University of Michigan Medical Center, Department of Emergency Medicine, TC B134 1500 East Medical Center Drive, Ann Arbor MI 48109-0303, USA
Received 19 January 2001; in revised form 17 August 2001; accepted 24 September 2001
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ABSTRACT |
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INTRODUCTION |
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Traumatic brain injury (TBI) accounts for much of the morbidity and mortality seen in both the MVC victims with and without alcohol present. The leading cause of traumatic brain injury is MVC. Investigators noted that alcohol intoxication was present in ~50% of patients who received attention for TBI (Edna, 1982; Brismar et al., 1983
; Gurney et al., 1992
; Zink et al., 1996
). A number of laboratory studies examining alcohol and TBI, using a variety of animal models and species, support the concept that alcohol worsens TBI (Flamm et al., 1977
; Albin and Bunegin, 1986
; Franco et al., 1988
; Zink et al., 1993
, 1996
, 1998
; Zink and Feustel, 1995
). While the laboratory data present a strong argument for the potentiating role of alcohol in TBI, clinical evidence has been less clear. Gurney et al. (1992) showed that intoxicated subjects were more likely to be intubated in the field. Support has also been found for a potentiating role of alcohol in a study of time to death in MVC patients with central nervous system injuries (Zink et al., 1996
). In addition, alcohol has been found to be positively associated with an increased incidence of mass lesions (Ruff et al., 1990
), prevalence of neurological impairment at discharge, and a poorer long-term outcome (Kraus et al., 1989
; Marshall et al., 1992
). Other clinical investigations have found negative results in regard to the potentiating role of alcohol (Bigler et al., 1996
) or showed no adverse effects attributable to acute alcohol use on TBI (Nath et al., 1986
; Jurkovich et al., 1993
). One study of 1200 trauma patients found no increase in head injury as a cause of death in intoxicated vs non-intoxicated patients (Ward et al., 1982
).
A limitation of alcohol-related brain injury studies is that the data have been collected only after hospital admission and crash characteristics or initial mechanisms of trauma have not been studied (Ward et al., 1982; Huth et al., 1983
; Marshall et al., 1992
; Jurkovich et al., 1993
). In addition, studies often do not account for victims who died on scene. These considerations may make it more difficult to detect a potentiating effect of alcohol, if one truly exists. Those studies that have controlled for crash characteristics have not independently investigated brain injury. The purpose of the present study was therefore to determine, using a specific measurement of brain injury, if alcohol potentiated severity of TBI in the MVC victim after controlling for crash characteristics. Specifically, we hypothesized that, after controlling for crash severity, injured patients who have alcohol present will have evidence of a more severe anatomic brain injury based on a standardized head CT scoring system, than their alcohol-negative counterparts.
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SUBJECTS AND METHODS |
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Patient population and setting
Subjects were patients 18 years old, who were occupants of automobiles or small trucks involved in an MVC and who presented directly from the crash scene to one of two university-affiliated Emergency Departments within 6 h of the crash. Pregnant patients, institutionalized patients, and transfer patients were excluded. Motorcyclists, occupants of trucks, pedestrians, or bicyclists were excluded. Site 1 is a university hospital verified as a Level One Trauma Center by the American College of Surgeons. Site 2 is a large community teaching hospital. Both of these hospitals are located in Ann Arbor, MI, USA, which is a city of ~125 000 citizens situated within a metropolitan statistical area (MSA) of 330 000, and surrounded by similarly populated counties. The University Hospital morgue was also monitored for patients delivered directly from a MVC. Data collection occurred over a 29-month period at the university hospital (April 1992 to August 1994) and over a 15-month period at the community hospital (April 1993 to June 1994). The initial prospective study found 2148 subjects in the sampling frame; of these, 1450 patients provided consent and had valid measures of crash characteristics and injury obtained. These cases were reviewed, and, after inclusion and exclusion criteria were applied (see Results for details), 58 patients were available for analysis.
Study protocol
At both Emergency Departments, subjects were recruited throughout the evening hours (15.3023.30), the time when most MVC subjects presented. Site 1 was also time-sampled during the day and midnight shifts. Data sources included ambulance reports, hospital records, autopsy records, crash reports, and head CT.
