthesis was mainly narrative with random effects model meta-analysis limited to mortality outcomes.

Results: No prospective comparative or randomized studies were identified. Sixteen case series and 11 comparative studies were included in the review. Seven studies included mixed populations of trauma and non-trauma patients. Twenty-five of 27 studies provided only very low quality evidence. No association between PHBP and survival was found (OR for mortality: 1.29, 95% CI: 0.84-1.96, P = 0.24). A single study showed improved survival in the first 24 h. No consistent physiological or biochemical benefit was identified, nor was there evidence of reduced in-hospital transfusion requirements. Transfusion reactions were rare, suggesting the short-term safety of PHBP administration.

Conclusions: While PHBP resuscitation appears logical, the clinical literature is limited, provides only poor quality evidence, and does not demonstrate improved outcomes. No conclusions as to efficacy can be drawn. The results of randomized controlled trials are awaited.

Conflict of interest statement

1“Military”: casualties of armed conflict.

FDP indicates Freeze Dried Plasma; mISS and mNISS, ISS and NISS derived from the military edition of the Abbreviated Injury Scale (2005).

Figures

Fig. 1
Fig. 1
PRISMA diagram for selection of included studies.
Fig. 2
Fig. 2
Mortality among PHBP recipients.
Fig. 3
Fig. 3
Meta-analysis of unadjusted risk of mortality.
Fig. 4
Fig. 4
Forest plot of adjusted mortality.
Fig. 5
Fig. 5
In-hospital transfusion requirements for (A) PRBC and (B) plasma.

