Pre-hospital Administration of Blood Products (PHBP) and Tranexamic acid (TXA): Is the Jury Still Out?

Transcription

1 Pre-hospital Administration of Blood Products (PHBP) and Tranexamic acid (TXA): Is the Jury Still Out? Jessica K. Reynolds, MD Assistant Professor of Surgery University of Kentucky, Department of Trauma and Acute Care Surgery

2 Disclosures: No relevant financial disclosures

3 Outline Blood & Plasma- why and how? Tranexamic acid (TXA) Ongoing trials Final thoughts

4 Introduction There continues to be significant debate regarding the efficacy of pre-hospital blood products (PHBP), risk of blood product transfusion, as well as logistical challenges associated with storage and administration Controversy regarding how to best manage trauma patients with severe injury and hemorrhage, including which patients would benefit from TXA administration

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6 What we know about the bleeding patient Hypothermia, Coagulopathy, and Acidosis is Deadly Massive blood loss is best corrected with early blood replacement 1:1:1 resuscitation is Key, early and directed Need definitive hemorrhage control and resources beyond the field Rapid delivery to definitive care remains a crucial component in survival

7 Why plasma? Corresponding mortality rates: Low- 92.5% Medium- 78% High- 37% Conclusion: massive transfusion protocols should utilize a 1:1 ratio of plasma to RBCs for all patients who are hypocoagulable with traumatic injuries.

8 Why plasma EARLY? Holcomb et al, Jama 2013 Lower Mortality Even Lower *In the first 6 hours, patients with ratios lower than 1:2 were 3 to 4 times more likely to die than patients with ratios of 1:1 or higher (Early plasma = increased survival)

9 Plasma Types 1. Fresh whole blood (FWB)-THEORETICAL 2. Stored whole blood (SWB)-FEASIBLE 3. Fresh frozen plasma (FFP, related to FP24)-SLOW 4. Thawed plasma (thawed FFP)-IDEAL 5. Liquid plasma (LP, never frozen)-ideal* 6. Dried plasma (DP, for reconstitution)-europe/us military

10 OBJECTIVE Designed to address the effectiveness and safety of a 1:1:1 transfusion ratio compared with a 1:1:2 transfusion ratio in patients with trauma who were predicted to receive a massive transfusion CONCLUSIONS AND RELEVANCE Among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio did not result in significant differences in mortality at 24 hours or at 30 days. However, more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group, no other safety differences were identified between the 2 groups.

11 Aim: systematic review to determine the extent to which PHBP resuscitation for trauma is supported by clinical evidence. Results: No prospective comparative or randomized studies were identified. (16 case series/11 comparative studies) Seven studies included mixed populations of trauma and non-trauma patients 25 of 27 studies provided only very low quality evidence No association between PHBP and survival was found No consistent physiological or biochemical benefit was identified No evidence of reduced in-hospital transfusion requirements Transfusion reactions were rare, suggesting the short-term safety of PHBP administration

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

13 Basis: Data from large clinical trials are lacking to show either the efficacy or the risks associated with plasma transfusion in the pre-hospital setting.

14 Results: 501 patients were evaluated: 230 patients received plasma and 271 received standard-care resuscitation Mortality at 30 days was significantly lower in the plasma group (23.2% vs. 33.0%) Median prothrombin-time ratio was lower in the plasma group than in the standard-care group (1.2 vs. 1.3 P<0.001) upon arrival at the trauma center No significant differences in multi-organ failure, acute lung injury acute respiratory distress syndrome, nosocomial infections, or allergic or transfusion-related reactions Conclusions: In injured patients at risk for hemorrhagic shock, the pre-hospital administration of thawed plasma was safe and resulted in lower 30-day mortality and a lower median prothrombin-time ratio than standard-care resuscitation

15 Using the Right Products In patients requiring blood after massive shock, the use of O-negative blood is still the standard due to its universal donor properties, minimized complications and adverse side effects Although the standard in-hospital plasma product is AB titer, providing this plasma is increasingly difficult Therefore, the use of low-titer A plasma is a safe alternative to the AB plasma group for emergent need and can be utilized in the same 1:1:1 damage control resuscitation protocol

16 1536 patients 120 received incompatible transfusion JTACS July 2017 Mortality Predictors (n=1536) Odds Ratio 95% CI p-value Incompatible Type A transfusion 0.98 (0.65,1.51) 0.99 # 4 hours 1.04 (1.03, 1.05) <0.01 ISS 1.03 (1.02,1.04) <0.01 Age 1.01 (1.01,1.02) <0.01 Stevens WT et al. EAST 2017 *Transfusion of type A plasma to patients with blood groups B and AB as part of a MTP does not appear to be associated with significant increases in morbidity or mortality

17 Safety of the use of group A plasma in trauma: the STAT study 354 B and AB patients 809 A patients Comparable (age, sex, TRISS, total blood products) No difference: in-hospital mortality early mortality hospital LOS for group B and AB patients compared to group A patients Transfusion June 2017

