Whole Blood in Trauma Resuscitation: What Is the Real Cost?

INTRODUCTION: Whole blood (WB) has gained popularity in trauma resuscitation within the past 5 y. Previously, its civilian use was limited due to advances in blood component fractionation and fears of hemolysis and infectious disease transmission. Although there are studies and review articles on the efficacy of WB, the analysis of cost pertaining to the use of WB is limited. MATERIALS AND METHODS: We performed a retrospective 1:1 propensity-matched analysis of 280 subjects comparing trauma patients receiving resuscitation with blood component therapy (BCT) to those receiving WB plus BCT between January 2014 and July 2019. WB was used for patients who arrived in hemorrhagic shock with systolic blood pressure <90 mmHg due to either penetrating or blunt trauma. Endpoints included the number of units of WB, packed red blood cells (PRBCs), fresh frozen plasma (FFP), platelets, and cryoprecipitate each patient received. Institution costs for each component were compared in the form of price ratios. Comparisons were made using Wilcoxon rank-sum tests with a P value of ≤0.05 considered statistically significant. RESULTS: The use of WB was associated with a statistically significant decrease in the number of PRBCs used when compared to BCT. This holds true with the cost of PRBCs being lower among the WB group when the price is controlled. Similarly, a trend was found where FFP, platelets, and cryoprecipitate use and cost showed an absolute decrease between WB and BCT groups. The use of WB is associated with decreased total cost as well (P = 0.1660), although not statistically significant. CONCLUSIONS: Adding WB to BCT for trauma resuscitation was associated with lower red blood cell use and cost. A similar trend was found that absolute total cost and absolute cost of FFP, platelets, and cryoprecipitate use was lower when WB was added. WB wastage was minimized due to repurposing WB into PRBCs when WB lifespan ended.

Assessment of Blood Flow Patterns Distal to Aortic Occlusion Using CT in Patients with Resuscitative Endovascular Balloon Occlusion of the Aorta.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is used to decrease hemorrhage below the level of aortic occlusion (AO); however, the amount of collateral blood flow below the level of occlusion is unknown. Our aim was to investigate blood flow patterns during complete AO in patients who underwent CT scan after REBOA. STUDY DESIGN: Between February 2013 and January 2017, patients who received REBOA and underwent CT scan with intravenous contrast during full AO were included. Patients were excluded if they had a CT scan performed with the balloon partially or fully deflated. RESULTS: Nine patients (8 men) were included; all had blunt trauma. Mean Injury Severity Score (±SD) was 48 ± 8 and mean age was 45 ± 19 years. Four had supra-celiac AO, and 5 had infra-renal AO. Arterial contrast enhancement was noted below the level of AO in all patients, and distal to REBOA sheath placement in 5. Collateralization from arteries above and below the AO was identified in all patients. Contrast extravasation distal to AO was identified in 4 patients, and hematomas in 8. Distal vascular enhancement patterns varied by level of AO and contrast administration site. CONCLUSIONS: Aortic occlusion appears to dramatically decrease, but does not completely impede, distal perfusion during REBOA due to multiple pathways of collateralization. Active extravasation and hematomas can still be detected in the setting of full AO, with purposefully timed contrast and image acquisition. Blood flow persists below the level of both the AO and in-dwelling sheath. Dynamic flow studies are needed to determine the contribution of AO and sheath placement to distal tissue ischemia.

Microfluidics: A high-throughput system for the assessment of the endotheliopathy of trauma and the effect of timing of plasma administration on ameliorating shock-associated endothelial dysfunction.

