Pre-operative fluid resuscitation in the emergency general surgery septic patient: does it really matter?

OBJECTIVE: Emergency general surgery (EGS) patients presenting with sepsis remain a challenge. The Surviving Sepsis Campaign recommends a 30 mL/kg fluid bolus in these patients, but recent studies suggest an association between large volume crystalloid resuscitation and increased mortality. The optimal amount of pre-operative fluid resuscitation prior to source control in patients with intra-abdominal sepsis is unknown. This study aims to determine if increasing volume of resuscitation prior to surgical source control is associated with worsening outcomes. METHODS: We conducted an 8-year retrospective chart review of EGS patients undergoing surgery for abdominal sepsis within 24 h of admission. Patients in hemorrhagic shock and those with outside hospital index surgeries were excluded. We grouped patients by increasing pre-operative resuscitation volume in 10 ml/kg intervals up to > 70 ml/kg and later grouped them into < 30 ml/kg or ≥ 30 ml/kg. A relative risk regression model compared amounts of fluid administration. Mortality was the primary outcome measure. Secondary outcomes were time to operation, ventilator days, and length of stay (LOS). Groups were compared by quick Sequential Organ Failure Assessment (qSOFA) and SOFA scoring systems. RESULTS: Of the 301 patients included, the mean age was 55, 51% were male, 257 (85%) survived to discharge. With increasing fluid per kg (< 10 to < 70 ml/kg), there was an increasing mortality per decile, 8.8% versus 31.6% (p = 0.004). Patients who received < 30 mL/kg had lower mortality (11.3 vs 21%) than those who received > 30 ml/kg (p = 0.02). These groups had median qSOFA scores (1.0 vs. 1.0, p = 0.06). There were no differences in time to operation (6.1 vs 4.9 h p = 0.11), ventilator days (1 vs 3, p = 0.08), or hospital LOS (8 vs 9 days, p = 0.57). Relative risk regression correcting for age and physiologic factors showed no significant differences in mortality between the fluid groups. CONCLUSIONS: Greater pre-operative resuscitation volumes were initially associated with significantly higher mortality, despite similar organ failure scores. However, fluid volumes were not associated with mortality following adjustment for other physiologic factors in a regression model. The amount of pre-operative volume resuscitation was not associated with differences in time to operation, ventilator days, ICU or hospital LOS.

Methylprednisolone may be associated with improved lung compliance in acute respiratory distress syndrome patients on veno-venous extracorporeal membrane oxygenation.

INTRODUCTION: Methylprednisolone has been used for acute respiratory distress syndrome with variable results. Veno-venous extracorporeal membrane oxygenation use in acute respiratory distress syndrome has increased. Occasionally, both are used. We hypothesized that methylprednisolone could improve lung compliance and ease weaning from extracorporeal membrane oxygenation in acute respiratory distress syndrome patients. METHODS: We retrospectively reviewed all patients in our veno-venous extracorporeal membrane oxygenation unit treated with methylprednisolone over a 20 month period. Methylprednisolone was initiated for inability to wean off veno-venous extracorporeal membrane oxygenation. Dynamic compliance (Cdyn) was calculated at cannulation, methylprednisolone initiation, and decannulation. Demographics, extracorporeal membrane oxygenation-specific data, and ventilator data were collected. Wilcoxon rank-sum test was used to test for differences in dynamic compliance. RESULTS: A total of 12 veno-venous extracorporeal membrane oxygenation patients received methylprednisolone. Mean age was 50 (±15) years. Seven had influenza. Methylprednisolone was started on median Day 16 (interquartile range: 11-22) of veno-venous extracorporeal membrane oxygenation. In total, 10 patients had veno-venous extracorporeal membrane oxygenation decannulation on median Day 12 (7-22) after methylprednisolone initiation. Two patients died before decannulation. The 10 decannulated patients had initial median dynamic compliance (mL × cm H2O-1) of 12 (7-23), then 16 (10-24) at methylprednisolone initiation, and then 44 (34-60) at decannulation. Dynamic compliance was higher at decannulation than methylprednisolone initiation (p = 0.002), and unchanged from cannulation to methylprednisolone initiation for all patients (p = 0.97). A total of 10 patients had significant infections. None had significant gastrointestinal bleed or wound healing issues. CONCLUSION: Methylprednisolone may be associated with improved compliance in acute respiratory distress syndrome allowing for decannulation from veno-venous extracorporeal membrane oxygenation. High rates of infection are associated with methylprednisolone use in veno-venous extracorporeal membrane oxygenation. Further studies are required to identify appropriate patient selection for methylprednisolone use in patients on veno-venous extracorporeal membrane oxygenation.

A new aortic injury score predicts early rupture more accurately than clinical assessment.

