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Article 1
Plasma-first resuscitation to treat haemorrhagic shock during emergency ground transportation in an urban area: a randomised trial. Moore HB, Moore EE, Chapman MP, McVaney K, Bryskiewicz G, Blechar R, Chin T, Burlew CC, Pieracci F, West FB, Fleming CD, Ghasabyan A, Chandler J, Silliman CC, Banerjee A, Sauaua A. Lancet. 2018 Jul 28;392(10144):283-291.
This study by Moore and colleagues from the Denver Health Medical Center presents the results of the Control of Major Bleeding After Trauma (COMBAT) Trial. This was a randomized controlled clinical trial from April 2014 through March 2017 whose aim was to investigate the use of prehospital plasma during ground transport in patients with hemorrhagic shock after trauma. The primary outcome of the study was 28-day mortality. After randomizing 144 patients and including 125 eligible patients in an as-treated analysis, they found no difference in 28-day mortality between patients receiving plasma (15%) vs. those who received normal saline control (10%) (p=0.37).
The findings of COMBAT are immediately applicable to clinical practice for anyone who takes care of trauma patients. Plasma has been shown to have many favorable effects on trauma patients and, combined with the anticipated FDA approval of lyophilized plasma, this prompted the creation of this RCT to investigate its effects in the prehospital setting. The authors included adult patients with SBP< 70 mmHg or SBP 71-90 mmHg plus heart rate 108 bpm. Prisoners, pregnant patients, and those with isolated GSW to the head, asystole, or CPR before randomization, known objection to blood products, opt-out bracelets, or family objection to enrollment were excluded. The 33 ambulances based out of Denver Health Medical Center were loaded with coolers every morning containing plasma and dummy loads, and patients were randomly allocated in 1:1 blocks of 20. There were 125 eligible patients, with 65 in the plasma group and 60 in the control (normal saline) group. Transport times were similar between the two groups (median 19 minutes in the plasma group vs. 16 minutes in the control group). The primary outcome of 28-day mortality was similar between the plasma and control groups (15% vs. 10%, p=0.37). Other outcomes, including 24-hour mortality, acute lung injury within 28 days, MOF within 28 days, ventilator-free days, and intensive care-free days were similar between groups. The findings of COMBAT led the authors to conclude that prehospital administration of plasma in the setting of short prehospital times does not confer a survival advantage to severely injured trauma patients and that further study is required to determine its application in rural or austere environments with prolonged transport.
Article 2
Prehospital Plasma during Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock. Sperry JL, Guyette FX, Brown JB, Yazer MH, Triulzi DJ, Early-Young BJ, Adams PW, Daley BJ, Miller RS, Harbrecht BG, Claridge JA, Phelan HA, Witham WR, Putman AT, Duane TM, Alarcon LH, Callaway CW, Zuckerbaun BS, Neal MD, Rosengart MR, Forsythe RM, Billiar TR, Yealy DM, Peitzman AB, Zenati MS, Pamper Study Group. N Engl J Med. 2018 Jul 26;379(4):315-326.
The Prehospital Air Medical Plasma (PAMPer) trial was developed to investigate the efficacy and safety of using thawed plasma in trauma patients transported by air to several level I trauma centers. It was a pragmatic, multicenter, cluster-randomized, phase 3 superiority trial that took place over a 3-year period from 2014 – 2017. 501 patients were randomized to receive either plasma (n=230) or standard-care resuscitation (n=271), defined as crystalloid solution as the primary resuscitative fluid. Patients transported to one of the participating sites via air were eligible if they had at least one episode of hypotension, defined as SBP < 90 mmHg, and tachycardia, defined as HR > 108, or if they had severe hypotension, defined as SBP < 70 mmHg. They were excluded if they were older than 90 years of age or younger than 18 years of age, if IV/IO access could not be established, if they were an isolated fall from standing, if they had a documented cervical cord injury, prisoners, pregnant patients, traumatic arrest > 5 minutes, penetrating brain injury, drowning, hanging, burns > 20% TBSA, or if they opted out. The primary outcome was 30-day mortality and the authors found that patients in the plasma group had significantly lower mortality than those in the standard-care group (23.3% vs. 33.0%, p=0.03). There were no differences in secondary outcomes, including MOF, acute lung injury or ARDS, nosocomial infections, or allergic or transfusion-related reactions.
