Factors Associated With Mortality Among Patients Managed for Large Volume Hemorrhage in a Medical Intensive Care Unit.

PURPOSE: Our goal was to describe resuscitation practices in critically ill medical patients with active hemorrhage requiring large volume resuscitation and identify factors associated with poor outcomes. PATIENTS AND METHODS: This was a single center retrospective observational cohort study. Patients admitted to the medical intensive care unit from 2011 to 2017 who received ≥5 units of packed red blood cells (pRBCs) within 24 h were included. Data including volume of blood products and crystalloid administered, baseline sequential organ failure assessment (SOFA) scores, and outcomes were abstracted. Univariate and multivariate analyses were performed to determine clinical factors associated with hospital mortality. RESULTS: Two hundred forty-six patients were identified. Mean volumes of 2,448 mL of pRBCs and 3.9L of crystalloid were transfused over 24 h. Inpatient mortality for the entire cohort was 48%. Multivariable analysis identified factors associated with hospital mortality; higher BMI (OR 1.047, 95% CI 1.013-1.083), higher ratio of fresh frozen plasma (FFP) to pRBCs (OR 2.744, 95% CI 1.1-6.844), and higher baseline SOFA scores (OR 1.3, 95% CI 1.175-1.437). CONCLUSION: In a cohort of critically ill medical patients undergoing resuscitation for hemorrhage, higher BMI, increased ratio of FFP to pRBCs, and higher SOFA scores were associated with increased mortality. Further studies are needed to clarify resuscitation practices associated with outcomes in this population.

Clinical decision support for severe trauma patients: Machine learning based definition of a bundle of care for hemorrhagic shock and traumatic brain injury.

BACKGROUND: Deviation from guidelines is frequent in emergency situations, and this may lead to increased mortality. Probably because of time constraints, 55% is the greatest reported guidelines compliance rate in severe trauma patients. This study aimed to identify among all available recommendations a reasonable bundle of items that should be followed to optimize the outcome of hemorrhagic shocks (HSs) and severe traumatic brain injuries (TBIs). METHODS: We first estimated the compliance with French and European guidelines using the data from the French TraumaBase registry. Then, we used a machine learning procedure to reduce the number of recommendations into a minimal set of items to be followed to minimize 7-day mortality. We evaluated the bundles using an external validation cohort. RESULTS: This study included 5,924 trauma patients (1,414 HS and 4,955 TBI) between 2011 and August 2019 and studied compliance to 36 recommendation items. Overall compliance rate to recommendation items was 71.6% and 66.9% for HS and TBI, respectively. In HS, compliance was significantly associated with 7-day decreased mortality in univariate analysis but not in multivariate analysis (risk ratio [RR], 0.91; 95% confidence interval [CI], 0.90-1.17; p = 0.06). In TBI, compliance was significantly associated with decreased mortality in univariate and multivariate analysis (RR, 0.85; 95% CI, 0.75-0.92; p = 0.01). For HS, the bundle included 13 recommendation items. In the validation cohort, when this bundle was applied, patients were found to have a lower 7-day mortality rate (RR, 0.46; 95% CI, 0.27-0.63; p = 0.01). In TBI, the bundle included seven items. In the validation cohort, when this bundle was applied, patients had a lower 7-day mortality rate (RR, 0.55; 95% CI, 0.34-0.71; p = 0.02). DISCUSSION: Using a machine-learning procedure, we were able to identify a subset of recommendations that minimizes 7-day mortality following traumatic HS and TBI. These two bundles remain to be evaluated in a prospective manner. LEVEL OF EVIDENCE: Care Management, level II.

Mortalidade materna: perfil clínico e epidemiológico de uma maternidade pública do Amazonas / Maternal mortality: clinical and epidemiological profile of a public maternity hospital in Amazonas

Objetivo: Avaliar o perfil clínico e epidemiológico das mortes maternas ocorridas em uma maternidade pública de Manaus no período de janeiro de 2016 a dezembro de 2019. Métodos: Trata-se de um estudo do tipo descritivo e retrospectivo realizado a partir de dados contidos em prontuários médicos do Serviço de Arquivo Médico e Estatística (SAME) da Maternidade Ana Braga na cidade de Manaus-AM. A amostra foi constituída por pacientes admitidas na Maternidade Ana Braga e que evoluíram com óbito no ciclo gravídico puerperal, que consiste em grávidas, em trabalho de parto, que deram à luz ou que abortaram dentro de um período de até 42 dias. Resultados: Foram avaliados 29 prontuários de pacientes que foram a óbito no ciclo gravídico puerperal. Essas mulheres tinham entre 14 e 42 anos de idade. Quanto à escolaridade, 56,3% delas tinham ensino médio. Quanto à etnia, as mulheres negras e pardas representaram a maioria, as solteiras, o maior percentual. No óbito materno, observou-se que 10 mulheres realizaram menos de seis consultas pré-natal, a principal via de parto foi a cesariana e o choque séptico foi o mais prevalente como causa de morte. Conclusão: Esse resultado sugere a necessidade de avaliação do acesso oportuno das gestantes à assistência pré-natal, ao parto e ao puerpério adequada, além de melhorias na promoção de políticas públicas que busquem a redução da mortalidade materna.(AU)