BACKGROUND: Early resuscitation after trauma-hemorrhagic shock with plasma rather than crystalloid may ameliorate systemic endothelial cell (EC) injury and dysfunction (endotheliopathy of trauma). We postulated that endothelial-lined microfluidic networks would be a useful platform to study the EC activation/injury under flow conditions to mimic trauma-hemorrhagic shock. We then used the microfluidic system to further characterize the protective effects and optimal timing of plasma infusion on the development of "endotheliopathy of trauma" in our model. METHODS: Human umbilical vein ECs were added to microfluidic flow channels, and after overnight perfusion, the cells were subsequently treated with epinephrine and exposed to hypoxia reoxygenation. Media alone or 5% human plasma was perfused either immediately following treatment (early plasma) or after a 3-hour delay (late plasma). Glycocalyx injury was indexed by fluorescent microscopy and shedding of syndecan 1 and hyaluronic acid. Endothelial markers of activation/injury were also measured and included soluble thrombomodulin, tissue plasminogen activator, plasminogen activator inhibitor 1, and angiopoietins 1 and 2. Sheddase activity was indexed by ADAM metallopeptidase domain 17. RESULTS: Endothelial cell and glycocalyx barrier function studies using microfluidic devices are a more realistic model of the glycocalyx endothelial vascular barrier than studies performed on ECs using static (no flow) conditions. Conditions that mimic the internal milieu following hemorrhagic shock result in glycocalyx degradation and an inflammatory prothrombotic response by the endothelium. "Early" use of plasma in the microfluidic channel perfusate mitigated against these effects. Later perfusion with plasma had no protective effect. CONCLUSIONS: A temporal effect to plasma administration was noted in our biomimetic model of the endothelial vascular barrier following shock. This suggests a protective role to "early" plasma administration in the severely injured patient.

Barriers to safe abortion access: uterine rupture as complication of unsafe abortion in a Ugandan girl.

A 15-year-old girl at 18 weeks gestation by the last menstrual period presented to a rural Ugandan healthcare facility for termination of her pregnancy as a result of rape by her uncle. Skilled healthcare workers at the facility refused to provide the abortion due to fear of legal repercussions. The patient subsequently obtained an unsafe abortion by vaginal insertion of local herbs and sharp objects. She developed profuse vaginal bleeding and haemorrhagic shock. She was found to have uterine rupture and emergent hysterectomy was performed. Young and poor women are at high risk of unplanned pregnancy and subsequent mortality during pregnancy and childbirth. Unsafe abortion is a leading and entirely preventable cause of maternal mortality worldwide. Multiple barriers restrict access to safe abortions including social and moral stigma, gender-based power imbalances, inadequate contraceptive use and sexual education, high cost and poor availability, and restrictive abortion laws.

Safety and feasibility of sublingual microcirculation assessment in the emergency department for civilian and military patients with traumatic haemorrhagic shock: a prospective cohort study.

OBJECTIVES: Sublingual microcirculatory monitoring for traumatic haemorrhagic shock (THS) may predict clinical outcomes better than traditional blood pressure and cardiac output, but is not usually performed until the patient reaches the intensive care unit (ICU), missing earlier data of potential importance. This pilot study assessed for the first time the feasibility and safety of sublingual video-microscopy for THS in the emergency department (ED), and whether it yields useable data for analysis. SETTING: A safety and feasibility assessment was undertaken as part of the prospective observational MICROSHOCK study; sublingual video-microscopy was performed at the UK-led Role 3 medical facility at Camp Bastion, Afghanistan, and in the ED in 3 UK Major Trauma Centres. PARTICIPANTS: There were 15 casualties (2 military, 13 civilian) who presented with traumatic haemorrhagic shock with a median injury severity score of 26. The median age was 41; the majority (n=12) were male. The most common injury mechanism was road traffic accident. PRIMARY AND SECONDARY OUTCOME MEASURES: Safety and feasibility were the primary outcomes, as measured by lack of adverse events or clinical interruptions, and successful acquisition and storage of data. The secondary outcome was the quality of acquired video clips according to validated criteria, in order to determine whether useful data could be obtained in this emergency context. RESULTS: Video-microscopy was successfully performed and stored for analysis for all patients, yielding 161 video clips. There were no adverse events or episodes where clinical management was affected or interrupted. There were 104 (64.6%) video clips from 14 patients of sufficient quality for analysis. CONCLUSIONS: Early sublingual microcirculatory monitoring in the ED for patients with THS is safe and feasible, even in a deployed military setting, and yields videos of satisfactory quality in a high proportion of cases. Further investigations of early microcirculatory behaviour in this context are warranted. TRIAL REGISTRATION NUMBER: NCT02111109.

