Sigh Ventilation in Patients With Trauma: The SiVent Randomized Clinical Trial.

Importance: Among patients receiving mechanical ventilation, tidal volumes with each breath are often constant or similar. This may lead to ventilator-induced lung injury by altering or depleting surfactant. The role of sigh breaths in reducing ventilator-induced lung injury among trauma patients at risk of poor outcomes is unknown. Objective: To determine whether adding sigh breaths improves clinical outcomes. Design, Setting, and Participants: A pragmatic, randomized trial of sigh breaths plus usual care conducted from 2016 to 2022 with 28-day follow-up in 15 academic trauma centers in the US. Inclusion criteria were age older than 18 years, mechanical ventilation because of trauma for less than 24 hours, 1 or more of 5 risk factors for developing acute respiratory distress syndrome, expected duration of ventilation longer than 24 hours, and predicted survival longer than 48 hours. Interventions: Sigh volumes producing plateau pressures of 35 cm H2O (or 40 cm H2O for inpatients with body mass indexes >35) delivered once every 6 minutes. Usual care was defined as the patient's physician(s) treating the patient as they wished. Main Outcomes and Measures: The primary outcome was ventilator-free days. Prespecified secondary outcomes included all-cause 28-day mortality. Results: Of 5753 patients screened, 524 were enrolled (mean [SD] age, 43.9 [19.2] years; 394 [75.2%] were male). The median ventilator-free days was 18.4 (IQR, 7.0-25.2) in patients randomized to sighs and 16.1 (IQR, 1.1-24.4) in those receiving usual care alone (P = .08). The unadjusted mean difference in ventilator-free days between groups was 1.9 days (95% CI, 0.1 to 3.6) and the prespecified adjusted mean difference was 1.4 days (95% CI, -0.2 to 3.0). For the prespecified secondary outcome, patients randomized to sighs had 28-day mortality of 11.6% (30/259) vs 17.6% (46/261) in those receiving usual care (P = .05). No differences were observed in nonfatal adverse events comparing patients with sighs (80/259 [30.9%]) vs those without (80/261 [30.7%]). Conclusions and Relevance: In a pragmatic, randomized trial among trauma patients receiving mechanical ventilation with risk factors for developing acute respiratory distress syndrome, the addition of sigh breaths did not significantly increase ventilator-free days. Prespecified secondary outcome data suggest that sighs are well-tolerated and may improve clinical outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02582957.

Nephrectomy Is Not Associated with Increased Risk of Mortality or Acute Kidney Injury after High-Grade Renal Trauma: A Propensity Score Analysis of the Trauma Quality Improvement Program (TQIP).

PURPOSE: Patients with high-grade renal trauma (HGRT) undergoing nephrectomy may be at higher risk for mortality compared to those treated conservatively. However, no study has controlled for degree of hemorrhage as a measure of shock. We hypothesized that after controlling for blood transfusions and other factors, nephrectomy after HGRT would be associated with increased mortality and acute kidney injury (AKI). MATERIALS AND METHODS: We identified adult patients with HGRT (American Association for the Surgery of Trauma grade III-V) in TQIP (2013-2017). Propensity scoring was used to adjust for the probability of nephrectomy. Conditional logistic regression was used to analyze the association between nephrectomy and mortality and AKI. We adjusted for patient characteristics, injury specifics, and physiological factors including blood transfusions. RESULTS: There were 12,780 patients with HGRT, and 1,014 (7.9%) underwent nephrectomy. Mortality was 10.6% and 4.2% in the nephrectomy and nonnephrectomy groups, respectively (p <0.001). In nephrectomy patients, 8.6% experienced AKI vs 2.4% of nonnephrectomy patients (p <0.001). In the adjusted analysis, there was no association between nephrectomy and mortality (OR=0.367, 95% CI 0.09-1.497, p=0.162). There was also no association between nephrectomy and AKI. Increasing age, nonCaucasian race, increasing Injury Severity Score, decreasing Glasgow Coma Score and blood transfusions were associated with higher mortality. For AKI, independent predictors included increasing age, male sex, and blood transfusions. CONCLUSIONS: After adjusting for volume of blood transfused in the first 24 hours, nephrectomy after HGRT was not associated with increased mortality or AKI. As a clinical principle, trauma nephrectomy should be avoided when possible.

Early Prehospital Tranexamic Acid Following Injury Is Associated With a 30-day Survival Benefit: A Secondary Analysis of a Randomized Clinical Trial.

