Mary J. Vassar

3% NaCl and 7.5% NaCl/dextran 70 in the resuscitation of severely injured patients.

Cardiovascular resuscitation of the severely injured patient in the field remains unsatisfactory because large volumes of intravenous fluid are needed to keep up with ongoing blood losses and because only small volumes of fluid can be given. In the first study reported here, small volumes (less than or equal to 12 mL/kg) of 3% NaCl were given to patients who were having surgery for severe injuries. The 3% NaCl restored blood pressure, pH, and urine output with approximately one half of the cumulative fluid requirement of patients who received isotonic fluids (p less than 0.05). In a second study, 7.5% NaCl/dextran 70, 250 mL, was given in a prospective, randomized, and double-blinded trial to injured patients in the field. Blood pressure in the hypertonic/hyperoncotic group increased 49 mmHg during transport (p less than 0.005); blood pressure in patients given lactated Ringers solution increased 19 mmHg (NS). Survival favored the hypertonic/hyperoncotic group. The 7.5% NaCl/dextran 70 solution appears particularly promising for treatment of injured patients in the field.

Prostaglandin E1 and survival in patients with the adult respiratory distress syndrome. A prospective trial

A 7-day infusion of prostaglandin E1 (PGE1), an immunomodulator, was evaluated in a prospective, randomized, placebo-controlled, double-blinded trial in surgical patients with the adult respiratory distress syndrome (ARDS). The drug seemed to improve pulmonary function—only two PGE1 patients died with severe pulmonary failure compared with nine placebo patients (p = 0.01). Survival at 30 days after the end of the infusion— the predetermined end point of the study—was significantly better in the patients given PGE1 (p = 0.03), with 15 of 21 PGE1 patients (71%) alive at this time compared with seven of 20 placebo patients (35%). Improvement in overall survival in the PGE, patients did not reach statistical significance (p = 0.08). Overall survival in patients initially free of severe organ failure, however, was significantly better in the PGE, patients (p = 0.03). Of the six PGE1 patients free of severe organ failure at time of entry, all survived to leave the hospital; of the 10 placebo patients initially free of severe organ failure, four survived. The drug had no serious side effects and did not potentiate susceptibility to infection. PGE1 is a promising agent for the treatment of ARDS.

Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot: Multicenter Implementation of the Common Data Elements for Traumatic Brain Injury

Traumatic brain injury (TBI) is among the leading causes of death and disability worldwide, with enormous negative social and economic impacts. The heterogeneity of TBI combined with the lack of precise outcome measures have been central to the discouraging results from clinical trials. Current approaches to the characterization of disease severity and outcome have not changed in more than three decades. This prospective multicenter observational pilot study aimed to validate the feasibility of implementing the TBI Common Data Elements (TBI-CDEs). A total of 650 subjects who underwent computed tomography (CT) scans in the emergency department within 24 h of injury were enrolled at three level I trauma centers and one rehabilitation center. The TBI-CDE components collected included: 1) demographic, social and clinical data; 2) biospecimens from blood drawn for genetic and proteomic biomarker analyses; 3) neuroimaging studies at 2 weeks using 3T magnetic resonance imaging (MRI); and 4) outcome assessments at 3 and 6 months. We describe how the infrastructure was established for building data repositories for clinical data, plasma biomarkers, genetics, neuroimaging, and multidimensional outcome measures to create a high quality and accessible information commons for TBI research. Risk factors for poor follow-up, TBI-CDE limitations, and implementation strategies are described. Having demonstrated the feasibility of implementing the TBI-CDEs through successful recruitment and multidimensional data collection, we aim to expand to additional study sites. Furthermore, interested researchers will be provided early access to the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) data set for collaborative opportunities to more precisely characterize TBI and improve the design of future clinical treatment trials. (ClinicalTrials.gov Identifier NCT01565551.).