References

    1. Bailey JA, Morrison JJ, Rasmussen TE. Military trauma system in Afghanistan: lessons for civil systems? Curr Opin Crit Care 2013; 19 6:569–577.
    1. Penn-Barwell JG, Roberts SA, Midwinter MJ, Bishop JR. Improved survival in UK combat casualties from Iraq and Afghanistan: 2003-2012. J Trauma Acute Care Surg 2015; 78 5:1014–1020.
    1. Dawes R, Thomas GO. Battlefield resuscitation. Curr Opin Crit Care 2009; 15 6:527–535.
    1. Bhangu A, Nepogodiev D, Doughty H, Bowley DM. Meta-analysis of plasma to red blood cell ratios and mortality in massive blood transfusions for trauma. Injury 2013; 44 12:1693–1699.
    1. Murad MH, Stubbs JR, Gandhi MJ, Wang AT, Paul A, Erwin PJ, Montori VM, Roback JD. The effect of plasma transfusion on morbidity and mortality: a systematic review and meta-analysis. Transfusion 2010; 50 6:1370–1383.
    1. Haas B, Gomez D, Steel A, Nathens A. Ratio of units of red blood cells to fresh frozen plasma for severely injured patients undergoing massive transfusion (Protocol). Cochrane Database Syst Rev (3):CD009033, 2011. Available at: Accessed August 22, 2015.
    1. Karam O, Tucci M, Combescure C, Lacroix J, Rimensberger PC: Plasma transfusion strategies for critically ill patients. Cochrane Database Syst Rev (12):CD010654, 2013. Available at: Accessed August 22, 2015.
    1. Holcomb JB, del Junco DJ, Fox EE, Wade CE, Cohen MJ, Schreiber MA, Alarcon LH, Bai Y, Brasel KJ, Bulger EM, et al. the PROMMTT Study Group. The prospective, observational, multicenter, major trauma transfusion (PROMMTT) study: comparative effectiveness of a time-varying treatment with competing risks. JAMA Surg 2013; 148 2:127–136.
    1. del Junco DJ, Holcomb JB, Fox EE, Brasel KJ, Phelan HA, Bulger EM, Schreiber MA, Muskat P, Alarcon LH, Cohen MJ, et al. the PROMMTT Study Group. Resuscitate early with plasma and platelets or balance blood products gradually: findings from the PROMMTT study. J Trauma Acute Care Surg 2013; 75 (1 Suppl 1):S24–S30.
    1. Holcomb JB, Tilley BC, Baraniuk S, Fox EE, Wade CE, Podbielski JM, del Junco DJ, Brasel KJ, Bulger EM, Callcut RA, et al. the PROPPR Study Group. 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 2015; 313 5:471–482.
    1. Kiel F. Development of a blood program in Vietnam. Mil Med 1966; 131 12:1469–1482.
    1. Dalton AM. Use of blood transfusions by helicopter emergency medical services: is it safe? Injury 1993; 24 8:509–510.
    1. Calderbank P, Woolley T, Mercer S, Schrager J, Kazel M, Bree S, Bowley DM. Doctor on board? What is the optimal skill-mix in military pre-hospital care? Emerg Med J 2011; 28 10:882–883.
    1. Barkana Y, Stein M, Maor R, Lynn M, Eldad A. Prehospital blood transfusion in prolonged evacuation. J Trauma 1999; 46 1:176–180.
    1. Malsby RF, Quesada J, Powell-Dunford N, Kinoshita R, Kurtz J, Gehlen W, Adams C, Martin D, Shackelford S. Prehospital blood product transfusion by U.S. army MEDEVAC during combat operations in Afghanistan: a process improvement initiative. Mil Med 2013; 178 7:785–791.
    1. Morrison JJ, Oh J, DuBose JJ, O’Reilly DJ, Russell RJ, Blackbourne LH, Midwinter MJ, Rasmussen TE. En-route care capability from point of injury impacts mortality after severe wartime injury. Ann Surg 2013; 257 2:330–334.
    1. Chaiwat O, Lang JD, Vavilala MS, Wang J, MacKenzie EJ, Jurkovich GJ, Rivara FP. Early packed red blood cell transfusion and acute respiratory distress syndrome after trauma. Anesthesiology 2009; 110 2:351–360.
    1. Johnson JL, Moore EE, Kashuk JL, Banerjee A, Cothren CC, Biffl WL, Sauaia A. Effect of blood products transfusion on the development of postinjury multiple organ failure. Arch Surg 2010; 145 10:973–977.
    1. Malone DL, Dunne J, Tracy JK, Putnam AT, Scalea TM, Napolitano LM. Blood transfusion, independent of shock severity, is associated with worse outcome in trauma. J Trauma 2003; 54 5:898–905.
    1. Dunne JR, Malone DL, Tracy JK, Napolitano LM. Allogenic blood transfusion in the first 24 hours after trauma is associated with increased systemic inflammatory response syndrome (SIRS) and death. Surg Infect 2004; 5 4:395–404.