OBJECTIVE: We sought to characterize the timing of administration of prehospital tranexamic acid (TXA) and associated outcome benefits. BACKGROUND: TXA has been shown to be safe in the prehospital setting post-injury. METHODS: We performed a secondary analysis of a recent prehospital randomized TXA clinical trial in injured patients. Those who received prehospital TXA within 1 hour (EARLY) from time of injury were compared to those who received prehospital TXA beyond 1 hour (DELAYED). We included patients with a shock index of >0.9. Primary outcome was 30-day mortality. Kaplan-Meier and Cox Hazard regression were utilized to characterize mortality relationships. RESULTS: EARLY and DELAYED patients had similar demographics, injury characteristics, and shock severity but DELAYED patients had greater prehospital resuscitation requirements and longer prehospital times. Stratified Kaplan-Meier analysis demonstrated significant separation for EARLY patients (N = 238, log-rank chi-square test, 4.99; P = 0.03) with no separation for DELAYED patients (N = 238, log-rank chi-square test, 0.04; P = 0.83). Stratified Cox Hazard regression verified, after controlling for confounders, that EARLY TXA was associated with a 65% lower independent hazard for 30-day mortality [hazard ratio (HR) 0.35, 95% confidence interval (CI) 0.19-0.65, P = 0.001] with no independent survival benefit found in DELAYED patients (HR 1.00, 95% CI 0.63-1.60, P = 0.999). EARLY TXA patients had lower incidence of multiple organ failure and 6-hour and 24-hour transfusion requirements compared to placebo. CONCLUSIONS: Administration of prehospital TXA within 1 hour from injury in patients at risk of hemorrhage is associated with 30-day survival benefit, lower incidence of multiple organ failure, and lower transfusion requirements.

The American Association for the Surgery of Trauma Renal Grading System-Should Segmental Kidney Infarction be Classified as a Grade IV Injury?

PURPOSE: In 2018 the American Association for the Surgery of Trauma revised renal injury grading. One change was inclusion of segmental kidney infarction under grade IV injuries. We aimed to assess how segmental kidney infarction will change the scope of grade IV injuries and compare bleeding control interventions in those with and without isolated segmental kidney infarction. METHODS: We used high grade renal trauma data from 7 level 1 trauma centers from 2013 to 2018 as part of the Multi-institutional Genito-Urinary Trauma Study. Initial computerized tomography scans were reviewed to regrade the injuries. Injuries were categorized as isolated segmental kidney infarction if segmental parenchymal infarction was the only reason for inclusion under grade IV injury. All other grade IV injuries (including combined injury patterns) were categorized as without isolated segmental kidney infarction. Bleeding interventions were compared between those with and without isolated segmental kidney infarction. RESULTS: From 550 patients with high grade renal trauma and available computerized tomography, 250 (45%) were grade IV according to the 2018 American Association for the Surgery of Trauma grading system. Of these, 121 (48%) had isolated segmental kidney infarction. The majority of patients with isolated segmental kidney infarction (88%) would have been assigned a lower grade using the original 1989 grading system. Rate of bleeding control interventions was lower in isolated segmental kidney infarction compared to other grade IV injuries (7% vs 21%, p=0.002). Downgrading all patients with isolated segmental kidney infarction to grade III did not change the grading system's associations with bleeding interventions. CONCLUSIONS: Approximately half of the 2018 American Association for the Surgery of Trauma grade IV injuries have isolated segmental kidney infarction. Including isolated segmental kidney infarction in grade IV injuries increases the heterogeneity of these injuries without increasing the grading system's ability to predict bleeding interventions. In future iterations of the American Association for the Surgery of Trauma renal trauma grading isolated segmental kidney infarction could be reclassified as grade III injury.

Patient Willingness to Accept Antibiotic Side Effects to Reduce Surgical Site Infection After Colorectal Surgery.

