The evolution of white matter microstructural changes after mild traumatic brain injury: A longitudinal DTI and NODDI study.

Neuroimaging biomarkers that can detect white matter (WM) pathology after mild traumatic brain injury (mTBI) and predict long-term outcome are needed to improve care and develop therapies. We used diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) to investigate WM microstructure cross-sectionally and longitudinally after mTBI and correlate these with neuropsychological performance. Cross-sectionally, early decreases of fractional anisotropy and increases of mean diffusivity corresponded to WM regions with elevated free water fraction on NODDI. This elevated free water was more extensive in the patient subgroup reporting more early postconcussive symptoms. The longer-term longitudinal WM changes consisted of declining neurite density on NODDI, suggesting axonal degeneration from diffuse axonal injury for which NODDI is more sensitive than DTI. Therefore, NODDI is a more sensitive and specific biomarker than DTI for WM microstructural changes due to mTBI that merits further study for mTBI diagnosis, prognosis, and treatment monitoring.

Toward Precision and Reproducibility of Diffusion Tensor Imaging: A Multicenter Diffusion Phantom and Traveling Volunteer Study.

BACKGROUND AND PURPOSE: Precision medicine is an approach to disease diagnosis, treatment, and prevention that relies on quantitative biomarkers that minimize the variability of individual patient measurements. The aim of this study was to assess the intersite variability after harmonization of a high-angular-resolution 3T diffusion tensor imaging protocol across 13 scanners at the 11 academic medical centers participating in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury multisite study. MATERIALS AND METHODS: Diffusion MR imaging was acquired from a novel isotropic diffusion phantom developed at the National Institute of Standards and Technology and from the brain of a traveling volunteer on thirteen 3T MR imaging scanners representing 3 major vendors (GE Healthcare, Philips Healthcare, and Siemens). Means of the DTI parameters and their coefficients of variation across scanners were calculated for each DTI metric and white matter tract. RESULTS: For the National Institute of Standards and Technology diffusion phantom, the coefficients of variation of the apparent diffusion coefficient across the 13 scanners was <3.8% for a range of diffusivities from 0.4 to 1.1 × 10-6 mm2/s. For the volunteer, the coefficients of variations across scanners of the 4 primary DTI metrics, each averaged over the entire white matter skeleton, were all <5%. In individual white matter tracts, large central pathways showed good reproducibility with the coefficients of variation consistently below 5%. However, smaller tracts showed more variability, with the coefficients of variation of some DTI metrics reaching 10%. CONCLUSIONS: The results suggest the feasibility of standardizing DTI across 3T scanners from different MR imaging vendors in a large-scale neuroimaging research study.

Surgeons and injury prevention: what you don't know can hurt you!

BACKGROUND: The most effective treatment for traumatic injuries is to prevent them from occurring. Currently, few surgeons receive any formal training in injury' control and prevention. This study was designed to test the knowledge of injury prevention principles among practicing surgeons, in order to identify areas in need of intensified educational efforts. STUDY DESIGN: Survey questions designed by members of the American College of Surgeons Committee on Trauma were programmed into a specialized touch-screen computer, which was displayed at four different surgery and trauma meetings, including the ACS Clinical Congress in 1999 and 2000. Participants were questioned about their knowledge of trauma epidemiology, bicycle helmet effectiveness, child safety seat usage, suicide, and domestic violence. RESULTS: Seventy-nine surveys were completed by surgeons, including 33 specializing in trauma care, and by 106 nurses attending trauma courses. Overall, the percentage of correct answers was 50%. There were no significant differences in survey scores between trauma surgeons and general surgeons, although both scored higher than trauma nurses. Areas where knowledge deficits were the most apparent included proper use of child safety seats, the effectiveness of airbags, the prevalence of suicide, and the annual cost of injury in America. CONCLUSIONS: The majority of practicing surgeons and nurses, including those working at trauma centers, are unaware of the basic concepts of injury prevention. Advancements in the field of injury control will require efforts to educate medical professionals and the public.

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.

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.

Hospitalizations for firearm-related injuries. A population-based study of 9562 patients.