OBJECTIVE: The optimal timing for repair of a high-grade blunt thoracic aortic injury (BTAI) is uncertain. Delayed repair is common and associated with improved outcomes, but some lesions may rupture during observation. To determine optimal patient selection for appropriate management, we developed a pilot clinical risk score to evaluate aortic stability and predict rupture. METHODS: Patients presenting in stable condition with Society for Vascular Surgery grade III or IV BTAI diagnosed on computed tomography (CT) were retrospectively reviewed. To determine clinical and radiographic factors associated with aortic rupture, patients progressing to aortic rupture (defined by contrast extravasation on CT or on operative or autopsy findings) were compared with those who had no intervention ≤48 hours of admission. A model targeting 100% sensitivity for rupture was generated and internally validated by bootstrap analysis. Clinical utility was tested by comparison with clinical assessment by surgeons experienced in BTAI management who were provided with CT images and clinical data but were blinded to outcome. RESULTS: The derivation cohort included 18 patients whose aorta ruptured and 31 with stable BTAI. There was no difference in age, gender, injury mechanism, nonchest injury severity, blood pressure, or Glasgow Coma Scale on admission between patient groups. As dichotomous factors, admission lactate >4 mM, posterior mediastinal hematoma >10 mm, and lesion/normal aortic diameter ratio >1.4 on the admission CT were independently associated with aortic rupture. The model had an area under the receiver operator curve of .97, and in the presence of any two factors, was 100% sensitive and 84% specific for predicting aortic rupture. No aortic lesions ruptured in patients with fewer than two factors. In contrast, clinical assessment had lower accuracy (65% vs 90% total accuracy, P < .01). CONCLUSIONS: This novel risk score can be applied on admission using clinically relevant factors that incorporate patient physiology, size of the aortic lesion, and extent of the mediastinal hematoma. The model reliably identifies and distinguishes patients with high-grade BTAI who are at risk for early rupture from those with stable lesions. Although preliminary, because it is more accurate than clinical assessment alone, the score may improve patient selection for emergency or delayed intervention.

S-100ß does not predict outcome after mild traumatic brain injury.

OBJECTIVE: To determine the usefulness of S-100ß, a marker for central nervous system damage, in the prediction of long-term outcomes after mild traumatic brain injury (MTBI) Hypothesis: Mid- and long-term outcomes of MTBI (i.e. 3, 6 and 12 months post-injury and return-to-work or school (RTWS)) may be predicted based on pre-injury and injury factors as well as S-100ß. METHODS: MTBI subjects without abnormal brain computed tomography requiring intervention, focal neurological deficits, seizures, amnesia > 24 hours and severe or multiple injuries were recruited at a level I trauma centre. Admission S-100ß measurements and baseline Concussion Symptom Checklist were obtained. Symptoms and RTWS were re-assessed at follow-up visits (3-10 days and 3, 6 and 12 months). Outcomes included number of symptoms and RTWS at follow-up. Chi-square tests, linear and logistic regression models were used and p < 0.05 was considered statistically significant. RESULTS: One hundred and fifty of 180 study subjects had S-100ß results. Eleven per cent were unable to RTWS at 12 months. S-100ß levels were not associated with post-concussive symptomatology at follow-up. In addition, no association was found between S-100ß levels and RTWS. CONCLUSION: Amongst MTBI patients, S-100ß levels are not associated with prolonged post-concussive syndrome or the inability to RTWS.

Intracranial pressure dose and outcome in traumatic brain injury.

OBJECTIVE: Detecting and treating elevated intracranial pressure (ICP) is a cornerstone of management in patients with severe traumatic brain injury. The aim of this study was to determine the association between area under the curve measurement of elevated ICP and clinical outcome. METHODS: Single center observational study using prospectively collected data at a University hospital, level one-trauma center. Sixty prospective patients with severe traumatic brain injury were prospectively enrolled over a 2-year period. Intracranial pressure measurements were captured using a real-time automated, high resolution vital signs data recording system. Mortality and functional outcome were assessed at 30 days, 3 and 6 months using Extended Glasgow Outcome Scale. RESULTS: Increasing elevated intracranial pressure time dose was associated with mortality (OR 1.08; 95 % confidence interval [CI], 1.01-1.15, p = 0.03) and poor functional outcome at 3 (OR 1.04; CI 1.00-1.07, p = 0.03) and 6 months (1.04; CI 1.01-1.08, p = 0.02). However, there was no association between episodic ICP data and outcome. CONCLUSIONS: These results suggest that pressure time dose measurement of intracranial pressure may be used to predict outcome in severe traumatic brain injury and may be a candidate biomarker in this disease.

Observed relationships between driver and passenger restraint use in the front and rear seats.

