Resuscitation Strategies Research Articles

A comparative Study between the Effect of Resuscitation Strategy targeting Capillary Refill Time And Lactate Level To predict Mortality Among Patients With Septic Shock

A comparative Study between the Effect of Resuscitation Strategy targeting Capillary Refill Time And Lactate Level To predict Mortality Among Patients With Septic Shock

13 Thromboelastographic Coagulation Assessment in Burn Patients Receiving Plasma Inclusive Resuscitation

Abstract Introduction As resuscitative strategies in burn patients are re-evaluated, a consensus has not been reached on the role for colloids, as lactated ringers remain the fluid of choice with variable use of colloids. Colloids, such as fresh frozen plasma (FFP), may be effective at maintaining oncotic pressure, resupplying coagulation factors, mitigating coagulopathy, and treating the endothelium. This work aims to characterize the coagulation profile of burn patients treated with plasma inclusive resuscitation (PIR) using rapid thromboelastography (rTEG) by comparing it to burn patients primarily resuscitated with crystalloids alone. Methods Patients admitted to a regional burn center who had greater than 20% total body surface area (TBSA) burns that received PIR were included in the study. Patients admitted with burn injuries and resuscitated primarily with lactated ringers were included in the comparison group. Demographic data and blood samples were collected at 4 time points: baseline, before FFP, immediately following the initial unit of FFP, and following the completion of consecutive units of FFP. Samples collected from patients that received LR only were approximated to the FFP group time points. Coagulation parameters were measured using rTEG in blood samples. Descriptive analysis was used to compare demographic and burn injury characteristics at admission. A mixed effects model was used to compare the two groups through the observation period overall and at each time point. Results There were 35 patients in the FFP group and 15 patients in the comparison group. The groups were primarily male (74.3% vs 73.3%), and there was no difference in demographics, TBSA (34.0% (27.0-48.5) vs 33.0% (26.5-46.5, p=0.82)), Baux score, inhalation injury, and mortality rate (28.6% vs 26.7%, p=0.99). Major coagulation markers of rTEG (k, α-angle, MA, and ly30) were not different between these groups and were within normal ranges. The R time in the crystalloid group was greater than the normal range at all 4 time points. There were significant differences in R time at pre-FFP (30.0(25.0-32.5) secs vs 48.0 (36.0-54.0) secs, p< 0.001) and after all units (27.5(20.9-33.8) secs vs 48.0(48.0-54.0) secs, p< 0.0001) when compared to the FFP group where R time was in the normal range. Conclusions Plasma inclusive burn resuscitation did not result in hypercoagulability or changes in lysis when compared to patients primarily resuscitated with crystalloids. The elevated R time in the crystalloid group, which was not seen in the FFP group, may be due to the lack of replenishment in coagulation factors that FFP would provide. Further understanding of PIR’s role in the inflammatory response is needed to evaluate its impact during resuscitation. Applicability of Research to Practice Plasma inclusive resuscitation may be another tool to treat the multifactorial nature of burn shock and burn induced coagulopathy.

Cost Savings of Whole Blood Versus Component Therapy at a Community Level 1 Trauma Center.

Blood product component-only resuscitation (CORe) has been the standard of practice in both military and civilian trauma care with a 1:1:1 ratio used in attempt to recreate whole blood (WB) until recent data demonstrated WB to confer a survival advantage, leading to the emergence of WB as the contemporary resuscitation strategy of choice. Little is known about the cost and waste reduction associated with WB vs CORe. This study is a retrospective single-center review of adult trauma patients admitted to a community trauma center who received WB or CORe as part of their massive transfusion protocol (MTP) resuscitation from 2017 to 2021. The WB group received a minimum of one unit WB while CORe received no WB. Univariate and multivariate analyses were completed. Statistical analysis was conducted using a 95% confidence level. Non-normally distributed, continuous data were analyzed using the Wilcoxon rank sum test. 576 patients were included (201 in WB and 375 in CORe). Whole blood conveyed a survival benefit vs CORe (OR 1.49 P < .05, 1.02-2.17). Whole blood use resulted in an overall reduction in products prepared (25.8%), volumes transfused (16.5%), product waste (38.7%), and MTP activation (56.3%). Cost savings were $849923 annually and $3399693 over the study period. Despite increased patient volumes over the study period (43.7%), the utilization of WB as compared to CORe resulted in an overall $3.39million cost savings while improving mortality. As such, we propose WB should be utilized in all resuscitation strategies for the exsanguinating trauma patient.

