Use of Cold-Stored Whole Blood is Associated With Improved Mortality in Hemostatic Resuscitation of Major Bleeding: A Multicenter Study.

OBJECTIVE: The aim of this study was to identify a mortality benefit with the use of whole blood (WB) as part of the resuscitation of bleeding trauma patients. BACKGROUND: Blood component therapy (BCT) is the current standard for resuscitating trauma patients, with WB emerging as the blood product of choice. We hypothesized that the use of WB versus BCT alone would result in decreased mortality. METHODS: We performed a 14-center, prospective observational study of trauma patients who received WB versus BCT during their resuscitation. We applied a generalized linear mixed-effects model with a random effect and controlled for age, sex, mechanism of injury (MOI), and injury severity score. All patients who received blood as part of their initial resuscitation were included. Primary outcome was mortality and secondary outcomes included acute kidney injury, deep vein thrombosis/pulmonary embolism, pulmonary complications, and bleeding complications. RESULTS: A total of 1623 [WB: 1180 (74%), BCT: 443(27%)] patients who sustained penetrating (53%) or blunt (47%) injury were included. Patients who received WB had a higher shock index (0.98 vs 0.83), more comorbidities, and more blunt MOI (all P <0.05). After controlling for center, age, sex, MOI, and injury severity score, we found no differences in the rates of acute kidney injury, deep vein thrombosis/pulmonary embolism or pulmonary complications. WB patients were 9% less likely to experience bleeding complications and were 48% less likely to die than BCT patients ( P <0.0001). CONCLUSIONS: Compared with BCT, the use of WB was associated with a 48% reduction in mortality in trauma patients. Our study supports the use of WB use in the resuscitation of trauma patients.

Whole Blood Resuscitation is Safe in Pediatric Trauma Patients: A Multicenter Study.

INTRODUCTION: Whole blood (WB) resuscitation has been associated with a mortality benefit in trauma patients. Several small series report the safe use of WB in the pediatric trauma population. We performed a subgroup analysis of the pediatric patients from a large prospective multicenter trial comparing patients receiving WB or blood component therapy (BCT) during trauma resuscitation. We hypothesized that WB resuscitation would be safe compared to BCT resuscitation in pediatric trauma patients. METHODS: This study included pediatric trauma patients (0-17 y), from ten level-I trauma centers, who received any blood transfusion during initial resuscitation. Patients were included in the WB group if they received at least one unit of WB during their resuscitation, and the BCT group was composed of patients receiving traditional blood product resuscitation. The primary outcome was in-hospital mortality with secondary outcomes being complications. Multivariate logistic regression was performed to assess for mortality and complications in those treated with WB vs BCT. RESULTS: Ninety patients, with both penetrating and blunt mechanisms of injury (MOI), were enrolled in the study (WB: 62 (69%), BCT: 28 (21%)). Whole blood patients were more likely to be male. There were no differences in age, MOI, shock index, or injury severity score between groups. On logistic regression, there was no difference in complications. Mortality was not different between the groups (P = .983). CONCLUSION: Our data suggest WB resuscitation is safe when compared to BCT resuscitation in the care of critically injured pediatric trauma patients.

Examining trends in gun violence injuries before and during the COVID-19 pandemic across six trauma centers.

OBJECTIVES: The onset of the national stay-at-home orders accompanied by a surge in firearm sales has elevated the concerns of clinicians and public health authorities. The purpose of this study was to examine the impact of the stay-at-home orders among gunshot wound (GSW) trauma admissions. METHODS: This was a retrospective cohort study at six level I trauma centers across four states. Patients admitted after the onset of COVID-19 restrictions (March 16, 2020-June 30, 2020) were compared with those admitted during the same period in 2019. We compared (1) rate of patients with GSW and (2) characteristics of patients with GSW, by period using Χ2 tests or Fisher's exact tests, as appropriate. RESULTS: There were 6996 trauma admissions across the study period; 3707 (53%) in 2019 and 3289 (47%) in 2020. From 2019 to 2020, there was a significant increase in GSW admissions (4% vs. 6%, p=0.001); 4 weeks specifically had significant increases (March 16-March 23: 4%, April 1-April 8: 5%, April 9-April 16: 6%, and May 11-May 18: 5%). Of the 334 GSWs, there were significant increases in patients with mental illness (5% vs. 11%, p=0.03), alcohol use disorder (2% vs. 10%, p=0.003), substance use disorder (11% vs. 25%, p=0.001), and a significant decrease in mortality (14% vs. 7%, p=0.03) in 2020. No other significant differences between time periods were identified. CONCLUSION: Our data suggest that trauma centers admitted significantly more patients with GSW following the national guidelines, including an increase in those with mental illness and substance use-related disorders. This could be attributable to the stay-at-home orders. LEVEL OF EVIDENCE: Level III, retrospective study.