OBJECTIVE: Seat belt usage has increased substantially since the 1960s, yet driver use continues to affect passenger usage. Recent observational restraint use findings for Maryland will examine the relationship between driver and passenger usage, including adults and children in the rear seat. METHODS: Analyses were based on observational front and rear seat studies administered in parallel from 2016 to 2019. A statistically rigorous front seat project yielded weighted results among drivers and outboard passengers. A study of adults and children in the rear seat was based on a convenience sample of vehicles. Restraint usage results were presented as frequencies and proportions among occupants with known belt use, along with the 95% confidence interval for overall rates. RESULTS: Overall restraint usage rates averaged 90.9% in the front seat study and 81.1% in the rear seat sample. In vehicles with two front seat occupants and a belted driver, the proportion of belted passengers averaged 93.0% over four years. However, among unbelted drivers, only 41.6% of passengers were belted on average. In the rear seat study, an average of 82.7% were belted in vehicles driven by a restrained driver, differing for children (92.0%) versus adults (70.4%). Analysis of vehicles with an unbelted driver revealed an average of 45.0% of belted rear seat occupants, with a considerable difference for children (65.0%) compared with adults (21.0%). CONCLUSIONS: Observational seat belt studies in Maryland in recent years have shown that, despite overall rates above 80%, passenger use in both the front and rear seats is associated with driver restraint use.

Emergency General Surgery Procedures and Cost of Care for Older Adults in the State of Maryland.

BACKGROUND: Older adults (OAs) ≥ 65 years of age, representing the fastest growing segment in the United States, are anticipated to require a greater percentage of emergency general surgery procedures (EGSPs) with an associated increase in health care costs. The aims of this study were to identify the frequency of EGSP and charges incurred by OA compared to their younger counterparts in the state of Maryland. METHODS: A retrospective review of the Maryland Health Services Cost Review Commission from 2009 to 2018 was undertaken. Patients undergoing urgent or emergent ESGP were divided into 2 groups (18-64 years and ≥65 years). Data collected included demographics, APR-severity of illness (SOI), APR-risk of mortality (ROM), the EGSP (partial colectomy [PC], small bowel resection [SBR], cholecystectomy, operative management of peptic ulcer disease, lysis of adhesions, appendectomy, and laparotomy), length of stay (LOS), and hospital charges. P-values (P < .05) were significant. RESULTS: Of the 181,283 patients included in the study, 55,401 (38.1%) were ≥65 years of age. Older adults presented with greater APR-SOI (major 37.7% vs 21.3%, extreme 5.2% vs 9.3%), greater APR-ROM (major 25.3% vs 8.7%, extreme 22.3% vs 5.3%), underwent PC (24.5% vs 10.9%) and SBR (12.8% vs 7.0%) more frequently, and incurred significantly higher median hospital charges for every EGSP, consistently between 2009 and 2018 due to increased LOS and complications when compared to those ≤65 years of age. CONCLUSION: These findings stress the need for validated frailty indices and quality improvement initiatives focused on the care of OAs in emergency general surgery to maximize outcomes and optimize cost.

Cost Differences Between Teaching and Nonteaching Hospitals for Older Adults Requiring Emergency General Surgery Procedures in the State of Maryland.

BACKGROUND: Older adults (OAs; ≥ 65 years) comprise a growing population in the United States and are anticipated to require an increasing number of emergency general surgery procedures (EGSPs). The aims of this study were to identify the frequency of EGSPs and compare cost of care in OAs managed at teaching hospitals (THs) vs nonteaching hospitals (NTHs). METHODS: A retrospective review of data from the Maryland Health Services Cost Review Commission database from 2009 to 2018 for OAs undergoing EGSPs was undertaken. Data collected included demographics, all patient-refined (APR)-severity of illness (SOI), APR-risk of mortality (ROM), Charlson Comorbidity Index (CCI), EGSPs (partial colectomy (PC), small bowel resection, cholecystectomy, operative management of peptic ulcers, lysis of adhesions, appendectomy, and laparotomy, categorized hospital charges, length of stay (LOS), and mortality. RESULTS: Of the 55,401 OAs undergoing EGSPs in this study, 28,575 (51.6%) were treated at THs and 26,826 (48.4%) at NTHs. OAs at THs presented with greater APR-ROM (major 25.6% vs 24.9%, extreme 22.6% vs 22.0%, P=.01), and CCI (3.1±3 vs 2.7±2.8, P<.001) compared to NTHs. Lysis of adhesions, cholecystectomy, and PC comprised the overall most common EGSPs. Older adults at THs incurred comparatively higher median hospital charges for every EGSP due to increased room charges and LOS. Mortality was higher at THs (6.13% vs 5.33%, P<.001). CONCLUSION: While acuity of illness appears similar, cost of undergoing EGSPs for OAs is higher in THs vs NTHs due to increased LOS. Future work is warranted to determine and mitigate factors that increase LOS at THs.

Age-based variability in the association between restraint use and injury type and severity in multi-occupant crashes.