Objective: To evaluate the clinical and epidemiological profile of maternal deaths that occurred in a public maternity hospital in Manaus from January 2016 to December 2019. Methods: This is a descriptive and retrospective study carried out based on data contained in medical records doctors from the Medical Archive and Statistics Service (SAME) of the Ana Braga Maternity Hospital in the city of Manaus-AM. The sample consisted of patients admitted to the Ana Braga Maternity Hospital and who died in the pregnancy-puerperal cycle, which consists of pregnant women, in labor, who gave birth or who aborted within a period of up to 42 days. Results: Were evaluated 29 records of patients who died in the pregnancy-puerperal cycle, these women were between 14 and 42 years old, and 56.3% had high school education. As for ethnicity, black and brown women represented the majority, single women the highest percentage. In maternal death, it was observed that 10 women had less than six prenatal consultations, the main mode of delivery was cesarean section and septic shock was the most prevalent cause of death. Conclusion: This result suggests the need to assess the timely access of pregnant women to adequate prenatal care, childbirth and postpartum care, in addition to improvements in the promotion of public policies that seek to reduce maternal mortality.(AU)

High resuscitative endovascular balloon occlusion of the aorta procedural volume is associated with improved outcomes: An analysis of the AORTA registry.

BACKGROUND: The use of resuscitative endovascular balloon occlusion of the aorta (REBOA) is controversial. We hypothesize that REBOA outcomes are improved in centers with high REBOA utilization. METHODS: We examined the Aortic Occlusion in Resuscitation for Trauma and Acute Care Surgery registry over a 5-year period (2014-2018). Resuscitative endovascular balloon occlusion of the aorta outcomes were analyzed by stratifying institutions into low-volume (<10), average-volume (11-30), and high-volume (>30) deployment centers. A multivariable model adjusting for volume group, mechanism of injury, signs of life, systolic blood pressure at initiation, operator level, device type, zone of placement, and hemodynamic response to aortic occlusion was created to analyze REBOA mortality and REBOA-related complications. RESULTS: Four hundred ninety-five REBOA placements were included. High-volume centers accounted for 63%, while low accounted for 13%. High-volume institutions were more likely to place a REBOA in the emergency department (81% vs. 63% low volume, p = 0.003), had a lower mean systolic blood pressure at insertion (53 ± 38 vs. 64 ± 40, p = 0.001), and more Zone I deployments (64% vs. 55%, p = 0.002). Median time from admission to REBOA placement was significantly less in patients treated at high-volume centers (15 [7-30] minutes vs. 35 [20-65] minutes, p = 0.001). Resuscitative endovascular balloon occlusion of the aorta mortality was significantly higher at low-volume centers (67% vs. 57%; adjusted odds ratio, 1.29; adj p = 0.040), while average- and high-volume centers were similar. Resuscitative endovascular balloon occlusion of the aorta complications were less frequent at high-/average-volume centers, but did not reach statistical significance (adj p = 0.784). CONCLUSION: Resuscitative endovascular balloon occlusion of the aorta survival is increased at high versus low utilization centers. Increased experience with REBOA may be associated with earlier deployment and subsequently improved patient outcomes. LEVEL OF EVIDENCE: Therapeutic/Care Management, level IV.

Pediatric age-adjusted shock index as a tool for predicting outcomes in children with or without traumatic brain injury.

BACKGROUND: The pediatric age-adjusted shock index (SIPA) accurately identifies severely injured children following trauma without accounting for neurological status. Understanding how the presence of traumatic brain injury (TBI) affects the generalizability of SIPA as a bedside triage tool is important given high rates of TBI in the pediatric trauma population. We hypothesized that SIPA combined with TBI (SIPAB+) would more accurately identify severely injured children. METHODS: Patients (1-18 years old) in the American College of Surgeons Pediatric Trauma Quality Improvement Program database (2014-2017) with an elevated SIPA upon arrival to a pediatric trauma center were included. Pediatric age-adjusted shock index combined with TBI was defined as elevated SIPA with Glasgow Coma Scale score of ≤8. Pediatric age-adjusted shock index without TBI (SIPAB-) was defined as elevated SIPA with Glasgow Coma Scale score of >9. Patients were stratified into SIPAB+ and SIPAB-. A subanalysis of patients with isolated brain injury and those with brain injury and multisystem injuries was also performed. Data were compared through univariate models and three separate logistic regression models. RESULTS: Overall, 25,068 had an elevated SIPA, with 12.3% classified as SIPAB+ and the remainder SIPAB-. Patients classified as SIPAB+ received more blood transfusions within 4 hours of injury and had higher mortality rates. On logistic regression, SIPAB+ patients had significantly higher odds of early blood transfusion and a combination of both. Mortality and early blood transfusion were also higher in SIPAB+ patients on subanalysis for patients with isolated TBI and those with multisystem injuries. CONCLUSION: The use of SIPAB+ as a bedside triage tool accurately identifies traumatically injured children at high risk for early blood transfusion and/or death while incorporating the presence of neurological injury. This is true for patients with isolated TBI and those with multisystem injury, indicating its utility in predicting outcomes for TBI patients with elevated SIPA regardless of presence of concomitant injuries. Incorporation of this as a triage tool should be considered to better predict resources in this population. LEVEL OF EVIDENCE: Prognostic, level III.