BACKGROUND: Mechanical bowel preparation with antibiotics is associated with decreased surgical site infections (SSI) after colorectal surgery. However, antibiotics have side effects, such as vomiting. It is unknown how patient willingness to take antibiotics is affected by side effect severity. MATERIALS AND METHODS: This was a single-center study of 86 patients (37 undergoing colorectal surgery) using a modified standard gamble technique. We presented patients with four hypothetical scenarios, holding SSI reduction constant and varying antibiotic side effect severity. Patients reported willingness to take antibiotics using a scale from 0 to 100. Patients also reported the maximum level of side effects they would accept. We examined the association between side effect severity and willingness to take antibiotics with a multivariable mixed-effects regression model and investigated differences in surgical and nonsurgical patients. RESULTS: After adjusting for age, sex, and patient type, willingness scores decreased with increasing side effect severity. No side effects: 92 (CI 86,99), mild: 83 (CI 76,90), moderate: 76 (CI 69,83), and severe: 46 (CI 38,52), P < 0.001. Surgical patients were more willing to take antibiotics at all severity levels compared with nonsurgical patients, P < 0.001. Surgical (57%) and nonsurgical (58%) patients reported that they would accept moderate side effects. Patients with prior SSI (n = 5) would take antibiotics regardless of side effect severity. CONCLUSIONS: Increasing antibiotic side effect severity is associated with decreased willingness to take antibiotics during bowel preparation, despite a reduction in SSI. Adherence may be improved with strategies that increase patient education and decrease side effects during bowel preparation.

Current Management of Extraperitoneal Bladder Injuries: Results from the Multi-Institutional Genito-Urinary Trauma Study (MiGUTS).

PURPOSE: We studied the current management trends for extraperitoneal bladder injuries and evaluated the use of operative repair versus catheter drainage, and the associated complications with each approach. MATERIALS AND METHODS: We prospectively collected data on bladder trauma from 20 level 1 trauma centers across the United States from 2013 to 2018. We excluded patients with intraperitoneal bladder injury and those who died within 24 hours of hospital arrival. We separated patients with extraperitoneal bladder injuries into 2 groups (catheter drainage vs operative repair) based on their initial management within the first 4 days and compared the rates of bladder injury related complications among them. Regression analyses were used to identify potential predictors of complications. RESULTS: From 323 bladder injuries we included 157 patients with extraperitoneal bladder injuries. Concomitant injuries occurred in 139 (88%) patients with pelvic fracture seen in 79%. Sixty-seven patients (43%) initially underwent operative repair for their extraperitoneal bladder injuries. The 3 most common reasons for operative repair were severity of injury or bladder neck injury (40%), injury found during laparotomy (39%) and concern for pelvic hardware contamination (28%). Significant complications were identified in 23% and 19% of the catheter drainage and operative repair groups, respectively (p=0.55). The only statistically significant predictor for complications was bladder neck or urethral injury (RR 2.69, 95% 1.21-5.97, p=0.01). CONCLUSIONS: In this large multi-institutional cohort, 43% of patients underwent surgical repair for initial management of extraperitoneal bladder injuries. We found no significant difference in complications between the initial management strategies of catheter drainage and operative repair. The most significant predictor for complications was concomitant urethral or bladder neck injury.

Shock associated with endothelial dysfunction in omental microvessels.

BACKGROUND: Impaired microvascular function leads to a poor outcome in a variety of medical conditions. Our aim was to determine whether vasodilator responses to acetylcholine (Ach) are impaired in human omental arterioles from patients with severe trauma. MATERIALS AND METHODS: Patients with massive blood loss and severe shock requiring damage control procedures were included. Tissues were collected at the first (FEL) and the second explorative laparotomy (SEL). Control tissues were collected from nontrauma patients. Freshly isolated 50-200-µm-diameter omental arterioles were analysed using videomicroscopy. Dihydroethidine and DCF-DA fluorescence were used to assess reactive oxygen species (ROS) production. MnTBAP was used to determine the contribution of excess vascular superoxide contribution to endothelial dysfunction. RESULTS: After constriction (30-50%) with endothelin-1, dilation to graded doses of Ach (10-9 -10-4 M) was greater in control vessels compared to FEL and SEL (max dilation at 10-4 M (MD) = 25 ± 3%, n = 8; and 59 ± 8%, n = 8, respectively, and controls MD = 93 ± 10%, n = 6, P < 0·05). Fluorescence imaging of ROS production showed significant increases in superoxide (225·46 ± 12·86; 215·77 ± 10·75 vs. 133·75 ± 7·26, arbitrary units; P < 0·05) and peroxide-related ROS (240·8 ± 20·42; 234·59 ± 28·86, vs. 150·78 ± 15·65, arbitrary units; P < 0·05), in FEL and SEL microvessels compared to control, respectively. FEL pretreated with MnTBAP demonstrated significant improvement in Ach-induced vasodilation (25·5 ± 3·0% vs. 79·5 ± 8·2%; P < 0·05). CONCLUSIONS: Severe shock associated with microvascular endothelial dysfunction enhances production of ROS in human omental tissues. The altered flow regulation may contribute to a mismatch between local blood supply and demand, exacerbating abnormal tissue perfusion and function.