OBJECTIVE: To determine the incidence, nature, demographics, severity, and hospital charges associated with inpatient treatment of firearm-related injuries. DESIGN: A retrospective, 1-year, population-based study of firearm-related hospitalizations based on the 1991 California Hospital Discharge Abstract Data Tapes. SETTING: California acute care hospitals that reported firearm-related discharges. PATIENTS: A total of 9562 patients discharged with firearm-related injuries. MAIN OUTCOME MEASURES: Per capita hospital discharge rates, according to age, race, and sex. RESULTS: A total of 9562 firearm-injured persons were discharged from California hospitals in 1991, representing a rate of 32 discharges per 100 000 population. Males aged 15 to 24 years accounted for 72% of the hospitalizations. For all causes of firearm-related injury, the highest age- and race-specific discharge rate was 439 per 100,000 for black persons aged 15 to 24 years. The highest county discharge rate was 55 per 100,000 for Los Angeles County. Statewide, there were 1.8 hospital discharges per firearm-related fatality (both in the hospital and in the community). Assaults accounted for 74% of cases. Among black males aged 15 to 24 years, assaults accounted for 598 discharges per 100 000 population. Hospital charges for 9193 patients exceeded $164 million; mean and median charges per patient discharged were $17,888 and $8535, respectively. Publicly financed health insurance programs sponsored 56% of patients; 25% had private insurance, and 19% were uninsured. Fifty-three percent of the discharges occurred at 13 of the 371 hospitals that discharged patients with firearm-related injuries. CONCLUSIONS: Firearm-related violence is a major cause of hospitalization of young urban black males and represents a significant cost to publicly financed health care. The impact on individual hospitals is highly disproportionate. While hospital discharge data can be used for population-based surveillance of firearm-related trauma, there is need for improvement in local, state, and national surveillance of these injuries.

Hospitalization charges, costs, and income for firearm-related injuries at a university trauma center.

OBJECTIVE: To quantify the actual cost of inpatient medical care for firearm-related injuries at a university trauma center. DESIGN: Retrospective case series of all hospital admissions for firearm-related injuries for the 3 years 1990 through 1992. Total inpatient financial data were examined by means of a recently instituted cost-accounting methodology. SETTING: Level I trauma center at a university hospital that provides trauma care and tertiary care to 3.7 million residents of 23 counties. PATIENTS: A total of 787 consecutive patients were admitted to the hospital with firearm-related injuries. Information from the trauma registry and hospital finance records were linked for 750 (95%) of these patients. MAIN OUTCOME MEASURES: Total inpatient hospital charges, costs, revenues, and net income according to payer source. RESULTS: Men aged 15 to 44 years accounted for 77% of patients with firearm-related injuries. The overall mean and median hospital charges per admission were $52,271 and $28,033, respectively, whereas the overall mean and median hospital costs per admission were $13,794 and $7964, respectively. The net income per patient ranged from an average loss of $6980 for each patient having no insurance to an average profit of $28,557 for each patient with a health maintenance organization contract. The losses sustained on nonsponsored and Medicaid patients were more than offset by net income from patients having private health insurance, Medicare, or other insurance coverage such that there was an average profit of $5809 per admission for a firearm-related injury. CONCLUSIONS: Treatment of firearm-related injuries produces net income for this university trauma center by virtue of the cost shifting built into its pricing structure. If data from this institution are extrapolated to the nation, then the actual cost of providing medical care for firearm-related injuries in the United States in 1995 is projected to be $4.0 billion. The majority of this cost will be paid indirectly by private health insurance.

The case against using the APACHE system to predict intensive care unit outcome in trauma patients.

