BLOOD ALCOHOL IS THE BEST INDICATOR OF HAZARDOUS ALCOHOL DRINKING IN YOUNG ADULTS AND WORKING-AGE PATIENTS WITH TRAUMA

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1 Alcohol & Alcoholism Vol. 39, No. 4, pp , 2004 doi: /alcalc/agh064, available online at BLOOD ALCOHOL IS THE BEST INDICATOR OF HAZARDOUS ALCOHOL DRINKING IN YOUNG ADULTS AND WORKING-AGE PATIENTS WITH TRAUMA OLLI SAVOLA 1 *, ONNI NIEMELÄ 2 and MATTI HILLBOM 1 1 Department of Neurology, Oulu University Hospital, Oulu and 2 Department of Laboratory Medicine, Tampere University, Tampere and Seinäjoki Central Hospital, Seinäjoki, Finland (Received 19 September 2003; first review notified 1 December 2003; in revised form 18 March 2004; accepted 20 March 2004) Abstract Aims: To determine the most effective marker of hazardous alcohol drinking in trauma patients. Methods: A prospective study of 349 trauma patients aged years admitted into a general hospital trauma centre. Information on the amount and pattern of alcohol drinking was obtained by interview. Blood or breath alcohol concentration (BAC), serum gammaglutamyl transferase (GGT), aspartate aminotransferase (AST), carbohydrate-deficient transferrin (CDT) and the mean corpuscular volume (MCV) of erythrocytes were measured as markers of alcohol consumption. Results: In this series, 8% of all trauma patients were found to be dependent drinkers, while 61% were frequent binge drinkers, 17% infrequent binge drinkers, 8% light-to-moderate drinkers and 6% nondrinkers. On admission, the BAC test was positive in 68% of the hazardous drinkers (i.e. dependent drinkers or frequent binge drinkers). Using a cut-off level of >0 mg/dl, the sensitivity and specificity of the BAC test for identifying hazardous drinking were 68% (95% confidence intervals [CI], 61 73%) and 94% (95% CI, 87 97%), respectively, and the positive predictive value was 96% (95% CI, 92 98%). GGT, MCV, CDT and AST were less accurate indicators of hazardous drinking. BAC was the least expensive marker. Conclusions: Two-thirds of trauma patients were hazardous drinkers, and blood alcohol on admission was an accurate indicator of this. BAC should be systematically used in trauma centres if patients are to be selected for an alcohol intervention. INTRODUCTION Alcohol drinking and its consequences are currently one of the major health hazards worldwide (Kristenson et al., 1982; Hasin et al., 1990; Anderson et al., 1993; Lieber, 1995; Chikritzhs et al., 2001), creating significant financial burdens for societies (Rice et al., 1991; Goldberg, 2002). Excessive alcohol consumption is closely linked with trauma-related hospital admissions, especially in young adults and working-age individuals (Peppiatt et al., 1978; Baker et al., 1992; Jurkovich et al., 1992; Rivara et al., 1993; Nilssen et al., 1994; Corrigan, 1995). Alcohol potentiates vulnerability to injury (Waller et al., 1986), causes diagnostic and therapeutic difficulties in the management of trauma patients (Jurkovich et al., 1992), and has an exacerbating effect on the outcome of injury (Waller et al., 1986; Rönty et al., 1993; Corrigan, 1995). There is a high incidence of hazardous drinkers among the patients admitted to accident and emergency departments (Soderstrom and Cowley, 1987; Charalambous, 2002). Their early identification is needed for the initiation of a brief alcohol intervention. However, alcohol-related health problems continue to escape detection by clinicians. Despite accumulating evidence showing that brief alcohol interventions are effective in reducing alcohol drinking (Antti- Poika et al., 1988; Walsh et al., 1991; Maheswaran et al., 1992; Fleming et al., 1997) and the risk of injury recurrence (Dinh-Zarr et al., 1999; Gentilello et al., 1999), there continues to be a lack of attention to alcohol problems (Soderstrom and Cowley, 1987). It would be particularly important to detect not only dependent drinkers but also the patients who are binge drinkers as early as possible, because