Propofol is associated with favorable outcomes compared with benzodiazepines in ventilated intensive care unit patients.

RATIONALE: Mechanically ventilated intensive care unit (ICU) patients are frequently managed using a continuous-infusion sedative. Although recent guidelines suggest avoiding benzodiazepines for sedation, this class of drugs is still widely used. There are limited data comparing sedative agents in terms of clinical outcomes in an ICU setting. OBJECTIVES: Comparison of propofol to midazolam and lorazepam in adult ICU patients. METHODS: Data were obtained from a multicenter ICU database (2003-2009). Patient selection criteria included age greater than or equal to 18 years, single ICU admission with single ventilation event (>48 h), and treatment with continuously infused sedation (propofol, midazolam, or lorazepam). Propensity score analysis (1:1) was used and mortality measured. Cumulative incidence and competing risk methodology were used to examine time to ICU discharge and ventilator removal. MEASUREMENTS AND MAIN RESULTS: There were 2,250 propofol-midazolam and 1,054 propofol-lorazepam matched patients. Hospital mortality was statistically lower in propofol-treated patients as compared with midazolam- or lorazepam-treated patients (risk ratio, 0.76; 95% confidence interval [CI], 0.69-0.82 and risk ratio, 0.78; 95% CI, 0.68-0.89, respectively). Competing risk analysis for 28-day ICU time period showed that propofol-treated patients had a statistically higher probability for ICU discharge (78.9% vs. 69.5%; 79.2% vs. 71.9%; P < 0.001) and earlier removal from the ventilator (84.4% vs. 75.1%; 84.3% vs. 78.8%; P < 0.001) when compared with midazolam- and lorazepam-treated patients, respectively. CONCLUSIONS: In this large, propensity-matched ICU population, patients treated with propofol had a reduced risk of mortality and had both an increased likelihood of earlier ICU discharge and earlier discontinuation of mechanical ventilation.

Prehospital tranexamic acid is associated with a survival benefit without an increase in complications: results of two harmonized randomized clinical trials.

INTRODUCTION: Recent randomized clinical trials have demonstrated that prehospital tranexamic acid (TXA) administration following injury is safe and improves survival. However, the effect of prehospital TXA on adverse events, transfusion requirements and any dose response relationships require further elucidation. METHODS: A secondary analysis was performed using harmonized data from two large, double-blinded, randomized prehospital TXA trials. Outcomes, including 28-day mortality, pertinent adverse events and 24-hour red cell transfusion requirements were compared between TXA and placebo groups. Regression analyses were utilized to determine the independent associations of TXA after adjusting for study enrollment, injury characteristics and shock severity across a broad spectrum of injured patients. Dose response relationships were similarly characterized based upon grams of prehospital TXA administered. RESULTS: A total of 1744 patients had data available for secondary analysis and were included in the current harmonized secondary analysis. The study cohort had an overall mortality of 11.2% and a median injury severity score of 16 (IQR: 5-26). TXA was independently associated with a lower risk of 28-day mortality (HR: 0.72, 95% CI 0.54, 0.96, p = 0.03). Prehospital TXA also demonstrated an independent 22% lower risk of mortality for every gram of prehospital TXA administered (HR: 0.78, 95% CI 0.63, 0.96, p = 0.02). Multivariable linear regression verified that patients who received TXA were independently associated with lower 24-hour red cell transfusion requirements (ß: -0.31, 95% CI -0.61, -0.01, p = 0.04) with a dose-response relationship (ß: -0.24, 95% CI -0.45, -0.02, p = 0.03). There was no independent association of prehospital TXA administration on VTE, seizure, or stroke. CONCLUSIONS: In this secondary analysis of harmonized data from two large randomized interventional trials, prehospital TXA administration across a broad spectrum of injured patients is safe. Prehospital TXA is associated with a significant 28-day survival benefit, lower red cell transfusion requirements at 24 hours and demonstrates a dose-response relationship. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Missingness matters: a secondary analysis of thromboelastography measurements from a recent prehospital randomized tranexamic acid clinical trial.

