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Pre-hospital freeze-dried plasma for critical bleeding after trauma: A pilot randomized controlled trial
Mitra B, Meadley B, Bernard S, Maegele M, Gruen RL, Bradley O, Wood EM, McQuilten ZK, Fitzgerald M, St Clair T, et al
Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 2023
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Editor's Choice
Abstract
OBJECTIVES Transfusion of a high ratio of plasma to packed red blood cells (PRBC), to treat or prevent acute traumatic coagulopathy, has been associated with survival after major trauma. However, the effect of pre-hospital plasma on patient outcomes has been inconsistent. The aim of this pilot trial was to assess the feasibility of transfusing freeze-dried plasma with red blood cells (RBC) using a randomized controlled design in an Australian aeromedical pre-hospital setting. METHODS Patients attended by Helicopter Emergency Medical Service (HEMS) paramedics with suspected critical bleeding after trauma managed with pre-hospital RBC were randomized to receive two units of freeze-dried plasma (Lyoplas N-w) or standard care (no plasma). The primary outcome was the proportion of eligible patients enrolled and provided the intervention. Secondary outcomes included preliminary data on effectiveness, including mortality censored at 24 hours and at hospital discharge, and adverse events. RESULTS During the study period of 01 June to 31 October 2022, there were 25 eligible patients, of whom 20 (80%) were enrolled in the trial and 19 (76%) received the allocated intervention. Median time from randomization to hospital arrival was 92.5 mins (IQR 68-101.5). Mortality may have been lower in the freeze-dried plasma group at 24h (RR 0.24; 95%CI: 0.03 - 1.73) and at hospital discharge (RR 0.73; 95%CI: 0.24 - 2.27). No serious adverse events related to the trial interventions were reported. CONCLUSIONS This first reported experience of freeze-dried plasma use in Australia suggests pre-hospital administration is feasible. Given longer prehospital times typically associated with HEMS attendance, there is potential clinical benefit from this intervention and rationale for a definitive trial.
PICO Summary
Population
Patients attended by Helicopter Emergency Medical Service (HEMS) paramedics with suspected critical bleeding after trauma (n= 20).
Intervention
Two units of freeze-dried plasma (Lyoplas N-w), (n= 9).
Comparison
Standard care (no plasma), (n= 11).
Outcome
The primary outcome was the proportion of eligible patients enrolled and provided the intervention. Secondary outcomes included preliminary data on effectiveness, including mortality censored at 24 hours and at hospital discharge, and adverse events. Nineteen patients (76%) received the allocated intervention. Median time from randomization to hospital arrival was 92.5 mins (IQR 68-101.5). Mortality may have been lower in the freeze-dried plasma group at 24h (RR 0.24; 95% CI [0.03, 1.73]) and at hospital discharge (RR 0.73; 95% CI [0.24, 2.27]. No serious adverse events related to the trial interventions were reported.
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The impact of using fresh frozen plasma in cardiopulmonary bypass preparation on thromboelastometric parameters and receiving blood products among pediatric patients undergoing cardiac surgery
Abedzadeh, M., Kachoueian, N., Fazli, A., Pazhoha, M., Orouji Omid, S., Vahid, P., Givtaj, N.
Journal of cardiovascular and thoracic research. 2023;15(1):9-13
Abstract
Introduction: The aim of this study was to determine the effect of fresh frozen plasma (FFP) for priming of cardiopulmonary bypass (CPB) circuit on rotational thromboelastometry (ROTEM) and transfusion in pediatric cardiac surgery. Methods: Eighty patients younger than seven years old, were divided into case (FFP) (n=40) and control (n=40) groups. In the case group,10-20 mL/kg fresh frozen plasm was used for priming the CPB. The control group received 10-20 mL/kg of hydroxyethyl starch. ROTEM was done before surgical incision and after separation from CPB. The amount of transfusion (platelet and FFP) in the operating room and 24 hours after surgery were recorded. Results: Statistically significant difference was found between the case and control group in terms of changes in the Rotem parameters. The amount of transfusion of platelets in the operating room was significantly higher in the control group than in the case group. Conclusion: It seems that adding FFP to the prime solution is more effective in young patients and infants due to the higher susceptibility of the infant coagulation system to coagulation and hemorrhagic disorders in comparison with other patients.
