High Dimensional Multiomics Reveals Unique Characteristics of Early Plasma Administration in Polytrauma Patients With TBI.

OBJECTIVES: The authors sought to identify causal factors that explain the selective benefit of prehospital administration of thawed plasma (TP) in traumatic brain injury (TBI) patients using mediation analysis of a multiomic database. BACKGROUND: The Prehospital Air Medical Plasma (PAMPer) Trial showed that patients with TBI and a pronounced systemic response to injury [defined as endotype 2 (E2)], have a survival benefit from prehospital administration of TP. An interrogation of high dimensional proteomics, lipidomics and metabolomics previously demonstrated unique patterns in circulating biomarkers in patients receiving prehospital TP, suggesting that a deeper analysis could reveal causal features specific to TBI patients. METHODS: A novel proteomic database (SomaLogic Inc., aptamer-based assay, 7K platform) was generated using admission blood samples from a subset of patients (n=149) from the PAMPer Trial. This proteomic dataset was combined with previously reported metabolomic and lipidomic datasets from these same patients. A 2-step analysis was performed to identify factors that promote survival in E2-TBI patients who had received early TP. First, features were selected using both linear and multivariate-latent-factor regression analyses. Then, the selected features were entered into the causal mediation analysis. RESULTS: Causal mediation analysis of observable features identified 16 proteins and 41 lipids with a high proportion of mediated effect (>50%) to explain the survival benefit of early TP in E2-TBI patients. The multivariate latent-factor regression analyses also uncovered 5 latent clusters of features with a proportion effect >30%, many in common with the observable features. Among the observable and latent features were protease inhibitors known to inhibit activated protein C and block fibrinolysis (SERPINA5 and CPB2), a clotting factor (factor XI), as well as proteins involved in lipid transport and metabolism (APOE3 and sPLA(2)-XIIA). CONCLUSIONS: These findings suggest that severely injured patients with TBI process exogenous plasma differently than those without TBI. The beneficial effects of early TP in E2-TBI patients may be the result of improved blood clotting and the effect of brain protective factors independent of coagulation.

Prehospital Blood Product and Crystalloid Resuscitation in the Severely Injured Patient: A Secondary Analysis of the Prehospital Air Medical Plasma Trial.

OBJECTIVE: The aim of this study was to determine whether prehospital blood products reduce 30-day mortality in patients at risk for hemorrhagic shock compared with crystalloid only resuscitation. SUMMARY OF BACKGROUND DATA: Hemorrhage is the primary cause of preventable death after injury. Large volume crystalloid resuscitation can be deleterious. The benefits of prehospital packed red blood cells (PRBCs), plasma, or transfusion of both products among trauma patients is unknown compared with crystalloid. METHODS: Secondary analysis of the multicenter PAMPer trial was performed on hypotensive injured patients from the scene. The trial randomized 27 helicopter bases to prehospital plasma or standard resuscitation. Standard resuscitation at the sites was equally divided between crystalloid and crystalloid + PRBC. This led to 4 prehospital resuscitation groups: crystalloid only; PRBC; plasma; and PRBC+plasma. Cox regression determined the association between resuscitation groups and risk-adjusted 30-day mortality. The dose effect of resuscitation fluids was also explored. RESULTS: Four hundred seven patients were included. PRBC+plasma had the greatest benefit [hazard ratio (HR) 0.38; 95% confidence interval (95% CI) 0.26-0.55, P < 0.001], followed by plasma (HR 0.57; 95% CI 0.36-0.91, P = 0.017) and PRBC (HR 0.68; 95% CI 0.49-0.95, P = 0.025) versus crystalloid only. Mortality was lower per-unit of PRBC (HR 0.69; 95% CI 0.52-0.92, p = 0.009) and plasma (HR 0.68; 95% CI 0.54-0.88, P = 0.003). Crystalloid volume was associated with increased mortality among patients receiving blood products (HR 1.65; 95% CI 1.17-2.32, P = 0.004). CONCLUSION: Patients receiving prehospital PRBC+plasma had the greatest mortality benefit. Crystalloid only had the worst survival. Patients with hemorrhagic shock should receive prehospital blood products when available, preferably PRBC+plasma. Prehospital whole blood may be ideal in this population.

Prehospital Plasma during Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock.