frequent binge drinking is a growing problem in most Western countries and often precedes the sequence of events leading to chronic alcoholism (Chikritzhs et al., 2001; Goldberg, 2002; Naimi et al., 2003). The present study set out to compare the usefulness of various diagnostic tools for identifying hazardous drinking among trauma patients. SUBJECTS AND METHODS Patients The study was conducted at a hospital that treats all trauma patients, with or without referral from primary health care, in a city of inhabitants. We logged 385 consecutive admissions in the age range years showing evidence of physical trauma needing assessment and treatment by the emergency room physician. We could not include in the analysis 36 patients in whom completed interview material (see below) was not obtained (this included three fatal cases). Thus our series comprised 349 patients (252 men, 97 women). After immediate critical care, all clinical data, including the cause, type and extent of the injury, and the patient s health status, which also included history of infections (HIV/AIDS, hepatitis B and C), liver status, use of alcohol, medications, illicit drugs and smoking, were recorded by trained emergency department physicians based on a structured questionnaire designed for this purpose. The Injury Severity Score (ISS) (Baker et al., 1974; Copes et al., 1988) was used as an index of trauma severity. The study was approved by the ethics committee of the hospital, and informed consent was obtained from all patients or their close relatives. *Author to whom correspondence should be addressed at: Department of Neurology, Oulu University Hospital, Box 25, Oulu, FIN-90029, Finland. Tel.: ; Fax: ; osavola@paju.oulu.fi Alcohol data Venous blood samples were obtained from all the patients for determinations of the mean corpuscular volume (MCV) of 340 Alcohol & Alcoholism Vol. 39, No. 4 Medical Council on Alcohol 2004; all rights reserved

2 ALCOHOL MARKERS AND INJURY 341 erythrocytes, serum gammaglutamyl transferase (GGT), aspartate aminotransferase (AST), and carbohydrate-deficient transferrin (CDT). Alcohol concentration (BAC) was determined either from breath air (BrAC) (n = 184) or from serum samples (BlAC) (n = 165). The amount and pattern of alcohol consumption was recorded by one of us (O.S.), blinded to the data on the biochemical markers of alcohol consumption and BAC. Interviews were carried out using a structured interview protocol during a follow-up visit within 6 weeks of injury. The history of alcohol consumption included the following information: how many drinks of alcohol (standard drink = 12 g ethyl alcohol corresponding to one beer, one glass of table wine or 4 cl 40% proof spirit) the patient had consumed during (1) 24 h, and (2) 1 week preceding injury. Daily alcohol consumption during the period 1 year prior to the trauma was assessed using time-line follow back (Sobell and Sobell, 1995). Based on the data, the patients were classified into groups as follows: dependent drinkers ( alcoholics ), binge drinkers, light-to-moderate drinkers and nondrinkers. The dependent drinkers were those who showed clinical evidence of pathological alcohol use, social impairment and tolerance/withdrawal. In these individuals, the daily alcohol consumption had exceeded a mean of 80 g. Binge drinking was defined as an ethanol intake of six or more (men) or four or more (women) standard drinks of alcohol in one session. Binge drinkers were further divided into two groups: frequent binge drinkers reported binge-type drinking more than once monthly. Infrequent binge drinkers reported binging 1 11 times per year. Light-to-moderate drinkers consumed one to two standard drinks per day either daily or less frequently. Nondrinkers had not drunk any alcohol during the year preceding the injury. They included both life-long abstainers and ex-drinkers. Dependent drinkers and frequent binge drinkers together made up the group referred to as hazardous drinkers. Laboratory