    1. Robinson WP, Ahn J, Stiffler A, Rutherford EJ, Hurd H, Zarzaur BL, Baker CC, Meyer AA, Rich PB. Blood transfusion is an independent predictor of increased mortality in nonoperatively managed blunt hepatic and splenic injuries. J Trauma 2005; 58 3:437–445.
    1. Holcomb JB, Donathan DP, Cotton BA, Del Junco DJ, Brown G, Wenckstern TV, Podbielski JM, Camp EA, Hobbs R, Bai Y, et al. Prehospital transfusion of plasma and red blood cells in trauma patients. Prehosp Emerg Care 2015; 19 1:1–9.
    1. Weaver AE, Eshelby S, Norton J, Lockey DJ. The introduction of on-scene blood transfusion in a civilian physician-led pre-hospital trauma service. Scand J Trauma Resusc Emerg Med 2013; 21 suppl 1:S27.
    1. Zielinski MD, Smoot DL, Stubbs JR, Jenkins DH, Park MS, Zietlow SP. The development and feasibility of a remote damage control resuscitation prehospital plasma transfusion protocol for warfarin reversal for patients with traumatic brain injury. Transfusion 2013; 53 suppl 1:59S–64S.
    1. Sherren PB, Burns B. Prehospital blood transfusion: 5-year experience of an Australian helicopter emergency medical service. Crit Care 2013; 17:S112.
    1. Bodnar D, Rashford S, Williams S, Enraght-Moony E, Parker L, Clarke B. The feasibility of civilian prehospital trauma teams carrying and administering packed red blood cells. Emerg Med J 2014; 31 2:93–95.
    1. Chapman MP, Moore EE, Chin TL, Ghasabyan A, Chandler J, Stringham J, Gonzalez E, Moore HB, Banerjee A, Silliman CC, et al. COMBAT: initial experience with a randomized clinical trial of plasma-based resuscitation in the field for traumatic hemorrhagic shock. Shock 2015; 44 suppl 1:63–70.
    1. Wild G, Anderson D, Lund P. Round Afghanistan with a fridge. J R Army Med Corps 2013; 159 1:24–29.
    1. Dretzke J, Smith IM, James RH, Midwinter MJ. Protocol for a systematic review of the clinical effectiveness of pre-hospital blood components compared to other resuscitative fluids in patients with major traumatic haemorrhage. Syst Rev 2014; 3 1:123.
    1. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg 2010; 8 5:336–341.[Erratum appears in Int J Surg 8(8):658, 2010].
    1. Wells G, Shea B, O’Connell D, Peterson J, Welch V, Losos M, Tugwell P. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses, 2008. Available at: Accessed October 14, 2014.
    1. National Heart, Lung and Blood Institute. Quality assessment tool for Before-After (Pre-Post) studies with no control group. Bethesda, NHLBI, 2014. Available at: Accessed January 14, 2015.
    1. National Heart, Lung and Blood Institute. Quality assessment tool for case series studies. Bethesda, NHLBI, 2014. Available at: Accessed January 14, 2015.
    1. Kerwin AJ, Haut ER, Burns JB, Como JJ, Haider A, Stassen N, Dahm P. Eastern Association for the Surgery of Trauma Practice Management Guidelines Ad Hoc C. The Eastern Association of the Surgery of Trauma approach to practice management guideline development using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. J Trauma Acute Care Surg 2012; 73 (5 Suppl 4):S283–S287.
    1. Brown JB, Cohen MJ, Minei JP, Maier RV, West MA, Billiar TR, Peitzman AB, Moore EE, Cuschieri J, Sperry JL. Pretrauma center red blood cell transfusion is associated with reduced mortality and coagulopathy in severely injured patients with blunt trauma. Ann Surg 2015; 261 5:997–1005.
    1. Brown JB, Sperry JL, Fombona A, Billiar TR, Peitzman AB, Guyette FX. Pre-trauma center red blood cell transfusion is associated with improved early outcomes in air medical trauma patients. J Am Coll Surg 2015; 220 5:797–808.
    1. Kim BD, Zielinski MD, Jenkins DH, Schiller HJ, Berns KS, Zietlow SP. The effects of prehospital plasma on patients with injury. J Trauma Acute Care Surg 2012; 73 (2 Suppl 1):S49–S53.
    1. Badjie KS, Berns KS, Button LM, Stubbs JR. The impact of thawed plasma usage during emergency medical helicopter transport. Transfusion 2012; 52 suppl 3:197A–198A.
    1. Badjie KS, Berns KS, Bryant SC, Button LM, Kreuter J, Van Buskirk CM. 1:1 Fresh frozen plasma: red blood cell (FFP: RBC) ratio improves patient survival during emergency medical air helicopter transport. Transfusion 2013; 53 suppl 2:197A.
