Outcomes after ultramassive transfusion in the modern era: An Eastern Association for the Surgery of Trauma multicenter study.

BACKGROUND: Despite the widespread institution of modern massive transfusion protocols with balanced blood product ratios, survival for patients with traumatic hemorrhage receiving ultramassive transfusion (UMT) (defined as ≥20 U of packed red blood cells [RBCs]) in 24 hours) remains low and resource consumption remains high. Therefore, we aimed to identify factors associated with mortality in trauma patients receiving UMT in the modern resuscitation era. METHODS: An Eastern Association for the Surgery of Trauma multicenter retrospective study of 461 trauma patients from 17 trauma centers who received ≥20 U of RBCs in 24 hours was performed (2014-2019). Multivariable logistic regression and Classification and Regression Tree analysis were used to identify clinical characteristics associated with mortality. RESULTS: The 461 patients were young (median age, 35 years), male (82%), severely injured (median Injury Severity Score, 33), in shock (median shock index, 1.2; base excess, -9), and transfused a median of 29 U of RBCs, 22 U of fresh frozen plasma (FFP), and 24 U of platelets (PLT). Mortality was 46% at 24 hours and 65% at discharge. Transfusion of RBC/FFP ≥1.5:1 or RBC/PLT ≥1.5:1 was significantly associated with mortality, most pronounced for the 18% of patients who received both RBC/PLT and RBC/FFP ≥1.5:1 (odds ratios, 3.11 and 2.81 for mortality at 24 hours and discharge; both p < 0.01). Classification and Regression Tree identified that age older than 50 years, low initial Glasgow Coma Scale, thrombocytopenia, and resuscitative thoracotomy were associated with low likelihood of survival (14-26%), while absence of these factors was associated with the highest survival (71%). CONCLUSION: Despite modern massive transfusion protocols, one half of trauma patients receiving UMT are transfused with either RBC/FFP or RBC/PLT in unbalanced ratios ≥1.5:1, with increased associated mortality. Maintaining focus on balanced ratios during UMT is critical, and consideration of advanced age, poor initial mental status, thrombocytopenia, and resuscitative thoracotomy can aid in prognostication. LEVEL OF EVIDENCE: Prognostic, level III.

Development of atrial fibrillation following trauma increases short term risk of cardiovascular events.

CONTEXT: New onset atrial fibrillation (AF) is associated with poor outcomes in several different patient populations. OBJECTIVES: To assess the effect of developing AF on cardiovascular events such as myocardial infarction (MI) and cerebrovascular accident (CVA) during the acute index hospitalization for trauma patients. METHODS: The Healthcare Cost and Utilization Project State Inpatient Databases for California and Florida were used to identify adult trauma patients (18 years of age or older) who were admitted between 2007 and 2010. After excluding patients with a history of AF and prior history of cardiovascular events, patients were evaluated for MI, CVA, and death during the index hospitalization. A secondary analysis was performed using matched propensity scoring based on age, race, and preexisting comorbidities. RESULTS: During the study period, 1,224,828 trauma patients were admitted. A total of 195,715 patients were excluded for a prior history of AF, MI, or CVA. Of the remaining patients, 15,424 (1.5%) met inclusion criteria and had new onset AF after trauma. There was an associated increase in incidence of MI (2.9 vs. 0.7%; p<0.001), CVA (2.6 vs. 0.4%; p<0.001), and inpatient mortality (8.5 vs. 2.1%; p<0.001) during the index hospitalization in patients who developed new onset AF compared with those who did not. Cox proportional hazards regression demonstrated an increased risk of MI (odds ratio [OR], 2.35 [2.13-2.60]), CVA (OR, 3.90 [3.49-4.35]), and inpatient mortality (OR, 2.83 [2.66-3.00]) for patients with new onset AF after controlling for all other potential risk factors. CONCLUSIONS: New onset AF in trauma patients was associated with increased incidence of myocardial infarction (MI), cerebral vascular accident (CVA), and mortality during index hospitalization in this study.