BACKGROUND: After a person has been injured, prehospital administration of plasma in addition to the initiation of standard resuscitation procedures in the prehospital environment may reduce the risk of downstream complications from hemorrhage and shock. Data from large clinical trials are lacking to show either the efficacy or the risks associated with plasma transfusion in the prehospital setting. METHODS: To determine the efficacy and safety of prehospital administration of thawed plasma in injured patients who are at risk for hemorrhagic shock, we conducted a pragmatic, multicenter, cluster-randomized, phase 3 superiority trial that compared the administration of thawed plasma with standard-care resuscitation during air medical transport. The primary outcome was mortality at 30 days. RESULTS: A total of 501 patients were evaluated: 230 patients received plasma (plasma group) and 271 received standard-care resuscitation (standard-care group). Mortality at 30 days was significantly lower in the plasma group than in the standard-care group (23.2% vs. 33.0%; difference, -9.8 percentage points; 95% confidence interval, -18.6 to -1.0%; P=0.03). A similar treatment effect was observed across nine prespecified subgroups (heterogeneity chi-square test, 12.21; P=0.79). Kaplan-Meier curves showed an early separation of the two treatment groups that began 3 hours after randomization and persisted until 30 days after randomization (log-rank chi-square test, 5.70; P=0.02). The median prothrombin-time ratio was lower in the plasma group than in the standard-care group (1.2 [interquartile range, 1.1 to 1.4] vs. 1.3 [interquartile range, 1.1 to 1.6], P<0.001) after the patients' arrival at the trauma center. No significant differences between the two groups were noted with respect to multiorgan failure, acute lung injury-acute respiratory distress syndrome, nosocomial infections, or allergic or transfusion-related reactions. CONCLUSIONS: In injured patients at risk for hemorrhagic shock, the prehospital administration of thawed plasma was safe and resulted in lower 30-day mortality and a lower median prothrombin-time ratio than standard-care resuscitation. (Funded by the U.S. Army Medical Research and Materiel Command; PAMPer ClinicalTrials.gov number, NCT01818427 .).

Dexmedetomidine versus propofol for prolonged sedation in critically ill trauma and surgical patients.

BACKGROUND: and Purpose: Currently, dexmedetomidine versus propofol has primarily been studied in medical and cardiac surgery patients with outcomes indicating safe and effective sedation. The purpose of this study was to assess the efficacy of dexmedetomidine versus propofol for prolonged sedation in trauma and surgical patients. METHODS: This was a single-center prospective study conducted in the Trauma/Surgical Intensive Care Unit (ICU) at a Level I academic trauma center. It included patients 18 years of age or older requiring mechanical ventilation who were randomly assigned based on unit bed location to receive either dexmedetomidine or propofol. The primary outcome was duration of mechanical ventilation. Secondary outcomes included mortality; proportion of time in target sedation; incidence of delirium, hypotension, and bradycardia; and ICU and hospital length of stay (LOS). RESULTS: A total of 57 patients were included. Baseline characteristics were similar between groups. There was no significant difference in duration of mechanical ventilation (median [IQR]) between the dexmedetomidine (78.5[125] hours) and propofol (105[130] hours; p = 0.15) groups. There was no difference between groups in ICU mortality, ICU and hospital LOS, or incidence of delirium. Safety outcomes were also similar. Patients in the dexmedetomidine group spent a significantly greater percentage of time in target sedation (98[8] %) compared to propofol group (92[10] %; p = 0.02). CONCLUSIONS: Our results suggest that, similar to medical and cardiac surgery patients, dexmedetomidine and propofol are safe and effective sedation agents in critically ill trauma and surgical patients; however, dexmedetomidine achieves target sedation better than propofol for this specific population.

Quetiapine for delirium prophylaxis in high-risk critically ill patients.

BACKGROUND: Delirium is common in patients admitted to the surgical trauma intensive care unit (ICU), and the risk factors for these patients differ from medical patients. Given the morbidity and mortality associated with delirium, efforts to prevent it may improve patient outcomes, but previous efforts pharmacologically have been limited by side effects and insignificant results. We hypothesized that scheduled quetiapine could reduce the incidence of delirium in this population. METHODS: The study included 71 adult patients who were at high-risk for the development of delirium (PRE-DELIRIC Score ≥50%, history of dementia, alcohol misuse, or drug abuse). Patients were randomized to receive quetiapine 12.5 mg every 12 h for delirium or no pharmacologic prophylaxis within 48 h of admission to the ICU. The primary end point was the incidence of delirium during admission to the ICU. Secondary end points included time to onset of delirium, ICU and hospital length of stay (LOS), ICU and hospital mortality, duration of mechanical ventilation, and adverse events. RESULTS: The incidence of delirium during admission to the ICU was 45.5% (10/22) in the quetiapine group and 77.6% (38/49) in the group that did not receive pharmacological prophylaxis. The mean time to onset of delirium was 1.4 days for those who did not receive prophylaxis versus 2.5 days for those who did (p = 0.06). The quetiapine group significantly reduced ventilator duration from 8.2 days to 1.5 days (p = 0.002). CONCLUSIONS: The findings suggested that scheduled, low-dose quetiapine is effective in preventing delirium in high-risk, surgical trauma ICU patients.

Whole Blood Administration: Comparison of In Vitro Platelet Function of Pressure Bag, Pressure Bag With Fluid Warming Device, and Rapid Infuser Methods.