The use of outcome indices as a means of evaluating institutional performance for delivery of medical care is at the forefront of federal health policy reforms. Because an enormous number of clinical and financial data are generated by ICU patients, it is inevitable that integrated bedside computers will be necessary to supply the type of information that is being sought by governmental and private insurance agencies involved in assessment of hospital performance. The Health Care Financing Administration already has adopted the APACHE data collection protocols and predictive models for the severity of illness adjustments that were used in assessing the 1986 hospital-specific death rate for acute myocardial infarction, congestive heart failure, stroke, and pneumonia. In our opinion, however, it is unlikely that any single system will be developed that can accurately estimate more than 50% of ICU deaths. The intention of the APACHE III system to include 78 diagnostic categories seems unrealistic. Furthermore, the number of data needed to document outcomes for both low- and high-risk admissions is impractical. We are evaluating APACHE III to determine whether the revisions to the definition for head trauma will represent a significant improvement in predicting outcomes for trauma patients. In the interim, the financial investment in the APACHE III automated bedside data collection system cannot be justified for trauma patients. Neither should it be used in ICUs that admit a large number of trauma patients as a tool for monitoring unit efficiency, guiding triage decisions, allocating staff and ICU beds, identifying risks of iatrogenic or other potential complications, or assessing quality of life, in spite of marketing efforts by the APACHE Corporation. We believe that using any of the APACHE systems for these purposes, at best, is premature, and potentially misrepresents the trauma patient population. Standards for patient classification already are in place for use in making determinations for institutional reimbursement from governmental and insurance agencies. The inequities for certain subgroups of patients, including trauma patients, could create situations in which care is rationed rather than allocated according to a plan that distributes resources efficiently. The APACHE system has several shortcomings and adds little, if anything, to the potential solutions for trauma quality assurance and resource allocation. Nor has the APACHE system established procedures for documenting institutional review of unexpected trauma deaths that would be equivalent, for example, to the type of audit filters applied by the American College of Surgeons in conjunction with the TRISS methodology.(ABSTRACT TRUNCATED AT 400 WORDS)

A multicenter trial for resuscitation of injured patients with 7.5% sodium chloride. The effect of added dextran 70. The Multicenter Group for the Study of Hypertonic Saline in Trauma Patients.

OBJECTIVE: To evaluate the use of 250 mL of a 7.5% sodium chloride solution, both with and without added dextran 70, for the prehospital resuscitation of hypotensive trauma patients. DESIGN: Double-blind randomized trial. SETTING: Six trauma systems served by helicopter transport. PATIENTS: Injured patients with systolic blood pressures less than 90 mm Hg at any time in the field or during helicopter transport. INTERVENTIONS: Infusion of study solution, in the field or during transport, followed by conventional isotonic solutions as needed. Solutions studied in four cohorts were as follows: (1) lactated Ringer's; (2) 7.5% sodium chloride (hypertonic saline); (3) 7.5% sodium chloride combined with 6% dextran 70; and (4) 7.5% sodium chloride combined with 12% dextran 70. MAIN OUTCOME MEASURES: Blood pressure response; survival to time of hospital discharge among the treatment groups; and survival compared with that predicted by norms from the Major Trauma Outcome Study (MTOS). RESULTS: The mean (+/- SD) change in systolic blood pressure on arrival in the emergency department was significantly higher in the hypertonic saline solution group than that in the lactated Ringer's solution group (34 +/- 46 vs 11 +/- 49 mm Hg, P < .03). Overall survival in the four treatment groups was 49%, 60%, 56%, and 45% (not statistically significant). Survival in the hypertonic saline solution group, however, was significantly higher than that predicted by the MTOS norms (60% vs 48%, P < .001). Survival to hospital discharge in patients with baseline Glasgow Coma Scale scores of 8 or less was correlated with treatment group (P < .05 by logistic regression and P < .01 by Cox proportional-hazards analysis; with survival in the hypertonic saline solution group [34%] vs lactated Ringer's solution group [12%]). CONCLUSIONS: Prehospital infusion of 250 mL of 7.5% sodium chloride is associated with an increase in blood pressure and an increase in survival to hospital discharge compared with survival predicted by the MTOS norms. Patients with low baseline Glasgow Coma Scale scores seem to benefit the most from 7.5% sodium chloride resuscitation. Hypertonic saline solution without added dextran 70 is as effective as the more expensive solutions that contain dextran 70.

Prehospital resuscitation of hypotensive trauma patients with 7.5% NaCl versus 7.5% NaCl with added dextran: a controlled trial.