Does time to surgery for traumatic hip fracture impact the efficacy of fascia iliaca blocks? A brief report.

Objectives: Outcomes after traumatic hip fracture have shown to be significantly improved with timely surgical management. This study determined whether there were differences in efficacy of fascia iliaca compartment block (FICB) on pain outcomes in patients with hip fracture, once stratified by time to surgery. Methods: Trauma patients (55-90 years) admitted to five Level I/II trauma centers within 12 hours of hip fracture were included. Patients with coagulopathy, significant multi-trauma (injury severity score >16), bilateral hip fractures, and postoperative FICBs were excluded. The primary exposure was analgesia modality: adjunctive FICB or systemic analgesics (no FICB). Study endpoints were incidence of delirium through 48 hours postoperatively (%), preoperative and postoperative oral morphine equivalents (OMEs), and preoperative and postoperative pain (0-10 scale). Adjusted regression models were used to examine the effect of FICB on outcomes; all models were stratified by time from arrival to surgery, ≤24 hours (earlier surgery; n=413) and >24 hours (later surgery; n=143). Results: FICB use was similar with earlier and later surgery (70.2% vs 76.2%), and there were no demographic differences by utilization of FICB, by time to surgery. In the earlier surgery group, preoperative pain was lower for patients with FICB versus no FICB (3.6 vs 4.5, p<0.001), with no difference by FICB for delirium (OR 1.00, p>0.99) or OMEs (p=0.75 preoperative, p=0.91 postoperative). In the later surgery group, there was a nearly twofold reduction in preoperative OMEs with FICB than no FICB (25.5 mg vs 45.2 mg, p=0.04), with no differences for delirium (OR 4.21, p=0.18), pain scores (p=0.25 preoperative, p=0.27 postoperative), and postoperative OMEs (p=0.34). Conclusions: Compared with systemic analgesia, FICB resulted in improved pain scores at the preoperative assessment among patients with earlier surgery, whereas FICB reduced opioid consumption over the preoperative period only when surgery was later than 24 hours from arrival. Level of evidence: II, prospective, therapeutic.

Characterization of peritoneal reactive ascites collected from acute appendicitis and small bowel obstruction patients.

BACKGROUND: Pathological abdominal adhesions can cause bowel obstructions. A history of appendectomy (appy) increases patient rehospitalization risk directly related to adhesions. To potentially identify strategies for adhesion treatment, we characterized reactive ascites (rA) collected during appy or adhesiolysis for small bowel obstruction (SBO). METHODS: This is a non-randomized, prospective observational study recruiting patients with non-perforated appendicitis or SBO from three Level 1 trauma centers in the United States. rA were analyzed via liquid chromatography-mass spectrometry (LC-MS) (n = 31), bead-based quantification cytokines and chemokines (n = 32) and soluble receptors (n = 30), and LC-MS metabolomics (n = 18). RESULTS: LC-MS showed that samples contained albumin, apolipoprotein A1, and transthyretin and that metabolites increased in SBO vs appy rA were biomarkers of oxidative stress. Multi-plex analyses showed levels of 17 cytokines/chemokines and 6 soluble receptors were significantly different in appy vs SBO rA. Top increased proteins in appy compared to SBO rA by 20.14-, 11.53-, and 8.18-fold were granulocyte-colony stimulating factor, C-X-C motif chemokine ligand 10, and interleukin-10, respectively. CONCLUSIONS: These data further define pro- and anti-inflammatory mediators and metabolites that may drive formation or perpetuate chronic abdominal adhesions. Future research is to further explore whether attenuation of these factors may decrease pathologic adhesion formation.