    1. O’Reilly DJ, Morrison JJ, Jansen JO, Apodaca AN, Rasmussen TE, Midwinter MJ. Prehospital blood transfusion in the en route management of severe combat trauma: a matched cohort study. J Trauma Acute Care Surg 2014; 77 (3 Suppl 2):S114–S120.
    1. O’Reilly DJ, Morrison JJ, Jansen JO, Nordmann G, Rasmussen TE, Midwinter MJ, Doughty H. Initial UK experience of prehospital blood transfusion in combat casualties. J Trauma Acute Care Surg 2014; 77 (3 Suppl 2):S66–S70.
    1. Morrison JJ, Dubose JJ, Rasmussen TE, Midwinter MJ. Military Application of Tranexamic Acid in Trauma Emergency Resuscitation (MATTERs) Study. Arch Surg 2012; 147 2:113–119.
    1. Smith IM, Beech ZKM, Lundy JB, Bowley DM. A prospective observational study of abdominal injury management in contemporary military operations: damage control laparotomy is associated with high survivability and low rates of fecal diversion. Ann Surg 2015; 261 4:765–773.
    1. Hasler RM, Nuesch E, Juni P, Bouamra O, Exadaktylos AK, Lecky F. Systolic blood pressure below 110mmHg is associated with increased mortality in blunt major trauma patients: multicentre cohort study. Resuscitation 2011; 82 9:1202–1207.
    1. Hasler RM, Nuesch E, Juni P, Bouamra O, Exadaktylos AK, Lecky F. Systolic blood pressure below 110 mmHg is associated with increased mortality in penetrating major trauma patients: multicentre cohort study. Resuscitation 2012; 83 4:476–481.
    1. Smith IM, Bishop JR, Streets CG, Woolley T, Midwinter MJ. Pre-hospital blood product resuscitation: benefits unclear. Paper presented at Military Health System Research Symposium. 2014. Fort Lauderdale, FL.
    1. Jansen JO, Morrison JJ, Midwinter MJ, Doughty H. Changes in blood transfusion practices in the UK Role 3 Medical Treatment Facility in Afghanistan, 2008-2011. Transfus Med 2014; 24 3:154–161.
    1. Sumida MP, Quinn K, Lewis PL, Jones Y, Barker DE, Ciraulo DL, Cowell V, Luk S, Murphy D, Jacobs L. Prehospital blood transfusion versus crystalloid alone in the air medical transport of trauma patients. Air Med J 2000; 19 4:140–143.
    1. Price DD, Norton RL, Zechnich AD, Eldurkar J, Chok J, Mann NC. Out-of-hospital blood administration for critically injured patients transported by helicopter. Ann Emerg Med 1999; 34 (4 Part 2):S50–S51.
    1. Bodnar D, Rashford S, Hurn C, Quinn J, Parker L, Isoardi K, Williams S. Characteristics and outcomes of patients administered blood in the prehospital environment by a road based trauma response team. Emerg Med J 2014; 31 7:583–588.
    1. Chew E, Gilbertson M, Kelsey G, Hogan C, Hammer F, Barkmeyer M, Haeusler M. An Australian experience in out-of-hospital transfusion of red cell concentrates by air ambulance personnel. Vox Sang 2013; 105 (Suppl s1):26.
    1. Prause G, Dacar D, Gimpl R, Vadon M, Lanzer G. Prehospital use of packed red cells: preparation, storage and first experience [German]. Die applikation von ery-konzentraten am notfallort - Vorbereitung, lagerung und erste erfahrungen im hubschrauberdienst. Notarzt 1999; 15 1:9–12.
    1. Sunde GA, Vikenes B, Strandenes G, Flo KC, Hervig TA, Kristoffersen EK, Heltne JK. Freeze dried plasma and fresh red blood cells for civilian prehospital hemorrhagic shock resuscitation. J Trauma Acute Care Surg 2015; 78 (6 Suppl 1):S26–S30.
    1. Powell-Dunford N, Quesada JF, Malsby RF, Chou V, Gerhardt RT, Gross KR, Shackelford SA. Risk management analysis of air ambulance blood product administration in combat operations. Aviat Space Environ Med 2014; 85 11:1130–1135.
    1. Higgins GL, 3rd, Baumann MR, Kendall KM, Watts MA, Strout TD. Red blood cell transfusion: experience in a rural aeromedical transport service. Prehosp Disaster Med 2012; 27 3:231–234.
    1. Gross K, Shackelford S, Powell-Dunford N, Orman J, Howard J, Quesada J, Bailey J. En route blood transfusion from point of injury in a theater of operations positively impacts shock index. Poster presented at Military Health System Research Symposium. 2014. Fort Lauderdale, FL.
