Multivariate outcome prediction in traumatic brain injury with focus on laboratory values.

Traumatic brain injury (TBI) is a major cause of morbidity and mortality. Identifying factors relevant to outcome can provide a better understanding of TBI pathophysiology, in addition to aiding prognostication. Many common laboratory variables have been related to outcome but may not be independent predictors in a multivariate setting. In this study, 757 patients were identified in the Karolinska TBI database who had retrievable early laboratory variables. These were analyzed towards a dichotomized Glasgow Outcome Scale (GOS) with logistic regression and relevance vector machines, a non-linear machine learning method, univariately and controlled for the known important predictors in TBI outcome: age, Glasgow Coma Score (GCS), pupil response, and computed tomography (CT) score. Accuracy was assessed with Nagelkerke's pseudo R². Of the 18 investigated laboratory variables, 15 were found significant (p<0.05) towards outcome in univariate analyses. In contrast, when adjusting for other predictors, few remained significant. Creatinine was found an independent predictor of TBI outcome. Glucose, albumin, and osmolarity levels were also identified as predictors, depending on analysis method. A worse outcome related to increasing osmolarity may warrant further study. Importantly, hemoglobin was not found significant when adjusted for post-resuscitation GCS as opposed to an admission GCS, and timing of GCS can thus have a major impact on conclusions. In total, laboratory variables added an additional 1.3-4.4% to pseudo R².

Analyses of cerebral microdialysis in patients with traumatic brain injury: relations to intracranial pressure, cerebral perfusion pressure and catheter placement.

BACKGROUND: Cerebral microdialysis (MD) is used to monitor local brain chemistry of patients with traumatic brain injury (TBI). Despite an extensive literature on cerebral MD in the clinical setting, it remains unclear how individual levels of real-time MD data are to be interpreted. Intracranial pressure (ICP) and cerebral perfusion pressure (CPP) are important continuous brain monitors in neurointensive care. They are used as surrogate monitors of cerebral blood flow and have an established relation to outcome. The purpose of this study was to investigate the relations between MD parameters and ICP and/or CPP in patients with TBI. METHODS: Cerebral MD, ICP and CPP were monitored in 90 patients with TBI. Data were extensively analyzed, using over 7,350 samples of complete (hourly) MD data sets (glucose, lactate, pyruvate and glycerol) to seek representations of ICP, CPP and MD that were best correlated. MD catheter positions were located on computed tomography scans as pericontusional or nonpericontusional. MD markers were analyzed for correlations to ICP and CPP using time series regression analysis, mixed effects models and nonlinear (artificial neural networks) computer-based pattern recognition methods. RESULTS: Despite much data indicating highly perturbed metabolism, MD shows weak correlations to ICP and CPP. In contrast, the autocorrelation of MD is high for all markers, even at up to 30 future hours. Consequently, subject identity alone explains 52% to 75% of MD marker variance. This indicates that the dominant metabolic processes monitored with MD are long-term, spanning days or longer. In comparison, short-term (differenced or Δ) changes of MD vs. CPP are significantly correlated in pericontusional locations, but with less than 1% explained variance. Moreover, CPP and ICP were significantly related to outcome based on Glasgow Outcome Scale scores, while no significant relations were found between outcome and MD. CONCLUSIONS: The multitude of highly perturbed local chemistry seen with MD in patients with TBI predominately represents long-term metabolic patterns and is weakly correlated to ICP and CPP. This suggests that disturbances other than pressure and/or flow have a dominant influence on MD levels in patients with TBI.

Extended analysis of early computed tomography scans of traumatic brain injured patients and relations to outcome.

Traumatic brain injury (TBI) is responsible for up to 45% of in-hospital trauma mortality. Computed tomography (CT) is central to acute TBI diagnostics, and millions of brain CT scans are conducted yearly worldwide. Though many studies have addressed individual predictors of outcome from findings on CT scans, few have done so from a multivariate perspective. As these parameters are interrelated in a complex manner, there is a need for a better understanding of them in this context. CT scans from 861 TBI patients were reviewed according to an extensive protocol. An extended analysis of CT parameters with respect to outcome was performed using linear and non-linear methods. We identified complex interactions and mutual information in many of the parameters. Variables predicting death differ from those predicting unfavorable versus favorable outcomes (Glasgow Outcome Scale scores of 1-3 versus 4-5 [GOS]). The most important parameter for prediction of unfavorable outcome is the magnitude of midline shift. In fact, this parameter, as a continuous variable, is by itself a better predictor and is better calibrated than the Marshall CT score, even for predicting death. In addition, hematoma volumes are nearly co-linear with midline shift and can be substituted for it. A score of traumatic subarachnoid/intraventricular blood components adds substantially to model calibration. A CT scoring system geared toward dichotomous GOS scores is suggested. CT parameters were found to add 6-10% additional estimated explained variance in the presence of the important clinical variables of age, Glasgow Coma Scale score, and pupillary response. Finally we present a practical clinical "rule of thumb" to help predict the probability of unfavorable outcome using clinical and CT variables.