BACKGROUND: Use of low-titer group O whole blood for emergent transfusion of patients with unknown blood type became AABB approved in January 2018. Since that time, there is increasing use of whole blood in massive transfusion protocols. Whole blood stored at refrigerator temperature (2-4 °C) contains functional platelets that some research proposes may provide better clot dynamics than standard platelets, which are stored at room temperature (20-24 °C). Conventional teaching does not promote infusion of platelet products with pressure or warming, due to concerns of activation and subsequent inactivity of the infused platelets. Although a few reports found no significant changes in platelet function with warming or pressure during infusion of conventional room-temperature-stored platelets, there is limited data to support use of warming or pressure for infusion of whole blood products containing cold-stored platelets. METHODS: This study design is to evaluate and compare three commonly used methods of administering blood products in a massive transfusion setting for their potential effects on platelets contained within whole blood units (pressure bag alone, pressure bag with fluid warming line, and rapid infuser). RESULTS: Platelet function of 10 units tested pre- and post-infusion by thromboelastography (TEG) and platelet aggregation studies found no significant difference in platelet activity pre- and post-infusion with any of the three methods evaluated. CONCLUSIONS: This study supports the use of rapid infuser or pressure bag devices (with or without warming) as acceptable for infusion of whole blood products. Infusion of whole blood with warming is preferable to prevent potential transfusion-associated hypothermia.

Rapid Ground Transport of Trauma Patients: A Moderate Distance From Trauma Center Improves Survival.

BACKGROUND: There is debate within the emergency medical services (EMS) community over the value of calling a helicopter for trauma patients within a moderate distance/<45 min, of a trauma center. Helicopter EMS (HEMS) generally have a wider scope and more advanced training than the ground EMS (GEMS). GEMS, on the other hand, have the benefit of being able to immediately initiate rapid transport to the trauma center without the delay involved with HEMS flying to the scene, landing, and assuming patient care. METHODS: We retrospectively analyzed patients brought to a level I trauma center who were admitted with blunt traumatic injuries between 2010 and 2015 in the Trauma Quality Improvement Program database. Two analyses were performed, one in which the patient's reported initial scene vitals met criteria for step one of the Centers for Disease Control's 2011 National Field Triage Guidelines (NFTG) and the other in which the patient's initial scene vitals met those same guidelines and/or had a pulse greater than 110 beats per minute. Patients were categorized on scene to emergency department (ED) transport mode, either HEMS or GEMS. Inclusion criteria were a HEMS response time to the scene that was between 15 and 45 min with a transport time from the scene to the ED that was between 10 and 35 min or a GEMS transport time from the scene to the ED that was between 15 and 45 min. Statistical significance (P < 0.05) was established through logit regression. Mortality rates were then calculated within each transport mode-based population. RESULTS: Four hundred subjects were included in the analysis of patients meeting the first step of the NFTG, with 212 HEMS patients and 188 in the GEMS group. HEMS had a higher mortality rate at 0.184 and GEMS at 0.101, which was statistically significant (P = 0.019). When 606 subjects meeting the first step of the NFTG or with a pulse greater than 110 beats per minute were analyzed, the results were statistically significant (P < 0.001), with the HEMS category having a higher mortality rate at 0.154 and the GEMS category having a lower mortality at 0.056. CONCLUSIONS: Our data demonstrate that scene-to-ED time is paramount, and rapid ground transport should be used in blunt trauma patients when the scene is up to a moderate ground distance away from the trauma center and there would be a moderate-to-prolonged HEMS response time. In both analyses, hemodynamically unstable trauma patients had lower rates of mortality following ground transport. We recognize that there may be a subset of patients at these distances who could benefit from HEMS response, particularly if the flight crew can offer more advanced and specialized techniques; however, every effort should be made to minimize the scene-to-ED time, and HEMS response, scene, and transport time must be considered. This study only analyzed the patients within a moderate distance of the trauma center and at longer distances or in different environments; HEMS transport may indeed minimize the scene to ED time.

Taking the Blood Bank to the Field: The Design and Rationale of the Prehospital Air Medical Plasma (PAMPer) Trial.

Hemorrhage and trauma induced coagulopathy remain major drivers of early preventable mortality in military and civilian trauma. Interest in the use of prehospital plasma in hemorrhaging patients as a primary resuscitation agent has grown recently. Trauma center-based damage control resuscitation using early and aggressive plasma transfusion has consistently demonstrated improved outcomes in hemorrhaging patients. Additionally, plasma has been shown to have several favorable immunomodulatory effects. Preliminary evidence with prehospital plasma transfusion has demonstrated feasibility and improved short-term outcomes. Applying state-of-the-art resuscitation strategies to the civilian prehospital arena is compelling. We describe here the rationale, design, and challenges of the Prehospital Air Medical Plasma (PAMPer) trial. The primary objective is to determine the effect of prehospital plasma transfusion during air medical transport on 30-day mortality in patients at risk for traumatic hemorrhage. This study is a multicenter cluster randomized clinical trial. The trial will enroll trauma patients with profound hypotension (SBP ≤ 70 mmHg) or hypotension (SBP 71-90 mmHg) and tachycardia (HR ≥ 108 bpm) from six level I trauma center air medical transport programs. The trial will also explore the effects of prehospital plasma transfusion on the coagulation and inflammatory response following injury. The trial will be conducted under exception for informed consent for emergency research with an investigational new drug approval from the U.S. Food and Drug Administration utilizing a multipronged community consultation process. It is one of three ongoing Department of Defense-funded trials aimed at expanding our understanding of the optimal therapeutic approaches to coagulopathy in the hemorrhaging trauma patient.