Impact of time to surgery on mortality in hypotensive patients with noncompressible torso hemorrhage: An AAST multicenter, prospective study.

BACKGROUND: Death from noncompressible torso hemorrhage (NCTH) may be preventable with improved prehospital care and shorter in-hospital times to hemorrhage control. We hypothesized that shorter times to surgical intervention for hemorrhage control would decrease mortality in hypotensive patients with NCTH. METHODS: This was an AAST-sponsored multicenter, prospective analysis of hypotensive patients aged 15+ years who presented with NCTH from May 2018 to December 2020. Hypotension was defined as an initial systolic blood pressure (SBP) ≤ 90 mm Hg. Primary outcomes of interest were time to surgical intervention and in-hospital mortality. RESULTS: There were 242 hypotensive patients, of which 48 died (19.8%). Nonsurvivors had higher mean age (47.3 vs. 38.8; p = 0.02), higher mean New Injury Severity Score (38 vs. 29; p < 0.001), lower admit systolic blood pressure (68 vs. 79 mm Hg; p < 0.01), higher incidence of vascular injury (41.7% vs. 21.1%; p = 0.02), and shorter median (interquartile range, 25-75) time from injury to operating room start (74 minutes [48-98 minutes] vs. 88 minutes [61-128 minutes]; p = 0.03) than did survivors. Multivariable Cox regression showed shorter time from emergency department arrival to operating room start was not associated with improved survival (p = 0.04). CONCLUSION: Patients who died arrived to a trauma center in a similar time frame as did survivors but presented in greater physiological distress and had significantly shorter times to surgical hemorrhage intervention than did survivors. This suggests that even expediting a critically ill patient through the current trauma system is not sufficient time to save lives from NCTH. Civilian prehospital advance resuscitative care starting from the patient first contact needs special consideration. LEVEL OF EVIDENCE: Prognostic/Epidemiologic, Level III.

Incorporating age improves the Glasgow Coma Scale score for predicting mortality from traumatic brain injury.

BACKGROUND: The Glasgow Coma Scale (GCS) score has been adapted into categories of severity (mild, moderate, and severe) and are ubiquitous in the trauma setting. This study sought to revise the GCS categories to account for an interaction by age and to determine the discrimination of the revised categories compared with the standard GCS categories. METHODS: The American College of Surgeons National Trauma Data Bank registry was used to identify patients with traumatic brain injury (TBI; ICD-9 codes 850-854.19) who were admitted to participating trauma centers from 2010 to 2015. The primary exposure variables were GCS score and age, categorized by decade (teens, 20s, 30s…, 80s). In-hospital mortality was the primary outcome for examining TBI severity/prognostication. Logistic regression was used to calculate the conditional probability of death by age decade and GCS in a development dataset (75% of patients). These probabilities were used to create a points-based revision of the GCS, categorized as low (mild), moderate, and high (severe). Performance of the revised versus standard GCS categories was compared in the validation dataset using area under the receiver operating characteristic (AUC) curves. RESULTS: The final population included 539,032 patients with TBI. Age modified the performance of the GCS, resulting in a novel categorization schema for each age decile. For patients in their 50s, performance of the revised GCS categories mirrored the standard GCS categorization (3-8, 9-12, 13-15); all other revised GCS categories were heavily modified by age. Model validation demonstrated the revised GCS categories statistically significantly outperformed the standard GCS categories at predicting mortality (AUC: 0.800 vs 0.755, p<0.001). The revised GCS categorization also outperformed the standard GCS categories for mortality within pre-specified subpopulations: blunt mechanism, isolated TBI, falls, non-transferred patients. DISCUSSION: We propose the revised age-adjusted GCS categories will improve severity assessment and provide a more uniform early prognostic indicator of mortality following traumatic brain injury. LEVEL OF EVIDENCE: III epidemiologic/prognostic.