Comparison of a single indicator and gravimetric technique for estimation of extravascular lung water in endotoxemic pigs.

OBJECTIVES: To compare the single thermal indicator dilution (STID) technique for measurement of extravascular lung water (EVLW(STID)) with gravimetrically determined EVLW (EVLW(GRAV)) in anesthetized pigs under sham and endotoxemic conditions. DESIGN: Open experimental comparative animal study. SETTING: University animal research laboratory. SUBJECTS: Fifteen anesthetized landrace pigs. INTERVENTIONS: Endotoxin infusion during 5 hrs in five pigs. Six animals were only anesthetized and rested for 5 hrs. In four additional animals, the impact on EVLW(STID) measurements by changes in pulmonary perfusion, ventilation, and the combination of the two was studied. The alterations in ventilation and perfusion were induced by caval balloon inflation, inflation of the pulmonary artery catheter balloon, and bronchial plugging respectively. MEASUREMENTS AND MAIN RESULTS: The STID technique, with default settings of the intrathoracic blood volume (ITBV) to global end-diastolic volume (GEDV) (i.e., the extrapulmonary intravascular volume between the point of injection of the indicator, and the point of detection) relationship (ITBV = 1.25GEDV), systematically overestimated the EVLW index compared with the gravimetrical method (mean bias of 5.4 mL/kg). By adapting the ITBV to GEDV relationship to the current model (ITBV = 1.52GEDV + 49.7), the accuracy of the STID technique improved. Moreover, the measurement of EVLW(STID) proved to be reduced by manipulation of pulmonary perfusion and ventilation. However, the STID technique could detect an increase in EVLW during endotoxemia independent of the ITBV/GEDV relationship used. CONCLUSION: Despite technological improvement, the dilution techniques for the measurement of EVLW might still be influenced by changes in perfusion and ventilation. The STID technique, in addition, might demand adjustment of the ITBV/GEDV relationship to the particular condition and species subjected to measurement. The STID technique may, however, be a useful tool for monitoring changes of EVLW over time, but further studies are warranted to confirm this.

Cerebral microdialysis of patients with severe traumatic brain injury exhibits highly individualistic patterns as visualized by cluster analysis with self-organizing maps.

OBJECTIVE: To analyze patterns of cerebral microdialysis in patients with traumatic brain injury and, with a neural network methodology, investigate pattern relationships to intracranial pressure and cerebral perfusion pressure. DESIGN: Retrospective. SETTING: University hospital, adult neurosurgical intensive care unit. PATIENTS: Twenty-six patients with severe traumatic brain injury. All consecutive traumatic brain injured patients (Glasgow Coma Scale < or =8) with microdialysis monitoring, analyzing glutamate, lactate, pyruvate, and glucose in both penumbral and nonpenumbral tissue. INTERVENTIONS: None; patients received the unit's standard neurointensive care procedure. MEASUREMENTS AND MAIN RESULTS: We used 2084 hrs of complete microdialysis data sets (eight markers) to train Kohonen self-organizing maps. The self-organizing map algorithm is a data-clustering method that reduces high-dimensional information to a two-dimensional representation on a grid (map), retaining local relationships in the data. Maps were colored (overlaid) for intracranial pressure, cerebral perfusion pressure, and outcome, to explore relationships with underlying microdialysis patterns. The maps exhibited a striking clustering of patients, with unique microdialysis patterns that were recognizable throughout the analysis period. This also held true for most microdialysis patterns characteristic of ischemia. These patients with ischemic patterns can have good outcomes, suggesting a disparity between microdialysis values and severity of traumatic brain injury. CONCLUSION: Using an artificial neural network-like clustering technique, Kohonen self-organizing maps, we have shown that cerebral microdialysis, in traumatic brain injury, exhibits strikingly individualistic patterns that are identifiable throughout the analysis period. Because patients form their own clusters, microdialysis patterns, during periods of increased intracranial pressure or decreased cerebral perfusion pressure, will be found within these clusters. Consequently, no common pattern of microdialysis can be seen among patients within the range of our data. We suggest that these individualistic patterns reflect not only metabolic states of traumatic brain injury but also local gradients seen with small volume sampling. Future investigation should focus on relating these patterns, and movement within and from clusters, to metabolic states of the complex pathophysiology of traumatic brain injury.