Impact of haemorrhagic shock intensity on the dynamic of alarmins release in porcine poly-trauma animal model.

PURPOSE: Traumatic insults result in an altered inflammatory response, in which alarmins release has a central role. The impact of haemorrhagic shock intensity on the long-term kinetics of alarmins is not yet fully elucidated. We investigated these aspects in a combined trauma (chest, abdominal, and extremities injury) porcine model with different severities and durations of haemorrhagic shock. METHODS: After induction of combined trauma (tibia fracture, lung contusion, and liver laceration), haemorrhagic shock was induced at different intensities: moderate haemorrhage (MH; n = 15): mean arterial pressure (MAP) <30 ± 5 mmHg [maximum loss of total blood volume (TBVmax): 45 %] for 90 min, and severe haemorrhage (SH; n = 10): MAP <25 ± 5 mmHg (TBVmax 50 %) for 120 min. Resuscitation was performed using a standardized crystalloid infusion protocol. Animals were mechanically ventilated and underwent ICU-monitoring for 48 h (MH) and 48.5 h (SH). Blood samples were collected over the clinical time course, and systemic levels of serum alarmins [High-Mobility Group Protein B-1 (HMGB-1) and Heat Shock Protein 70 (HSP70)] were measured using an ELISA kit. RESULTS: Heart rate, systemic blood pressure, lactate, and base excess were significantly altered as a function of haemorrhagic shock in both trauma groups (MH and SH). Systemic HMGB-1 levels were significantly elevated in both trauma groups when compared to the sham group. Haemorrhagic shock severity and duration were positively correlated with HMGB-1 levels and compared to baseline values, concentrations remained significantly increased in SH when compared to MH. On the other hand, we observed a significant decrease in the systemic HSP70 levels of trauma groups (MH, and SH) when compared to the sham group, which was significantly decreased compared to baseline values in SH over the entire time course. CONCLUSION: Our data show that haemorrhagic shock duration and severity affect the systemic levels of HMGB-1 and HSP70. This early alarmins release after trauma can be used to guide the treatment strategies (e.g. surgical procedures) of polytrauma patients.

Temporal trends of postinjury multiple-organ failure: still resource intensive, morbid, and lethal.

BACKGROUND: While the incidence of postinjury multiple-organ failure (MOF) has declined during the past decade, temporal trends of its morbidity, mortality, presentation patterns, and health care resources use have been inconsistent. The purpose of this study was to describe the evolving epidemiology of postinjury MOF from 2003 to 2010 in multiple trauma centers sharing standard treatment protocols. METHODS: "Inflammation and Host Response to Injury Collaborative Program" institutions that enrolled more than 20 eligible patients per biennial during the 2003 to 2010 study period were included. The patients were aged 16 years to 90 years, sustained blunt torso trauma with hemorrhagic shock (systolic blood pressure < 90 mm Hg, base deficit ≥ 6 mEq/L, blood transfusion within the first 12 hours), but without severe head injury (motor Glasgow Coma Scale [GCS] score < 4). MOF temporal trends (Denver MOF score > 3) were adjusted for admission risk factors (age, sex, body max index, Injury Severity Score [ISS], systolic blood pressure, and base deficit) using survival analysis. RESULTS: A total of 1,643 patients from four institutions were evaluated. MOF incidence decreased over time (from 17% in 2003-2004 to 9.8% in 2009-2010). MOF-related death rate (33% in 2003-2004 to 36% in 2009-2010), intensive care unit stay, and mechanical ventilation duration did not change over the study period. Adjustment for admission risk factors confirmed the crude trends. MOF patients required much longer ventilation and intensive care unit stay, compared with non-MOF patients. Most of the MOF-related deaths occurred within 2 days of the MOF diagnosis. Lung and cardiac dysfunctions became less frequent (57.6% to 50.8%, 20.9% to 12.5%, respectively), but kidney and liver failure rates did not change (10.1% to 12.5%, 15.2% to 14.1%). CONCLUSION: Postinjury MOF remains a resource-intensive, morbid, and lethal condition. Lung injury is an enduring challenge and should be a research priority. The lack of outcome improvements suggests that reversing MOF is difficult and prevention is still the best strategy. LEVEL OF EVIDENCE: Epidemiologic study, level III.