Coronary Artery Calcification and Risk of Cardiac Complication in Geriatric Trauma Population.

BACKGROUND: Better means of identifying patients with increased cardiac complication (CC) risk is needed. Coronary artery calcification (CAC) is reported on routine chest CT scans. We assessed the correlation of CAC and CCs in the geriatric trauma population. STUDY DESIGN: A prospective, observational study of patients 55 years and older who had chest CT scan from May to September 2022 at a level 1 trauma center. Radiologists scored CAC as none, mild, moderate, or severe. None-to-mild CAC (NM-CAC) and moderate-to-severe CAC (MS-CAC) were grouped and in-hospital CCs assessed (arrhythmia, ST elevation myocardial infarction [STEMI], non-STEMI, congestive heart failure, pulmonary edema, cardiac arrest, cardiogenic shock, and cardiac mortality). Univariate and bivariate analyses were performed. RESULTS: Five hundred sixty-nine patients had a chest CT, of them 12 were excluded due to missing CAC severity. Of 557 patients, 442 (79.3%) had none-to-mild CAC and 115 (20.7%) has MS-CAC; the MS-CAC group was older (73.3 vs 67.4 years) with fewer male patients (48.7% vs 54.5%), had higher cardiac-related comorbidities, and had higher abbreviated injury scale chest injury scores. The MS-CAC group had an increased rate of CC (odds ratio [OR] 1.81, p = 0.016). Cardiac complications statistically more common in MS-CAC were congestive heart failure (OR 3.41, p = 0.003); cardiogenic shock (OR 3.3, p = 0.006); non-STEMI I or II (OR 2.8, p = 0.017); STEMI (OR 5.9, p = 0.029); and cardiac-caused mortality (OR 5.27, p = 0.036). No statistical significance between pulmonary edema (p = 0.6), new-onset arrhythmia (p = 0.74), or cardiac arrest (p = 0.193). CONCLUSIONS: CAC as reported on chest CT scans demonstrates a significant correlation with CC and should warrant additional cardiac monitoring.

Characterization of adverse events in injured patients at risk of hemorrhagic shock: a secondary analysis of three harmonized prehospital randomized clinical trials.

Background: The reporting of adverse events (AEs) is required and well defined in the execution of clinical trials, but is poorly characterized particularly in prehospital trials focusing on traumatic injury. In the setting of prehospital traumatic injury trials, no literature currently exists analyzing the clinical implications of AEs and their associations with mortality and morbidity. We sought to analyze AEs from three prehospital hemorrhagic shock trials and characterize their time course, incidence, severity, associated clinical outcomes, and relatedness. Methods: We performed a secondary analysis of three prehospital randomized clinical trials. We analyzed AEs at both the patient level as well as the individual AE level. We categorized patients who had no AEs, a single documented AE and those with multiple events (>1 AE). We characterized AE timing, severity, relatedness and attributable mortality outcomes. Results: We included 1490 patients from the three harmonized clinical trials, with 299 (20.1%) individual patients having at least a single AE documented with 529 AEs documented overall as a proportion of patients had multiple events. Over 44% of patients had a death-related misclassified AE. Patients with at least a single documented AE had a significantly higher 28-day mortality (log-rank χ2=81.27, p<0.001) compared with those without an AE documented. Patients with a single AE had a significant higher mortality than those with multiple AEs, potentially due to survival bias (log-rank χ2=11.80, p=0.006). When relatedness of each individual AE was characterized, over 97% of AEs were classified as 'definitely not related' or 'probably not related' to the intervention. Conclusions: AEs in hemorrhagic shock trials are common, occur early and are associated with mortality and survival bias. The potential for inaccurate reporting exists, and education and training remain essential for appropriate treatment arm comparison. The current results have important relevance to injury-related clinical trials. Trial registration numbers: NCT01818427, NCT02086500 and NCT03477006. Level of evidence: II.

Mechanism matters: mortality and endothelial cell damage marker differences between blunt and penetrating traumatic injuries across three prehospital clinical trials.