PURPOSE: Previous studies have shown older adults receive relatively less protection from seat belts against fatal injuries, however it is unknown how seat belt protection against severe and torso injury changes with age. We estimated age-based variability in seat belt protection against fatal injuries, injuries with maximum abbreviated injury scale greater than two (MAIS 3+), and torso injuries. METHODS: We leveraged the Crash Outcome Data Evaluation System to analyze binary indicators of fatal, MAIS 3+, and torso injuries. Using a matched cohort design and conditional Poisson regression, we estimated age-based relative risks (RR) of the outcomes associated with seat belt use. RESULTS: Our results suggested that seat belts were highly protective against fatal injuries for all ages. For ages 16-30, seat belt use was associated with 66% lower risk of MAIS3+ injury (RR 0.34, 95% CI 0.30, 0.38) for occupants of the same vehicle, whereas for ages 75 and older, seat belt use was associated with 38% lower risk of MAIS3+ injury (RR 0.62; 95% CI 0.45, 0.86) for occupants in the same vehicle. The association between restraint use and torso injury also attenuated with age. CONCLUSIONS: In multi-occupant crashes, seat belts were highly protective against fatal and MAIS3+ injury, however seat belt protection against MAIS3+ and torso injury attenuated with age.

Factors associated with stroke formation in blunt cerebrovascular injury: An EAST multicenter study.

BACKGROUND: Stroke risk factors after blunt cerebrovascular injury (BCVI) are ill-defined. We hypothesized that factors associated with stroke for BCVI would include medical therapy (i.e., Aspirin), radiographic features, and protocolization of care. METHODS: An Eastern Association for the Surgery of Trauma-sponsored, 16-center, prospective, observational trial was undertaken. Stroke risk factors were analyzed individually for vertebral artery (VA) and internal carotid artery (ICA) BCVI. Blunt cerebrovascular injuries were graded on the standard 1 to 5 scale. Data were from the initial hospitalization only. RESULTS: Seven hundred seventy-seven BCVIs were included. Stroke rate was 8.9% for all BCVIs, with an 11.7% rate of stroke for ICA BCVI and a 6.7% rate for VA BCVI. Use of a management protocol (p = 0.01), management by the trauma service (p = 0.04), antiplatelet therapy over the hospital stay (p < 0.001), and Aspirin therapy specifically over the hospital stay (p < 0.001) were more common in ICA BCVI without stroke compared with those with stroke. Antiplatelet therapy over the hospital stay (p < 0.001) and Aspirin therapy over the hospital stay (p < 0.001) were more common in VA BCVI without stroke than with stroke. Percentage luminal stenosis was higher in both ICA BCVI (p = 0.002) and VA BCVI (p < 0.001) with stroke. Decrease in percentage luminal stenosis (p < 0.001), resolution of intraluminal thrombus (p = 0.003), and new intraluminal thrombus (p = 0.001) were more common in ICA BCVI with stroke than without, while resolution of intraluminal thrombus (p = 0.03) and new intraluminal thrombus (p = 0.01) were more common in VA BCVI with stroke than without. CONCLUSION: Protocol-driven management by the trauma service, antiplatelet therapy (specifically Aspirin), and lower percentage luminal stenosis were associated with lower stroke rates, while resolution and development of intraluminal thrombus were associated with higher stroke rates. Further research will be needed to incorporate these risk factors into lesion specific BCVI management. LEVEL OF EVIDENCE: Prognostic and Epidemiologic, Level IV.

The Occluded Artery Trial (OAT) Viability Ancillary Study (OAT-NUC): influence of infarct zone viability on left ventricular remodeling after percutaneous coronary intervention versus optimal medical therapy alone.

BACKGROUND: The Occluded Artery Trial (OAT) showed no difference in outcomes between percutaneous coronary intervention (PCI) versus optimal medical therapy (MED) in patients with persistent total occlusion of the infarct-related artery 3 to 28 days post-myocardial infarction. Whether PCI may benefit a subset of patients with preservation of infarct zone (IZ) viability is unknown. METHODS AND RESULTS: The OAT nuclear ancillary study hypothesized that (1) IZ viability influences left ventricular (LV) remodeling and that (2) PCI as compared with MED attenuates adverse remodeling in post-myocardial infarction patients with preserved viability. Enrolled were 124 OAT patients who underwent resting nitroglycerin-enhanced technetium-99m sestamibi single-photon emission computed tomography (SPECT) before OAT randomization, with repeat imaging at 1 year. All images were quantitatively analyzed for infarct size, IZ viability, LV volumes, and function in a core laboratory. At baseline, mean infarct size was 26% ± 18 of the LV, mean IZ viability was 43% ± 8 of peak uptake, and most patients (70%) had at least moderately retained IZ viability. There were no significant differences in 1-year end-diastolic or end-systolic volume change between those with severely reduced versus moderately retained IZ viability, or when compared by treatment assignment PCI versus MED. In multivariable models, increasing baseline viability independently predicted improvement in ejection fraction (P = .005). There was no interaction between IZ viability and treatment assignment for any measure of LV remodeling. CONCLUSIONS: In the contemporary era of MED, PCI of the infarct-related artery compared with MED alone does not impact LV remodeling irrespective of IZ viability.

Evaluation of dexmedetomidine: safety and clinical outcomes in critically ill trauma patients.