Emergency focussed assessment with sonography in trauma (FAST) and haemodynamic stability.

BACKGROUND: Focussed assessment with sonography in trauma (FAST) has assumed a key role in the rapid non-invasive assessment of thoracoabdominal trauma and assists in decreasing disposition time. This study evaluates FAST's efficacy with respect to haemodynamic stability in a South African emergency department (ED). METHODS: Data were collected prospectively by four emergency medicine doctors trained in emergency ultrasonography. FAST scans were performed by one ED doctor and timings, scan result and disposition were recorded. Patient haemodynamic stability was assessed by the emergency doctor performing the scan; subjectively at the time of scanning and objectively using calculation of the shock index. All scan results were subsequently verified by a second ED doctor in a blinded fashion and by CT scanning or operative intervention when clinically indicated. RESULTS: 166 FAST scans were conducted of which 36 (21.7%) were positive. Mean age was 30.6 years (SD 12.8). 74.1% of patients sustained blunt traumatic injury. Doctors' subjective haemodynamic stability assessments had higher specificity, sensitivity and predictive values than shock index alone. Haemodynamic instability and a positive FAST result were significantly related (p=0.004). Sensitivities and specificities of FAST scans for blunt and penetrating trauma were 93.1% and 100%, and 90.0% and 100%, respectively. Corresponding values for pneumothoraces were 84.6% and 100%. DISCUSSION: This study showed a valuable role for FAST in all traumas, particularly in haemodynamic compromise. As an addition to the physician's repertoire of bedside assessment tools, it improves diagnostic capabilities in comparison with simple haemodynamic assessments alone.

Assessment of coagulopathy, endothelial injury, and inflammation after traumatic brain injury and hemorrhage in a porcine model.

BACKGROUND: Traumatic brain injury (TBI) and hemorrhagic shock (HS) can be associated with coagulopathy and inflammation, but the mechanisms are poorly understood. We hypothesized that a combination of TBI and HS would disturb coagulation, damage the endothelium, and activate inflammatory and complement systems. METHODS: A total of 33 swine were allocated to either TBI + HS (n = 27, TBI and volume-controlled 40% blood loss) or controls (n = 6, anesthesia and instrumentation). TBI + HS animals were left hypotensive (mean arterial pressure, 30-35 mm Hg) for 2 hours. Blood samples were drawn at baseline, 3 minutes and 15 minutes after injury, as well as following 2 hours of hypotension. Markers of coagulation, anticoagulation, endothelial activation/glycocalyx shedding, inflammation, complement, and sympathoadrenal function were measured. RESULTS: The TBI + HS group demonstrated an immediate (3 minutes after injury) activation of coagulation (prothrombin fragment 1 + 2, 289 ng/mL vs. 232 ng/mL, p = 0.03) and complement (C5a, 2.83 ng/mL vs. 2.05 ng/mL, p = 0.05). Shedding of the endothelial glycocalyx (syndecan 1) was evident 15 minutes after injury (851.0 ng/ml vs. 715.5 ng/ml, p = 0.03) while inflammation (tumor necrosis factor α [TNF-α], 81.1 pg/mL vs. 50.8 pg/mL, p = 0.03) and activation of the protein C system (activated protein C, 56.7 ng/mL vs. 26.1 ng/mL, p = 0.01) were evident following the 2-hour hypotension phase. CONCLUSION: The combination of TBI and shock results in an immediate activation of coagulation and complement systems with subsequent endothelial shedding, protein C activation, and inflammation.

Use of the non-pneumatic anti-shock garment (NASG) for life-threatening obstetric hemorrhage: a cost-effectiveness analysis in Egypt and Nigeria.