Diffusion Tensor Imaging for Outcome Prediction in Mild Traumatic Brain Injury: A TRACK-TBI Study

We evaluated 3T diffusion tensor imaging (DTI) for white matter injury in 76 adult mild traumatic brain injury (mTBI) patients at the semiacute stage (11.2±3.3 days), employing both whole-brain voxel-wise and region-of-interest (ROI) approaches. The subgroup of 32 patients with any traumatic intracranial lesion on either day-of-injury computed tomography (CT) or semiacute magnetic resonance imaging (MRI) demonstrated reduced fractional anisotropy (FA) in numerous white matter tracts, compared to 50 control subjects. In contrast, 44 CT/MRI-negative mTBI patients demonstrated no significant difference in any DTI parameter, compared to controls. To determine the clinical relevance of DTI, we evaluated correlations between 3- and 6-month outcome and imaging, demographic/socioeconomic, and clinical predictors. Statistically significant univariable predictors of 3-month Glasgow Outcome Scale-Extended (GOS-E) included MRI evidence for contusion (odds ratio [OR] 4.9 per unit decrease in GOS-E; p=0.01), ≥1 ROI with severely reduced FA (OR, 3.9; p=0.005), neuropsychiatric history (OR, 3.3; p=0.02), age (OR, 1.07/year; p=0.002), and years of education (OR, 0.79/year; p=0.01). Significant predictors of 6-month GOS-E included ≥1 ROI with severely reduced FA (OR, 2.7; p=0.048), neuropsychiatric history (OR, 3.7; p=0.01), and years of education (OR, 0.82/year; p=0.03). For the subset of 37 patients lacking neuropsychiatric and substance abuse history, MRI surpassed all other predictors for both 3- and 6-month outcome prediction. This is the first study to compare DTI in individual mTBI patients to conventional imaging, clinical, and demographic/socioeconomic characteristics for outcome prediction. DTI demonstrated utility in an inclusive group of patients with heterogeneous backgrounds, as well as in a subset of patients without neuropsychiatric or substance abuse history.

Prediction of outcome in intensive care unit trauma patients: A multicenter study of acute physiology and chronic health evaluation (APACHE), trauma and injury severity score (TRISS), and a 24-hour intensive care unit (ICU) point system

OBJECTIVE To conduct a multicenter study to validate the accuracy of the Acute Physiology and Chronic Health Evaluation (APACHE) II system, APACHE III system, Trauma and Injury Severity Score (TRISS) methodology, and a 24-hour intensive care unit (ICU) point system for prediction of mortality in ICU trauma patient admissions. METHODS The study population consisted of retrospectively identified, consecutive ICU trauma admissions (n = 2,414) from six Level I trauma centers. Probabilities of death were calculated by using logistic regression analysis. The predictive power of each system was evaluated by using decision matrix analysis to compare observed and predicted outcomes with a decision criterion of 0.50 for risk of hospital death. The Youden Index (YI) was used to compare the proportion of patients correctly classified by each system. Measures of model calibration were based on goodness-of-fit testing (Hosmer-Lemeshow statistic less than 15.5) and model discrimination were based on the area under the receiver operating characteristic curve (AUC). RESULTS Overall, APACHE II (sensitivity, 38%; specificity, 99%; YI, 37%; H-L statistic, 92.6; AUC, 0.87) and TRISS (sensitivity, 52%; specificity, 94%; YI, 46%; H-L statistic, 228.1; AUC, 0.82) were poor predictors of aggregate mortality, because they did not meet the acceptable thresholds for both model calibration and discrimination. APACHE III (sensitivity, 60%; specificity, 98%; YI, 58%; H-L statistic, 7.0; AUC, 0.89) was comparable to the 24-hour ICU point system (sensitivity, 51%; specificity, 98%; YI, 50%; H-L statistic, 14.7; AUC, 0.89) with both systems showing strong agreement between the observed and predicted outcomes based on acceptable thresholds for both model calibration and discrimination. The APACHE III system significantly improved upon APACHE II for estimating risk of death in ICU trauma patients (p < 0.001). Compared with the overall performance, for the subset of patients with nonoperative head trauma, the percentage correctly classified was decreased to 46% for APACHE II; increased to 71% for APACHE III (p < 0.001 vs. APACHE II); increased to 59% for TRISS; and increased to 62% for 24-hour ICU points. For operative head trauma, the percentage correctly classified was increased to 60% for APACHE II; increased to 61% for APACHE III; decreased to 43% for TRISS (p < 0.004 vs. APACHE III); and increased to 54% for 24-hour ICU points. For patients without head injuries, all of the systems were unreliable and considerably underestimated the risk of death. The percentage of nonoperative and operative patients without head trauma who were correctly classified was decreased, respectively, to 26% and 30% for APACHE II; 33% and 29% for APACHE III; 33% and 19% for TRISS; 20% and 23% for 24-hour ICU points. CONCLUSION For the overall estimation of aggregate ICU mortality, the APACHE III system was the most reliable; however, performance was most accurate for subsets of patients with head trauma. The 24-hour ICU point system also demonstrated acceptable overall performance with improved performance for patients with head trauma. Overall, APACHE II and TRISS did not meet acceptable thresholds of performance. When estimating ICU mortality for subsets of patients without head trauma, none of these systems had an acceptable level of performance. Further multicenter studies aimed at developing better outcome prediction models for patients without head injuries are warranted, which would allow trauma care providers to set uniform standards for judging institutional performance.