Injury mechanism is an important consideration when conducting clinical trials in trauma. Mechanisms of injury may be associated with differences in mortality risk and immune response to injury, impacting the potential success of the trial. We sought to characterize clinical and endothelial cell damage marker differences across blunt and penetrating injured patients enrolled in three large, prehospital randomized trials which focused on hemorrhagic shock. In this secondary analysis, patients with systolic blood pressure < 70 or systolic blood pressure < 90 and heart rate > 108 were included. In addition, patients with both blunt and penetrating injuries were excluded. The primary outcome was 30-day mortality. Mortality was characterized using Kaplan-Meier and Cox proportional-hazards models. Generalized linear models were used to compare biomarkers. Chi squared tests and Wilcoxon rank-sum were used to compare secondary outcomes. We characterized data of 696 enrolled patients that met all secondary analysis inclusion criteria. Blunt injured patients had significantly greater 24-h (18.6% vs. 10.7%, log rank p = 0.048) and 30-day mortality rates (29.7% vs. 14.0%, log rank p = 0.001) relative to penetrating injured patients with a different time course. After adjusting for confounders, blunt mechanism of injury was independently predictive of mortality at 30-days (HR 1.84, 95% CI 1.06-3.20, p = 0.029), but not 24-h (HR 1.65, 95% CI 0.86-3.18, p = 0.133). Elevated admission levels of endothelial cell damage markers, VEGF, syndecan-1, TM, S100A10, suPAR and HcDNA were associated with blunt mechanism of injury. Although there was no difference in multiple organ failure (MOF) rates across injury mechanism (48.4% vs. 42.98%, p = 0.275), blunt injured patients had higher Denver MOF score (p < 0.01). The significant increase in 30-day mortality and endothelial cell damage markers in blunt injury relative to penetrating injured patients highlights the importance of considering mechanism of injury within the inclusion and exclusion criteria of future clinical trials.

Contemporary outcomes of vertebral artery injury.

OBJECTIVE: Vertebral artery injury (VAI) associated with cervical trauma is being increasingly recognized with more aggressive screening. Disparate results from previous literature have led to uncertainty of the significance, natural history, and optimal therapy for VAI. METHODS: To understand the natural history and treatment outcomes from our experience, we performed a retrospective, single-center review from a level I trauma center for the previous 10 years of all VAI. Injuries were identified from search of an administrative trauma database, a resident-run working database, and all radiology dictations for the same period. All VAI were classified according to segmental involvement, Denver grading scale, and laterality. Analysis of associated injuries, demographics, neurologic outcome, mortality, length of stay, treatment plan, and follow-up imaging was also performed. RESULTS: Fifty-one patients with VAI were identified from 2001 to 2011 from a total of 36,942 trauma admissions (0.13% incidence). Associated injuries were significant with an average New Injury Severity Score of 29.6. Penetrating trauma occurred in 14%. Cervical spine fracture was present in 88% with VAI. Diagnosis was obtained with computed tomographic angiography (CTA) in 95%. Screening was prompted by injury pattern or high-risk mechanism in all cases. Injuries classified according to the Denver grading scale were grade I = 24%, grade II = 35%, grade III = 4%, grade IV = 35%, and grade V = 2%. Distribution across segments included V1 = 18%, V2 = 67%, V3 = 31%, and V4 = 6%. Only one posterior circulation stroke was attributable to VAI. Overall mortality was 8%, with each mortality being associated with significant other organ injuries. Treatment rendered for VAI was antiplatelet therapy (50%), observation (31%), warfarin (17%), and stent (2%). There were no significant differences between treatment groups on any variable with the exception of body mass index (P = .047). Follow-up was obtained for 13% (n = 6) of survivors. The CTA demonstrated injury stability in four patients and resolution in two patients. Accuracy of the administrative trauma database was 53% compared with 96% for the resident-run working database. CONCLUSIONS: Neurologic sequelae attributable to VAI were rare. Grade of VAI or vertebral artery segment did not correlate with morbidity. We did not observe any differences in short-term outcomes between systemic anticoagulation and antiplatelet therapy. Of those patients seen at follow-up, injury resolution or stability was documented by CTA. A conservative approach with either observation or antithrombotic therapy is suggested. If the natural history of VAI includes a very low stroke rate, then therapies with a lower therapeutic index, such as systemic anticoagulation, in the severely injured trauma patient are not supported. Our search strategy urges awareness of the limitations of administrative databases for retrospective vascular study.

Nutritional considerations for head and neck cancer patients: a review of the literature.

PURPOSE: Approximately 35% to 60% of all patients with head and neck cancer are malnourished at the time of their diagnosis because of tumor burden and obstruction of intake or the anorexia and cachexia associated with their cancer. The purpose of this article is to provide a contemporary review of the nutritional aspects of care for patients with head and neck cancer. MATERIALS AND METHODS: A literature search was performed in Medline, Cochrane, and other available databases from 1990 through 2012 for the clinical effectiveness of nutritional support, treatment modalities, and methods of delivery in relation to patients with head and neck malignancies. Human studies published in English and having nutritional status and head and neck cancer as a predictor variable were included. Randomized controlled trials, meta-analyses, prospective clinical studies, and systemic reviews were selected based on their relevance to the abovementioned subtitles. The resultant articles were analyzed and summarized into the definition, impact, assessment, treatment, and modes of administration of nutrition on the outcome of patients with head and neck cancer. RESULTS: Articles were reviewed that focused on the etiology and assessment of malnutrition and current nutritional treatments for cancer-induced anorexia and cachexia. Two hundred forty-eight articles were found: 2 clinical trials, 10 meta-analyses, 210 review studies, and 26 systematic reviews. Because of the lack of prospective data, a summative review of the conclusions of the studies is presented. CONCLUSION: Nutritional interventions should be initiated before cancer treatment begins and these interventions need to be ongoing after completion of treatment to ensure optimal outcomes for patients. A nutritional assessment must be part of all comprehensive treatment plans for patients with head and neck cancer. Alternative medical interventions, such as immune-enhancing nutrients or anticytokine pharmaceutical agents, also may be effective as adjuvant therapies, but more research is needed to quantify their clinical effect.