Effects of different types of Ringer’s solution on patients with traumatic haemorrhagic shock: a prospective cohort study

ObjectiveTo compare the fluid resuscitation effect of sodium acetate Ringer’s solution and sodium bicarbonate Ringer’s solution on patients with traumatic haemorrhagic shock.MethodWe conducted a prospective cohort study in our emergency department on a total of 71 patients with traumatic haemorrhagic shock admitted between 1 December 2020 and 28 February 2022. Based on the time of admission, patients were randomly divided into a sodium bicarbonate Ringer’s solution group and sodium acetate Ringer’s solution group, and a limited rehydration resuscitation strategy was adopted in both groups. General data were collected separately, and the patients’ vital signs (body temperature, respiration, blood pressure and mean arterial pressure (MAP)), blood gas indices (pH, calculated bicarbonate (cHCO3−), partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (pCO2) and clearance of lactate (CLac)), shock indices, peripheral platelet counts, prothrombin times and plasma fibrinogen levels were measured and compared before and 1 h after resuscitation.ResultsThe post-resuscitation heart rate of the sodium bicarbonate Ringer’s solution group was significantly lower than that of the sodium acetate Ringer’s solution group (p < 0.05), and the MAP was also significantly lower (p < 0.05). The patients in the sodium bicarbonate Ringer’s solution group had significantly higher pH, cHCO3− and PaO2 values and lower pCO2 and CLac values (p < 0.05) than those in the sodium acetate Ringer’s solution group, and the post-resuscitation peripheral platelet counts and fibrinogen levels were significantly higher, with shorter plasma prothrombin times and smaller shock indices (p < 0.001).ConclusionSodium bicarbonate Ringer’s solution is beneficial for maintaining MAP at a low level after resuscitation. The use of sodium bicarbonate Ringer’s solution in limited fluid resuscitation has positive results and is of high clinical value.

Preferential whole blood transfusion during the early resuscitation period is associated with decreased mortality and transfusion requirements in traumatically injured patients

IntroductionWhole blood (WB) transfusion represents a promising resuscitation strategy for trauma patients. However, a paucity of data surrounding the optimal incorporation of WB into resuscitation strategies persists. We hypothesized that...

Does an early, balanced resuscitation strategy reduce the incidence of hypofibrinogenemia in hemorrhagic shock?

ObjectivesSome centers have recommended including concentrated fibrinogen replacement in massive transfusion protocols (MTPs). Given our center’s policy of aggressive early balanced resuscitation (1:1:1), beginning prehospital, we hypothesized that our rates...

Blood Transfusion for Major Trauma in Emergency Department.

Severe bleeding is the leading cause of death in patients with major trauma admitted to the emergency department. It is estimated that about 50% of deaths happen within a few minutes of the traumatic event due to massive hemorrhage; 30% of deaths are related to neurological dysfunction and typically happen within two days of trauma; and approximately 20% of patients died of multiorgan failure and sepsis within days to weeks of the traumatic event. Over the past ten years, there has been an increased understanding of the underlying mechanisms and pathophysiology associated with traumatic bleeding leading to improved management measures. Traumatic events cause significant tissue damage, with the potential for severe blood loss and the release of cytokines and hormones. They are responsible for systemic inflammation, activation of fibrinolysis pathways, and consumption of coagulation factors. As the final results of this (more complex in real life) cascade, patients can develop tissue hypoxia, acidosis, hypothermia, and severe coagulopathy, resulting in a rapid deterioration of general conditions with a high risk of mortality. Prompt and appropriate management of massive bleeding and coagulopathy in patients with trauma remains a significant challenge for emergency physicians in their daily clinical practice. Our review aims to explore literature studies providing evidence on the treatment of hemorrhage with blood support in patients with trauma admitted to the Emergency Department with a high risk of death. Advances in blood transfusion protocols, along with improvements in other resuscitation strategies, have become one of the most important issues to face and a key topic of recent clinical research in this field.