BACKGROUND: To compare safety and clinical outcomes of prolonged infusions with standard-dose (≤0.7 µg/kg/h) dexmedetomidine (SDD) or high-dose (>0.7 µg/kg/h) dexmedetomidine (HDD) to propofol in critically ill trauma patients. METHODS: This was a retrospective review of 127 adult mechanically ventilated trauma patients between 2008 and 2009, who received propofol, SDD, or HDD for >24 hours. Primary outcomes were significant changes in blood pressure or heart rate. Secondary outcomes included hospital and intensive care unit (ICU) length of stay (LOS), ventilator time, and any concomitant analgesic, sedative, and antipsychotic use. Pairwise comparisons were based on Wilcoxon rank-sum test for continuous data and Pearson's chi-square test for categorical data. Statistical significance was defined as p value <0.05. RESULTS: Patients in HDD group had higher rate of hypotension (98% vs. 78%; p = 0.02) but no significant differences in heart rate compared with propofol group. These patients had median longer hospital LOS (25 days vs. 12 days; p < 0.001), ICU LOS (20 days vs. 12 days; p = 0.004), and longer ventilator time (14 days vs. 7 days; p = 0.008). They also had increased requirements for oxycodone (74% vs. 40%; p = 0.003), midazolam (36% vs. 8%; p = 0.004), and haloperidol (50% vs. 24%; p = 0.02). Patients in SDD group had longer hospital LOS compared with propofol group (21 days vs. 13 days; p < 0.001). CONCLUSION: Higher doses of dexmedetomidine may result in higher incidence of hypotension, longer LOS, and increased concomitant analgesic, sedative, and antipsychotic use, requiring further evaluation in trauma patients.

Occupant and crash characteristics for case occupants with cervical spine injuries sustained in motor vehicle collisions.

BACKGROUND: Motor vehicle collisions (MVCs) are the leading cause of spine and spinal cord injuries in the United States. Traumatic cervical spine injuries (CSIs) result in significant morbidity and mortality. This study was designed to evaluate both the epidemiologic and biomechanical risk factors associated with CSI in MVCs by using a population-based database and to describe occupant and crashes characteristics for a subset of severe crashes in which a CSI was sustained as represented by the Crash Injury Research Engineering Network (CIREN) database. METHODS: Prospectively collected CIREN data from the eight centers were used to identify all case occupants between 1996 and November 2009. Case occupants older than 14 years and case vehicles of the four most common vehicle types were included. The National Automotive Sampling System's Crashworthiness Data System, a probability sample of all police-reported MVCs in the United States, was queried using the same inclusion criteria between 1997 and 2008. Cervical spinal cord and spinal column injuries were identified using Abbreviated Injury Scale (AIS) score codes. Data were abstracted on all case occupants, biomechanical crash characteristics, and injuries sustained. Univariate analysis was performed using a χ analysis. Logistic regression was used to identify significant risk factors in a multivariate analysis to control for confounding associations. RESULTS: CSIs were identified in 11.5% of CIREN case occupants. Case occupants aged 65 years or older and those occupants involved in rollover crashes were more likely to sustain a CSI. In univariate analysis of the subset of severe crashes represented by CIREN, the use of airbag and seat belt together (reference) were more protective than seat belt alone (odds ratio [OR]=1.73, 95% confidence interval [CI]=1.32-2.27) or the use of neither restraint system (OR=1.45, 95% CI=1.02-2.07). The most frequent injury sources in CIREN crashes were roof and its components (24.8%) and noncontact sources (15.5%). In multivariate analysis, age, rollover impact, and airbag-only restraint systems were associated with an increased odds of CSI. Using the population-based National Automotive Sampling System's Crashworthiness Data System data, 0.35% of occupants sustained a CSI. In univariate analysis, older age was noted to be a significant risk factor for CSI. Airbag-only restraint systems and both rollover and lateral crashes were also identified as risk factors for CSI. In addition, increasing delta v was highly associated with CSIs. In multivariate analysis, similar risk factors were noted. Of all the restraint systems, seat belt use without airbag deployment was found to be the most protective restraint system (OR=0.29, 95% CI=0.16-0.50), whereas airbag-only restraint was associated with the highest risk of CSI (OR=3.54, 95% CI=2.29-5.46). CONCLUSIONS: Despite advances in automotive safety, CSIs sustained in MVC continue to occur too often. Older case occupants are at an increased risk of CSI. Rollover crashes and severe crashes led to a much higher risk of CSI than other types and severity of MVCs. Seat belt use is very effective in preventing CSI, whereas airbag deployment may increase the risk of occupants sustaining a CSI. More protection for older occupants is needed and protection in both rollover and lateral crashes should remain a focus of the automotive industry. The design of airbag restraint systems should be evaluated so that they are not causative of serious injury. In addition, engineers should continue to focus on improving automotive design to minimize the risk of spinal injury to occupants in high severity crashes.

Relationship of serum and cerebrospinal fluid biomarkers with intracranial hypertension and cerebral hypoperfusion after severe traumatic brain injury.