Efficacy of past, present, and future fluid strategies in an improved large animal model of non-compressible intra-abdominal hemorrhage.

BACKGROUND: Noncompressible hemorrhage is a leading cause of potentially survivable combat death, with the vast majority of such deaths occurring in the out-of-hospital environment. While large animal models of this process are important for device and therapeutic development, clinical practice has changed over time and past models must follow suit. Developed in conjunction with regulatory feedback, this study presents a modernized, out-of-hospital, noncompressible hemorrhage model, in conjunction with a randomized study of past, present, and future fluid options following a hypotensive resuscitation protocol consistent with current clinical practice. METHODS: We performed a randomized controlled experiment comparing three fluid resuscitation options in Yorkshire swine. Baseline data from animals of same size from previous experiments were analyzed (n = 70), and mean systolic blood pressure was determined, with a permissive hypotension resuscitation target defined as a 25% decrease from normal (67 mm Hg). After animal preparation, a grade IV to V liver laceration was induced. Animals bled freely for a 10-minute "time-to-responder" period, after which resuscitation occurred with randomized fluid in boluses to the goal target: 6% hetastarch in lactated electrolyte injection (HEX), normal saline (NS), or fresh whole blood (FWB). Animals were monitored for a total simulated "delay to definitive care" period of 2 hours postinjury. RESULTS: At the end of the 2-hour study period, 8.3% (1 of 12 swine) of the HEX group, 50% (6 of 12 swine) of the NS group, and 75% (9 of 12 swine) of the FWB had survived (p = 0.006), with Holm-Sidak pairwise comparisons showing a significant difference between HEX and FWB and (p = 0.005). Fresh whole blood had significantly higher systemic vascular resistance and hemoglobin levels compared with other groups (p = 0.003 and p = 0.001, respectively). CONCLUSION: Survival data support the movement away from HEX toward NS and, preferably, FWB in clinical practice and translational animal modeling. The presented model allows for future research including basic science, as well as translational studies of novel diagnostics, therapeutics, and devices.

Prehospital whole blood reduces early mortality in patients with hemorrhagic shock.

BACKGROUND: Low titer O+ whole blood (LTOWB) is being increasingly used for resuscitation of hemorrhagic shock in military and civilian settings. The objective of this study was to identify the impact of prehospital LTOWB on survival for patients in shock receiving prehospital LTOWB transfusion. STUDY DESIGN AND METHODS: A single institutional trauma registry was queried for patients undergoing prehospital transfusion between 2015 and 2019. Patients were stratified based on prehospital LTOWB transfusion (PHT) or no prehospital transfusion (NT). Outcomes measured included emergency department (ED), 6-h and hospital mortality, change in shock index (SI), and incidence of massive transfusion. Statistical analyses were performed. RESULTS: A total of 538 patients met inclusion criteria. Patients undergoing PHT had worse shock physiology (median SI 1.25 vs. 0.95, p < .001) with greater reversal of shock upon arrival (-0.28 vs. -0.002, p < .001). In a propensity-matched group of 214 patients with prehospital shock, 58 patients underwent PHT and 156 did not. Demographics were similar between the groups. Mean improvement in SI between scene and ED was greatest for patients in the PHT group with a lower trauma bay mortality (0% vs. 7%, p = .04). No survival benefit for patients in prehospital cardiac arrest receiving LTOWB was found (p > .05). DISCUSSION: This study demonstrated that trauma patients who received prehospital LTOWB transfusion had a greater improvement in SI and a reduction in early mortality. Patient with prehospital cardiac arrest did not have an improvement in survival. These findings support LTOWB use in the prehospital setting. Further multi-institutional prospective studies are needed.

Placenta Accreta Spectrum Treatment With Intraoperative Multivessel Embolization: the PASTIME protocol.