Whole blood resuscitation for injured patients requiring transfusion: A systematic review, meta-analysis, and practice management guideline from the Eastern Association for the Surgery of Trauma.

Whole blood (WB) resuscitation has reemerged as a resuscitation strategy for injured patients. However, the effect of WB-based resuscitation on outcomes has not been established. The primary objective of this guideline was to develop evidence-based recommendations on whether WB should be considered in civilian trauma patients receiving blood transfusions. An Eastern Association for the Surgery of Trauma working group performed a systematic review and meta-analysis using the Grading of Recommendations Assessment, Development and Evaluation methodology. One Population, Intervention, Comparison, and Outcomes question was developed to analyze the effect of WB resuscitation in the acute phase on mortality, transfusion requirements, infectious complications, and intensive care unit length of stay. English language studies including adult civilian trauma patients comparing in-hospital WB to component therapy were included. Medline, Embase, Cochrane CENTRAL, CINAHL Plus, and Web of Science were queried. GRADEpro (McMaster University; Evidence Prime, Inc.; Ontario) was used to assess quality of evidence and risk of bias. The study was registered on International Prospective Register of Systematic Reviews (CRD42023451143). A total of 21 studies were included. Most patients were severely injured and required blood transfusion, massive transfusion protocol activation, and/or a hemorrhage control procedure in the early phase of resuscitation. Mortality was assessed separately at the following intervals: early (i.e., emergency department, 3 hours, or 6 hours), 24 hours, late (i.e., 28 days or 30 days), and in-hospital. On meta-analysis, WB was not associated with decreased mortality. Whole blood was associated with decreased 4-hour red blood cell (mean difference, -1.82; 95% confidence interval [CI], -3.12 to -0.52), 4-hour plasma (mean difference, -1.47; 95% CI, -2.94 to 0), and 24-hour red blood cell transfusions (mean difference, -1.22; 95% CI, -2.24 to -0.19) compared with component therapy. There were no differences in infectious complications or intensive care unit length of stay between groups. We conditionally recommend WB resuscitation in adult civilian trauma patients receiving blood transfusions, recognizing that data are limited for certain populations, including women of childbearing age, and therefore this guideline may not apply to these populations. Systematic Review/Meta-Analysis; Level III.

Evaluating the efficacy of different volume resuscitation strategies in acute pancreatitis patients: a systematic review and meta-analysis

IntroductionAcute pancreatitis poses a significant health risk due to the potential for pancreatic necrosis and multi-organ failure. Fluid resuscitation has demonstrated positive effects; however, consensus on the ideal intravenous fluid type and infusion rate for optimal patient outcomes remains elusive.MethodsA comprehensive literature search was conducted using PubMed, Embase, the Cochrane Library, Scopus, and Google Scholar for studies published between 2005 and January 2023. Reference lists of potential studies were manually searched to identify additional relevant articles. Randomized controlled trials and retrospective studies comparing high (≥ 20 ml/kg/h), moderate (≥ 10 to < 20 ml/kg/h), and low (5 to < 10 ml/kg/h) fluid therapy in acute pancreatitis were considered.ResultsTwelve studies met our inclusion criteria. Results indicated improved clinical outcomes with low versus moderate fluid therapy (OR = 0.73; 95% CI [0.13, 4.03]; p = 0.71) but higher mortality rates with low compared to moderate (OR = 0.80; 95% CI [0.37, 1.70]; p = 0.55), moderate compared to high (OR = 0.58; 95% CI [0.41, 0.81], p = 0.001), and low compared to high fluids (OR = 0.42; 95% CI [0.16, 1.10]; P = 0.08). Systematic complications improved with moderate versus low fluid therapy (OR = 1.22; 95% CI [0.84, 1.78]; p = 0.29), but no difference was found between moderate and high fluid therapy (OR = 0.59; 95% CI [0.41, 0.86]; p = 0.006).DiscussionThis meta-analysis revealed differences in the clinical outcomes of patients with AP receiving low, moderate, and high fluid resuscitation. Low fluid infusion demonstrated better clinical outcomes but higher mortality, systemic complications, and SIRS persistence than moderate or high fluid therapy. Early fluid administration yielded better results than rapid fluid resuscitation.