BACKGROUND: There is little that can be done to treat or reverse the primary injury that occurs at the time of a traumatic brain injury (TBI). Initial management of the patient with severe TBI focuses on prevention of subsequent secondary insults, namely, intracranial hypertension (ICH) and cerebral hypoperfusion (CH). Currently, there is no reliable way to predict which patients will develop ICH and CH other than clinical acumen; therefore, indicators of impending secondary intracranial insults may be useful in predicting these events and allowing for prevention and early intervention. This study was undertaken to investigate the relationship of cytokine levels with intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in patients with severe TBI. METHODS: Patients at the R Adams Cowley Shock Trauma Center were prospectively enrolled for a 6-month period. Inclusion criteria were older than 17 years, admission within the first 6 hours after injury, Glasgow Coma Scale<9 on admission, and placement of a clinically indicated ICP monitor. Serum and cerebrospinal fluid, when available, were collected on admission and twice daily for 7 days. Cytokine levels of interleukin (IL)-1ß, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α were analyzed by multiplex bead array assays. Hourly values for ICP and CPP were recorded, and means, minimum (for CPP) or maximum (for ICP) values, percentage time ICP>20 mm Hg (%ICP20) and CPP<60 mm Hg (%CPP60), and cumulative Pressure Times Time Dose (PTD; mm Hg·h) for ICP>20 mm Hg (PTD ICP20) and CPP<60 mm Hg (PTD CPP60) were compared with the serum and cerebrospinal fluid levels that were drawn before 12-hour time periods (PRE) and after 12-hour time periods (POST) of monitoring. RESULTS: Twenty-four patients were enrolled. In-hospital mortality was 12.5%, and good functional outcome was noted in 58%. Two hundred and seventy-five serum samples were taken and analyzed. IL-6 levels in the serum were found in the highest concentration of the cytokines measured. PTD ICP20 and PTD CPP60 were moderately correlated with increased PRE IL-8 levels (r=0.34, p<0.001; r=0.53, p<0.001). PTD ICP20 was also correlated with PRE TNF-α levels (r=0.27, p<0.001) as was PTD CPP60 (r=0.25, p<0.001). POST IL-8 levels were found to be correlated with PTD ICP20 (r=0.46, p<0.001) and PTD CPP60 (r=0.54, p<0.001). POST TNF-α was associated with PTD ICP20 (r=0.45, p<0.001). PTD CPP60 was also moderately correlated with POST TNF-α levels (r=0.26, p<0.001). When comparing patients with good versus poor outcome, median daily serum IL-8 levels were associated with poor outcome. CONCLUSIONS: IL-8 and, to a lesser extent, TNF-α demonstrated the most promise in this study to be candidate serum markers of impending ICH and CH. The clinical relevance of this is the suggestion that we may be able to predict impending secondary insults after TBI before the clinical manifestation of these events. Given the known morbidity of ICH and CH, early intervention and prevention may have a significant impact on outcome. This becomes even more important when decisions must be made about timing of interventions. Increased levels of IL-8 and TNF-α in the serum during episodes of ICH and CH imply there are significant systemic effects of these events. These serum biomarkers are promising as diagnostic targets. In addition, further study of the precise role of these molecules may have significant implications for inflammatory system manipulation in the management of severe TBI.

Association of CSF biomarkers and secondary insults following severe traumatic brain injury.

BACKGROUND: Management of severe traumatic brain injury (TBI) focuses on mitigating secondary insults. There are a number of biomarkers that are thought to play a part in secondary injury following severe TBI. Two of these, S100ß and neuron-specific enolase (NSE), have been extensively studied in the setting of neurological injury. This pilot study was undertaken to investigate the relationship of S100ß and NSE to clinical markers of severity and poor outcome: intracranial hypertension (ICH), and cerebral hypoperfusion (CH). METHODS: Patients at the R Adams Cowley Shock Trauma Center were prospectively enrolled over an 18-month period. Inclusion criteria were: age > 18, admission within the first 6 h after injury, Glasgow Coma Scale (GCS) < 9 on admission, isolated TBI, and placement of an intraventricular catheter (IVC). Patients were managed according to an institutional protocol based on the Brain Trauma Foundation Guidelines. CSF was collected from the IVC on admission and twice daily for 7 days. S100ß and NSE levels were analyzed by ELISA. CSF levels drawn before (PRE) and after (POST) 12-h time periods were compared to percentage time intracranial pressure (ICP) > 20 mmHg (% ICP(20)) and cerebral perfusion pressure (CPP) < 60 mmHg (% CPP(60)), and cumulative "Pressure times Time Dose" (PTD) for episodes of ICP > 20 mmHg (PTD ICP(20)) and CPP < 60 mmHg (PTD CPP(60)). Statistical analysis was performed using the Student's t test to compare means and non-parametric Wilcoxon statistic to compare ranked data. Linear regression methods were applied to compare levels of S100ß and NSE with ICP and CPP(.) RESULTS: Twenty-three patients were enrolled. The cohort of patients was severely injured and neurologically compromised on admission (admission GCS = 5.6 ± 3.1, Injury Severity Score (ISS) = 31.9 ± 10.6, head Abbreviated Injury Scale (AIS) = 4.4 ± 0.7, Marshall score = 2.6 ± 0.9). Elevated levels of S100ß and NSE were found in all 223 CSF samples analyzed. ICH was found to be associated with PRE and POST S100ß levels when measured as % ICP(20) (r = 0.20 and r = 0.23, P < 0.01) and PTD ICP(20) (r = 0.35 and r = 0.26, P < 0.001). POST increasing NSE levels were weakly correlated with increasing PTD ICP(20) (r = 0.17, P = 0.01). PRE S100ß levels were associated with episodes of CH as measured by % CPP(60) (r = 0.20, P = 0.002) and both PRE and POST S100ß levels were associated with PTD CPP(60) (r = 0.24 and r = 0.23, P < 0.001). PRE and POST NSE levels were also associated with episodes of CH as measured by % CPP(60) (r = 0.22 and r = 0.18, P < 0.01) and PTD CPP(60) (r = 0.20 and r = 0.21, P < 0.01). CONCLUSIONS: In this preliminary analysis, S100ß levels were associated with ICH and CH over a full week of ICP monitoring. We also found associations between CH and NSE levels in CSF of patients with severe TBI. Our results suggest that there is an association between levels of ICH and CH and these biomarkers when measured before episodes of clinically significant secondary insults. These markers of neuronal cell death demonstrate promise as both indicators of impending clinical deterioration and targets of future therapeutic interventions.