Time to early resuscitative intervention association with mortality in trauma patients at risk for hemorrhage.

BACKGROUND: Hemorrhage is the leading cause of preventable death after injury. Others have shown that delays in massive transfusion cooler arrival increase mortality, while prehospital blood product resuscitation can reduce mortality. Our objective was to evaluate if time to resuscitation initiation impacts mortality. METHODS: We combined data from the Prehospital Air Medical Plasma (PAMPer) trial in which patients received prehospital plasma or standard care and the Study of Tranexamic Acid during Air and ground Medical Prehospital transport (STAAMP) trial in which patients received prehospital tranexamic acid or placebo. We evaluated the time to early resuscitative intervention (TERI) as time from emergency medical services arrival to packed red blood cells, plasma, or tranexamic acid initiation in the field or within 90 minutes of trauma center arrival. For patients not receiving an early resuscitative intervention, the TERI was calculated based on trauma center arrival as earliest opportunity to receive a resuscitative intervention and were propensity matched to those that did to account for selection bias. Mixed-effects logistic regression assessed the association of 30-day and 24-hour mortality with TERI adjusting for confounders. We also evaluated a subgroup of only patients receiving an early resuscitative intervention as defined above. RESULTS: Among the 1,504 propensity-matched patients, every 1-minute delay in TERI was associated with 2% increase in the odds of 30-day mortality (adjusted odds ratio [aOR], 1.020; 95% confidence interval [CI], 1.006-1.033; p < 0.01) and 1.5% increase in odds of 24-hour mortality (aOR, 1.015; 95% CI, 1.001-1.029; p = 0.03). Among the 799 patients receiving an early resuscitative intervention, every 1-minute increase in TERI was associated with a 2% increase in the odds of 30-day mortality (aOR, 1.021; 95% CI, 1.005-1.038; p = 0.01) and 24-hour mortality (aOR, 1.023; 95% CI, 1.005-1.042; p = 0.01). CONCLUSION: Time to early resuscitative intervention is associated with morality in trauma patients with hemorrhagic shock. Bleeding patients need resuscitation initiated early, whether at the trauma center in systems with short prehospital times or in the field when prehospital time is prolonged. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Optimal Prehospital Crystalloid Resuscitation Volume in Trauma Patients at Risk for Hemorrhagic Shock.

BACKGROUND: Prehospital resuscitation guidelines vary widely, and blood products, although likely superior, are not available for most patients in the prehospital setting. Our objective was to determine the prehospital crystalloid volume associated with the lowest mortality among patients in hemorrhagic shock. STUDY DESIGN: This is a secondary analysis of the Prehospital Air Medical Plasma trial. Injured patients from the scene with hypotension and tachycardia or severe hypotension were included. Segmented regression and generalized additive models were used to evaluate nonlinear effects of prehospital crystalloid volume on 24-hour mortality. Logistic regression evaluated the association between risk-adjusted mortality and prehospital crystalloid volume ranges to identify optimal target volumes. Inverse propensity weighting was performed to account for patient heterogeneity. RESULTS: There were 405 patients included. Segmented regression suggested the nadir of 24-hour mortality lay within 377 to 1,419 mL prehospital crystalloid. Generalized additive models suggested the nadir of 24-hour mortality lay within 242 to 1,333 mL prehospital crystalloid. A clinically operationalized range of 250 to 1,250 mL was selected based on these findings. Odds of 24-hour mortality were higher for patients receiving less than 250 mL (adjusted odds ratio [aOR] 2.46; 95% CI 1.31 to 4.83; p = 0.007) and greater than 1,250 mL (aOR 2.57; 95% CI 1.24 to 5.45; p = 0.012) compared with 250 to 1,250 mL. Propensity-weighted regression similarly demonstrated odds of 24-hour mortality were higher for patients receiving less than 250 mL (aOR 2.62; 95% CI 1.34 to 5.12; p = 0.005) and greater than 1,250 mL (aOR 2.93; 95% CI 1.36 to 6.29; p = 0.006) compared with 250 to 1,250 mL. CONCLUSIONS: Prehospital crystalloid volumes between 250 and 1,250 mL are associated with lower mortality compared with lower or higher volumes. Further work to validate these finding may provide practical volume targets for prehospital crystalloid resuscitation.

Optimizing Transitions of Care and Enhancing Surgical Education on Acute Care Surgery: A Multi-Institutional Survey Study.