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Prehospital plasma is associated with survival principally in patients transferred from the scene of injury: A secondary analysis of the PAMPer trial
Lewis RE, Muluk SL, Reitz KM, Guyette FX, Brown JB, Miller RS, Harbrecht BG, Claridge JA, Phelan HA, Yazer MH, et al
Surgery. 2022
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Editor's Choice
Abstract
BACKGROUND We sought to characterize if prehospital transfer origin from the scene of injury (SCENE) or from a referral emergency department (REF) alters the survival benefit attributable to prehospital plasma resuscitation in patients at risk of hemorrhagic shock. METHODS We performed a secondary analysis of data from a recently completed prehospital plasma clinical trial. All of the enrolled patients from either the SCENE or REF groups were included. The demographics, injury characteristics, shock severity and resuscitation needs were compared. The primary outcome was a 30-day mortality. Kaplan-Meier analysis and Cox-hazard regression were used to characterize the independent survival benefits of prehospital plasma for transport origin groups. RESULTS Of the 501 enrolled patients, the REF group patients (n = 111) accounted for 22% with the remaining (n = 390) originating from the scene. The SCENE group patients had higher injury severity and were more likely intubated prehospital. The REF group patients had longer prehospital times and received greater prehospital crystalloid and blood products. Kaplan-Meier analysis revealed a significant 30-day survival benefit associated with prehospital plasma in the SCENE group (P < .01) with no difference found in the REF group patients (P = .36). The Cox-regression verified after controlling for relevant confounders that prehospital plasma was independently associated with a 30-day survival in the SCENE group patients (hazard ratio 0.59; 95% confidence interval 0.39-0.89; P = .01) with no significant relationship found in the REF group patients (hazard ratio 1.03, 95% confidence interval 0.4-3.0). CONCLUSION Important differences across the SCENE and REF cohorts exist that are essential to understand when planning prehospital studies. Prehospital plasma is associated with a survival benefit primarily in SCENE group patients. The results are exploratory but suggest transfer origin may be an important determinant of prehospital plasma benefit.
PICO Summary
Population
Severely injured trauma patients enrolled in the PAMPer trial (n= 501).
Intervention
Thawed plasma (n= 230).
Comparison
Standard pre-hospital air medical care (n= 271).
Outcome
For this secondary analysis of the PAMPer trial, the study population was composed of 390 (78%) patients with an air medical transfer origin from the scene of injury (SCENE) and 111 (22%) patients transferred from an outside referral emergency department (REF). Randomization to plasma or standard of care was equally distributed across each transfer origin group. The SCENE group had higher injury severity and were more likely intubated pre-hospital. The REF group had longer pre-hospital times and received greater pre-hospital crystalloid and blood products. Kaplan-Meier analysis revealed a significant 30-day survival benefit associated with pre-hospital plasma in the SCENE group with no difference found in the REF group. The Cox-regression verified after controlling for relevant confounders that pre-hospital plasma was independently associated with a 30-day survival in the SCENE group with no significant relationship found in the REF group.
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Effects of surgical and FFP2 masks on cardiopulmonary exercise capacity in patients with heart failure
Kogel, A., Hepp, P., Stegmann, T., Tünnemann-Tarr, A., Falz, R., Fischer, P., Mahfoud, F., Laufs, U., Fikenzer, S.