Electrophysiological effects of late percutaneous coronary intervention for infarct-related coronary artery occlusion: the Occluded Artery Trial-Electrophysiological Mechanisms (OAT-EP).

BACKGROUND: The Occluded Artery Trial-Electrophysiological Mechanisms (OAT-EP) tested the hypothesis that opening a persistently occluded infarct-related artery by percutaneous coronary intervention and stenting (PCI) after the acute phase of myocardial infarction compared with optimal medical therapy alone reduces markers of vulnerability to ventricular arrhythmias. METHODS AND RESULTS: Between April 2003 and December 2005, 300 patients with an occluded native infarct-related artery 3 to 28 days (median, 12 days) after myocardial infarction were randomized to PCI or optimal medical therapy. Ten-minute digital Holter recordings were obtained before randomization, at 30 days, and at 1 year. The primary end point was the change in alpha1, a nonlinear heart rate variability parameter, between baseline and 1 year. Major secondary end points were the changes in the filtered QRS duration on the signal-averaged ECG and variability in T-wave morphology (T-wave variability) between baseline and 1 year. There were no significant differences in the changes in alpha1 (-0.04; 95% CI, -0.12 to 0.04), filtered QRS (2.2 ms; 95% CI, -1.4 to 5.9 ms), or T-wave variability (3.0 microV; 95% CI, -4.8 to 10.7 microV) between the PCI and medical therapy groups (medical therapy change minus PCI change). Multivariable analysis revealed that the results were unchanged after adjustment for baseline clinical variables and medication treatments during the Holter recordings. CONCLUSIONS: PCI with stenting of a persistently occluded infarct-related artery during the subacute phase after myocardial infarction compared with medical therapy alone had no significant effect on changes in heart rate variability, the time-domain signal-averaged ECG, or T-wave variability during the first year after myocardial infarction. These findings are consistent with the lack of clinical benefit, including no reduction in sudden death, with PCI for stable patients with persistently occluded infarct-related arteries after myocardial infarction in the main OAT.

The impact of a new casino on the motor vehicle crash patterns in suburban Maryland.

BACKGROUND: Many states have legalized casino gambling, and casinos create increased vehicle traffic, but the strength of the association between casino construction and vehicle crashes is unknown. METHODS: Retrospective analyses of motor vehicle crashes (MVCs) occurring within Anne Arundel County, Maryland (2010-2014) were conducted. The ratio of crashes within one mile of the casino's location after it was opened were compared to the ratio occurring in the same area before it was opened to determine how the incidence of MVCs near the casino changed with time. Logistic regression was used to determine how crash characteristics may have influenced the incidence of MVCs near the casino after it opened. RESULTS: 101,860 persons were involved in 43,328 MVCs in Anne Arundel County during the study period; 29,476 (68.0 %) had an at-fault driver ≥21 years of age and complete data. MVCs proximal to the casino occurred most commonly during the day (N = 421, 76.6 %) and involved drivers <40 years of age (N = 366, 66.6 %) and male (N = 316, 57.4 %). After adjustment for impairment and day of the week, there was a significant association with crashes close to the casino after it opened (ORAdjusted = 1.23, 95 % CI: 1.04-1.46, p = 0.02). Crashes occurring close to the casino, after it opened, involved drivers <40 years of age (OR = 1.74, 95 % CI:1.45-2.08) and occurred on weekends (OR = 1.39, 95 %CI:1.15-1.67). CONCLUSIONS: In this single-site study the opening of a casino was associated with an increase in crashes nearby. The generalizability of this finding should be confirmed with analysis of MVC data near other gambling venues.

Early predictors of postconcussive syndrome in a population of trauma patients with mild traumatic brain injury.