Effect of the COVID-19 pandemic on health insurance coverage among trauma patients: a study of six level I trauma centers.

BACKGROUND: Increased unemployment during the COVID-19 pandemic has likely led to widespread loss of employer-provided health insurance. This study examined trends in health insurance coverage among trauma patients during the COVID-19 pandemic, including differences in demographics and clinical characteristics by insurance type. METHODS: This was a retrospective study on adult patients admitted to six level 1 trauma centers between January 1, 2018 and June 30, 2020. The primary exposure was hospital admission date: January 1, 2018 to December 31, 2018 (Period 1), January 1, 2019 to March 15, 2020 (Period 2), and March 16, 2020 to June 30, 2020 (Period 3). Covariates included demographic and clinical variables. χ² tests examined whether the rates of patients covered by each insurance type differed between the pandemic and earlier periods. Mann-Whiney U and χ² tests investigated whether patient demographics or clinical characteristics differed within each insurance type across the study periods. RESULTS: A total of 31 225 trauma patients admitted between January 1, 2018 and June 30, 2019 were included. Forty-one per cent (n=12 651) were admitted in Period 1, 49% (n=15 258) were from Period 2, and 11% (n=3288) were from Period 3. Percentages of uninsured patients increased significantly across the three periods (Periods 1 to 3: 15%, 16%, 21%) (ptrend=0.02); however, there was no accompanying decrease in the percentages of commercial/privately insured patients (Periods 1 to 3: 40%, 39%, 39%) (ptrend=0.27). There was a significant decrease in the percentage of patients on Medicare during the pandemic period (Periods 1 to 3: 39%, 39%, 34%) (p<0.01). DISCUSSION: This study found that job loss during the COVID-19 pandemic resulted in increases of uninsured trauma patients. However, there was not a corresponding decrease in commercial/privately insured patients, as may have been expected; rather, a decrease in Medicare patients was observed. These findings may be attributable to a growing workforce during the study period, in combination with a younger overall patient population during the pandemic. LEVEL OF EVIDENCE: Retrospective, level III study.

Effect of the COVID-19 pandemic on the ability of level 1 trauma centers to meet American College of Surgeons research requirements.

INTRODUCTION: The COVID-19 pandemic has had major effects on hospitals' ability to perform scientific research while providing patient care and minimizing virus exposure and spread. Many non-COVID-19 research has been halted, and funding has been diverted to COVID-19 research and away from other areas. METHODS: A 28-question survey was administered to all level 1 trauma centers in the USA that included questions about how the pandemic affected the trauma centers' ability to fulfill the volume and research requirements of level 1 verification by the American College of Surgeons (ACS). RESULTS: The survey had a 29% response rate (40/137 successful invitations). Over half of respondents (52%) reported reduced trauma admissions during the pandemic, and 7% reported that their admissions dropped below the volume required for level 1 verification. Many centers diverted resources from research during the pandemic (44%), halted ongoing consenting studies (33%), and had difficulty fulfilling research requirements because of competing clinical priorities (40%). DISCUSSION: Results of this study show a need for flexibility in the ACS verification process during the COVID-19 pandemic, potentially including reduction of the required admissions and/or research publication volumes. LEVEL OF EVIDENCE: Level IV, cross-sectional study.

Are trauma research programs in academic and non-academic centers measured by equal standards? A survey of 137 level I trauma centers in the United States.