Background: Tranexamic acid (TXA) has been hypothesized to mitigate coagulopathy in patients after traumatic injury. Despite previous prehospital clinical trials demonstrating a TXA survival benefit, none have demonstrated correlated changes in thromboelastography (TEG) parameters. We sought to analyze if missing TEG data contributed to this paucity of findings. Methods: We performed a secondary analysis of the Study of Tranexamic Acid During Air Medical and Ground Prehospital Transport Trial. We compared patients that received TEG (YES-TEG) and patients unable to be sampled (NO-TEG) to analyze subgroups in which to investigate TEG differences. TEG parameter differences across TXA intervention arms were assessed within subgroups disproportionately present in the NO-TEG relative to the YES-TEG cohort. Generalized linear models controlling for potential confounders were applied to findings with p<0.10 on univariate analysis. Results: NO-TEG patients had lower prehospital systolic blood pressure (SBP) (100 (78, 140) vs 125 (88, 147), p<0.01), lower prehospital Glascow Coma Score (14 (3, 15) vs 15 (12, 15), p<0.01), greater rates of prehospital intubation (39.4% vs 24.4%, p<0.01) and greater mortality at 30 days (36.4% vs 6.8%, p<0.01). NO-TEG patients had a greater international normalized ratio relative to the YES-TEG subgroup (1.2 (1.1, 1.5) vs 1.1 (1.0, 1.2), p=0.04). Within a severe prehospital shock cohort (SBP<70), TXA was associated with a significant decrease in clot lysis at 30 min on multivariate analysis (ß=-27.6, 95% CI (-51.3 to -3.9), p=0.02). Conclusions: Missing data, due to the logistical challenges of sampling certain severely injured patients, may be associated with a lack of TEG parameter changes on TXA administration in the primary analysis. Previous demonstration of TXA's survival benefit in patients with severe prehospital shock in tandem with the current findings supports the notion that TXA acts at least partially by improving clot integrity. Level of evidence: Level II.

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.

PROPOSED REVISION OF THE AMERICAN ASSOCIATION FOR SURGERY OF TRAUMA RENAL TRAUMA ORGAN INJURY SCALE: SECONDARY ANALYSIS OF THE MULTI-INSTITUTIONAL GENITOURINARY TRAUMA STUDY.

BACKGROUND: This study updates the American Association for Surgery of Trauma (AAST) Organ Injury Scale (OIS) for renal trauma using evidence-based criteria for bleeding control intervention. METHODS: This was a secondary analysis of a multi-center retrospective study including patients with high grade renal trauma from 7 Level-1 trauma centers from 2013-2018. All eligible patients were assigned new renal trauma grades based on revised criteria. The primary outcome used to measure injury severity was intervention for renal bleeding. Secondary outcomes included intervention for urinary extravasation, units of packed red blood cells (PRBCs) transfused within 24 hours, and mortality. To test the revised grading system, we performed mixed effect logistic regression adjusted for multiple baseline demographic and trauma covariates. We determined the area under the receiver-operator curve (AUC) to assess accuracy of predicting bleeding interventions from the revised grading system and compared this to 2018 AAST organ injury scale. RESULTS: based on the 2018 OIS grading system, we included 549 patients with AAST Grade III-V injuries and CT scans (III: 52% (n = 284), IV: 45% (n = 249), and V: 3% (n = 16)). Among these patients, 89% experienced blunt injury (n = 491) and 12% (n = 64) underwent intervention for bleeding. After applying the revised grading criteria, 60% (n = 329) of patients were downgraded and 4% (n = 23) were upgraded; 2.8% (n = 7) downgraded from grade V to IV, and 69.5% (n = 173) downgraded from IV to III. The revised renal trauma grading system demonstrated improved predictive ability for bleeding interventions (2018 AUC = 0.805, revised AUC = 0.883; p = 0.001) and number of units of PRBCs transfused. When we removed urinary injury from the revised system, there was no difference in its predictive ability for renal hemorrhage intervention. CONCLUSIONS: A revised renal trauma grading system better delineates the need for hemostatic interventions than the current AAST OIS renal trauma grading system. LEVEL OF EVIDENCE: II.

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.

Prehospital tranexamic acid is associated with a dose-dependent decrease in syndecan-1 after trauma: A secondary analysis of a prospective randomized trial.