procedures Venous blood samples were obtained immediately after admission and not later than 6 h after the trauma event, centrifuged and stored at 20 C until analysed for the various markers in an accredited (SFS-EN 45001, ISO/IEC Guide 25) clinical chemistry laboratory. MCV, GGT, AST and CDT were measured from every patient, with the exception of MCV, which was determined from 288 patients (83%). Blood alcohol concentrations were measured using a Vitros 250 clinical chemistry analyser (Johnson and Johnson, Rochester, NY). ALCO-SENSOR III (Intoximeters, St Louis, MO) was used for the breath analyses. Serum CDT was measured with a competitive radioimmunoassay after microcolumn separation (CDTect; AxisShield, Oslo, Norway). MCV, GGT and AST were measured using standard laboratory methods. In the analyses for the diagnostic characteristics of the markers, the following cut-off s were used: MCV (>96 fl for women and men), GGT (>50 U/l for women, >80 U/l for men), AST (>35 U/l for women, >50 U/l for men) and CDT (>26 U/l for women, >20 U/l for men). The costs of the different markers of alcohol consumption were also calculated. The costs of obtaining a blood sample, the assay procedure, labour work and overheads were included. Costs were expressed as US dollars. Statistical methods Sensitivities, specificities, positive and negative predictive values, and 95% confidence intervals (CI) of the different markers of alcohol consumption for detecting hazardous drinking were calculated by the exact method using the CIA statistical software for Windows. Odds ratios and 95% CI, Student s t-test, Mann Whitney U-test, and univariate associations of continuous variables were tested with Spearman s rank correlation coefficients (r s ) when appropriate and by using SPSS version 10.0 for Windows. RESULTS Clinical characteristics and causes of injury are shown in Table 1. Men and women were of the same age (31.3 ± 10 vs 30.8 ± 11 years, Student s t-test: P = 0.726). Eight per cent of the patients were classified as dependent drinkers, while 61% were frequent binge drinkers and 17% infrequent binge drinkers (Table 2). The group of light-to-moderate drinkers and nondrinkers represented 8 and 6% of the study population, respectively. Smoking was common among the dependent drinkers (81%) and the frequent binge drinkers (64%). Use of illicit drugs at the time of injury was verified in five patients, all of whom were frequent binge drinkers. Sex Men were frequent binge drinkers or dependent drinkers more often than women (OR 2.7, 95% CI ). In addition, men (72/252, 27%) were clinically strongly intoxicated more often than women (15/97, 15%) (OR 2.2, 95% CI ). In those patients who had alcohol in blood, men had higher concentrations than women (2.0 ± 1.0 vs 1.7 ± 0.8, Student s t-test: P < 0.05). Table 1. Clinical characteristics of the trauma patients Variable Total Men Women No. patients (72%) 97 (28%) Age, mean ± SD (years) 31 ± ± ± 11 Causes of injury: Traffic accident 79 (23%) 53 (21%) 26 (27%) Fall 83 (24%) 56 (22%) 27 (28%) Assault 54 (15%) 46 (18%) 8 (8%) Sport 22 (6%) 16 (7%) 6 (6%) Others 111 (32%) 81 (32%) 30 (31%) Injury Severity Score, 4 ± 4 (1 25) 4 ± 4 3 ± 3 mean ± SD (range) Operation room 44 (13%) 35 (14%) 9 (9%) surgery, n (%) Hospital stay >2 days, 74 (21%) 57 (23%) 17 (18%) n (%) Alcohol consumption, mean ± SD: During 24 h prior 96 ± ± ± 73 to injury (g) During 1 week prior 258 ± ± ± 154 to injury (g) During 1 year prior 27 ± ± ± 13 to injury (g/day)