BACKGROUND: Multidisciplinary care of placenta accreta spectrum cases improves pregnancy outcomes, but the specific components of such a multidisciplinary collaboration varies between institutions. As experience with placenta accreta spectrum increases, it is crucial to assess new surgical techniques and protocols to help improve maternal outcomes and to advocate for hospital resources. OBJECTIVE: This study aimed to assess a novel multidisciplinary protocol for the treatment of placenta accreta spectrum that comprises cesarean delivery, multivessel uterine embolization, and hysterectomy in a single procedure within a hybrid operative suite. STUDY DESIGN: This was a matched prepost study of placenta accreta spectrum cases managed before (2010-2017) and after implementation of the Placenta Accreta Spectrum Treatment With Intraoperative Multivessel Embolization protocol (2018-2021) at a tertiary medical center. Historical cases were managed with internal iliac artery balloon placement in selected cases with the decision to inflate the balloons intraoperatively at the discretion of the primary surgeon. Intraoperative Embolization cases were compared with historical cases in a 1:2 ratio matched on the basis of placenta accreta spectrum severity and surgical urgency. The primary outcome was a requirement for transfusion with packed red blood cells. Secondary outcomes included estimated surgical blood loss, operative and postoperative complications, procedural time, length of stay, and neonatal outcomes. RESULTS: A total of 15 Placenta Accreta Spectrum Treatment With Intraoperative Multivessel Embolization cases and 30 matched historical cases were included in the analysis. There were no demographic differences noted between the groups. A median (interquartile range) of 0 units (0-2 units) of packed red blood cells were transfused in the Intraoperative Embolization group compared with 2 units (0-4.5 units) in the historical group (P=.045); 5 of 15 (33.3%) Intraoperative Embolization cases required blood transfusions compared with 19 of 30 (63.3%) cases in the historical group (P=.11). The estimated blood loss was significantly less in the Intraoperative Embolization group with a median (interquartile range) of 750 mL (450-1050 mL) compared with 1750 mL (1050-2500 mL) in the historical group (P=.003). There were no cases requiring massive transfusion (≥10 red blood cell units in 24 hours) in the Intraoperative Embolization group compared with 5 of 30 (16.7%) cases in the historical group (P=.15). There were no intraoperative deaths from hemorrhagic shock using the Intraoperative Embolization protocol, whereas this occurred in 2 of the historical cases. The mean duration of the interventional radiology procedure was longer in the Intraoperative Embolization group (67.8 vs 34.1 minutes; P=.002). Intensive care unit admission and postpartum length of stay were similar, and surgical and postoperative complications were not significantly different between the groups. The gestational age and neonatal birthweights were similar; however, the neonatal length of stay was longer in the Intraoperative Embolization group (median duration, 32 days vs 15 days; P=.02) with a trend toward low Apgar scores. Incidence of arterial umbilical cord blood pH <7.2 and respiratory distress syndrome and intubation rates were not statistically different between the groups. CONCLUSION: A multidisciplinary pathway including a single-surgery protocol with multivessel uterine embolization is associated with a decrease in blood transfusion requirements and estimated blood loss with no increase in operative complications. The Placenta Accreta Spectrum Treatment With Intraoperative Multivessel Embolization protocol provides a definitive surgical method that warrants consideration by other centers specializing in placenta accreta spectrum treatment.

Complications of Hemorrhagic Shock and Massive Transfusion-a Comparison Before and After the Damage Control Resuscitation Era.

ABSTRACT: Trauma remains a leading cause of death, and hemorrhage is the leading cause of preventable trauma deaths. Resuscitation strategies in trauma have changed dramatically over the last 20 years. In the pre damage control resuscitation (DCR) era, we used large volume crystalloid resuscitation and packed red blood cells as the primary resuscitative fluids. Now, a 1:1:1 ratio of packed red blood cells, fresh plasma, and platelets with minimal crystalloids is the preferred resuscitative strategy (DCR era). As we have changed how we resuscitate patients, the detrimental effects associated with large volume resuscitation have also changed. In this article, we review the effects of large volume blood product resuscitation, and where possible present a contrast between the pre-DCR era and the DCR era resuscitation strategies.

After 800 Mtp Events, Mortality Due to Hemorrhagic Shock Remains High and Unchanged Despite Several In-Hospital Hemorrhage Control Advancements.