OBJECTIVE: Critically ill and injured patients are routinely managed on the Trauma and Acute Care Surgery (ACS) service and receive care from numerous residents during hospital admission. The Clinical Learning Environment Review (CLER) program established by the ACGME identified variability in resident transitions of care (TC) while observing quality care and patient safety concerns. The aim of our multi-institutional study was to review surgical trainees' impressions of a specialty-specific handoff format in order to optimize patient care and enhance surgical education on the ACS service. DESIGN: A survey study was conducted with a voluntary electronic 20-item questionnaire that utilized a 5 point Likert scale regarding TC among resident peers, supervised handoffs by trauma attendings, and surgical education. It also allowed for open-ended responses regarding perceived advantages and disadvantages of handoffs. SETTING: Ten American College of Surgeons-verified Level 1 adult trauma centers. PARTICIPANTS: All general surgery residents and trauma/acute/surgical critical care fellows were surveyed. RESULTS: The study task was completed by 147 postgraduate trainees (125 residents, 14 ACS fellows, and 8 surgical critical care fellows) with a response rate of 61%. Institutional responses included: university hospital (67%), community hospital-university affiliate (16%), and private hospital-university affiliate (17%). A majority of respondents were satisfied with morning TC (62.6%) while approximately half were satisfied with evening TC (52.4%). Respondees believe supervised handoffs improved TC and prevented patient care delays (80.9% and 74.8%, respectively). A total of 35% of trainees utilized the open-ended response field to highlight specific best practices of their home institutions. CONCLUSIONS: Surgical trainees view ACS morning handoff as an effective standard to provide the highest level of clinical care and an opportunity to enhance surgical knowledge. As TC continue to be a focus of certifying bodies, identifying best practices and opportunities for improvement are critical to optimizing quality patient care and surgical education.

Evaluation of critical care burden following traumatic injury from two randomized controlled trials.

Trauma resuscitation practices have continued to improve with new advances targeting prehospital interventions. The critical care burden associated with severely injured patients at risk of hemorrhage has been poorly characterized. We aim to describe the individual and additive effects of multiorgan failure (MOF) and nosocomial infection (NI) on delayed mortality and resource utilization. A secondary analysis of harmonized data from two large prehospital randomized controlled trials (Prehospital Air Medical Plasma (PAMPer) Trial and Study of Tranexamic Acid during Air and Ground Medical Prehospital Transport (STAAMP) Trial) was conducted. Only those patients who survived beyond the first 24 hours post-injury and spent at least one day in the ICU were included. Patients were stratified by development of MOF only, NI only, both, or neither and diagnosis of early (≤ 3 days) versus late MOF (> 3 days). Risk factors of NI and MOF, time course of these ICU complications, associated mortality, and hospital resource utilization were evaluated. Of the 869 patients who were enrolled in PAMPer and STAAMP and who met study criteria, 27.4% developed MOF only (n = 238), 10.9% developed NI only (n = 95), and 15.3% were diagnosed with both MOF and NI (n = 133). Patients developing NI and/or MOF compared to those who had an uncomplicated ICU course had greater injury severity, lower GCS, and greater shock indexes. Early MOF occurred in isolation, while late MOF more often followed NI. MOF was associated with 65% higher independent risk of 30-day mortality when adjusting for cofounders (OR 1.65; 95% CI 1.04-2.6; p = 0.03), however NI did not significantly affect odds of mortality. NI was individually associated with longer mechanical ventilation, ICU stay, hospital stay, and rehabilitation requirements, and the addition of MOF further increased the burden of inpatient and post-discharge care. MOF and NI remain common complications for those who survive traumatic injury. MOF is a robust independent predictor of mortality following injury in this cohort, and NI is associated with higher resource utilization. Timing of these ICU complications may reveal differences in pathophysiology and offer targets for continued advancements in treatment.

Improving Opioid Prescribing Post-Discharge for Trauma Patients With Rib Fractures: Factors in Prevention of Prolonged Use and Dependency.

BACKGROUND: Rib fracture (RF) pain management provides analgesia while reducing opioids. We postulated: (1) Prescriber factors affect opiate duration, and (2) lidocaine infusion curtails dependency. MATERIALS AND METHODS: Retrospective study of RF patients undergoing multimodal analgesia at ACS-verified Level 1 Trauma Center April 2018-February 2020. Exclusions: age<18 y/o, GCS < 14, hospital length of stay (LOS) <3 d, <3 RF, ventilator support, injury-related mortality, disclosed/discoverable, acute/chronic opiate Rx within 90 days preadmission, substance abuse, patient inaccessible via Controlled Substance Monitoring Database (CSMD), and/or not using opioids in-/post-hospitalization. CSMD queried regarding opioid prescriptions filled by cohort. Cohort variable analysis performed on SPSS Version 27sf (Armonk, NY: IBM Corp). RESULTS: 153 patients included - 113 (74%) stopped opiates by 30 days post-discharge (NORx30), 40 (26%) continued beyond 30 days (Rx+). No significant differences in age, gender, ISS, number of RF, bilaterality, flail chest, and discharge disposition. Significant differences included hospital LOS (7.62 NORx30 vs. 10.22 Rx+, p = .02), number of prescribers (1.73 NORx30 vs. 2.98 Rx+, p < .01), average MME/day during initial 30 days post-discharge (36.7 ± 17 NORx30 vs. 45.4 ± 30.2 Rx+, p = .03), and number of pills (49 ± 38 NORx30 vs. 120 ± 85 Rx+, p < .01). Patients who received lidocaine infusion (LIDO+) had lower MME/day prescribed (32.24 ± 19.9, p = .03), were younger (61.2 vs. 65.6, p < .01), had more RFs (7.1 vs. 6.05, p = .03), and shorter LOS (7.71 vs 10.2, p = .01). DISCUSSION: Prescriber attention to MME/day and number of pills dispensed affects opioid dependency. We recommend 35-40 MME/day with 50 pill/month limit prescribed by a single provider monitoring patient and CSMD. Early LI offers post-discharge opioid cessation advantage.