Outcome Prediction after Mild and Complicated Mild Traumatic Brain Injury: External Validation of Existing Models and Identification of New Predictors Using the TRACK-TBI Pilot Study

Although the majority of patients with mild traumatic brain injury (mTBI) recover completely, some still suffer from disabling ailments at 3 or 6 months. We validated existing prognostic models for mTBI and explored predictors of poor outcome after mTBI. We selected patients with mTBI from TRACK-TBI Pilot, an unselected observational cohort of TBI patients from three centers in the United States. We validated two prognostic models for the Glasgow Outcome Scale Extended (GOS-E) at 6 months after injury. One model was based on the CRASH study data and another from Nijmegen, The Netherlands. Possible predictors of 3- and 6-month GOS-E were analyzed with univariate and multi-variable proportional odds regression models. Of the 386 of 485 patients included in the study (median age, 44 years; interquartile range, 27-58), 75% (n=290) presented with a Glasgow Coma Score (GCS) of 15. In this mTBI population, both previously developed models had a poor performance (area under the receiver operating characteristic curve, 0.49-0.56). In multivariable analyses, the strongest predictors of lower 3- and 6-month GOS-E were older age, pre-existing psychiatric conditions, and lower education. Injury caused by assault, extracranial injuries, and lower GCS were also predictive of lower GOS-E. Existing models for mTBI performed unsatisfactorily. Our study shows that, for mTBI, different predictors are relevant as for moderate and severe TBI. These include age, pre-existing psychiatric conditions, and lower education. Development of a valid prediction model for mTBI patients requires further research efforts.

Comparison of Apache Ii, Triss, and a Proposed 24-hour Icu Point System for Prediction of Outcome in Icu Trauma Patients

The APACHE II system for predicting outcomes in critically ill patients is now being used to evaluate quality of care for patients in surgical intensive care units, including trauma patients. The trauma data, however, on which the APACHE outcomes are based, were derived from only 364 ICU trauma patients. We compared the outcome predictions by APACHE II, TRISS, and a proposed 24-hour ICU point system in 1,000 ICU patients. [table: see text] p less than 0.025 by unpaired t test for predictive power of ICU point system versus APACHE II. Values of more than 15.5 represent poor agreement between the outcomes estimated from the model and the observed outcomes; a low value represents good agreement. The APACHE system significantly overestimated the risk of death in the lower ranges of predicted risk and underestimated the deaths in the higher ranges. Although TRISS was not developed for ICU trauma patients, it tended to perform better than APACHE II in our sample. The 24-hour ICU point system performed well, with accurate agreement between the outcomes estimated from the model and the observed outcomes.