BACKGROUND: Numerous advancements in hemorrhage control and volume replacement that comprise damage control resuscitation (DCR) have been implemented in the last decade to reduce deaths from bleeding. We sought to determine the impact of DCR interventions on mortality over 12 years in a massive transfusion protocol (MTP) population. We hypothesized that mortality would be decreased in later years, which would have used more DCR interventions. STUDY DESIGN: This was a retrospective review of all MTP patients treated at a large regional Level I trauma center from 2008 to 2019. Interventions by year of implementation examined included MTP 1:1 ratio (2009), liquid plasma (2010), tranexamic acid (2012), prehospital tourniquets (2013), REBOA/TEG (2017), satellite blood station (2018), and whole blood transfusion (2019). Relative risk and odds of mortality for DCR interventions were examined. RESULTS: There were 824 MTP patients included. The cohort was primarily male (80.6%) injured by penetrating mechanism (68.1%) with median (interquartile range) age 31 years (23-44) and New Injury Severity Score 25 (16-34). Overall mortality was unchanged [(38.3%-56.6%); P = 0.26]. Tourniquets (P = 0.02) and whole blood (WB) (P = 0.03) were associated with lower unadjusted mortality; only tourniquets remained significant after adjustment (OR: 0.39; 95% CI: 0.17-0.89; P = 0.03). CONCLUSIONS: Despite lower mortality with use of tourniquets and WB, mortality rates due to hemorrhage have not improved at our high MTP volume institution, suggesting implementation of new in-hospital strategies is insufficient to reduce mortality. Future efforts should be directed toward moving hemorrhage control and effective resuscitation interventions to the injury scene.

Safety and efficacy of low-titer O whole blood resuscitation in a civilian level I trauma center.

BACKGROUND: Military experience has shown low-titer O whole blood (LTOWB) to be safe and beneficial in the resuscitation of hemorrhaging trauma patients. However, few civilian centers use LTOWB for trauma resuscitation. We evaluated the early experience and safety of a LTOWB program at a level 1 civilian trauma center. METHODS: We retrospectively reviewed our trauma registry from January 2018 to June 2020 for patients admitted in shock (defined as ≥1 of the following: heart rate, >120 beats per minute; systolic blood pressure, <90 mm Hg; or shock index, >0.9) who received blood products within 24 hours. Patients were grouped by resuscitation provided: LTOWB (group 1), component therapy (CT; group 2), and LTOWB-CT (group 3). Safety, outcomes, and variables associated with LTOWB transfusion and mortality were analyzed. RESULTS: 216 patients were included: 34 in Group 1, 95 in Group 2, and 87 in Group 3. Patientsreceiving LTOWB were more commonly male (p<0.001) and had a penetrating injury (p=0.005). Groups 1 and 3 had higher median ISS scores compared to Group 2 (19 and 20 vs 17; p=0.01). Group 3 received more median units of blood product in the first 4h (p<0.001) and in the first 24h (p<0.001). There was no difference between groups in 24h mortality or transfusion-related complications (all p>0.05). Arrival ED SBP was associated with LTOWB transfusion (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.95-1.00, p=0.03). ED lactate was independently associated with 24h mortality. (OR 1.27, CI 1.02-1.58, p=0.03). LTOWB transfusion was not associated with mortality (p=0.49). Abstract. CONCLUSION: Severely injured patients received LTOWB-CT and more overall product units but had similar 24 h mortality when compared with the LTOWB or CT groups. No increase in transfusion-related complications was seen after LTOWB transfusion. Low-titer O whole blood should be strongly considered in the resuscitation of trauma patients at civilian centers. LEVEL OF EVIDENCE: Retrospective, therapeutic, level IV.

Lactate as a mediator of prehospital plasma mortality reduction in hemorrhagic shock.

BACKGROUND: Prehospital plasma transfusion in trauma reduces mortality. However, the underlying mechanism remains unclear. Reduction in shock severity may play a role. Lactate correlates with physiologic shock severity and mortality after injury. Our objective was to determine if prehospital plasma reduces lactate and if this contributes to the mortality benefit of plasma. METHODS: Patients in the Prehospital Air Medical Plasma trial in the upper quartile of injury severity (Injury Severity Score, >30) were included to capture severe shock. Trial patients were randomized to prehospital plasma or standard care resuscitation (crystalloid ± packed red blood cells). Regression determined the associations between admission lactate, 30-day mortality, and plasma while adjusting for demographics, prehospital crystalloid, time, mechanism, and injury characteristics. Causal mediation analysis determined what proportion of the effect of plasma on mortality is mediated by lactate reduction. RESULTS: A total of 125 patients were included. The plasma group had a lower adjusted admission lactate than standard of care group (coefficient, -1.64; 95% confidence interval [CI], -2.96 to -0.31; p = 0.02). Plasma was associated with lower odds of 30-day mortality (odds ratio [OR], 0.27; 95% CI, 0.08-0.90; p = 0.03). When adding lactate to this model, the effect of plasma on 30-day mortality was no longer significant (OR, 0.36; 95% CI, 0.07-1.88; p = 0.23), while lactate was associated with mortality (OR, 1.74 per 1 mmol/L increase; 95% CI, 1.10-2.73; p = 0.01). Causal mediation demonstrated 35.1% of the total effect of plasma on 30-day mortality was mediated by the reduction in lactate among plasma patients. CONCLUSION: Prehospital plasma is associated with reduced 30-day mortality and lactate in severely injured patients. More than one third of the effect of plasma on mortality is mediated by a reduction in lactate. Thus, reducing the severity of hemorrhagic shock appears to be one mechanism of prehospital plasma benefit. Further study should elucidate other mechanisms and if a dose response exists. LEVEL OF EVIDENCE: Therapeutic, level II.