3 342 O. SAVOLA et al. Table 2. Characteristics of the patients classified according to the history of alcohol consumption (n = 349) Clinically Consumption of alcohol BAC (mg/dl) on intoxicated during the preceding Patients Women Age (years) admission on admission year (g/day) mean ± Smoking n (%) n (%) mean ± SD mean ± SD n (%) SD, women/men n (%) Dependent drinkers 26 (8) 0 38 ± ± (77) 137 ± (81) Frequent binge drinkers 214 (61) 51 (24) 30 ± ± (58) 16 ± 15/27 ± (64) Infrequent binge drinkers 59 (17) 25 (42) 33 ± ± 70 5 (8) 6 ± 3/6 ± 6 15 (25) Light-to-moderate drinkers 28 (8) 14 (50) 31 ± 12 0 ± 10 1 (4) 2 ± 1/4 ± 4 5 (18) Nondrinkers 22 (6) 7 (32) 30 ± /0 6 (27) BAC, blood alcohol concentration (100 mg/dl = 22 mmol/l). Data from hospital record; men only. Table 3. Spearman s rank correlation coefficients between reported consumption of alcohol and laboratory markers (n = 349) Reported alcohol consumption BAC GGT MCV CDT AST Preceding 24 h Preceding week Preceding year P < Table 4. Percentages of trauma patients showing alcohol in blood and positiveness of biochemical markers suggesting alcohol use (n = 349) Sensitivity mg/dl BAC >0 mg/dl BAC 100 mg/dl BAC 150 mg/dl BAC 200 +ve GGT +ve MCV +ve CDT +ve AST Dependent drinkers Frequent binge drinkers Infrequent binge drinkers Light-to-moderate drinkers Non-drinkers Cut-off values: AST (50/35 U/l, men/women); CDT (20/26 U/l, men/women); GGT (80/50 U/l, men/women); MCV (96 fl, men and women). MCV was measured from 288 (83%) of the interviewed patients (n = 349). BAC, blood alcohol concentration (100 mg/dl = 22 mmol/l). Table 3 summarizes Spearman s rank correlation coefficients between self-reported alcohol consumption at different time periods prior to sampling and laboratory marker values. BAC, as measured either from breath air (BrAC) or serum (BlAC) at admission, correlated with reported alcohol intake at each of the three time periods more strongly than any of the other markers. BAC correlated strongly not only with acute drinking as would be expected, but also with both recent drinking (preceding week) and chronic drinking (past year). The relationships between markers and pattern of drinking are shown in Table 4. BAC, even at several different cut-off points, appeared to be the most sensitive indicator of hazardous drinking. Altogether 81% of dependent drinkers, 66% of frequent binge drinkers, and 10% of infrequent binge drinkers were BAC-positive on admission. Among the binge drinkers, the proportion of BAC-positive patients decreased sharply with increasing BAC cut-offs, whereas 58% of the dependent drinkers were at or above the cut-off level of 200 mg/dl. GGT, MCV, CDT and AST showed sensitivities of 42, 22, 46 and 42% among the dependent drinkers, respectively. The sensitivities for the frequent binge drinkers were 16, 18, 32 and 14%, respectively. These markers were also positive for some of the light-to-moderate drinkers and even abstainers. The sensitivities, specificities and positive and negative predictive values of the different alcohol markers for detecting hazardous alcohol drinking (including dependent drinkers and frequent binge drinkers) are shown in Table 5. Taken together, 240 (69%) of the consecutive trauma patients reported hazardous alcohol drinking. Of these, 137 (57%) had BAC (blood/breath alcohol) above 100 mg/dl. When a cut-off of >0 mg/dl was used, the sensitivity of identifying hazardous alcohol drinkers increased to 68% (95% CI, 61 73%) with a positive predictive value of 96% (95% CI, 92 98%). Thus, 96% of the BAC-positive trauma patients proved to be hazardous alcohol drinkers. We also studied the correlation between markers and alcohol intake separately for men and women. MCV, CDT and BAC correlated statistically significantly to the amount of alcohol consumed during the preceding year (Mann Whitney U-test: P < 0.01) both in men and women, but AST and GGT correlated more strongly with alcohol intake in men than in women. In the cost analyses of the various markers, measurement of alcohol from breath air was found to be the least expensive method for assessing hazardous drinking (Table 5). We further analysed the usefulness of various combinations of biochemical markers. BAC (>0 mg/dl) together with CDT was the most sensitive combination, which correctly identified 73% of the target population. However, even though both CDT and GGT slightly improved sensitivity when combined with BAC, the additional effect did not reach significance.