Fractures in access to and assessment of trauma systems

BACKGROUND Trauma is a major public health problem and organized systems of trauma care have been shown to substantially reduce trauma-related mortality. Currently California and many other states have incompletely developed systems of trauma care delivery. This study was undertaken to determine how frequently patients incurring serious trauma in California receive treatment at a trauma center. STUDY DESIGN Hospital discharge records for 360,743 acute trauma patients for 1995 to 1997 were analyzed. Abbreviated Injury Scale scores were calculated from discharge diagnosis codes. Severity of trauma and the need for trauma center treatment was defined by eight Abbreviated Injury Scale criteria combined with patient age and type of injury. RESULTS According to study criteria, 67,718 patients needed trauma center care and 56% were treated at a trauma center. Among patients less than 55 years of age, 62% were treated at a trauma center compared with 40% of those aged 55 years or more (p < 0.0001). For patients less than 55 years old with brain injuries, 66% were treated at a trauma center compared with 44% for patients aged 55 years or more (p < 0.0001). Of the 29,849 patients who met Abbreviated Injury Scale criteria but were not treated at trauma centers, 59% were in counties with designated trauma centers and 41% were in counties without trauma centers. CONCLUSIONS Only 56% of seriously injured patients in California were treated at trauma centers, despite most of the injuries occurring in the catchment areas of designated trauma care systems. Substantial undertriage of serious trauma patients to trauma centers appears to be occurring, especially in older persons and in persons with brain injuries. Efforts to understand why undertriage is occurring so frequently are hampered by fragmentation of the systems of care, inadequate data management systems, and lack of trauma care performance reporting by non-trauma center hospitals.

Emergency department diagnosis of abdominal disorders in the elderly

To assess the accuracy of emergency department (ED) provisional diagnosis (ProDx) as compared with the hospital discharge diagnosis (HDDx) and the impact on hospital morbidity and mortality among nonelderly and elderly persons presenting with acute nontraumatic abdominal complaints, a retrospective review was conducted of 1,863 nonelderly (younger than 65 years) and 428 elderly (65 years or older) adults admitted to a university hospital from its ED. The sensitivity/ specificity of the ProDx was 82%/86% for patients younger than 65 versus 68%/76% for those 65 or older. When the ProDx and HDDx did not agree, the overall disease-related morbidity was 16% for patients younger than 65 versus 45% for those 65 or older (P < .02). There were no differences in mortality based on agreement of the ProDx and HDDx. Prospective studies to determine the factors that are most useful in the ED diagnosis of acute nontraumatic abdominal disorders in the elderly are needed to improve the accuracy of diagnosis and reduce the incidence of morbidity in this high-risk group.

Use of Hypertonic-Hyperoncotic Fluids for Resuscitation of Trauma Patients

Hypertonic sodium chloride solutions in concentrations ranging from 1.5% to 24% have been studied for use in the resuscitation of burn and hemorrhagic shock victims for many years. In animal studies, in the setting of small volume resuscitation, hypertonic sodium chloride is superior to standard isotonic crystalloid resuscitation for restoration of hemodynamic stability. The combination of hypertonic sodium chloride with a hyperoncotic colloid solution sustains hemodynamic improvements for an additional hour. Hypertonic-hyperoncotic solutions restore vascular volume primarily by drawing water out of the cell and then selectively partitioning some of the newly recruited fluid within the plasma space. The hyperosmolar state also augments microcirculatory flow, reduces cerebral edema formation, and perhaps increases myocardial contractility. The ability to increase cardiac output with small volume hypertonic-hyperoncotic resuscitation may solve some of the problems related to fluid resuscitation in the prehospital setting when transport times are prolonged or mass casualties need to be treated. Decreasing the volume of fluid required during resuscitation may also prove beneficial in the setting of craniocerebral trauma where the administration of large volumes of crystalloid can increase intracranial pressure. The largest clinical experiences have been reported with the administration of 4 mL/kg of 7.5% sodium chloride combined with 6% dextran 70. These studies have shown that this solution is safe to administer and effective for reversal of hypotension. Whether or not the ability to reverse hypotension will translate into improved survival remains undetermined at present and will require larger multi-institutional trials.