Electronic Medical Record Versus Bedside Assessment: How to Evaluate Frailty in Trauma and Emergency General Surgery Patients?

BACKGROUND: Screening patients for frailty is traditionally done at the bedside. However, recent electronic medical record (EMR)-based, comorbidity-focused frailty assessments have been developed. Our objective was to determine how a common bedside frailty assessment, the trauma and emergency surgery (TEGS) frailty index (FI), compares to an EMR-based frailty assessment in predicting geriatric TEGS outcomes. MATERIALS AND METHODS: We retrospectively reviewed our quality improvement project database consisting of TEGS patients ≥ 65 y old. Patients were screened with the TEGS FI, a 15-question bedside assessment, including comorbidities, physical activity, emotional health, and nutrition. Six of 15 items were retrievable from the enterprise data warehouse (EDW), storing all EMR data from Northwestern Memorial Hospital, and use to calculate the EDW frailty score. Patient characteristics and outcomes were compared between different groups. RESULTS: Two hundred thirty-six geriatric TEGS patients were included, of which 75 (31.8%) were TEGS FI frail and 60 (25.4%) were EDW frail. TEGS FI frail patients had increased length of stay (LOS), loss of independence (LOI), and complications compared to TEGS FI nonfrail patients. EDW frail patients had higher LOS and complications than EDW nonfrail patients but similar LOI. TEGS FI and EDW frail patients had similar outcomes except TEGS FI-only patients more often have LOI. CONCLUSIONS: Bedside frailty assessments and EMR-based assessments are both effective in identifying geriatric TEGS patients at risk for increased LOS and complications. However, bedside frailty screening was better at identifying patients who have LOI and may be a more appropriate choice when screening for frailty.

Frailty screening and a frailty pathway decrease length of stay, loss of independence, and 30-day readmission rates in frail geriatric trauma and emergency general surgery patients.

BACKGROUND: Frail geriatric trauma and emergency general surgery (TEGS) patients have longer lengths of stay (LOS), more readmissions, and higher rates of postdischarge institutionalization than their nonfrail counterparts. Despite calls to action by national trauma coalitions, there are few published reports of prospective interventions. The objective of this quality improvement project was to first develop a frailty screening program, and, then, if frail, implement a novel frailty pathway to reduce LOS, 30-day readmissions, and loss of independence. METHODS: This was a before-after study of a prospective cohort of all geriatric (≥65-years-old) patients admitted to the TEGS service from October 2016 to October 2017. All patients were screened for frailty for 3 months (preintervention) to obtain baseline outcomes. Subsequently, frail patients were entered into our frailty pathway (postintervention). Nonparametric statistical tests were used to assess significant differences in continuous variables; χ and Fisher exact tests were used for categorical variables, where appropriate. Both process and outcome measures were evaluated. RESULTS: Of 239 geriatric TEGS patients screened, 70 (29.3%) were frail. All TEGS geriatric patients were screened within 24 hours of admission. Following frailty pathway implementation, median LOS for frail patients decreased from 9 to 6 days (p = 0.4), readmissions decreased from 36.4% to 10.2% (p = 0.04), and loss of independence decreased by 40%, (100% vs 60%; p = 0.01). Outcomes for nonfrail geriatric patients did not differ between cohorts. CONCLUSIONS: Screening for frailty followed by implementing a frailty pathway decreased LOS, loss of independence, and 30-day readmission rates for frail geriatric TEGS patients at a single urban academic institution. The pathway required no additional resources; rather, we shifted focus toward frail patients without negatively affecting outcomes in nonfrail geriatric TEGS patients. Implementation of this pathway with larger patient cohorts and in varied settings is needed to confirm a causal relationship between our intervention and improved outcomes. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Hemoglobin-Based Oxygen Carrier for Traumatic Hemorrhagic Shock Treatment in a Jehovah's Witness.