OBJECTIVE: To assess the cost-effectiveness of a non-pneumatic anti-shock garment (NASG) for obstetric hemorrhage in tertiary hospitals in Egypt and Nigeria. METHODS: We combined published data from pre-intervention/NASG-intervention clinical trials with costs from study sites. For each country, we used observed proportions of initial shock level (mild: mean arterial pressure [MAP] >60 mmHg; severe: MAP ≤60 mmHg) to define a standard population of 1,000 women presenting in shock. We examined three intervention scenarios: no women in shock receive the NASG, only women in severe shock receive the NASG, and all women in shock receive the NASG. Clinical data included frequencies of adverse health outcomes (mortality, severe morbidity, severe anemia), and interventions to manage bleeding (uterotonics, blood transfusions, hysterectomies). Costs (in 2010 international dollars) included the NASG, training, and clinical interventions. We compared costs and disability-adjusted life years (DALYs) across the intervention scenarios. RESULTS: For 1000 women presenting in shock, providing the NASG to those in severe shock results in decreased mortality and morbidity, which averts 357 DALYs in Egypt and 2,063 DALYs in Nigeria. Differences in use of interventions result in net savings of $9,489 in Egypt (primarily due to reduced transfusions) and net costs of $6,460 in Nigeria, with a cost per DALY averted of $3.13. Results of providing the NASG for women in mild shock has smaller and uncertain effects due to few clinical events in this data set. CONCLUSION: Using the NASG for women in severe shock resulted in markedly improved health outcomes (2-2.9 DALYs averted per woman, primarily due to reduced mortality), with net savings or extremely low cost per DALY averted. This suggests that in resource-limited settings, the NASG is a very cost-effective intervention for women in severe hypovolemic shock. The effects of the NASG for mild shock are less certain.

[The homeostasis assessment by hemorrhagic shock].

The comparative analysis of different protocols of infusion therapy of the hemorrhagic shock stage III was performed. The infusion of the colloid solution of hydroxiethylstarch 200/0.5 and non-balanced crystalloid 0.9% solution of natrium chloride leads to the development of negative changes in homeostasis. Whereas infusion of the 4% solution of the modified gelatin and balanced crystalloid solition (sterofundin) allows to avoid the registered changes in electrolyte and alkaline balance.

[Assessment of efficacy of hypertonic saline - hydroxyethylstarch in haemorrhagic shock]. / Intérêt du mélange sérum salé hypertonique-hydroxyéthylamidon lors du choc hémorragique.

OBJECTIVE: Assessment of haemodynamic, respiratory and renal effects of hypertonic saline-hydroxyethyl starch (HyperHES) in critically ill-patients with hemorrhagic shock. PATIENTS AND METHODS: Seventeen mechanically ventilated patients with hemorragic shock benefiting from a cardiovascular monitoring by PiCCO device and requiring rapid volume loading. Two hundred and fifty milliliters of HyperHES were given over 5 minutes. The efficacy of volume loading was assessed by the measure of the systolic arterial pressure (SAP), cardiac index (CI), stroke volume variation (SVV) and the indexed systemic vascular resistance (iSVR). Studied parameters were assessed at baseline, 5, 30, 60 and 180 minutes after the end of HyperHES infusion. RESULTS: SAP (105 + or - 23 vs 77 + or - 10; p<0.001) and CI (4.8 + or - 1.1 vs 3.5 + or - 0.9; p<0.001) were significantly increased whereas iSVR (1175 + or - 310 vs 1501 + or - 337; p<0.01) and SVV (13 + or - 7 vs 20 + or - 5; p<0.01) were significantly decreased 5 minutes after the HyperHES infusion. Sodium (145 + or - 6 vs 136 + or - 5; p<0.001) and chloride (118 + or - 7 vs 107 + or - 6; p<0.001) were increased 5 minutes after the infusion. The PaO(2)/FiO(2) ratio as the extravascular lung water was not influenced by the infusion. The follow-up of renal parameters during the three first days (creatinemia, uremia and diuresis) did not revelead significant variations. CONCLUSION: In patients with hemorrhagic shock, the infusion of hypertonic saline (7.5%) hydroxyethyl starch association was followed by an increase in SAP, CI serum sodium and chloride concentrations. STUDY DESIGN: Prospective observational study.