Lethal extracranial hemorrhage due to intracranial clivalchordoma: An autopsy case.

We present a case of a 48-year-old man's unexpected death affected by a relapsed clivalchordoma. After partial excision surgery of the neoplasm, he manifested 5 days later, in conditions of well-being, a sudden lethal extracranial hemorrhage from nose and mouth. The autopsy examination and the subsequent histological investigations did not allow us to clarify the exact origin of the bleeding. Based on the negativity of the accurate examinations performed, the extent of the bleeding, and the findings highlighted by the means of the nuclear magnetic resonance (NMR) carried out a few days before death, we have considered reasonable to localize the source of hemorrhage in the intrapetrous tract of the left internal carotid artery. Since this is a unique event, never previously documented, we believe that our report may be of interest to the scientific community.

Estrogen as a Safe Therapeutic Adjunct in Reducing the Inflammatory Storm in Trauma Hemorrhagic Shock Patients.

ABSTRACT: Trauma is a major cause of death and disability throughout the world. It is a leading cause of death with or without sepsis in about 50% of patients. Limited therapeutic options are available besides definitive care with a mortality benefit. Preclinical studies have demonstrated the mortality benefit of estrogen in trauma hemorrhagic shock (THS). Based on encouraging results from preclinical studies, we hypothesized that early administration of estrogen in male THS patients may reduce the inflammatory storm, prevent sepsis-associated problems, and subsequently reduce mortality. The authors studied the safety of early administration of estrogen as a therapeutic adjunct in the emergency department (ED) and its effects on the inflammatory storm, prevention of sepsis, and mortality during the intensive care unit stay. Forty THS patients were recruited. THS patients were divided into experimental and placebo control groups based on the estrogen administration in the ED. Serum levels of cytokines and immune cells were measured at different time points on days 0, 3, 7, and 14 in both groups of THS patients. The experimental group received intravenous estrogen (25 mg) at a single time point in the ED beside standard of care as per advanced trauma life support guidelines. Patients did not develop any major or minor adverse events and showed favorable clinical outcomes in the experimental group. The levels of T regulatory cells, monocytes, and systemic cytokines significantly reduced and showed a balanced inflammatory response in THS patients who received estrogen.In conclusion, this preliminary study showed that intravenous estrogen therapy is safe and reduced the inflammatory insult due to trauma hemorrhagic shock. It may protect THS patients from sepsis-associated complications. Future clinical trials are required to study the efficacy and mechanistic pathway.

Four-factor prothrombin complex concentrate in adjunct to whole blood in trauma-related hemorrhage: Does whole blood replace the need for factors?

BACKGROUND: The use of whole blood (WB) for the treatment of hemorrhagic shock and coagulopathy is increasing in civilian trauma patients. Four-factor prothrombin complex concentrate (4-PCC) in adjunct to component therapy showed improved outcomes in trauma patients. Our study aims to evaluate the outcomes of trauma patients who received 4-PCC and WB (4-PCC-WB) compared with WB alone. METHODS: We performed a 3-year (2015-2017) analysis of the American College of Surgeons-Trauma Quality Improvement Program database. All adult (age, ≥18 years) trauma patients who received WB were included. We excluded patients who were on preinjury anticoagulants. Patients were stratified into two groups, 4-PCC-WB versus WB alone, and matched in a 1:2 ratio using propensity score matching. Outcome measures were packed red blood cells, plasma, platelets, and cryoprecipitate transfused, in-hospital complications, hospital and intensive care unit (ICU) length of stay (LOS) among survivors, and mortality. RESULTS: A total of 252 patients (4-PCC-WB, 84; WB alone, 168) were matched. The mean ± SD age was 47 ± 21 years, 63% were males, median Injury Severity Score was 30 (21-40), and 87% had blunt injuries. Patients who received 4-PCC-WB had decreased requirement for packed red blood cell (8 U vs. 10 U, p = 0.04) and fresh frozen plasma (6 U vs. 8 U, p = 0.01) transfusion, lower rates of acute kidney injury (p = 0.03), and ICU LOS (5 days vs. 8 days, p = 0.01) compared with WB alone. There was no difference in the platelet transfusion (p = 0.19), cryoprecipitate transfusion (p = 0.37), hospital LOS (p = 0.72), and in-hospital mortality (p = 0.72) between the two groups. CONCLUSION: Our study demonstrates that the use of 4-PCC as an adjunct to WB is associated with a reduction in transfusion requirements and ICU LOS compared with WB alone in the resuscitation of trauma patients. Further studies are required to evaluate the role of PCC with WB in the resuscitation of trauma patients. LEVEL OF EVIDENCE: Therapeutic, level III.