PloS one. 2022;17(8):e0269470
Abstract
AIMS: Surgical and FFP2 masks are recommended to reduce transmission of SARS-CoV-2. The cardiopulmonary effects of facemasks in patients with chronic heart failure are unknown. This prospective, cross-over study quantified the effects of wearing no mask (nm), surgical mask (sm), and FFP2 mask (ffpm) in patients with stable heart failure. METHODS 12 patients with clinically stable chronic heart failure (HF) (age 63.8±12 years, left ventricular ejection fraction (LVEF) 43.8±11%, NTProBNP 573±567 pg/ml) underwent spiroergometry with and without masks in a randomized sequence. Comfort/discomfort was assessed using a standardized questionnaire. RESULTS Maximum power was reduced with both types of masks (nm: 108.3 W vs. sm: 101.2 W vs. ffpm: 95.6 W, p<0.01). Maximum respiratory oxygen uptake (1499ml/min vs. 1481 ml/min vs. 1300 ml/min, p = 0.95 and <0.01), peak ventilation (62.1 l/min vs. 56.4 l/min vs. 50.3 l/min, p = 0.15 and p<0.05) and O2-pulse (11.6 ml/beat vs. 11.8 ml/beat vs. 10.6 ml/beat, p = 0.87 and p<0.01) were significantly changed with ffpm but not sm. Discomfort was moderately but significantly increased (nm: 1.6 vs. sm: 3.4 vs. ffpm: 4.4, p<0.05). CONCLUSION Both surgical and FFP masks reduce exercise capacity in heart failure patients, while FFP2 masks reduce oxygen uptake and peak ventilation. This reduction in cardiopulmonary performance should be considered in heart failure patients whose daily life activities are often just as challenging as exercise is for healthy adults.
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Clinical and Radiographic Evaluation of Applying Atorvastatin 1.2% Bio Adhesive with Plasma Rich in Growth Factor (PRGF) for Treatment of Mandibular Class II Furcation Defects: a Randomized Clinical Trial
Jenabian N, Mohammadpour S, Haghanifar S, Kazemi S, Hajiahmady M
Journal of dentistry (Shiraz, Iran). 2022;23(2):86-94
Abstract
STATEMENT OF THE PROBLEM Molar teeth with furcation involvement are one of the most common problems in patients with periodontal disease. Regeneration methods are of the most controversial treatment strategies for these lesions. PURPOSE The purpose of this study was to determine the effect of plasma rich in growth factors (PRGF) with 1.2% Atorvastatin (ATV) in the treatment of furcation involvement of mandibular molars. MATERIALS AND METHOD The present randomized clinical trial was conducted on 15 patients with moderate periodontitis and class II furcation involvements; 24 defects were located in four groups of six, including debridement, ATV1.2%, PRGF, PRGF with ATV1.2%. The parameters of vertical probing depth (VPD), vertical clinical attachment level (VCAL), gingival index (GI), horizontal probing depth (HPD) and gingival recession (GR) were measured at baseline (T0), immediately before surgery (T1), 3 (T2), and 6 (T3) months after surgery. Moreover, the bone conditions were evaluated by digital subtraction radiography before and six months after surgery. Data were analyzed using SPSS23 software. RESULTS No significant difference in radiographic parameters was observed among the groups (p= 0.08). There was no significant difference in the mean levels of VPD, VCAL and HPD among the groups at different times (p<0.05). Comparison of clinical parameters of VPD, VCAL and GI in the treatment groups compared to the baseline showed a significant improvement in each group (p< 0.05) but there was no significant difference among different groups (p< 0.05). CONCLUSION The use of PRGF with ATV 1.2% in grade II furcation involvement in mandi-bular molars was effective in the improvement of clinical and radiographic parameters six months after treatment, but this effect revealed no difference in comparison with the other groups.