Hypothermia in multisystem trauma.

Exsanguinating hemorrhage is a common clinical feature of multisystem trauma that results in death or severe disability. Cardiovascular collapse resulting from hemorrhage is unresponsive to conventional methods of cardiopulmonary resuscitation. Even when bleeding is controlled rapidly, adequate circulation cannot be restored in time to avoid neurologic consequences that appear after only 5 mins of cerebral ischemia and hypoperfusion. Reperfusion adds further insult to injury. A novel solution to this problem would be to institute a therapy that makes cells and organs more resistant to ischemic injury, thereby extending the time they can tolerate such an insult. Hypothermia can attenuate some effects of ischemia and reperfusion. Accumulating preclinical data demonstrate that hypothermia can be induced safely and rapidly to achieve emergency preservation for resuscitation during lethal hemorrhage. Hypothermia may be an effective therapeutic approach for otherwise lethal traumatic hemorrhage, and a clinical trial to determine its utility is warranted.

[Assessment of the use of transfusion therapy and complications in orthopedic surgery in patients with sickle-cell anemia: retrospective study]. / Analyse des pratiques transfusionnelles et complications chez le patient drépanocytaire en situation de chirurgie orthopédique: étude rétrospective.

Red blood cells (RBCs) transfusion is a common practice in the treatment or for the prevention of complications of patients with sickle-cell disease. In surgery, pre-operative transfusions are frequently given to prevent peri-operative complications. There is no consensus however on the best regimen of transfusion for this purpose. The transfusion techniques are muliple. In addition, pre-operative transfusion therapy is reported to be largely responsible for an increased morbidity and mortality in patients with sickle cell anemia undergoing surgery. During the period 1990-2000, 16 patients (4 men and 12 women) with a mean age of 37 years and various major sickle cell hemoglobinopathies underwent 32 total hip arthroplasty for femoral head necrosis. Nine patients with sickle-cell trait were included as control group. Twelve of them had haemoglobin SS (HbSS), 2/16 had HbSC, 2/16 had HbS/betathalassemia. Operative transfusion were given in only 12/32 procedures, 4 were performed pre-operatively and 8 intra-operatively. Simple transfusion (mean: 2.5 packed red cells) were administered in all the procedures. The main complications observed in our patients were anemia by hemolysis and haemorrhagic shock, vaso-occlusive crisis and chest syndrome. Anemia requiring transfusions was significatively related to the procedures with pre-operative transfusion. In the light of our result, we would like to propose transfusional protocol--if needed--only intra-operatively.

Assessment of initial base deficit as a predictor of outcome: mechanism of injury does make a difference.

Initial base deficit in injured patients has been shown to predict the adequacy of resuscitation and outcome. The usefulness of base deficit as a predictor of outcome, however, may be dependent on the mechanism of injury. We conducted a retrospective review of the trauma registry, supplemented by chart review, of all trauma patients treated at a Level I trauma center from January 1995 through July 2001. Data collected included mechanism of injury, base deficit, Injury Severity Score, and outcome. From 1995 through 2001 a total of 3275 patients (23% of trauma admissions) at a mean age of 34 +/- 15 years had a base deficit recorded at the time of admission. The patients were 78 per cent male, and the mechanism of injury was blunt trauma in 58.2 per cent. Mortality increased with successive increases in base deficit but was markedly lower for a given base deficit in those patients having sustained stab wounds and/or severe lacerations as compared with those with gunshot wounds or blunt trauma. The value of the base deficit as a predictor of outcome depends upon the mechanism of injury and appears most useful for patients sustaining gunshot wounds or blunt trauma. Future studies in patients with penetrating trauma using base deficit as a predictor of outcome should separate patients with gunshot wounds from those with stab wounds or lacerations.