Blood failure: traumatic hemorrhage and the interconnections between oxygen debt, endotheliopathy, and coagulopathy.

This review explores the concept of "blood failure" in traumatic injury, which arises from the interplay of oxygen debt, the endotheliopathy of trauma (EoT), and acute traumatic coagulopathy (ATC). Traumatic hemorrhage leads to the accumulation of oxygen debt, which can further exacerbate hemorrhage by triggering a cascade of events when severe. Such events include EoT, characterized by endothelial glycocalyx damage, and ATC, involving platelet dysfunction, fibrinogen depletion, and dysregulated fibrinolysis. To manage blood failure effectively, a multifaceted approach is crucial. Damage control resuscitation strategies such as use of permissive hypotension, early hemorrhage control, and aggressive transfusion of blood products including whole blood aim to minimize oxygen debt and promote its repayment while addressing endothelial damage and coagulation. Transfusions of red blood cells, plasma, and platelets, as well as the use of tranexamic acid, play key roles in hemostasis and countering ATC. Whole blood, whether fresh or cold-stored, is emerging as a promising option to address multiple needs in traumatic hemorrhage. This review underscores the intricate relationships between oxygen debt, EoT, and ATC and highlights the importance of comprehensive, integrated strategies in the management of traumatic hemorrhage to prevent blood failure. A multidisciplinary approach is essential to address these interconnected factors effectively and to improve patient outcomes.

Trends in pre-hospital volume resuscitation of blunt trauma patients: a 15-year analysis of the British (TARN) and German (TraumaRegister DGU®) National Registries

IntroductionFluid resuscitation has long been a cornerstone of pre-hospital trauma care, yet its optimal approach remains undetermined. Although a liberal approach to fluid resuscitation has been linked with increased complications, the potential survival benefits of a restrictive approach in blunt trauma patients have not been definitively established. Consequently, equipoise persists regarding the optimal fluid resuscitation strategy in this population.MethodsWe analysed data from the two largest European trauma registries, the UK Trauma Audit and Research Network (TARN) and the German TraumaRegister DGU® (TR-DGU), between 2004 and 2018. All adult blunt trauma patients with an Injury Severity Score > 15 were included. We examined annual trends in pre-hospital fluid resuscitation, admission coagulation function, and mortality rates.ResultsOver the 15-year study period, data from 68,510 patients in the TARN cohort and 82,551 patients in the TR-DGU cohort were analysed. In the TARN cohort, 3.4% patients received pre-hospital crystalloid fluids, with a median volume of 25 ml (20–36 ml) administered. Conversely, in the TR-DGU cohort, 91.1% patients received pre-hospital crystalloid fluids, with a median volume of 756 ml (750–912 ml) administered. Notably, both cohorts demonstrated a consistent year-on-year decrease in the volume of pre-hospital fluid administered, accompanied by improvements in admission coagulation function and reduced mortality rates.ConclusionConsiderable variability exists in pre-hospital fluid resuscitation strategies for blunt trauma patients. Our data suggest a trend towards reduced pre-hospital fluid administration over time. This trend appears to be associated with improved coagulation function and decreased mortality rates. However, we acknowledge that these outcomes are influenced by multiple factors, including other improvements in pre-hospital care over time. Future research should aim to identify which trauma populations may benefit, be harmed, or remain unaffected by different pre-hospital fluid resuscitation strategies.