18 Brothers in Arms, will enable air medical crews to administer pre-hospital transfusions of whole blood, proven to counter blood loss and improve survival rates when tested in battlefield situations The program is targeting male O-positive donors because men tend to have lower levels of certain types of antibodies in their blood than women, reducing the possibility of adverse reactions in patients STBTC is working to sign up a committed pool of male O-positive donors to ensure a regular supply of specially tested whole blood for medical helicopters The goal is to eventually expand the program to provide whole blood to area emergency vehicles

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20 Lancet 2010 Significant limitations: Only approximately 5% of patients had bleeding as a cause of death No data regarding injury severity of the patient cohort No data regarding shock in the patient cohort (i.e. lactate and base deficit), inability to determine if cohorts were similar Small sample size of hypotensive (SBP < 90 mm Hg) (31.5%) and tachycardic (HR>107) (48%) patients which were the target populations No data regarding fibrinolysis on admission and no coagulation testing The most common cause of death was traumatic brain injury (TBI) TXA did not reduce blood transfusions Only 50% of study cohort received blood transfusions No adverse events were regarded as serious, unexpected, or suspected to be related to the study treatment: Concern about possible inadequate reporting Effect size was small The study determined a 0.8% absolute reduction in death caused by bleeding.

21 More applicable study, military based Evaluated patients who clearly needed an anti-fibrinolytic Patients who needed at least 1 unit of blood were divided into TXA or no TXA arms NNT was 1:7 (versus 1:67 in CRASH-2) Relative reduction in mortality was 6.7 % (versus 1.5% in CRASH-2) Those who received TXA received less blood products (No difference in CRASH-2) *Rates of PE and DVT among patients who received TXA were, respectively, 9 and 12 times the rates among those who did not (CRASH-2 PE 0.7% and DVT 0.4%)

22 Many trauma systems are examining whether to implement pre-hospital tranexamic acid (TXA) protocols because: hemorrhage remains the leading cause of potentially preventable early trauma mortality early in-hospital administration of TXA within 3 hours of injury is associated with reduced mortality However, robust evidence regarding the efficacy of pre-hospital administration of the antifibrinolytic drug TXA on trauma outcomes is lacking

23 Surveys regarding TXA use in Trauma An online survey of surgeons in US civilian trauma centers of the Eastern Association for the Surgery of Trauma (EAST) reported that TXA was available at 89.1% use of TXA was extremely variable Only 38% of respondents use TXA regularly for significant traumatic hemorrhage Reasons for not routine TXA use included: uncertain clinical benefit (47.7%) unfamiliarity (31.5%) Most respondents (90.5%) indicated that they desire national organizations to develop practice guidelines In this survey, a majority (78.4%) of respondents agreed that TXA has a role in civilian pre-hospital care

24 TXA is being administered already in many pre-hospital ground and air systems Insufficient evidence exists to support or refute administration Guidelines for best practice for TXA administration Endorsed by the ACS-COT, the American College of Emergency Physicians, and the National Association of EMS Physicians 2 current pre-hospital (civilian) trials looking at TXA use

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28 Do not delay definitive transfer One of the consistent concerns when dealing with pre-hospital innovation is the concern regarding the impact it may have on scene times There must be careful attention paid to not delaying the transport for definitive management EMS services must strongly consider the impact of PHBP administration and ensure that there is not unnecessary delay in transport Not all need for PHBP administration is due to trauma

29 Conclusions Although the use of PHBP has been robust in the military setting, the current data to support its use in the civilian setting has been equivocal Many of the larger studies performed have demonstrated logistical feasibility but not clear evidence of efficacy Exception: recent NEJM study July 2018 Remember, blood products and TXA do have potential side effects when used unnecessarily

30 At Present, the focus of pre-hospital care of the bleeding trauma patient should be Hemorrhage control Hemostatic resuscitation Rapid transport to definitive hemorrhage control and trauma care

31 References Napolitano LM. Trauma Surg Acute Care Open 2017;2:1 7. Shakur H, Roberts I, Bautista R, Caballero J, Coats T, Dewan Y, et al., CRASH-2 trial collaborators. Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet 2010;376: Morrison JJ, Dubose JJ, Rasmussen TE, et al. Military application of tranexamic acid in trauma emergency resuscitation (MATTERs) study. Arch Surg 2012;147: Holcomb JB, et al. The Prospective, Observational, Multicenter, Major Trauma Transfusion (PROMMTT) Study. JAMASURG/VOL148(NO.2), FEB2013 Smith IM, et al. PREHOSPITAL BLOOD PRODUCT RESUSCITATION FOR TRAUMA: A SYSTEMATIC REVIEW. SHOCK, Vol. 46, No. 1, pp. 3 16, 2016 Holcomb JB, et al. 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. AMA. 2015;313(5): Sperry JL, et al. Prehospital Plasma during Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock. N Engl J Med Jul 26;379(4):

32 Any Questions?

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