Measurements
Alcohol data. Blood-alcohol concentration (BAC) was determined by serum analysis (enzyme immunoassay), whole blood analysis (gas chromatography), or breath analyser (Alco-sensor III, Model #1020312; Intoximeters Inc., St Louis, MO, USA) conducted in the Emergency Departments. Blood or breath samples obtained within 6 h of the injury deaths at the scene were used to determine alcohol level. When blood samples were not available, post-mortem tests of vitreous humour were used. Gamma-glutamyltranspeptidase (GGT) has been used by some investigators to identify chronic alcohol misuse with levels >85 used as indicators of chronic misuse (Waller et al., 1999). GGT measurements (enzymatic assay) were obtained using Ektachem 700 XR analyser (Johnson and Johnson, Rochester NY, USA: institutional norms range: 135 IU/l).
Crash data. Data on the crashes were compiled from hard copies of crash reports, obtained from local enforcement agencies, within a few days of the crash event. Crash reports were abstracted by specially trained research assistants and provided occupant position, belt use, and TAD [traffic accident deformity score, which measures degree of vehicle deformation]. The TAD scale ranges from 1 to 7 and is a measure of vehicle crush that is highly correlated with occupant injury.
Injury severity. Information from medical records on injury was abstracted by certified nurses who had attended the Association for the Advancement of Automotive Medicine injury scoring course and had experience in injury scoring. Injury severity scores (ISS) (Baker et al., 1974), anatomic injury scores (AIS) (Committee on Injury Scaling, 1985
) and anatomic profile (AP) (Copes et al., 1990
) scores were calculated. The AIS is a consensus-derived, anatomically based system that classifies individual injuries by body region on a 6-point ordinal severity scale ranging from AIS 1 (minor) to AIS 6 (currently untreatable). The injury severity score was then calculated by using the sum of the squares of the highest AIS scores in the three different body regions and gives a better fit between overall severity and probability of survival. ISS scores range from 1 to 75. Scores were obtained using Tricode (Tricode Analytics, Bel Air, MD, USA), a computer software package for AIS (85) and ISS determination. AP scores were then calculated, using the three highest scoring major injuries within each of the three AP regions (or ISS components). The AP score takes into account the potentially confounding effects of multiple injuries occurring in any one component (Copes et al., 1990
).
TBI severity. In order to identify patients with TBI from this prospectively collected database, APA scores were reviewed. Patients with APA scores of >0 (where A is brain, head, and spinal cord) were examined. These groups of patients were then examined by chart review and were excluded if they had an isolated spinal or facial injury. Patients who died on scene or in the Emergency Department and who had a completed autopsy were reviewed and included if they had APA scores >0.
The Marshall Classification was used to scale severity of head injury on the presenting head CT or autopsy report. A neurosurgeon, who was blinded to any clinical or ethanol data, read the head CT and assigned a Marshall score. The Marshall score is originally based on patients with Glasgow Coma Score (GCS) <8, and has been shown to be predictive of clinical outcome (Marshall et al., 1991). For the purpose of this study the score served as a standard measure of anatomical classification of severity and does not account for initial GCS, and is therefore not predictive of clinical outcome. The original Marshall classification ranges from 1 to 4, and categorizes separately any lesion that is surgically evacuated (Marshall et al., 1992
). For the purpose of this study, scores were grouped into a modified Marshall classification. Small numbers precluded analysing differences in each Marshall category, therefore patients were divided into two Marshall groups (Table 1
). Clinically, patients with modified Marshall 02 have a less severe head injury and may be without focal deficits, whereas Marshall
3 patients demonstrate significant intracranial abnormalities.
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RESULTS |
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Assignation and anatomical description of the Marshall scores are shown in Tables 1 and 2. The mean presenting Glasgow Coma Score for Marshall 02 was 11.6, in comparison to 7.1 in the Marshall
3 category. Of the cases with Marshall 02 with Glasgow scores <10 (n = 10), seven had high alcohol levels of 100375 mg/dl, highlighting the limitations of GCS in the intoxicated patient. For the remainder of the analysis, cases were grouped into those with Marshall <3 and those with Marshall
3 (severe anatomical head injury).