Isotonic hydroxyethyl starch is ineffective in restoring blood pressure during experimental septic shock: Implications for fluid resuscitation strategies

Objectives: The objectives of the study were to evaluate the effect of isotonic or hypertonic hydroxyethyl starch (HES) solutions on blood pressure and to assess the influence of the neurohypophyseal system on this response during experimental septic shock. Male Wistar rats were randomly allocated to undergo either cecal and ligation puncture (CLP) or a simulated surgical procedure (sham). Materials and Methods: Of 6 h post-surgery, either isotonic saline (0.9% sodium chloride, 4 mL/kg), isotonic (HES; at doses of 4, 8 or 16 mL/kg), or hypertonic saline-HES (HS-HES; 4 mL/kg) was administered through the endovenous route, followed by the recording of blood pressure and heart rate. In addition, the levels of sodium, vasopressin, and oxytocin were evaluated after the fluid infusion. Results: The administration of HES did not have a significant effect on blood pressure in our study. However, the HS-HES solution increased plasma osmolality, sodium, vasopressin, and oxytocin levels. Furthermore, the HS-HES induced a transient elevation in blood pressure immediately after infusion, which could be completely blunted by the pre-administration of a V1-vasopressin antagonist. Conclusion: Our results demonstrate that the infusion of an isotonic blood volume expander during experimental septic shock is ineffective in restoring blood pressure due to blood vessel compliance. In contrast, the infusion of a hypertonic solution stimulates vasopressin secretion and can transiently restore blood pressure.

Effect of major trauma on the expected number of births in Finnish women: A nationwide population-based public data and register analysis.

The effect of major trauma on subsequent fertility is poorly described. If women have lower fertility after trauma, they would have a lower risk of anti-D mediated hemolytic disease of the fetus and newborn in a future pregnancy following the transfusion of RhD-positive blood to RhD-negative women during their resuscitation. Data was obtained from the Care Register for Health Care, National Medical Birth Register, and open access data from Statistic Finland to evaluate the effect of major trauma (traumatic brain injuries, spine, pelvic, hip/thigh fractures) on the age-specific number of births during years 1998-2018. The total number of births before a specific maternal age for different trauma populations was calculated and these were compared to the corresponding number of births in the general population. There were 50,923 injured women in this study. All injured women, including when analyzed by the nature of their injury, demonstrated lower expected numbers of births starting at approximately 28 years of age compared to the general population of women in Finland. At age 49, the expected number of births in the general population was approximately 1.8, whereas for all injured women 0.6, women with TBIs and spine fractures 0.6, women with pelvic fractures 0.5, and women with hip or thigh fractures 0.3. Injured women are predicted to have lower fertility rates compared to the general population of Finnish women. The lower fertility rate should be considered when planning a blood product resuscitation strategy for injured women.

Enteral Resuscitation: A Field-Expedient Treatment Strategy for Burn Shock during Wartime and in Other Austere Settings.

Burn injuries are a constant threat in war. Aspects of the modern battlefield increase the risk of burn injuries and pose challenges for early treatment. The initial resuscitation of a severely burn-injured patient often exceeds the resources available in front-line medical facilities. This stems mostly from the weight and volume of the intravenous fluids required. One promising solution to this problem is enteral resuscitation with an oral rehydration solution. In addition to being logistically easier to manage, enteral resuscitation may be able to mitigate secondary injuries to the gut related to burn shock and systemic immunoinflammatory activation. This has been previously studied in burn patients, primarily using electrolyte solutions, with promising results. Modern ORS containing sodium, potassium, and glucose in ratios that maximize gut absorption may provide additional benefits as a resuscitation strategy, both in terms of plasma volume expansion and protection of the barrier and immune functions of the gut mucosa. While enteral resuscitation is promising and should be used when other options are not available, further research is needed to refine an optimal implementation strategy.