4 ALCOHOL MARKERS AND INJURY 343 Table 5. Sensitivities, specificities, positive predictive values (PPV), negative predictive values (NPV), and costs of the different markers of alcohol consumption for detecting hazardous alcohol drinking (including dependent drinkers and frequent binge drinkers) in trauma patients (n = 349) Screening test Sensitivity Specificity PPV NPV Cost BAC >0 mg/dl, (95% CI) 68% (61 to 73%) 94% (87 to 97%) 96% (92 to 98%) 57% (49 to 64%) 0.56 /11.7 BAC >100 mg/dl 57% (51 to 63%) 94% (89 to 98%) 96% (91 to 98%) 50% (43 to 57%) GGT 11% (8 to 16%) 97% (92 to 99%) 90% (74 to 97%) 33% (28 to 39%) 2.3 MCV 18% (13 to 24%) 94% (88 to 98%) 88% (75 to 95%) 34% (28 to 40%) 3.0 CDT 33% (28 to 40%) 88% (81 to 93%) 86% (78 to 92%) 38% (32 to 44%) 11.5 AST 17% (13 to 22%) 94% (89 to 98%) 87% (74 to 94%) 34% (29 to 40%) 2.3 The calculations were performed between hazardous and non-hazardous drinkers: hazardous alcohol drinkers, frequent binge drinkers or alcohol dependent drinkers; non-hazardous alcohol drinkers, infrequent binge drinkers, light-to-moderate drinkers and non-drinkers. Cut-off values: AST (50/35 U/l, men/women); CDT (CDTect method) (20/26 U/l, men/women); GGT (80/50 U/l, men/women); MCV (96 fl, men and women). BAC, blood alcohol concentration (100 mg/dl = 22 mmol/l). Cost per one measurement as US dollars (USD): cost per one measurement from breath air; cost per one measurement from blood sample. MCV was measured from 288 (83) of the interviewed patients (n = 349). DISCUSSION BAC was the most accurate marker of hazardous alcohol drinking in trauma patients. Ninety-six per cent of the BACpositive trauma patients reported hazardous alcohol drinking. BAC was more sensitive and specific than the conventional biochemical markers of alcohol misuse. Therefore, BAC measurements should be systematically included in the assessment of trauma patients and used as a basis to guide patients to alcohol interventions at trauma centre. Binge-type drinking was the most common pattern of hazardous drinking (61%) among trauma patients, whereas chronic heavy drinking appeared to be less frequent (8%). These findings are consistent with the view that the harm caused by alcohol is not restricted to those who are dependent drinkers (Lieber, 1995; Niemelä, 2002; Naimi et al., 2003). Growing evidence is currently available to indicate that adverse social, health and economic consequences of periodic heavy drinking exceed those of the chronic effects (Chikritzhs et al., 2001; Goldberg, 2002). Although the latter may be responsible for most deaths, acute alcohol-related accidents may account for the greatest proportion of years of life lost (Chikritzhs et al., 2001). Early detection of binge-type drinking should therefore be emphasized, since possible interventions are expected to benefit especially those who are not yet dependent drinkers, but at the beginning of a path towards alcoholism. However, there continues to be a lack of attention in trauma centres to the patients who are hazardous drinkers (Soderstrom and Cowley, 1987; Charalambous, 2002). Patients with alcohol problems tend to remain without specific treatment, although a positive effect of brief alcohol intervention in reducing alcohol intake and its adverse consequences, such as readmissions due to trauma, has been found in several studies (Antti-Poika et al., 1988; Walsh et al., 1991; Maheswaran et al., 1992; Fleming et al., 1997; Dinh-Zarr et al., 1999; Gentilello et al., 1999; Longabaugh et al., 2001). This might be due to the lack of practical tools for identifying the target groups. Thus, a simple and inexpensive method for detecting hazardous drinkers would be of utmost importance. The occurrence of different drinking patterns in trauma patients has so far been poorly investigated. The methods used to detect alcohol misuse previously have varied greatly, and the incidences of hazardous drinking have therefore also varied from 10 to 66% (Peppiatt et al., 1978; Brismar et al., 1983; Rivara et al., 1993; Corrigan, 1995; Dikmen et al., 1995; McLeod et al., 1999; Ryb et al., 1999). The identification of alcohol misuse can be based on clinical history, specific questionnaires, and laboratory markers (Ewing, 1984; Skinner et al., 1986; Davis et al., 1987; Ross