    1. Wheeler R, von Recklinghausen FM, Brozen R. Blood administration in helicopter emergency medical services patients associated with hypothermia. Air Med J 2013; 32 1:47–51.
    1. Bates C, Hawthorn B, Iacano I. Impact of prehospital blood transfusion on serum lactate levels in the trauma patient. Air Med J 2012; 31 6:260.
    1. Berns KS, Zietlow SP. Blood usage in rotor-wing transport. Air Med J 1998; 17 3:105–108.
    1. Watts S, Nordmann G, Brohi K, Midwinter M, Woolley T, Gwyther R, Wilson C, Poon H, Kirkman E. Evaluation of prehospital blood products to attenuate acute coagulopathy of trauma in a model of severe injury and shock in anesthetized pigs. Shock 2015; 44 suppl 1:138–148.
    1. Alam HB, Bice LM, Butt MU, Cho SD, Dubick MA, Duggan M, Englehart MS, Holcomb JB, Morris MS, Prince MD, et al. Hemostatic Resuscitation Research Group. Testing of blood products in a polytrauma model: results of a multi-institutional randomized preclinical trial. J Trauma 2009; 67 4:856–864.
    1. Sondeen JL, Prince MD, Kheirabadi BS, Wade CE, Polykratis IA, de Guzman R, Dubick MA. Initial resuscitation with plasma and other blood components reduced bleeding compared to hetastarch in anesthetized swine with uncontrolled splenic hemorrhage. Transfusion 2011; 51 4:779–792.
    1. Spoerke N, Zink K, Cho SD, Differding J, Muller P, Karahan A, Sondeen J, Holcomb JB, Schreiber M. Lyophilized plasma for resuscitation in a swine model of severe injury. Arch Surg 2009; 144 9:829–834.
    1. Lefebvre C, Manheimer E, Glanville J. Chapter 6, Section 2.2.4: Searching for studies: Conference Abstracts and Proceedings. In Higgins JPT and Green S (eds): Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available at: Accessed December 21, 2015.
    1. Curry N, Hopewell S, Doree C, Hyde C, Brohi K, Stanworth S. The acute management of trauma hemorrhage: a systematic review of randomized controlled trials. Crit Care 2011; 15 2:R92.
    1. Curry N, Stanworth S, Hopewell S, Doree C, Brohi K, Hyde C. Trauma-induced coagulopathy: a review of the systematic reviews: is there sufficient evidence to guide clinical transfusion practice? Transfus Med Rev 2011; 25 3:217–231.
    1. Glassberg E, Nadler R, Gendler S, Abramovich A, Spinella PC, Gerhardt RT, Holcomb JB, Kreiss Y. Freeze-dried plasma at the point of injury: from concept to doctrine. Shock 2013; 40 6:444–450.
    1. Bickell WH, Wall MJ, Jr, Pepe PE, Martin RR, Ginger VF, Allen MK, Mattox KL. Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries. N Engl J Med 1994; 331 17:1105–1109.
    1. Haut ER, Kalish BT, Cotton BA, Efron DT, Haider AH, Stevens KA, Kieninger AN, Cornwell EE, 3rd, Chang DC. Prehospital intravenous fluid administration is associated with higher mortality in trauma patients: a National Trauma Data Bank analysis. Ann Surg 2011; 253 2:371–377.
    1. Hussmann B, Heuer M, Lefering R, Touma A, Schoeneberg C, Keitel J, Lendemans S: Prehospital volume therapy as an independent risk factor after trauma. Biomed Res Int, 2015. Article ID: 354367. Available at: Accessed May 27, 2015.
    1. Neal MD, Hoffman MK, Cuschieri J, Minei JP, Maier RV, Harbrecht BG, Billiar TR, Peitzman AB, Moore EE, Cohen MJ, et al. Crystalloid to packed red blood cell transfusion ratio in the massively transfused patient: when a little goes a long way. J Trauma Acute Care Surg 2012; 72 4:892–898.
    1. Claridge JA, Sawyer RG, Schulman AM, McLemore EC, Young JS. Blood transfusions correlate with infections in trauma patients in a dose-dependent manner. Am Surg 2002; 68 7:566–572.
    1. Moore FA, Moore EE, Sauaia A. Blood transfusion. An independent risk factor for postinjury multiple organ failure. Arch Surg 1997; 132 6:620–624.
    1. Mena-Munoz J, Srivastava U, Martin-Gill C, Suffoletto B, Guyette F. Characterization of out of hospital resuscitation utilizing blood transfusion. Circulation 2013; 128:A315.
    1. Chen J. Prehospital blood transfusions during aeromedical evacuations of trauma patients in Israel. Paper presented at Military Health System Research Symposium. 2014. Fort Lauderdale, FL.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다