Differentiated and dose-related cardiovascular effects of a dual endothelin receptor antagonist in endotoxin shock.

OBJECTIVE: To evaluate the effects of endothelin receptor antagonism on cardiac performance in endotoxin shock. DESIGN: Prospective, experimental study. SETTING: A university-affiliated research institution. SUBJECTS: Domestic anesthetized landrace pigs. INTERVENTIONS: Thirty-seven pigs were anesthetized and subjected to echocardiography, coronary sinus catheterization, and monitoring of central and regional hemodynamics in order to assess cardiac performance. All animals received endotoxin for 5 hrs. Twenty pigs served as endotoxin controls. Tezosentan, a dual endothelin-A and -B receptor antagonist, was administered during established endotoxemic shock. Seven pigs received an infusion of tezosentan of 1 mg x kg(-1) x hr(-1) (tezo1), and an additional ten pigs received a higher dose of 10 mg x kg(-1) x hr(-1) (tezo10). MEASUREMENTS AND MAIN RESULTS: Endotoxemia evoked a state of shock with pulmonary hypertension and metabolic acidosis. A decrease in stroke volume and coronary perfusion pressure as well as an increase in troponin I was also noted. Tezosentan administration resulted in a significant increase in cardiac index, stroke volume index, left ventricular stroke work index, and left ventricular end-diastolic area index. Decreases in systemic and pulmonary vascular resistance indexes were also evident after intervention. This was achieved without changes in heart rate or systemic arterial or pulmonary artery occlusion pressures in tezo, animals compared with controls. In addition, metabolic variables were improved by tezosentan. These effects were sustained only in the tezo, group. In the higher dosage, tezosentan resulted in a deterioration of cardiac performance and 50% mortality rate. The endotoxin-induced increase in troponin I was attenuated in the tezo, group compared with controls. CONCLUSIONS: In this porcine model of volume-resuscitated, endotoxemic shock, endothelin-receptor blockade with tezosentan improved cardiac performance. However, the effect was not sustained with higher doses of tezosentan, possibly due to reduced coronary perfusion pressure. These findings show differentiated, dose-dependent effects by dual endothelin receptor blockade on endotoxin-induced cardiovascular dysfunction.

Outcome of traumatic brain injuries in 1,508 patients: impact of prehospital care.

This article describes the outcome of 1,508 patients with traumatic brain injuries (TBI) treated in a single neurosurgical unit over an 8-year period. Our aim has been to compare those outcomes with our previous results and with other large patient series. Another important goal was to evaluate the effect of the introduction of a 4-year ongoing study initiated in January 1993 using a new strategy of prehospital care on postresuscitation Glasgow Coma Score (GCS) and Glasgow Outcome Score (GOS). Results from the 1,508 patients showed good recovery or moderate disability in 69%, severe disability or vegetative state in 11%, and a mortality rate of 20%. When outcome of the most severely injured patients (GCS < or = 8) was compared with those of our previous and other large international patient series, more favorable outcome figures were shown in the present study. To evaluate the impact of the improved prehospital care after half of the study period, a logistic regression analysis showed after January 1993 a significantly increased expected odds/ratio for a postresuscitation GCS 8-15 rather than a GCS 3-4 (odds/ratio: 2.2; p < 0.001). For patients with postresuscitation GCS 5-7 and 8-15, the expected odds/ratio for a GOS 4-5 instead of GOS 1 increased significantly (odds/ratio: 2.2 and 1.7, respectively; p < 0.05-0.01). For patients with GCS 3-4, an increased expected odds/ratio (2.0; p < 0.05) for a GOS 2-3 rather than a GOS 1 was seen. The principal conclusion is that outcome for the severely injured patients in the present study is more favorable than in other large series of TBI. We posit that the introduction of effective prehospital care most likely contributed to the improved postresuscitation neurological status and consequently to the better outcome observed after January 1993.