Is there a role for REBOA? A system assessment.

INTRODUCTION: To analyze our experience to quantify potential need for resuscitative endovascular balloon occlusion of the aorta (REBOA). METHODS: Retrospective review of patients over a three-year period who presented as a trauma with hemorrhagic shock. Patients were divided into two groups: REBOA Candidate vs. Non-candidates. Injuries, outcomes, and interventions were compared. RESULTS: Of 7643 trauma activations, only 37 (0.44%) fit inclusion criteria, of which 16 met criteria for candidacy for potential REBOA placement. The groups did not differ in terms of injury severity, physiology, age, timing of intervention, nor massive transfusion. Survival was linked to TRISS (p = 0.01) and Emergency Room Thoracotomy (p = 0.002). Of Candidates, 8 (50%) had injuries that could have benefited from REBOA, while 7 (44%) had injuries that could be associated with potential harm. DISCUSSION: The volume of patients who would potentially benefit from REBOA appears to be small and does not appear to support system wide adoption in the studied region. LEVEL OF EVIDENCE: IV.

Outcomes of resuscitative endovascular balloon occlusion of the aorta (REBOA) utilization in trauma patients with and without traumatic brain injuries: A national analysis of the American College of Surgeons Trauma Quality Improvement Program data set.

BACKGROUND: Hemorrhage remains a leading cause of death among trauma patients. Resuscitative endovascular balloon occlusion of the aorta has grown in popularity as an efficient, less invasive alternative to managing patients with noncompressible hemorrhage. The aim of this study to investigate the clinical outcomes of resuscitative endovascular balloon occlusion of the aorta use in adult civilian trauma patients with and without concomitant traumatic brain injury. METHODS: This a secondary analysis of the American College of Surgeons Trauma Quality Improvement Program database from the years 2015 to 2017 of adult trauma patients with and without traumatic brain injury and who had a resuscitative endovascular balloon occlusion of the aorta. Patients who were deceased on arrival, required resuscitative thoracotomy, or had missing information regarding traumatic brain injury status were excluded. Multivariable risk adjustment was performed. The primary outcome was inpatient mortality. RESULTS: Of 2,352,542 patients, 199 met the criteria for inclusion in the final analysis. resuscitative endovascular balloon occlusion of the aorta + traumatic brain injury patients were significantly more likely to have a lower Glasgow Coma Scale ≤8 (82.4% vs 54.4%, P < .001) and systolic blood pressure (89 ± 37.4 vs 107.2 ± 39.7; P = .002), and higher injury severity score >25 (83.5% vs 65.8%, P = .01) compared with resuscitative endovascular balloon occlusion of the aorta/non-traumatic brain injury patients. No differences in odds of inpatient mortality (62.4% vs 50.9%, P = .11) or complications (17.7% vs 11.4%, P = .21) were observed between groups. Subgroup analysis based on mechanism of injury, trauma center level, teaching hospital status, and pelvic fracture status also did not show any differences in mortality. CONCLUSION: Inpatient mortality with resuscitative endovascular balloon occlusion of the aorta use does not differ between patients with or without concomitant traumatic brain injury, despite those with traumatic brain injury having significantly higher injury severity and more severe hypotension on intake.

Is restrictive fluid resuscitation beneficial not only for hemorrhagic shock but also for septic shock?: A meta-analysis.

BACKGROUND: Whether to use limited fluid resuscitation (LFR) in patients with hemorrhagic shock or septic shock remains controversial. This research was aimed to assess the pros and cons of utilizing LFR in hemorrhagic shock or septic shock patients. METHODS: PubMed, Cochrane Library, Embase, Web of science, CNKI, VIP, and Wan Fang database searches included for articles published before December 15, 2020. Randomized controlled trials of LFR or adequate fluid resuscitation in hemorrhagic shock or septic shock patients were selected. RESULT: This meta-analysis including 28 randomized controlled trials (RCTs) and registered 3288 patients. The 7 of 27 RCTs were the patients with septic shock. Others were traumatic hemorrhagic shock patients. Comparing LFR or adequate fluid resuscitation in hemorrhagic shock or septic shock patients, the summary odds ratio (OR) was 0.50 (95% confidence interval [CI] 0.42-0.60, P < .00001) for mortality, 0.46 (95% CI 0.31-0.70, P = .0002) for multiple organ dysfunction syndrome (MODS), 0.35 (95% CI 0.25-0.47) for acute respiratory distress syndrome (ARDS), and 0.33 (95% CI 0.20-0.56) for disseminated intravascular coagulation (DIC). CONCLUSION: Limited fluid resuscitation is the benefit of both traumatic hemorrhagic shock patients and septic shock patients.