INTRODUCTION: Treatment of severe hemorrhagic shock due to acute blood loss from traumatic injuries in a Jehovah's witness (JW) trauma patient is very challenging since hemostatic blood product resuscitation is limited by refusal of the transfusion of allogeneic blood products. CASE PRESENTATION: We describe a multifaceted approach to the clinical care of a severely anemic JW trauma patient including the early administration of a bovine hemoglobin-based oxygen carrier (HBOC) as a bridge to resolution of critical anemia (nadir hemoglobin 3.9 g/dL). Hemoglobin-based oxygen carrier infusions were used to supplement oxygen delivery until endogenous erythropoiesis could restore adequate red blood cell mass. Subsequent endogenous bone marrow recovery was supported by early administration of high-dose erythropoiesis-stimulating agents and iron supplementation. CONCLUSIONS: Early HBOC administration can be used in the treatment of severe hemorrhagic shock in trauma patients who refuse allogeneic blood.

Perturbed MafB/GATA1 axis after burn trauma bares the potential mechanism for immune suppression and anemia of critical illness.

Patients who survive initial burn injury are susceptible to nosocomial infections. Anemia of critical illness is a compounding factor in burn patients that necessitates repeated transfusions, which further increase their susceptibility to infections and sepsis. Robust host response is dependent on an adequate number and function of monocytes/macrophages and dendritic cells. In addition to impaired RBC production, burn patients are prone to depletion of dendritic cells and an increase in deactivated monocytes. In steady-state hematopoiesis, RBCs, macrophages, and dendritic cells are all generated from a common myeloid progenitor within the bone marrow. We hypothesized in a mouse model of burn injury that an increase in myeloid-specific transcription factor V-maf musculoaponeurotic fibrosarcoma oncogene homolog B at the common myeloid progenitor stage steers their lineage potential away from the megakaryocyte erythrocyte progenitor production and drives the terminal fate of common myeloid progenitors to form macrophages vs. dendritic cells, with the consequences being anemia, monocytosis, and dendritic cell deficits. Results indicate that, even though burn injury stimulated bone marrow hematopoiesis by increasing multipotential stem cell production (LinnegSca1poscKitpos), the bone marrow commitment is shifted away from the megakaryocyte erythrocyte progenitor and toward granulocyte monocyte progenitors with corresponding alterations in peripheral blood components, such as hemoglobin, hematocrit, RBCs, monocytes, and granulocytes. Furthermore, burn-induced V-maf musculoaponeurotic fibrosarcoma oncogene homolog B in common myeloid progenitors acts as a transcriptional activator of M-CSFR and a repressor of transferrin receptors, promoting macrophages and inhibiting erythroid differentiations while dictating a plasmacytoid dendritic cell phenotype. Results from small interfering RNA and gain-of-function (gfp-globin transcription factor 1 retrovirus) studies indicate that targeted interventions to restore V-maf musculoaponeurotic fibrosarcoma oncogene homolog B/globin transcription factor 1 balance can mitigate both immune imbalance and anemia of critical illness.

Methylene blue for burn-induced vasoplegia: case report and review of literature.

We report the use of a single dose of methylene blue in a patient with burn-induced vasoplegia refractory to fluids, vasopressors, and steroids. Administration of methylene blue allowed for cessation of epinephrine infusion within 2 hours of administration, and reduction in excessive fluid resuscitation. The patient's clinical course continued for 2 months and was complicated by severe acute respiratory distress syndrome, pneumonia, septic shock, poor skin graft adherence, renal failure requiring continuous renal replacement therapy, cutaneous mucormycosis, and ultimately, withdrawal of care and death. Despite the eventual outcome, this is the longest reported survival following methylene blue administration for vasoplegia secondary to burn injury.

How do we treat life-threatening anemia in a Jehovah's Witness patient?

The refusal of allogeneic human blood and blood products by Jehovah's Witness (JW) patients complicates the treatment of life-threatening anemia. For JW patients, when hemoglobin (Hb) levels decrease beyond traditional transfusion thresholds (<7 g/dL), alternative methods to allogeneic blood transfusion can be utilized to augment erythropoiesis and restore endogenous Hb levels. The use of erythropoietin-stimulating agents and intravenous iron has been shown to restore red blood cell and Hb levels in JW patients, although these effects may be significantly delayed. When JW patients have evidence of life-threatening anemia (Hb <5 g/dL), oxygen-carrying capacity can be supplemented with the administration of Hb-based oxygen carriers (HBOCs). Although HBOCs are not Food and Drug Administration (FDA) approved, they may be obtained and administered with FDA, institutional review board, and patient approval. We describe a protocol-based algorithm to the management of life-threatening anemia in JW patients and review time to anemia reversal and patient outcomes using this approach.