BACKGROUND: American College of Surgeons level I trauma center verification requires an active research program. This study investigated differences in the research programs of academic and non-academic trauma centers. METHODS: A 28-question survey was administered to ACS-verified level I trauma centers in 11/12/2020-1/7/2021. The survey included questions on center characteristics (patient volume, staff size), peer-reviewed publications, staff and resources dedicated to research, and funding sources. RESULTS: The survey had a 31% response rate: 137 invitations were successfully delivered via email, and 42 centers completed at least part of the survey. Responding level I trauma centers included 36 (86%) self-identified academic and 6 (14%) self-identified non-academic centers. Academic and non-academic centers reported similar annual trauma patient volume (2190 vs. 2450), number of beds (545 vs. 440), and years of ACS verification (20 vs. 14), respectively. Academic centers had more full-time trauma surgeons (median 8 vs 6 for non-academic centers) and general surgery residents (median 30 vs 7) than non-academic centers. Non-academic centers more frequently ranked trauma surgery (100% vs. 36% academic), basic science (50% vs. 6% academic), neurosurgery (50% vs. 14% academic), and nursing (33% vs. 0% academic) in the top three types of studies conducted. Academic centers were more likely to report non-profit status (86% academic, 50% non-academic) and utilized research funding from external governmental or non-profit grants more often (76% vs 17%). CONCLUSIONS: Survey results suggest that academic centers may have more physician, resident, and financial resources available to dedicate to trauma research, which may make fulfillment of ACS level I research requirements easier. Structural and institutional changes at non-academic centers, such as expansion of general surgery resident programs and increased pursuit of external grant funding, may help ensure that academic and non-academic sites are equally equipped to fulfill ACS research criteria.

COVID-19 and trauma: how social distancing orders altered the patient population using trauma services during the 2020 pandemic.

BACKGROUND: Recent studies have reported changes in trauma volumes resulting from the COVID-19 pandemic and social distancing orders (SDOs) implemented by federal and state governments. However, literature is lacking on demographic, injury and outcome patterns. METHODS: This retrospective, cross-sectional study included patients aged ≥18 years at six US level 1 trauma centers. Patients not discharged by the date of data acquisition were excluded. Demographic, injury and outcome variables were assessed across four time periods: period 1 (January 1, 2019-December 31, 2019); period 1b (March 16, 2019-June 30, 2019); period 2 (January 1, 2020-March 15, 2020); and period 3 (March 16, 2020-June 30, 2020). Patients admitted in period 3 were compared with patients presenting during all other periods. Categorical data were compared with χ2 and Fisher's exact tests, and continuous data were assessed with Student's t-tests and Wilcoxon rank-sum tests. RESULTS: We identified 18 567 patients: 12 797 patients in period 1 (including 3707 in period 1b), 2488 in period 2 and 3282 in period 3. Compared with period 1, period 3 had a statistically significant decrease in mean patient volume, increase in portion of penetrating injuries, increase in higher levels of trauma activation, change in emergency department discharge disposition locations, increase in in-hospital mortality and a shorter hospital length of stay. Comparison between period 1b and period 3 demonstrated a decrease in mean patient volume, increase in penetrating injuries, increase in high acuity trauma activations and increase in in-hospital mortality rate. From period 2 to period 3, the penetrating injuries rose from 6.7% to 9.4% (p=0.004), injury severity scale ≥25 increased from 5.9% to 7.7% (p=0.002), full trauma team activations increased from 13.7% to 16.4% (p<0.001), interhospital transfers decreased from 36.7% to 31.6% (p<0.001) and the in-hospital mortality rate increased from 3.3% to 4.2% (p=0.003). DISCUSSION: Beyond altering social interactions among people, the federal SDO is associated with changes in trauma volumes, demographics and injury patterns among patients seeking care at six level 1 hospitals during the pandemic. LEVEL OF EVIDENCE: IV, prognostic and epidemiological.

Matched pilot study examining cannabis-based dronabinol for acute pain following traumatic injury.