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Post-injury Complement C4 Activation is Associated with Adverse Outcomes and is Potentially Influenced by Plasma Resuscitation
Schaid TR Jr, Hansen KC, Sauaia A, Moore EE, DeBot M, Cralley AL, Erickson C, Silliman CC, Banerjee A, Ghasabyan A, et al
The journal of trauma and acute care surgery. 2022
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Abstract
BACKGROUND Complement activation after trauma promotes hemostasis but is associated with increased morbidity and mortality. However, the specific pathways and downstream mediators remain unclear. Recently the anaphylatoxin C4a has been shown to bind to thrombin receptors. While plasma-based resuscitation has been shown to modify the endotheliopathy of trauma, it may provide complement zymogens that fuel ongoing inflammatory cascades. We sought to characterize the activation of complement after injury and the effect of fresh frozen plasma (FFP) on this inflammatory response. We hypothesized that trauma induces C4 activation, which is associated with worse outcomes and influenced by FFP resuscitation. METHODS Blood was collected from injured patients at a single Level I Trauma Center enrolled in the COMBAT randomized clinical trial. Proteomic analyses were performed through targeted liquid chromatography coupled with mass spectrometry. For the present observational study, concentrations of complement proteins were analyzed at multiple time points, compared between treatment groups, and correlated with outcomes. RESULTS C4 activation occurred over the first six hours post-injury with peak activation 6-24 hours. Tissue hypoperfusion, defined as base deficit >10 mEq/L, and requirement for massive transfusion were associated with greater C4 activation. C4 activation was associated with mortality, multiple organ failure, and longer ventilator requirement. Additionally, temporal trends of C1q, factor B, and C3 by outcome groups support the prevailing theory of primary classical pathway activation with alternative pathway amplification. Resuscitation with FFP over the first six hours was associated with increased C4 activation at 12 and 24 hours. CONCLUSIONS C4 activation has an important inflammatory role post-injury, and FFP has the potential to augment this complement activation during resuscitation. EVIDENCE Level III, Prognostic/Epidemiological.
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Prehospital Lyophilized Plasma Transfusion for Trauma-Induced Coagulopathy in Patients at Risk for Hemorrhagic Shock: A Randomized Clinical Trial
Jost, D., Lemoine, S., Lemoine, F., Derkenne, C., Beaume, S., Lanoë, V., Maurin, O., Louis-Delaurière, E., Delacote, M., Dang-Minh, P., et al
JAMA network open. 2022;5(7):e2223619
Abstract
IMPORTANCE Blood transfusion is a mainstay of therapy for trauma-induced coagulopathy, but the optimal modalities for plasma transfusion in the prehospital setting remain to be defined. OBJECTIVE To determine whether lyophilized plasma transfusion can reduce the incidence of trauma-induced coagulopathy compared with standard care consisting of normal saline infusion. DESIGN, SETTING, AND PARTICIPANTS This randomized clinical trial was performed at multiple centers in France involving prehospital medical teams. Participants included 150 adults with trauma who were at risk for hemorrhagic shock and associated coagulopathy between April 1, 2016, and September 30, 2019, with a 28-day follow-up. Data were analyzed from November 1, 2019, to July 1, 2020. INTERVENTION Patients were randomized in a 1:1 ratio to receive either plasma or standard care with normal saline infusion (control). MAIN OUTCOMES AND MEASURES The primary outcome was the international normalized ratio (INR) on arrival at the hospital. Secondary outcomes included the need for massive transfusion and 30-day survival. As a safety outcome, prespecified adverse events included thrombosis, transfusion-related acute lung injury, and transfusion-associated circulatory overload. RESULTS Among 150 randomized patients, 134 were included in the analysis (median age, 34 [IQR, 26-49] years; 110 men [82.1%]), with 68 in the plasma group and 66 in the control group. Median INR values were 1.21 (IQR, 1.12-1.49) in the plasma group and 1.20 (IQR, 1.10-1.39) in the control group (median difference, -0.01 [IQR, -0.09 to 0.08]; P = .88). The groups did not differ significantly in the need for massive transfusion (7 [10.3%] vs 4 [6.1%]; relative risk, 1.78 [95% CI, 0.42-8.68]; P = .37) or 30-day survival (hazard ratio for death, 1.07 [95% CI, 0.44-2.61]; P = .89). In the full intention-to-treat population (n = 150), the groups did not differ in the rates of any of the prespecified adverse events. CONCLUSIONS AND RELEVANCE In this randomized clinical trial including severely injured patients at risk for hemorrhagic shock and associated coagulopathy, prehospital transfusion of lyophilized plasma was not associated with significant differences in INR values vs standard care with normal saline infusion. Nevertheless, these findings show that lyophilized plasma transfusion is a feasible and safe procedure for this patient population. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02736812.