Continued Relevance of Initial Temperature Measurement in Trauma Patients.

OBJECTIVES: Hypothermia occurs in 30-50% of severely injured trauma patients and is associated with multiple metabolic derangements and worsened outcomes. However, hypothermia continues to be under-diagnosed which leads to inadequate triage and treatment in trauma patients. Our study set out to determine if hypothermia is an independent predictor of mortality in trauma patients. METHODS: We retrospectively reviewed data of all trauma activation patients over a 5-year period. Data were collected on patient demographics, initial core temperature, Glasgow Coma Scale (GCS) on presentation, and injury severity score (ISS). Patients were then stratified into groups based on presenting temperature, ISS, and GCS. Outcomes compared were mortality, blood products received, and intensive care unit (ICU) length of stay. Correlations and logistic regression were used to test the hypotheses. RESULTS: Survival and temperature data were reviewed on 15,567 patients. Initial temperature was not significantly associated with ICU length of stay or blood products transfused (P = .21 and P = .08, respectively). However, odds ratio of mortality in hypothermic patients (<35°C) compared to normothermic patients (35-39°C) was 3.95 (95% CI 2.90-5.41). When controlling for GCS and ISS, separately, temperature remained an independent predictor of mortality. CONCLUSIONS: Hypothermia is an independent risk factor for mortality in trauma patients. It remains crucial to obtain accurate presenting temperatures in trauma patients in order to triage and treat hypothermia. Based on our data, obtaining core temperatures and rapidly treating hypothermia continues to be a vital part of the secondary survey of trauma patients.

American College of Surgeons Objective Assessment of Skills in Surgery (ACS OASIS): A Formative Assessment of Junior Residents' Technical Skills.

OBJECTIVE: The objective assessment of technical skills of junior residents is essential in implementing competency-based training and providing specific feedback regarding areas for improvement. An innovative assessment that can be easily implemented by training programs nationwide has been developed by expert surgeon educators under the aegis of the American College of Surgeons (ACS) Division of Education. This assessment, ACS Objective Assessment of Skills in Surgery (ACS OASIS) uses eight stations to address technical skills important for junior residents within the domains of laparoscopic appendectomy, excision of lipoma, central line placement, laparoscopic cholecystectomy, trocar placement, exploratory laparotomy, repair of enterotomy, and tube thoracostomy. The purpose of this study was to implement ACS OASIS at a number of sites to study its psychometric rigor. DESIGN: The ACS OASIS was pre-piloted at two programs to establish feasibility and to gather information regarding implementation. Each skills station was 12 minutes long, and the faculty completed a checklist with 5 to 15 items, and a global assessment scale. The study was then repeated at three pilot sites and included 29 junior residents who were assessed by a total of 44 faculty. Psychometric data for the stations and checklists were collected and analyzed. SETTING: The pre-pilot sites were Geisinger and University of Tennessee Knoxville.Data were gathered from pilot sites that included Wellspan Health, Duke University, and University of California Los Angeles. RESULTS: The mean checklist score for all learners was 76% (IQR of 66%-85%). The average global rating was 3.36 on a 5-point scale with a standard deviation of 0.56. The overall cut score derived using the borderline group method was at 68% with 34% of performances requiring remediation. Using this criterion, the average number of stations that were completed by each learner without need for remediation was five.The station discrimination index ranged from 0.27 to 0.65 (all above the threshold of 0.25), demonstrating solid psychometric characteristics at the station level. The internal-consistency reliability was 0.76 with SEM of 5.8%. The inter-rater reliability (intraclass correlation) was high at 0.73 with general agreement of 79% between the two raters. The station discrimination was at 0.45 (range of 0.27 to 0.65) indicating a high level of differentiation between high and low performers. Using the generalizability theory, the G-coefficient reliability was at 0.72 with the reliability projection flattening after 8 stations. Overall, 75% to 82% the faculty and learners rated ACS OASIS as realistic and beneficial. CONCLUSIONS: ACS OASIS is a psychometrically sound technical skills assessment tool that can provide useful information for feedback to junior residents and support efforts to remediate gaps in performance.