Small volume infusions of hypertonic saline combined with dextran are very effective in resuscitating animals that have been subjected to hemorrhagic shock, and seem to be effective in resuscitating trauma patients with severe injuries. In this study, the contribution of the dextran component was investigated in a prospective, three-armed, double-blind, randomized trial. Trauma patients transported by ambulance to the hospital with a systolic blood pressure of 90 mm Hg or less were given 250 mL of (1) normal saline (NS); (2) 7.5% NaCl (HS, for hypertonic saline); or (3) 7.5% NaCl in 6% dextran 70 (HSD). Infusion of the study solution was followed by administration of conventional isotonic fluids as the patients' conditions indicated. By predetermined hypothesis, the observed survival rates in the three treatment groups were compared with the predicted survival rates from the TRISS methodology. The 7.5% NaCl solution significantly improved upon the predicted survival for the entire cohort and for high-risk patients when compared with the survival estimates from the TRISS methodology. The addition of a colloid, in the form of 6% dextran 70, did not offer any additional benefit, at least in this setting of rapid urban transport.

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.

Evaluation of prostaglandin E1 for prevention of respiratory failure in high risk trauma patients: a prospective clinical trial and correlation with plasma suppressive factors for neutrophil activation.

A group of 48 critically injured patients were entered into a prospective, double-blind, placebo-controlled trial to evaluate the efficacy of early infusion of PGE1 for reducing the incidence of severe respiratory failure and mortality. Secondary assessments examined the effects of the PGE1 infusion on plasma mediated suppression of PMN superoxide production and loss of PMN granule enzyme content. The incidence of severe respiratory failure was lower in the PGE1 group--13% versus 32%, but this did not reach significance. The overall morality was equivalent between the two groups--26% (PGE1) versus 28% (placebo). The suppressive activity of the patient plasma was assayed by measurement of normal PMN superoxide production relative to normal control plasma (ratio P:C). The baseline ratio P:C was 62 +/- 5% in the PGE1 group versus 60 +/- 5% in the placebo group. The day 1 plasma samples showed significant reversal of plasma suppressive activity in the PGE1 group--ratio P:C 88 +/- 5% versus 67 +/- 5% in the placebo group (P less than 0.02). In patients who received the full 7 days of infusion, the plasma suppressive activity remained significantly diminished in the PGE1 group--ratio P:C 77 +/- 4% versus 61 +/- 5% (P less than 0.04). The baseline lysozyme content of patient PMN's relative to that of normal control PMNs (ratio P:C) was 119 +/- 14% in the PGE1 group. A significant loss of lysozyme content was observed in the PGE1 group on day 1 of the infusion--ratio P:C 79 +/- 8% (P less than 0.03), and was associated with a reduction in the plasma suppressive activity.(ABSTRACT TRUNCATED AT 250 WORDS)

7.5% sodium chloride/dextran for resuscitation of trauma patients undergoing helicopter transport.

To evaluate the use of hypertonic saline/dextran solutions in the prehospital resuscitation of severely injured patients, we administered 250 mL of either 7.5% sodium chloride/dextran 70 (HSD) (n = 83) or lactated Ringer's solution (n = 83), followed by conventional isotonic fluids, to 166 trauma patients with systolic blood pressures less than or equal to 100 mm Hg, in a prospective, randomized, double-blinded clinical trial. Patients in the sodium chloride/dextran 70 group required less fluid before hospitalization and arrived in the emergency department with higher systolic blood pressures than patients in the lactated Ringer's solution group. The rate of survival to hospital discharge for the entire cohort was 64% for patients in the sodium chloride/dextran 70 group vs 59% for patients in the lactated Ringer's solution group. The rate of survival to hospital discharge for the patients with severe head injuries was 32% for the sodium chloride/dextran 70 group vs 16% for the lactated Ringer's solution group. Actuarial survival for patients with severe head injuries in the sodium chloride/dextran 70 group compared with patients with severe head injuries in the lactated Ringer's solution group did not quite reach statistical significance. There were no adverse side effects associated with sodium chloride/dextran 70 administration. Administration of small volumes of sodium chloride/dextran 70 before hospitalization increased the blood pressure of severely injured patients more effectively than did lactated Ringer's solution and showed tendencies toward improving survival in the patients with severe head injuries.