Towards the personalization of septic shock resuscitation: the fundamentals of ANDROMEDA-SHOCK-2 trial

Septic shock is a highly lethal and prevalent disease. Progressive circulatory dysfunction leads to tissue hypoperfusion and hypoxia, eventually evolving to multiorgan dysfunction and death. Prompt resuscitation may revert these pathogenic mechanisms, restoring oxygen delivery and organ function. High heterogeneity exists among the determinants of circulatory dysfunction in septic shock, and current algorithms provide a stepwise and standardized approach to conduct resuscitation.This review provides the pathophysiological and clinical rationale behind ANDROMEDA-SHOCK-2, an ongoing multicenter randomized controlled trial that aims to compare a personalized resuscitation strategy based on clinical phenotyping and peripheral perfusion assessment, versus standard of care, in early septic shock resuscitation.

Trauma and hemorrhage control: a systematic review

Worldwide, trauma is a leading cause of death and disability. Hemorrhage is responsible for up to 40% of trauma deaths. Recent strategies to improve mortality rates have focused on optimal methods of early hemorrhage control and correction of coagulopathy. This review aimed to evaluate hemorrhage control in trauma patients and to assess the effectiveness of interventions in bleeding and/or transfusion requirements; correction of trauma-induced coagulopathy and mortality. The Google Scholar, Web of Science, Cochrane, and PubMed databases were used to explore studies between 2012 and 2023. The keywords included &amp;quot;hemorrhage, control, trauma, patients, bleeding, coagulopathy, and mortality&amp;quot; and were used in various combinations. In addition, original research reporting hemorrhage control in trauma patients was evaluated. Full-text publications served as the inclusion criterion. Though 85 articles were obtained, only eight met the inclusion criteria. All the studies were retrospective. The study population was comprised of more than 9,634 trauma patients. Uncontrolled hemorrhagic shock was found to be the main reason for trauma patients&amp;apos; death. The resuscitation strategy should center upon permissive hypotension and early hemostatic resuscitation combined to identify and correct coagulopathy. Antiplatelet therapy patients with ground-level falls had a higher risk of traumatic intracranial hemorrhage than anticoagulation therapy patients. For patients suffering hemorrhagic shock, and especially from truncal hemorrhage, the recommended primary outcome was 3 to 6-hour all-cause mortality, chosen to coincide with the physiology of hemorrhagic death and to avoid bias from competing risks. For pelvic trauma patients, intervention for pelvic hemorrhage management was necessary.

Therapeutic assessment of crystalloid fluid resuscitation in experimental military injury.

A significant part of blast injury is accompanied by hemorrhagic shock (BS), while research on its fluid resuscitation strategies have not been reported. Although blood products are usually recommended in most resuscitation cases, they are less available in certain conditions. To this end, here, we focused on a widely used and more accessible fluid type- crystalloid fluid, in BS treatment. We conducted studies in rats comparing the therapeutic effects of 3 different crystalloid solutions at different time points after BS, and explored the underlying mechanisms. Generally, the survival rates gradually dropped along with the time when fluid resuscitation was given. Among different types of solution, the hypertonic saline (HS) group showed the highest survival rates. The lactated Ringer's solution (LR) only displayed lifesaving effect at 0.5h resuscitation time point. Moreover, it is worth noting that the survival rates of the normal saline (NS) group at all the time points were lower than the non-treatment control. Mechanism study in rats indicated that the therapeutic differences may be caused by varied degrees of pulmonary edema and inflammatory responses under different crystalloid fluid resuscitation. In conclusion, we assessed the effects and investigated the mechanisms of different crystalloid fluid resuscitation strategies for BS for the first time, which potentially contributes to the establishment of guidance for crystalloid fluid resuscitation of BS patients.