Like the COMBAT trial, PAMPer has important immediate clinical applicability. Despite similar age, mechanism of injury, and level of shock in the prehospital setting, those who received plasma had a clear survival advantage. This difference was evident as early as 3 hours after randomization and persisted up to 30 days post-randomization. The major differences between COMBAT and PAMPer, and likely the explanation behind the different conclusions of the two trials, were in the mode of transport and total prehospital time. While COMBAT looked at patients undergoing ground transport with short prehospital times, PAMPer investigated the use of plasma in patients transported by air with a median prehospital time of 40 minutes in the plasma group and 42 minutes in the standard-care group. Indeed, their results suggest a clear survival benefit for severely injured trauma patients receiving plasma in the prehospital setting when they are subjected to longer transport times. This is the first step in investigating the utility of prehospital plasma administration in rural and austere environments, as suggested by the COMBAT trialists, and has the potential to effect immediate benefit to patients in this situation.
Article 3
Tranexamic acid administration is associated with an increased risk of posttraumatic venous thromboembolism. Myers SP, Kutcher ME, Rosengart MR, Sperry JL, Peitzman AB, Brown JB, Neal MD. J Trauma Acute Care Surg. 2019 Jan;86(1):20-27.
Few topics in the field of trauma elicit such strong emotions and conflicting opinions among surgeons as venous thromboembolism (VTE) and the use of tranexamic acid (TXA). Since the publication of CRASH-2, significant controversy has existed regarding the benefit of using TXA in severely injured patients. Proponents of TXA cite the clear survival benefit of using TXA reported in CRASH-2, the largest multicenter randomized controlled trial in our discipline, as an absolute indication for its use in severely injured patients. Skeptics of CRASH-2 and TXA argue that the study is not generalizable to the severely injured trauma population outside of low-resource settings, especially since patients were randomized based on the treating physician's uncertainty with regard to the benefit of TXA and given that only approximately 50% of patients in the study required a blood transfusion or operation. Another criticism of the widespread use of TXA in severely injured trauma patients is the potential for venous thromboembolic complications secondary to its inhibition of plasmin.
Myers et al. set out to study the effect of TXA administration on development of VTE in severely injured trauma patients in a retrospective propensity score-matched cohort of 21,931 patients admitted to the University of Pittsburgh from 2012 – 2016. All adult trauma activations presenting during this time were eligible for inclusion. Exclusion criteria included preexisting use of anticoagulation, those with known VTE history or coagulopathy, and those who received prehospital TXA as part of a separate trial protocol at their center. TXA was administered based on the attending trauma surgeon's discretion and the propensity score was generated to predict the likelihood of receiving TXA based on various clinical parameters that could affect this decision, including age, sex, hemoglobin, lactate, INR, and SBP. The primary outcome was the composite variable of VTE, defined as DVT or PE, which was diagnosed based on imaging in symptomatic patients. The study sample included 189 well-matched pairs, with minimal differences between groups. The authors found that treatment with TXA was associated with a greater than 3-fold increase in VTE events (aOR 3.26, 95% CI 1.3-9.1, p=0.02). These findings underscore the importance of fully assessing the potential risks and benefits of any potential therapeutic option prior to its widespread adoption. While their findings differ from the CRASH-2 and MATTERs studies, an argument can be made that they are more applicable to patients being treated in a more resource-rich environment with immediate access to transfusion and surgery. While the study was limited in its retrospective, non-randomized design, its findings highlight the need for further prospective evaluation of TXA prior to its indiscriminate use in severely injured trauma patients.
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