Multicenter review of diaphragm pacing in spinal cord injury: successful not only in weaning from ventilators but also in bridging to independent respiration.

BACKGROUND: Ventilator-dependent spinal cord-injured (SCI) patients require significant resources related to ventilator dependence. Diaphragm pacing (DP) has been shown to successfully replace mechanical ventilators for chronic ventilator-dependent tetraplegics. Early use of DP following SCI has not been described. Here, we report our multicenter review experience with the use of DP in the initial hospitalization after SCI. METHODS: Under institutional review board approval for humanitarian use device, we retrospectively reviewed our multicenter nonrandomized interventional protocol of laparoscopic diaphragm motor point mapping with electrode implantation and subsequent diaphragm conditioning and ventilator weaning. RESULTS: Twenty-nine patients with an average age of 31 years (range, 17-65 years) with only two females were identified. Mechanism of injury included motor vehicle collision (7), diving (6), gunshot wounds (4), falls (4), athletic injuries (3), bicycle collision (2), heavy object falling on spine (2), and motorcycle collision (1). Elapsed time from injury to surgery was 40 days (range, 3-112 days). Seven (24%) of the 29 patients who were evaluated for the DP placement had nonstimulatable diaphragms from either phrenic nerve damage or infarction of the involved phrenic motor neurons and were not implanted. Of the stimulatable patients undergoing DP, 72% (16 of 22) were completely free of ventilator support in an average of 10.2 days. For the remaining six DP patients, two had delayed weans of 180 days, three had partial weans using DP at times during the day, and one patient successfully implanted went to a long-term acute care hospital and subsequently had life-prolonging measures withdrawn. Eight patients (36%) had complete recovery of respiration, and DP wires were removed. CONCLUSION: Early laparoscopic diaphragm mapping and DP implantation can successfully wean traumatic cervical SCI patients from ventilator support. Early laparoscopic mapping is also diagnostic in that a nonstimulatable diaphragm is a convincing evidence of an inability to wean from ventilator support, and long-term ventilator management can be immediately instituted. LEVEL OF EVIDENCE: Therapeutic study, level V.

Burn injury dampens erythroid cell production through reprioritizing bone marrow hematopoietic response.

BACKGROUND: Anemia in burn patients is due to surgical blood loss and anemia of critical illness. Because the commitment paradigm of common bone marrow progenitors dictates the production of erythroid, myeloid, and lymphoid cells, we hypothesized that skewed bone marrow lineage commitment decreases red cell production and causes anemia after a burn injury. METHODS: After anesthesia, B(6)D(2)F(1) mice received a 15% total body surface area dorsal scald burn. The sham group did not receive scald burn. Femoral bone marrow was harvested on 2, 5, 7, 14, and 21 postburn days (PBD). Total bone marrow cells were labeled with specific antibodies to erythroid (CD71/Ter119), myeloid (CD11b), and lymphoid (CD19) lineages and analyzed by flow cytometry. To test whether erythropoietin (EPO) could increase red blood cell production, EPO was administered to sham and burn animals and their reticulocyte response was measured on PBD 2 and PBD 7. RESULTS: Burn injury reduced the erythroid cells of the bone marrow from 35% in sham to 17% by PBD 5 and remained at similar level until PBD 21. Myeloid cells, however, increased from 42% in sham to 60% on PBD 5 and 77% on PBD 21. Burn injury reduced reticulocyte counts on PBD 2 and PBD 7 indicating that the erythroid compartment is severely depleted. This depleted compartment, however, responded to EPO but was not sufficient to change red cell production. CONCLUSION: Burn injury skews the bone marrow hematopoietic commitment away from erythroid and toward myeloid cells. Shrinkage of the erythroid compartment contributes to resistance to EPO and the anemia of critical illness.