Fluid management strategy in dengue acute respiratory distress syndrome with chronic kidney disease: A case report

Abstract Pulmonary manifestation in dengue is due to the involvement of both the upper and lower airways. Severe forms of dengue infection (pleural effusion, dengue hemorrhagic shock syndrome, and acute respiratory distress syndrome [ARDS]) are mainly due to the involvement of the lower respiratory tract. ARDS is a well-known respiratory complication following dengue infection. Patients with chronic kidney disease (CKD) diagnosed with dengue had a higher risk of unfavorable outcomes. Pulmonary involvement is one of the life-threatening complications in patients having CKD that contributes to increasing the mortality rate. Dysregulation of cytokines and apoptotic signaling pathway is a nonclassical mechanism of the kidney–lung crosstalk that results in the development of acute kidney injury in patients having ARDS. Severe worsening of renal function is common in CKD patients with dengue. Here, we discuss fluid management strategy in a patient having CKD who developed ARDS following dengue infection. The difficulty in the therapeutic dilemma is attributable to ambiguity in liberal versus conservative fluid therapy, contributing to a high risk of mortality. The narrow window of fluid tolerance in CKD patients further complicates the resuscitation strategy in patients with dengue ARDS.

A stochastic multicompartment model of hemostasis and oxygenation during trauma resuscitation as a platform for in silico trials of transfusion

Abstract Uncontrolled hemorrhage accounts for up to 40% of trauma related mortality, and approximately 30% of trauma related deaths occur in the hospital within the first 1-4 hours of injury. The Advanced Trauma Life Support (ATLS) guidelines still recommend initial resuscitation with crystalloid fluid as an integral part of maintaining or restoring hemodynamic stability, but are starting to recognize the role of early resuscitation with blood products in patients with evidence of Class III and IV hemorrhage, in line with recent clinical trial and observational data. Although there is a growing body of evidence that early transfusion with blood products may be associated with improved survival compared with crystalloid infusion, the optimal transfusion strategy still remains unclear and is being actively investigated in clinical trials. In silico models of resuscitation offer a means to evaluate the effectiveness and safety of resuscitation protocols, including effects on body fluid compartment volumes, tissue oxygenation, and hemostatic factors. Here we describe our work extending earlier deterministic models of trauma resuscitation to incorporate hemodynamic, hemostatic, resuscitation, biomarker, and tissue-oxygenation domains into a single comprehensive model. Additionally, this model expands upon previous deterministic models to create a stochastic computational model of hemostatic resuscitation that accounts for variations in blood component composition and temporal features of transfusion therapy. Using this stochastic model, an in silico trial was piloted to compare conventional component therapy, i.e. red cell, platelet and plasma components, to cold-stored whole blood using the following starting assumptions: patient weight of 81.3±21.8 kg, hematocrit of 41.8±4.3%, initial bleeding rate between 50 and 150 mL/min, systolic blood pressure of 125±18 mmHg, fibrinogen of 293±88 mg/dL, international normalized ratio of 1.0±0.1 and platelet count of 239±62x109/L, with blood component and whole blood constituent distributions based on laboratory quality control data. This in silico trial demonstrated that resuscitation with whole blood was associated with a 28-minute reduction in the time spent in the critical window defined by platelet count &amp;lt;50x109/L, INR≥2, hemoglobin &amp;lt;9 g/dL and fibrinogen &amp;lt;150 mg/dL compared with conventional component resuscitation over the course of a 4 hour simulation (p&amp;lt;0.001 based on median regression). We demonstrate how stochastic models of hemostatic resuscitation can be used to perform in silico trials of resuscitation strategies. Our work can guide inclusion and exclusion criteria for future clinical trials and facilitate identification of patient subgroups most likely to benefit from certain resuscitation strategies. This work was partially funded by the AABB Foundation (formerly the National Blood Foundation).

The intersection of coagulation activation and inflammation after injury: What you need to know.

IV, Review article.