Analysis of potential risks associated with 7.5% sodium chloride resuscitation of traumatic shock.

We evaluated the potential side effects of rapidly infusing 250 mL of either 7.5% sodium chloride or 7.5% sodium chloride per 6% dextran 70, using lactated Ringer's as the control, to 106 critically injured patients in two prospective double-blinded emergency department trials. Eight patients had a significant hyperchloremic acidemia in association with infusion of the hypertonic solutions, but all eight were moribund before infusion and many factors other than hyperchloremia could have contributed to their acidemia. Other blood chemistry changes that might have been associated with the hypertonic solutions, such as hyperosmolality or hypernatremia, were made insignificant by other factors, such as high blood alcohol levels or concomitant administration of sodium bicarbonate. There were no cases of central pontine myelinolysis; bleeding was not potentiated. There was no difficulty with crossmatching of blood. No anaphylactoid reactions occurred. In a setting of limited volume resuscitation, the solutions are likely to have a favorable risk-to-benefit ratio.

Use of a 7.5% NaCl/6% Dextran 70 solution in the resuscitation of injured patients in the emergency room.

Animal studies and preliminary field patient trials suggest that hypertonic saline solutions can achieve resuscitation of hypovolemic shock with extremely small volumes. In the study reported here, we evaluated the effects of a hypertonic 7.5% NaCl/6% Dextran 70 (HSD) solution in the resuscitation of patients in the emergency room. Thirty-two patients were randomized into a prospective, randomized, placebo-controlled, double-blinded trial in which 250 ml of either HSD or, as a control, lactated Ringers (LR) was used as the initial fluid for resuscitation of patients with systolic blood pressures of 80 mmHg or less. The test solution was given intravenously, usually through a saphenous vein cut-down, over a period of 2-5 minutes. Conventional isotonic solutions were then given as necessary with an average of 2500 ml of fluid being given over the first 30 minutes of resuscitation. Survival was not improved, and the trial proved to be of most interest with regard to measurement of physiological quantities, which might have been expected to have been substantially abnormal because, in many cases, the measurements were made shortly after the infusion ran in. Very few abnormalities, however, were in fact detected. With the exception of one patient, the highest sodium concentration was 156 mEq/l, the highest chloride concentration was 126 mEq/1, and the highest osmolality was 401 mOsm/kg, and this value was obtained in a patient in the control LR group. Osmolality correlated far better with blood alcohol levels (Spearman's rank correlation coefficient = 0.81) than with any other variable, including sodium and chloride concentrations. The HSD solution was safe to use.(ABSTRACT TRUNCATED AT 250 WORDS)

Perspectives on clinical trials for hypertonic saline/dextran solutions for the treatment of traumatic shock.

Animal studies with hypertonic solutions suggest that they can achieve resuscitation of hypovolemic shock with extremely small volumes. Such small volume resuscitation might be ideal in the field treatment of injured patients. Our studies to date, with 60 patients entered into a prospective, randomized, placebo-controlled, and double-blind clinical trial, suggest that the use of a 7.5% NaCl/Dextran 70 solution increases blood pressures during transport. The solutions have been safe, and we have encountered no adverse side effects from their use. Survival rates to date favor use of the solutions, but we do not have convincing statistical significance yet in that regard.

Patients with adult respiratory distress syndrome (ARDS) demonstrate in vivo neutrophil activation associated with diminished binding of neutrophil-specific monoclonal antibody 31D8.