BACKGROUND: In the Study of Tranexamic Acid During Air and Ground Prehospital Transport (STAAMP) Trial, prehospital tranexamic acid (TXA) was associated with lower mortality in specific patient subgroups. The underlying mechanisms responsible for a TXA benefit remain incompletely characterized. We hypothesized that TXA may mitigate endothelial injury and sought to assess whether TXA was associated with decreased endothelial or tissue damage markers among all patients enrolled in the STAAMP Trial. METHODS: We collected blood samples from STAAMP Trial patients and measured markers of endothelial function and tissue damage including syndecan-1, soluble thrombomodulin (sTM), and platelet endothelial cell adhesion molecule-1 at hospital admission (0 hours) and 12 hours, 24 hours, and 72 hours after admission. We compared these marker values for patients in each treatment group during the first 72 hours, and modeled the relationship between TXA and marker concentration using regression analysis to control for potential confounding factors. RESULTS: We analyzed samples from 766 patients: 383 placebo, 130 abbreviated dosing, 119 standard dosing, and 130 repeat dosing. Lower levels of syndecan-1, TM, and platelet endothelial cell adhesion molecule measured within the first 72 hours of hospital admission were associated with survival at 30 days ( p < 0.001). At hospital admission, syndecan-1 was lower in the TXA group (28.30 [20.05, 42.75] vs. 33.50 [23.00, 54.00] p = 0.001) even after controlling for patient, injury, and prehospital factors ( p = 0.001). For every 1 g increase in TXA administered over the first 8 hours of prehospital transport and hospital admission, there was a 4-ng/mL decrease in syndecan-1 at 12 hours controlling for patient, injury, and treatment factors ( p = 0.03). CONCLUSION: Prehospital TXA was associated with decreased syndecan-1 at hospital admission. Syndecan-1 measured 12 hours after admission was inversely related to the dose of TXA received. Early prehospital and in-hospital TXA may decrease endothelial glycocalyx damage or upregulate vascular repair mechanisms in a dose-dependent fashion. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

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.

Non-surgical management and analgesia strategies for older adults with multiple rib fractures: A systematic review, meta-analysis, and joint practice management guideline from the Eastern Association for the Surgery of Trauma and the Chest Wall Injury Society.

BACKGROUND: Chest wall injury in older adults is a significant cause of morbidity and mortality. Optimal nonsurgical management strategies for these patients have not been fully defined regarding level of care, incentive spirometry (IS), noninvasive positive pressure ventilation (NIPPV), and the use of ketamine, epidural, and other locoregional approaches to analgesia. METHODS: Relevant questions regarding older patients with significant chest wall injury with patient population(s), intervention(s), comparison(s), and appropriate selected outcomes were chosen. These focused on intensive care unit (ICU) admission, IS, NIPPV, and analgesia including ketamine, epidural analgesia, and locoregional nerve blocks. A systematic literature search and review were conducted, our data were analyzed qualitatively and quantitatively, and the quality of evidence was assessed per the Grading of Recommendations Assessment, Development, and Evaluation methodology. No funding was used. RESULTS: Our literature review (PROSPERO 2020-CRD42020201241, MEDLINE, EMBASE, Cochrane, Web of Science, January 15, 2020) resulted in 151 studies. Intensive care unit admission was qualitatively not superior for any defined cohort other than by clinical assessment. Poor IS performance was associated with prolonged hospital length of stay, pulmonary complications, and unplanned ICU admission. Noninvasive positive pressure ventilation was associated with 85% reduction in odds of pneumonia ( p < 0.0001) and 81% reduction in odds of mortality ( p = 0.03) in suitable patients without risk of airway loss. Ketamine use demonstrated no significant reduction in pain score but a trend toward reduced opioid use. Epidural and other locoregional analgesia techniques did not affect pneumonia, length of mechanical ventilation, hospital length of stay, or mortality. CONCLUSION: We do not recommend for or against routine ICU admission. We recommend use of IS to inform ICU status and conditionally recommend use of NIPPV in patients without risk of airway loss. We offer no recommendation for or against ketamine, epidural, or other locoregional analgesia. LEVEL OF EVIDENCE: Systematic Review/Meta-analysis; Level IV.

EGS plus: Predicting futility in LVAD patients with emergency surgical disease.