BACKGROUND: To determine whether adjunctive dronabinol, a licensed form of delta-9-tetrahydrocannabinol, reduces opioid consumption when used off-label for managing acute pain following traumatic injury. METHODS: This matched cohort study included patients who were admitted with a traumatic injury between 1 March 2017 and 30 October 2017. The hospital pharmacy database was used to identify patients who received dronabinol (cases), and they were matched 1:1 to patients who did not receive dronabinol (controls) using age, cause of injury and hospital length of stay. The primary outcome, change in opioid consumption, was calculated using morphine milligram equivalents (MME). The change in MME was calculated for cases as total MME over 48 hours with adjunctive dronabinol minus 48 hours prior to dronabinol, and for controls as total MME 48-96 hours from admission minus 0-48 hours from admission. Data are presented as mean and SE or median and IQR. Statistical analysis was performed using paired t-tests and McNemar's tests. RESULTS: There were 66 patients included: 33 cases and 33 matched controls. Dronabinol was initiated 55 (28-107) hours from admission. Cases and controls were well matched. Cases had a significant reduction in opioid consumption with adjunctive dronabinol (-79 (20) MME, p<0.001), while opioid consumption was unchanged for controls (-9 (20) MME, p=0.63). This resulted in a ninefold greater reduction in opioid consumption for cases versus controls that was statistically different between pairs (p=0.02). Nineteen (58%) cases reported using marijuana; in this subset, opioid consumption was reduced with adjunctive dronabinol (-97 (24) MME, p<0.001) versus a non-significant increase in opioid consumption in matched controls (11 (29) MME, p=0.70); difference between groups, p=0.01. CONCLUSIONS: The results of this study suggest adjunctive dronabinol reduces opioid consumption following traumatic injury. The opioid-sparing effect of dronabinol may be greater in patients who are marijuana users. LEVEL OF EVIDENCE: III.

Quantity of hemoperitoneum is associated with need for intervention in patients with stable blunt splenic injury.

BACKGROUND: In patients with hemodynamically stable blunt splenic injury (BSI), there is no consensus on whether quantity of hemoperitoneum (HP) is a predictor for intervention with splenic artery embolization (SAE) or failing nonoperative management (fNOM). We sought to analyze whether the quantity of HP was associated with need for intervention. METHODS: This retrospective cohort study included adult trauma patients with hemodynamically stable BSI admitted to six trauma centers between 2014 and 2016. Quantity of HP was defined as small (perisplenic blood or blood in Morrison's pouch), moderate (blood in one or both pericolic gutters), or large (additional finding of free blood in the pelvis). Multivariate logistic regression was performed to identify predictors of intervention with SAE or fNOM versus successful observation. RESULTS: There were 360 patients: hemoperitoneum was noted in 214 (59%) patients, of which the quantity was small in 92 (43%), moderate in 76 (35.5%), and large in 46 (21.5%). Definitive management was as follows: 272 (76%) were observed and 88 (24%) had intervention (83 SAE, 5 fNOM). The rate of intervention was univariately associated with quantity of HP, even after stratification by American Association for the Surgery of Trauma (AAST) grade. After adjustment, larger quantities of HP significantly increased odds of intervention (p=0.01). Compared with no HP, the odds of intervention were significantly increased for moderate HP (OR=3.51 (1.49 to 8.26)) and large HP (OR=2.89 (1.03 to 8.06)), with similar odds for small HP (OR=1.21 (0.46 to 2.76)). Other independent predictors of intervention were higher AAST grade, older age, and presence of splenic vascular injury. CONCLUSION: Greater quantity of HP was associated with increased odds of intervention, with no difference in risk for moderate versus large HP. These findings suggest quantity of HP should be incorporated in the management algorithm of BSI as a consideration for angiography and/or embolization to maximize splenic preservation and reduce the risk of splenic rupture. LEVEL OF EVIDENCE: III, retrospective epidemiological study.

Stress Hyperglycemia in Critically Ill Patients: Insight Into Possible Molecular Pathways.

Severe sepsis, systemic inflammatory response syndrome (SIRS), and traumatic brain injury are frequently associated with hyperglycemia in non-diabetic patients. In patients suffering from any of these conditions, hyperglycemia at admission to an intensive care unit (ICU) is directly correlated with increased mortality or morbidity. Although there was initial enthusiasm for insulin treatment to blood glucose levels below 110 mg/dL in these patients, recent understanding suggests that the potential for hypoglycemic complications make this approach potentially dangerous. More moderate glucose control seems to be more beneficial than the aggressive glucose lowering initially suggested. An important publication has shown that hyperlactatemia accompanying hyperglycemia could be the real culprit in bad outcomes. This suggests that coupling moderate glucose lowering with therapeutic agents which might treat the underlying metabolic disturbances in these conditions may be a better strategy. The key metabolic disturbance in these three conditions seems to be persistent glycolysis as an energy source even in the presence of adequate tissue oxygenation (the Warburg Effect). We look at recent advances in understanding aerobic glycolysis and possibly the action of DPP4 on incretins resulting in insulin dysregulation and suggest key metabolic pathways involved in hyperglycemia regulation.