Neutrophils (PMNs) from patients with adult respiratory distress syndrome (ARDS) were assessed for light scattering, membrane potential, and phagocytic responses using fluorescent probes and flow cytometry to evaluate individual cells. Qualitative and quantitative oxidant responses were measured by nitroblue tetrazolium (NBT) and cytochrome c reduction assays, respectively. The results were correlated with the proportion of cells binding the PMN subset-specific monoclonal antibody 31D8. Despite an increased forward scatter signal (4.3 +/- 1.6 vs. 1.3 +/- 1.1 ARDS vs. control, P = 0.041) and spontaneous NBT test (12.6 +/- 4.7% vs. 2.5 +/- 0.8% positive, ARDS vs. control, P = 0.033) indicating in vivo priming of ARDS PMNs, there were no significant differences between ARDS and control PMNs in assays of stimulated membrane potential, NBT, and O.2- production or phagocytosis. However, positive correlations between the degree of prestimulus forward light scatter and subsequent O.2- production to FMLP (r = 0.673, P = 0.006) and between the percentage of bands and the O.2- response to PMA (r = 0.660, P = 0.003), suggest that the great variability of the ARDS PMN functional responses may relate to varying degrees of in vivo cell priming and/or deactivation. ARDS PMNs demonstrated a significantly lower percentage of 31D8 positive cells (73.4 +/- 7.5% vs. 94.5 +/- 1.6%, P = 0.012) and a lower level of 31D8 staining when compared to normals (60.1 +/- 10.4% of control level, P = 0.001). The lower 31D8 expression did not directly correlate with any functional parameter tested or with the proportion of immature cells. However, patients receiving an intravenous PGE1 infusion demonstrated a significant increase in 31D8 staining relative to controls and inhibition of PMA-stimulated O.2- production. The data suggest that the function of PMNs from ARDS patients varies widely and reflects great in vivo variation in cell priming. While the mechanism responsible for the lowered expression of the 31D8 antigen and its apparent modulation by PGE1 is unknown, 31D8 may be an indirect marker for in vivo stress factors that regulate the preferential release of a structurally distinct PMN subset from the bone marrow.

Early fluid requirements in trauma patients. A predictor of pulmonary failure and mortality.

The fluid required for initial resuscitation of trauma patients should reflect, at least in part, the severity of the original injuries and shock. We examined the hypothesis that the initial fluid requirements might also predict development of subsequent pulmonary failure and death. Fluid balances were calculated for the first 24 hours in the intensive care unit for 100 high-risk trauma patients. The mean (+/- 1 SD) fluid balance for 63 patients who developed pulmonary failure was 4.6 +/- 5.5 L; the mean balances for the 37 patients who did not develop pulmonary failure were 1.0 +/- 3.1 L. The balances in 23 patients who died and in 77 who survived were 6.8 +/- 5.4 and 2.2 +/- 4.5 L, respectively. A cutoff value of 3 L determined prospectively before beginning the study predicted pulmonary failure with a sensitivity of 52% and a specificity of 89%. For mortality, the 3-L cutoff point gave a sensitivity of 74% and a specificity of 74%. The predictive value of the fluid balance was independent of other prognostic indicators, such as revised trauma scores, injury Severity Scores, and modified APACHE II scores. This simple measurement should help in allocating intensive care unit resources, as patients in positive fluid balance are likely to require Swan-Ganz catheterization and are likely to require long-term mechanical ventilation. The fluid balance should also be useful in stratifying patients for entry into clinical trials.

Measurement of 6-keto-PGF1 alpha and thromboxane B2 levels in critically ill surgical patients.

Systemic arterial and mixed venous plasma concentrations of 6-keto-PGF1 alpha and TxB2 were measured by radioimmunoassay in 63 critically ill patients with major trauma (n = 20) or sepsis (n = 43). Patients undergoing elective catheterization procedures served as controls (n = 10). Arterial and mixed venous 6-keto-PGF1 alpha and TxB2 levels were significantly elevated in patients with recent major trauma or active sepsis. The 6-keto-PGF1 alpha levels were found to be significantly elevated in the non-survivors and in patients with hepatic failure. The presence of severe pulmonary failure was not associated with increased levels of either 6-keto-PGF1 alpha or TxB2. Comparison of arterial and mixed plasma samples did not demonstrate increased pulmonary release of either compound. Increased eicosanoid production may account, in part, for the local vascular and humoral responses to tissue injury or infection.