PURPOSE: The purpose of this analysis was to determine which of the initial symptoms after mild traumatic brain injury (MTBI) can best predict the development of persistent postconcussive syndrome (PCS). METHODS: One hundred eighty MTBI patients admitted to a level I trauma center were enrolled in a prospective study and 110 followed for 3 months. MTBI was defined as a Glasgow Coma Score of 13 to 15 with a transient loss of consciousness or report of being dazed or confused. PCS was defined as the persistence of four or more symptoms long term. Patients were screened at admission and at 3 days to 10 days and 3 months. Symptom checklists were administered to ascertain the presence of symptoms (cognitive, emotional, and physical) after concussion. For a subset of patients that were physically able, balance tests were also conducted. Stepwise logistic regression was used to identify which symptoms best predicted PCS. RESULTS: The mean age of the subjects was 35 years, and 65% were men. Physical symptoms were the most prevalent in the 3 days to 10 days postinjury with most declining thereafter to baseline levels. Emotional and cognitive symptoms were less prevalent but more likely to remain elevated at 3 months; 41.8% of subjects reported PCS at 3 months. The strongest individual symptoms that predicted long-term PCS included anxiety, noise sensitivity (NS), and trouble thinking; reported by 49%, 27%, and 31% of the subjects at 3 days to 10 days, respectively. In multivariate regressions including age, gender, and early symptoms, only anxiety, NS and gender remained significant in the prediction of PCS. Interactions revealed that the effect of anxiety was seen primarily among women. NS had an odds ratio of 3.1 for PCS at 3 months. CONCLUSIONS: After MTBI, anxiety among women and NS are important predictors of PCS. Other physical symptoms, while more prevalent are poor predictors of PCS.

Expected differences and unexpected commonalities in mortality, injury severity, and injury patterns between near versus far occupants of side impact crashes.

OBJECTIVE: To compare injury patterns and outcomes of near- and far-side collisions. METHODS: Near- and far-side occupants in the Crash Injury Research and Engineering Network (CIREN) were compared for mortality and the occurrence of severe injuries (maximum abbreviated injury scale [MAIS] 3+). Regression models, adjusting for confounders, examined death and MAIS 3+ injuries as outcomes and near- or far-side position as an independent variable. CIREN findings were compared with those of the Crash Outcome Data Evaluation System (CODES), and the Maryland Automated Accident Reporting System. RESULTS: Of the 380 cases, 72% were in the near and 28% in the far position. Mortality was similar between groups within CIREN. Near-side occupants experienced a higher frequency of MAIS 3+ injuries for the thorax, abdomen, and lower extremities, and fewer MAIS 3+ head injuries than far-side occupants (35% vs. 46%, p = 0.06). Regression models revealed similar risk of MAIS 3+ head injuries among near- and far-side occupants. The most common structures contacting the head in far-side crashes (N = 62) were opposite side structures (52%) and other occupants (13%). Similar risks of head injuries among near- and far-side occupants were observed for the CODES data; however, lower risks of death were present among far-side drivers involved in crashes, based on CODES and Maryland Automated Accident Reporting System. CONCLUSIONS: Despite a lower incidence of thoracic, abdominal, and lower extremity injuries, far-side occupants experienced a similar risk of head injuries to that of near-side occupants. Contact patterns suggest that restraint systems fail to keep far-side occupants' heads from striking opposite side structures or other occupants.

Suicides, homicides, and unintentional injury deaths after trauma center discharge: cocaine use as a risk factor.

BACKGROUND: : To study whether trauma center patients with positive toxicology findings for cocaine-positive (COC+) are at a higher risk for suicide, homicide, and unintentional injury death after discharge than cocaine-negative (COC+) trauma patients. METHODS: : Patients admitted between July 1983 and June 1995 and discharged alive from a level I trauma center were prospectively followed up for 1.5 years to 14.5 years. The occurrence of suicide, homicide, and unintentional injury death was explored in relation to COC+ status at admission using Cox proportional hazards methodology. Models included possible confounders. Interactions with each of the main effects were explored. RESULTS: : Of the 27,399 admissions, 21,500 had urine COC toxicology testing performed and were included in the study. COC was positive in 11.4% of the studied population. COC+ patients were significantly younger, with 72% of COC+ versus 43% of COC- in the 25 to 44 years age group. COC+ patients were more likely to be men, positive for alcohol, and intentional injury victims. COC+ status was not associated with subsequent suicide. Furthermore, the COC+ status association with subsequent homicide became nonsignificant after adjusting for confounders. Unadjusted COC+ status was associated with unintentional injury death (odds ratio = 1.65 [1.14-2.40]). Interactions were found in the association with unintentional injury death such that COC+ status tripled the odds of injury death (odds ratio = 2.75 [1.58-4.78]) among the alcohol-negative patients within the 25 to 45 years age group. CONCLUSION: : COC+ trauma patients are at an increased risk of subsequent unintentional injury death after discharge from a trauma center. Suicide and homicide occurrence seems to be unaffected.