Surgical burn wound infections and their clinical implications.

Typically, burn wound infections are classified by the organisms present in the wound within the first several days after injury or later by routine surveillance cultures. With universal acceptance of early excision and grafting, classification of burn wound colonization in unexcised burn wounds is less relevant, shifting clinical significance to open burn-related surgical wound infections (SWIs). To better characterize SWIs and their clinical relevance, the authors identified the pathogens responsible for SWIs, their impact on rates of regrafting, and the relationship between SWI and nosocomial infection (NI) pathogens. Epidemiologic and clinical data for 71 adult patients with ≥ 20% TBSA burn were collected. After excision and grafting, if a grafted site had clinical characteristics of infection, a wound culture swab was obtained and the organism identified. Surveillance cultures were not obtained. SWI pathogen, anatomic location, postburn day of occurrence, and need for regrafting were compiled. A positive culture obtained from an isolated anatomic location at any time point after excision and grafting of that location was considered a distinct infection. Pathogens responsible for NIs (urinary tract infections, pneumonia, bloodstream and catheter-related bloodstream infections, pseudomembranous colitis, and donor site infections) and their postburn day were identified. The profiles of SWI pathogens and NI pathogens were then compared. Of the 71 patients included, 2 withdrew, 6 had no excision or grafting performed, and 1 had incomplete data. Of the remaining 62 patients, 24 (39%) developed an SWI. In these 24 patients, 70 distinct infections were identified, of which 46% required regrafting. Candida species (24%), Pseudomonas aeruginosa (22%), Serratia marcescens (11%), and Staphylococcus aureus (11%) comprised the majority of pathogens. Development of an SWI with the need for regrafting increased overall length of stay, area of autograft, number of operative events, and was closely associated with the number of NIs. The %TBSA burn and depth of the burn were the main risk factors for SWI with need for regrafting. The SWI pathogen was identified as an NI pathogen 56% of the time, with no temporal correlation between shared SWI and NI pathogens. SWIs are commonly found in severely burned patients and are associated with regrafting. As a result, patients with SWIs are subjected to increased operative events, autograft placement, and increased length of hospitalization. In addition, the presence of an SWI may be a risk factor for development of NIs.

Classifying transfusions related to the anemia of critical illness in burn patients.

BACKGROUND: Critically ill patients require transfusions because of acute blood loss and the anemia of critical illness. In critically ill burn patients, typically, no distinction is made between transfusions related to acute surgical blood loss and those related to the anemia of critical illness. We sought to identify the percentage of blood transfusions due to the anemia of critical illness and the clinical characteristics associated with these transfusions in severely burned patients. METHODS: Sixty adult patients with ≥20% total body surface area (TBSA) burn who were transfused at least 1 unit of packed red blood cells during their hospitalization were studied. Clinical variables including age, %TBSA burn, Acute Physiology and Chronic Health Evaluation (APACHE) II score, number of ventilator days, inhalation injury, and number of operative events were correlated with the total number of packed red blood cell units and percentage of nonsurgical transfusions in these patients. Nonsurgical transfusions were defined as transfusions occurring after postoperative day 1 for each distinct operative event and were classified as being caused by the anemia of critical illness. RESULTS: Patients were transfused an average of 16.6 units ± 21.2 units. Nonsurgical transfusions accounted for 52% of these transfusions. APACHE II score, %TBSA burn, number of ventilator days, and number of operative events, all correlated with total transfusions. However, nonsurgical transfusions correlated with only APACHE II score (p = 0.01) and number of ventilator days (p = 0.03). There was no correlation between nonsurgical transfusions and other clinical variables. CONCLUSION: The anemia of critical illness is responsible for >50% of all transfusions in severely burned patients. The initial severity of critical illness (APACHE II score) and duration of the critical illness (number of ventilator days) correlated with transfusions related to anemia of critical illness. Further investigation into the specific risk factors for these transfusions may help to develop strategies to further reduce transfusion rates.