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Systematic review of plasma to packed red blood cell ratio on survival in ruptured abdominal aortic aneurysms
Phillips AR, Tran L, Foust JE, Liang NL
Journal of vascular surgery. 2020
Abstract
BACKGROUND The ideal perioperative fluid resuscitation for ruptured abdominal aortic aneurysms (rAAA) is unknown. It has been shown in the trauma literature that a higher ratio of plasma and platelets to packed red blood cells confers a mortality benefit. There remains controversy whether this is true also in the ruptured aneurysm population. The objective of this study is to investigate the benefit of higher ratio of plasma to packed red blood cells in patients with ruptured abdominal aortic aneurysms. METHODS A health sciences librarian searched four electronic databases including PubMed, Embase, Cochrane, and ClinicalTrials.gov using concepts for the terms fluid resuscitation, survival, and ruptured abdominal aortic aneurysm. Two reviewers independently screened the studies that were identified through the search strategy and read in full any study that was potentially relevant. Papers were included if they compared mortality of patients with rAAA who received a higher ratio of plasma to other component therapy to patients who received a lower ratio. Risk of bias was assessed using the ROBINS-I validated tool and evidence quality was rated using the GRADE profile. No data synthesis or meta-analysis was planned or performed given the anticipated paucity of research on this topic and the high degree of heterogeneity of available studies. RESULTS Our search identified seven observational studies to be included in this review. Of these seven studies, three found an associated decrease in mortality with a higher ratio of plasma to packed red blood cells and the remaining four found no significant difference. The overall risk of bias was serious and the evidence quality was very low. CONCLUSIONS Overall, the available studies would suggest that for patients that have undergone open surgery for a ruptured abdominal aortic aneurysm, mortality rates tend to decrease when the amount of plasma transfused perioperatively is similar to the amount of packed red blood cells. However, this is very low-quality evidence based solely off of highly heterogenous observational studies and further research is warranted.
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Association of Prehospital Plasma With Survival in Patients With Traumatic Brain Injury: A Secondary Analysis of the PAMPer Cluster Randomized Clinical Trial
Gruen, D. S., Guyette, F. X., Brown, J. B., Okonkwo, D. O., Puccio, A. M., Campwala, I. K., Tessmer, M. T., Daley, B. J., Miller, R. S., Harbrecht, B. G., et al
JAMA network open. 2020;3(10):e2016869
Abstract
IMPORTANCE Prehospital plasma administration improves survival in injured patients at risk for hemorrhagic shock and transported by air ambulance. Traumatic brain injury (TBI) is a leading cause of death following trauma, but few early interventions improve outcomes. OBJECTIVE To assess the association between prehospital plasma and survival in patients with TBI. DESIGN, SETTING, AND PARTICIPANTS The Prehospital Air Medical Plasma (PAMPer) trial was a pragmatic, multicenter, phase 3, cluster randomized clinical trial involving injured patients who were at risk for hemorrhagic shock during air medical transport to a trauma center. The trial was conducted at 6 US sites with 9 level-I trauma centers (comprising 27 helicopter emergency services bases). The original trial analyzed 501 patients, including 230 patients who were randomized to receive plasma and 271 randomized to standard care resuscitation. This secondary analysis of a predefined subgroup included patients with TBI. Data analysis was performed from October 2019 to February 2020. INTERVENTIONS Patients were randomized to receive standard care fluid resuscitation or 2 units of thawed plasma. MAIN OUTCOMES AND MEASURES The primary outcome was mortality at 30 days. Patients with TBI were prespecified as a subgroup for secondary analysis and for measurement of markers of brain injury. The 30-day survival benefit of prehospital plasma in subgroups with and without TBI as diagnosed by computed tomography was characterized using Kaplan-Meier survival analysis and Cox proportional hazard regression. RESULTS In total, 166 patients had TBI (median [interquartile range] age, 43.00 [25.00-59.75] years; 125 men [75.3%]). When compared with the 92 patients who received standard care, the 74 patients with TBI who received prehospital plasma had improved 30-day survival even after adjustment for multiple confounders and assessment of the degree of brain injury with clinical variables and biomarkers (hazard ratio [HR], 0.55; 95% CI, 0.33-0.94; P = .03). Receipt of prehospital plasma was associated with improved survival among patients with TBI with a prehospital Glasgow Coma Scale score of less than 8 (HR, 0.56; 95% CI, 0.35-0.91) and those with polytrauma (HR, 0.50; 95% CI, 0.28-0.89). Patients with TBI transported from the scene of injury had improved survival following prehospital plasma administration (HR, 0.45; 95% CI, 0.26-0.80; P = .005), whereas patients who were transferred from an outside hospital showed no difference in survival for the plasma intervention (HR, 1.00; 95% CI, 0.33-3.00; P = .99). CONCLUSIONS AND RELEVANCE These findings are exploratory, but they suggest that receipt of prehospital plasma is associated with improved survival in patients with computed tomography-positive TBI. The prehospital setting may be a critical period to intervene in the care of patients with TBI. Future studies are needed to confirm the clinical benefits of early plasma resuscitation following TBI and concomitant polytrauma. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01818427.