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DISCUSSION |
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Alcohol may play a prominent role in the early response to TBI (Zink et al., 1996). The differences seen on initial head CT suggest that the effects of alcohol on TBI occur rapidly after the impact. These effects could be physiological, such as respiratory depression, or decreased cerebral perfusion (Zink et al., 1993
, 1996
, 1998
; Zink and Feustel, 1995
) or due to biomolecular changes in neuronal receptors and membrane function. Animal models suggest that alcohol exposure causes changes in cell membrane architecture and function (McCall et al., 1989
). Alcohol may cause osmotic shifts that lead to cellular swelling (Siggins et al., 1996
). Alterations in membrane-bound enzymes and cell membranes through abnormal free radical reactions in the presence of alcohol have been found (Flamm et al., 1977
). These effects in turn may lead to increased susceptibility to cell membrane breakdown, increasing the effect of the initial kinetic impact (Marshall et al., 1991
, 1992
). Further laboratory evidence suggests alcohol may cause a potentiating effect on TBI by changes in cerebral perfusion (Zink et al., 1993
).
While some previous clinical studies have found an association between alcohol and TBI, other studies, including an evaluation of severely head-injured patients in the Traumatic Coma Databank, have shown no effect on clinical course of alcohol on TBI (Ruff et al., 1990). In one study, alcohol-intoxicated patients hospitalized with TBI were more likely to require mechanical intubation (Gurney et al., 1992
). Another study noted poorer neurological outcome and increased permanent disability in severe TBI patients who had high levels of alcohol or a history of chronic alcohol misuse (Kraus et al., 1989
). However, it is important to note that no prior clinical study has accounted for crash characteristics. In addition, chronic alcohol use also has effects on haemostasis that may play a role in TBI, such as decreased platelet aggregation and function, as well as problems involving erythrocytes, leukocytes, and other haemostatic factors. In this study, the mean GGT (a measure of chronic alcohol use) was not significantly different between the two groups. Changes in haemostasis with acute ingestion are less well understood; however, current research supports the concept that coagulation is most likely less affected by acute alcohol ingestion than by chronic ingestion or sudden abstinence (Stein, 1999
).
If alcohol has a potentiating effect on the severity of TBI, independently of the initial crash, this would have far-reaching clinical and public health consequences. These effects may suggest that while current public health messages are aimed at drunk drivers, an intoxicated passenger may also be at increased risk for a more severe head injury in a MVC. In addition, although the alcohol legal limit' in many states is 100 mg/dl, it is not yet clear at what BAC these potentiating effects may begin or end, calling into question the arbitrary nature of the legal limit'.
Limitations of this study include a small sample size, hence a wide 0.95 CI. Post hoc power analysis, assuming the same proportion of patients with a Marshall score >3 found in this study (an alpha of 0.05 and power of 0.80), shows that 175 subjects per group would be needed to demonstrate a significant difference between the Marshall scores for the alcohol-positive and alcohol-negative groups. One further limitation in the use of initial head CT to describe TBI is that head CT represents a fixed point in time, whereas TBI is an evolving process. Initial CT does not fully describe the extent of pathology that may be present at 2472 h post injury, or what the differences in CT will be associated with in terms of long-term outcome. In addition, it should be noted that GGT is only one measurement for haemostatic dysfunction in chronic alcohol use, and future trials should address in more detail the effects of coagulation disorders and platelet function in acute and chronic alcohol use in relation to TBI. Finally, it is unclear whether the current study's findings apply to TBI resulting from mechanisms other than MVC, such as falls and assaults.
In conclusion, the present results suggest that alcohol may have a potentiating effect on TBI as shown by initial head CT in MVC victims. The outcome severity of the resulting brain injury is crucial not only to the individual physically, emotionally, and financially, but also to society as a whole. Further multi-centre studies are needed to elucidate the potentiating effect of alcohol in TBI. Results of such studies may aid in intervention both in the acute post-injury phase, to modulate the effects of alcohol on injury, as well as contribute to pre-injury/pre-drinking prevention efforts.
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ACKNOWLEDGEMENTS |
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FOOTNOTES |
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