BACKGROUND: While emergent, non-cardiac surgery can be safely performed in LVAD patients, the inherent perioperative challenges of these rare procedures and the perception that these patients may be poor surgical candidates can contribute to reluctance to perform necessary emergency general surgery (EGS) procedures. We, therefore, sought to identify predictors of inpatient mortality to assist perioperative decision-making. METHODS: The Nationwide Inpatient Sample (2010-2015Q3) was used to identify patients with previously placed LVADs with a subsequent EGS admission diagnosis. Multivariable logistic regression analysis was performed to identify independent predictors of 30-day mortality, and a risk-adjusted probability of death was calculated for significant patient subgroups across age. Additional demographic variables were included in the regression due to clinical relevance. RESULTS: There were 1805 (weighted) LVAD-EGS patients with an overall mortality rate of 11%. Independent predictors of mortality were intestinal ischemia and sepsis present on admission. Patients older than 70 with sepsis had an 80% probability of in-hospital mortality (10.6 OR, 1.70-65.5 95% CI) while those over 70 presenting with intestinal ischemia had a 38% probability of death (3.6 OR, 1.50-8.78 95% CI). Mortality risk for younger patients with sepsis was still approximately 50%. CONCLUSION: Older LVAD patients presenting with either sepsis or intestinal ischemia have a substantial mortality risk while younger patients have a modest risk. These results can be used to guide treatment discussions when emergency surgery is being considered in LVAD patients.

Trauma bay virtual reality-A game changer for ATLS instruction and assessment.

BACKGROUND: Medical educational research highlights the need for high-fidelity, multidisciplinary simulation training to teach complex decision-making skills, such as those taught in Advanced Trauma Life Support (ATLS). This approach is, however, expensive and time-intensive. Virtual reality (VR) education simulation may improve skill acquisition in a cost-effective and time-sensitive manner. We developed a novel trauma VR simulator (TVRSim) for providers to apply ATLS principles. We hypothesized in this pilot study that TVRSim could differentiate practitioner competency with increasing experience and would be well accepted. METHODS: Providers at a Level I trauma center (acute care surgeons, novice (MS4 & PGY1), junior (PGY2 & 3), senior (PGY4-6) residents) ran a blunt, polytrauma VR code. Ten critical decision points were assessed: intubation, cricothyroidotomy, chest tube, intravenous access, focused abdominal sonography for trauma examination, pelvic binder, activation of massive transfusion protocol, administration of hypertonic saline, hyperventilation and decision to go to the operating room (OR). Learner assessment was based on frequency and time to correct decisions. Participant satisfaction was measured using validated surveys. RESULTS: All 31 providers intubated and obtained intravenous access. Novices and juniors frequently failed at hypertonic saline and hyperventilation decisions. Juniors often failed at cricothyroidotomy (60%) and OR (100%) decisions. Mean time to all decisions except going to the OR was longer for all groups compared to acute care surgeons. Mean number of decisions/min was significantly higher for surgeons and seniors compared to juniors and novices. Mortality was 92.3% for novices, 80% for juniors, 25% for seniors and 0% for the attendings. Participants found TVRSim comfortable, easy to use/interact with/performance enhancing, and helped develop skills and learning. CONCLUSIONS: In this pilot study using a sample of convenience, TVRSim was able to discern decision-making abilities among trainees with increasing experience. All trainees felt that the platform enhanced their performance and facilitated skill acquisition and learning. TVRSim could be a useful adjunct to teach and assess ATLS skills. LEVEL OF EVIDENCE: Diagnostic Test or Criteria; Level IV.

"I need to have a fulfilling job": A qualitative study of surgeon well-being and professional fulfillment.

BACKGROUND: Burnout, often regarded as an individual failing, rather than a systemic one, negatively impacts quality of care, patient safety and healthcare costs. Focusing on improving well-being can help mitigate burnout. This study examined protective factors that promote well-being and professional fulfillment in surgeons. METHODS: Using a purposive sample, 32 semi-structured 30-60-min interviews were conducted with surgeons of varying sub-specialties and rank. Abductive exploratory analysis was used to code and interpret interview transcripts and to build a conceptual model of surgeon well-being. RESULTS: Emergent protective factors were placed into one of three levels of implementation: individual, team-level, and institutional (figure). Individual factors for well-being included autonomy and adequate time to pursue non-clinical endeavors. Team-level factors consisted of adaptability, boundaries, and cohesion. Institutional factors related to diversifying performance evaluations and celebrating and recognizing individual value and contributions. CONCLUSIONS: The conceptual model developed from the results of this study highlights factors important to surgeons' professional well-being. This model can be used to guide quality improvement efforts.