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CHARACTERIZATION OF UNEXPECTED SURVIVORS FOLLOWING A PREHOSPITAL PLASMA RANDOMIZED TRIAL
Gruen DS, Guyette FX, Brown JB, Daley BJ, Miller RS, Harbrecht BG, Claridge JA, Phelan HA, Yazer MH, Neal MD, et al
J Trauma Acute Care Surg. 2020
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Editor's Choice
Abstract
BACKGROUND Prehospital plasma improves survival for severely injured trauma patients transported by air ambulance. We sought to characterize the unexpected survivors, patients who survived despite having high predicted mortality following traumatic injury. METHODS The Prehospital Air Medical Plasma (PAMPer) trial randomized severely injured patients (n=501) to receive either standard care (crystalloid) or two units of prehospital plasma followed by standard care fluid resuscitation. We built a generalized linear model to estimate patient mortality. Area under the receiver operating characteristic curve (AUC) was used to evaluate model performance. We defined unexpected survivors as patients who had a predicted mortality >50% and survived to 30 days. We characterized patient demographics, clinical features, and outcomes of the unexpected survivors. Observed to expected (O/E) ratios and Z-statistics were calculated using model-estimated mortality for each cohort. RESULTS Our model predicted mortality better than ISS or RTS parameters and identified 36 unexpected survivors. Compared to expected survivors, unexpected survivors were younger (33 [24, 52] vs. 47 [32, 59] years, P=0.013), were more severely injured (ISS 34 [22, 50] vs. 18 [10, 27], P<0.001), had worse organ dysfunction and hospital resource outcomes (MOF, ICU and hospital length of stay, and ventilator days), and were more likely to receive prehospital plasma (67 vs. 46%, P=0.031). Nonsurvivors with high predicted mortality were more likely to receive standard care resuscitation (P<0.001). Unexpected survivors who received prehospital plasma had a lower observed to expected mortality than those that received standard care resuscitation (O/E 0.56 [0.33-0.84] vs. 1.0 [0.73-1.32]). The number of prehospital plasma survivors (24) exceeded the number of predicted survivors (n=10) estimated by our model (P<0.001). CONCLUSIONS Prehospital plasma is associated with an increase in the number of unexpected survivors following severe traumatic injury. Prehospital interventions may improve the probability of survival for injured patients with high predicted mortality based on early injury characteristics, vital signs, and resuscitation measures.Secondary Analysis LEVEL OF EVIDENCE II.
PICO Summary
Population
Severely injured patients enrolled in the Prehospital Air Medical Plasma (PAMPer) trial (n=501).
Intervention
Two units of prehospital plasma followed by standard care fluid resuscitation (n=230).
Comparison
Standard care (crystalloid) (n=271).
Outcome
The generalized linear model to estimate patient mortality predicted mortality better than ISS or RTS parameters and identified 36 unexpected survivors. Compared to expected survivors, unexpected survivors were younger, were more severely injured, had worse organ dysfunction and hospital resource outcomes, and were more likely to receive prehospital plasma (67 vs. 46%). Non-survivors with high predicted mortality were more likely to receive standard care resuscitation. Unexpected survivors who received prehospital plasma had a lower observed to expected mortality than those that received standard care resuscitation. The number of prehospital plasma survivors (24) exceeded the number of predicted survivors (10) estimated by the model.