Predictors of splenic artery embolization as an adjunct to non-operative management of stable blunt splenic injury: a multi-institutional study.

BACKGROUND: We sought to identify predictors of splenic artery embolization (SAE) over observation for hemodynamically stable patients with blunt splenic injury (BSI), by Organ Injury Scale (OIS) grade. METHODS: This was a multi-institutional retrospective study of all adults (≥18) with BSI who were initially managed non-operatively between 2014 and 2016. Multivariate logistic regression analysis was used to identify predictors of SAE by OIS grade. Covariates included radiographic characteristics (presence/quantity of hemoperitoneum, blush, vascular injury), demographics (age, sex, cause), Injury Severity Score, vital signs, and hemoglobin values. We also examined outcomes of death, length of stay (LOS), intensive care unit (ICU) admission, blood products, and failed non-operative management (NOM). RESULTS: Among 422 patients with stable BSI, 93 (22%) had SAE and 329 (78%) were observed. The rate of SAE increased by grade (p<0.001). In grade I and II BSI, 7% had SAE; significant predictors of SAE were blush (OR: 5.9, p=0.02), moderate or large hemoperitoneum (OR: 3.0, p=0.01), and male sex (OR: 6.3, p=0.05). In grade III BSI, 26% had SAE; significant predictors included moderate or large hemoperitoneum (OR: 3.9, p=0.04), motor vehicle crash (OR: 6.1, p=0.005), and age (OR=1.4, 40% with each decade increase in age, p=0.02). The rate of SAE was 52% for grade IV and 85% for grade V BSI; there were no independent predictors of SAE in either grade. Clinical outcomes were comparable by NOM strategy and grade, except longer LOS with SAE in grades I-III (p<0.05) and longer ICU LOS with SAE in grades I-IV (p<0.05). Only 5 (1.2%) patients failed NOM (4 observation, 1 SAE). CONCLUSION: These results strongly support SAE consideration for patients with stable grade IV and V BSI even if there are no other high-risk clinical or radiographic findings. For grades I-III, the identified predictors may help refine consideration for SAE. LEVEL OF EVIDENCE: Level III, retrospective epidemiological study.

The presence of S-sulfonated transthyretin in commercial human serum albumin solutions: Potential contribution to neuropathy.

BACKGROUND: Commercial solutions of human serum albumin (HSA) are administered to critically ill patients for the treatment of shock, restoration of blood volume, and the acute management of burns. Previously, conflicting results on the effects of HSA administration have been reported varying from a favorable increase in total plasma antioxidant capacity to a higher mortality rate in traumatic brain injury (TBI) patients. These results could be partially explained due to the known heterogeneity of HSA solutions. We report the discovery of S-sulfonated human transthyretin (hTTR) in HSA solutions. METHODS: Proteomics was performed on commercially available solutions of 5% HSA by LC-MS analysis. The MS charge envelope for hTTR was deconvolved to the uncharged native hTTR parent mass (13,762 Da). The parent mass was then integrated, and relative proportions of the 2 major species of hTTR, native and S-sulfonated hTTR (13,842 Da), were calculated. RESULTS: The majority of hTTR found in 5% commercial HSA solutions is in the S-sulfonated form regardless of the age of the HSA solution. S-sulfonation of hTTR at the free cysteine residue in position 10 appears to be the result of a mixed disulfide exchange possibly with S-cysteinylated hTTR or S-cysteinylated HSA. hTTR is a tetramer composed of four identical monomers each containing a reduced cysteine residue in position 10. S-sulfonation of hTTR at this cysteine residue can destabilize the hTTR tetramer, an important step in the formation of TTR-related amyloid fibrils. CONCLUSIONS: Administration of a commercial HSA solution that already contains S-sulfonated hTTR could potentially contribute to the development of amyloid-related/polyneuropathy in the critically ill.