Air-Evacuation-Relevant Hypobaria Following Traumatic Brain Injury Plus Hemorrhagic Shock in Rats Increases Mortality and Injury to the Gut, Lungs, and Kidneys.

ABSTRACT: Rats exposed to hypobaria equivalent to what occurs during aeromedical evacuation within a few days after isolated traumatic brain injury exhibit greater neurologic injury than those remaining at sea level. Moreover, administration of excessive supplemental O2 during hypobaria further exacerbates brain injury. This study tested the hypothesis that exposure of rats to hypobaria following controlled cortical impact (CCI)-induced brain injury plus mild hemorrhagic shock worsens multiple organ inflammation and associated mortality. In this study, at 24 h after CCI plus hemorrhagic shock, rats were exposed to either normobaria (sea level) or hypobaria (=8,000 ft altitude) for 6 h under normoxic or hyperoxic conditions. Injured rats exhibited mortality ranging from 30% for those maintained under normobaria and normoxia to 60% for those exposed to 6 h under hypobaric and hyperoxia. Lung histopathology and neutrophil infiltration at 2 days postinjury were exacerbated by hypobaria and hyperoxia. Gut and kidney inflammation at 30 days postinjury were also worsened by hypobaric hyperoxia. In conclusion, exposure of rats after brain injury and hemorrhagic shock to hypobaria or hyperoxia results in increased mortality. Based on gut, lung, and kidney histopathology at 2 to 30 days postinjury, increased mortality is consistent with multi-organ inflammation. These findings support epidemiological studies indicating that increasing aircraft cabin pressures to 4,000 ft altitude (compared with standard 8,000 ft) and limiting excessive oxygen administration will decrease critical complications during and following aeromedical transport.

The Influence of Macrophage-Activating Lipopeptide 2 (MALP-2) on Local and Systemic Inflammatory Response in a Murine Two-Hit Model of Hemorrhagic Shock and Subsequent Sepsis.

Pulmonary complications after severe trauma and sepsis remain to be the main cause for adverse outcome. MALP-2 has been described to exert beneficial effects on organ damage and the further course after isolated trauma and sepsis. However, the impact of MALP-2 on a clinically realistic two-hit scenario of trauma and subsequent sepsis remains unknown. We, therefore, investigated if the systemic inflammatory response and pulmonary immune response and damage are beneficially modulated by MALP-2 in a murine two-hit model. Blood pressure-controlled trauma-hemorrhage (TH) and cecal ligation and puncture (CLP) were induced in C57/BL6 mice. Mice were divided into 2 control groups (control 1: TH without CLP; control 2: TH and CLP) and 3 experimental groups treated with MALP-2 at different time points (ETH, end of TH; ECLP, end of CLP; and 6CLP 6 h after CLP). Survival rates were assessed over the observation period of 168 h after the induction of TH. Concentrations of plasma inflammatory cytokines and chemokines (TNF-α, IL-6, MIP-1α, IFN-γ, and IL-10) were assessed, and bacterial clearance of the lungs was determined. Furthermore, pulmonary MPO activity assay to evaluate the infiltration of polymorphonuclear neutrophils (PMN) and histological evaluation were performed. Survival rates were evaluated. Compared with control group 1, the level of TNF-α in the ECLP group showed a significant increase (ECLP, 2.27 pg./ml ± 1.39 vs. control 1: 0.16 pg./ml ± 0.11, p = 0.021). In contrast, levels of IFN-γ were significantly reduced in groups ETH and 6CLP compared with control group 1 (control 1: 8.92 pg./ml ± 4.38 vs. ETH: 1.77 pg./ml ± 4.34, p = 0.026 resp. vs. 6CLP: 1.83 pg./ml ± 4.49, p = 0.014). While systemic concentrations of inflammatory mediators were not affected by MALP-2 treatment, the lung tissue presented with significant alterations. Reduced MPO activity was lowest in group ECLP (ECLP 11,196.77 ± 547.81 vs. ETH 12,773.94 ± 1011.76; p = 0.023 resp. vs. 6CLP 13,155.19 ± 423.99, p = 0.016) in experimental groups. Also, histological damage after MALP-2 application was lowest in ECLP animals (ECLP 0.50 ± 0.08 vs. ETH 0.71 ± 0.05, p = 0.034 resp. vs. 6CLP 0.64 ± 0.08, p = 0.021). Furthermore, MALP-2 treatment was associated with a trend towards improved survival in the ECLP group (ECLP 83.3% vs. ETH 66.7 and 6CLP 58.3%, p > 0.05). Based on our results, MALP-2 might have beneficial effects on the clinical course after hemorrhage and sepsis by reducing pulmonary damage and PMN infiltration. This might also affect survival. According to our data, MALP-2 should be given at the earliest possible time point after the onset of sepsis. However, the optimal dosage and confirmation of our results in larger cohorts need to be the focus of further research.