et al., 1990; Nilssen et al., 1994). Questionnaires may be fairly sensitive and specific (Bernadt et al., 1982), but their realistic use among trauma patients is limited because they require time and full cooperation by the patient. Previous studies on various laboratory markers have concentrated primarily on dependent drinkers (Bernadt et al., 1982; Mihas and Tavassoli, 1992; Hartz et al., 1997). However, laboratory markers could be helpful compared to questionnaires, because many of the trauma patients are having blood taken anyway, and no extra procedure needs to be carried out (Huntley et al., 2001). The reported sensitivities have varied within 30 62% for GGT and AST, 30 40% for MCV and 83 90% for CDT (Bernadt et al., 1982; Mihas and Tavassoli, 1992; Niemelä, 2002). Nilssen et al. (1994) found elevated GGT in 21% of men and 15% of women with trauma, but elevated MCV in only 5%. Rivara et al. (1993) found increased GGT in 28% of intoxicated trauma patients and in 11% of nonintoxicated patients. Ryb et al. (1999) concluded that BAC is the best detector of alcohol dependence in trauma patients and that GGT, AST and MCV have little value as screening tests. Yates et al. (1987) reported that questionnaires were better than conventional biochemical markers to identify problem drinkers in the emergency department. In our study, the conventional biochemical markers (GGT, MCV, CDT and AST) were all found to lack sensitivity and specificity, especially for detecting binge drinkers. Interestingly, the specificity of CDT in this study was also markedly lower than that found in previous studies. It should be noted, however, that previous studies have usually contrasted teetotalers and alcoholics with severe dependence. The specificity of CDT (when analysed with the CDTect method) may also be poor in patients showing elevations in serum total transferrin levels, which may occur, for example, in patients with iron deficiency. However, it should be noted that, at this time, underreporting of alcohol consumption cannot be ruled out in individual patients. Combinations of various laboratory tests did not offer any additional benefit for this purpose, possibly due to a variety of sources causing unspecificity in these assays (Niemelä, 2002). Instead, BAC on admission was found to be a sensitive (68%) and specific (94%) marker of all types of hazardous alcohol use,

5 344 O. SAVOLA et al. including binge drinking and chronic alcoholism. Ninety-six per cent of all BAC-positive trauma patients turned out to be hazardous alcohol drinkers. Although false-positive findings may occur, our data suggest that they are rare. Therefore, those who guide all BAC-positive trauma patients towards an alcohol intervention will seldom be subjecting people to an unacceptable degree of stigma as problem drinkers. Indeed, due to the high sensitivity, specificity and positive predictive value and the relatively low costs of analysis, BAC can be recommended as a primary screening tool to guide patients towards an alcohol intervention before severe dependency develops. Here we focused on young adults and working-age individuals because the highest rates of morbidity, mortality and persistent functional and psychological impairment due to trauma are known to occur in this group (Soderstrom and Cowley, 1987; Kraus, 1993; Levin, 1993). Therefore, our findings cannot be generalized to all age groups. The drinking habits of adolescents and elderly people may differ from those observed here. An obvious limitation of the BAC test is that it does not detect hazardous drinkers who are not drinking prior to admission. Although false-positive findings may also be expected to occur, our data suggest that such findings are rare in trauma clinics. It should also be noted that this was a mixed-sex study and that there may be differences in the characteristics of biochemical markers of alcohol intake between men and women (Anton and Moak, 1998; Sillanaukee, et al., 1998; Wetterling et al., 1998; Tønnesen et al., 1999; Conigrave et al., 2002). However, we believe this does not change our main result, because BAC was found to be the best indicator of alcohol intake also when men and women were analyzed separately. 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