The Journal of Emergency Medicine, Vol. 9. pp. 307-311,1991
Printed in the USA. Copyright 0 1991 Pergamon Press plc
RATE OF CLEARANCE OF ETHANOL FROM THE BLOOD OF INTOXICATED PATIENTS IN THE EMERGENCY DEPARTMENT Howard Gershman,
MD, PhD,
and Jennifer Steeper,
MD
Department of Emergency Medicine, Mt. Sinai Medical Center, One Mt. Sinai Drive, University Circle, Cleveland, Ohio Reprint address: Howard Gershman, MD, MetroHealth Medical Clsnter, Department of Emergency Medicine, 3395 Scranton Rd., Cleveland. OH 44109
uation of possible head trauma can be complicated considerably by the presence of elevated blood ethanol that can render mental status and neurological examinations unreliable. In addition, psychiatric examinations may not be legally valid in a patient with an elevated blood ethanol level. The emergency department physician evaluating intoxicated, patients is often obligated to wait for serum ethanol levels to fall sufficiently to allow an accurate neurologic or psychiatric evaluation. An accurate prediction of the rate of clearance of ethanol from blood would greatly aid this process. The studies presented in this report are an attempt to derive a mean rate of ethanol clearance in an unselected population of intoxicated patients presenting to an innercity ED. We also attempted to establish whether or not demographic data (age, race, sex) or serum levels of liver or pancreatic enzymes or bilirubin were correlated with rates of clearance in such a way as to allow prediction of clearance rates.
IJ Abstract - One hundred and three patients presenting to the Mt. Siii Medical Center emergency department (ED), who appeared on clinical grounds to be acutely intoxicated, were studied to determine the rate of clearance of ethanol from blood. The mean presenting serum ethanol level was 299 mg/dL. The rate of clearance was found to be 20.43 mg/dL/b with a standard deviation of 6.86 mg/dL/h. No correlation was found between rate of ethanol clearance and serum levels of amylase, alkaline phosphatase, glutamate-oxaloacetate or glutamate-pyru vate transaminase, lactic dehydrogenase, or total bilirubin. Similarly, no correlation was found between rate of clearance and race, sex, age, or time of day. We conclude that although the average patient presenting to the emergency department will clear ethanol at about 20 mg/dL/h, a standard deviation of 6 mg/dL/h means that only 83% of these patients will have clearance rates between 8 and 32 mg/dL/b, and that if accurate estimates are necessary, serial determinations of two or more levels are needed.
?? Keywords - ethanol intoxication; ethanol clearance; ethanol metabolism
INTRODUCTION
METHODS
It is well-established that there is an association between ethanol intoxication and trauma (l-3). The eval-
All patients presenting to the Medical Center emergency department (ED) between October 1986 and July 1987 during ED shifts when the authors and several other participants were present, and who appeared by clinical criteria to be intoxicated, were entered into the study, provided they did not meet exclusion criteria.
Dr. Steeper’s current address is Kern Valley Hospital District, 6412 Laurel Ave., P.O. Box 1628, Lake Isabella, CA 93240-1628.
=
Original Contributions presents articles of interest to both academic and practicing physicians.
-
is coordinated
RECEIVED: 25 ACCEPTED: 12
This section of JEM
by John A. Marx, MD, of Denver General Hospital.
June 1990; FINALSUBMISSIONRECEIVED: 16 November 1990; December 1990 8’07
0736-4679/91 $3.00 + .OO
308
Howard Gershman
The exclusion criteria were 1) an initial blood ethanol level 30 20 “increased” 24.7 49.4 24.9
10 10 10
13.6 13.8 18.5
10
23.8
11
22.6*
11
25.7’
14 15 15 16 16
17.9 19.5 19.79 21 .o 20.0*
Patient population nonalcoholics alcoholics nonalcoholics alcoholics nonalcoholics alcoholics alcoholics with jaundice alcoholics nonalcoholics alcoholics, one month drinking nonalcoholics, one month drinking single volunteer, not drinking single volunteer, 2 weeks drinking unspecifiedt nonalcoholics nonalcoholics alcoholics nonalcoholics
‘Calculated from published clearance curves or tables. tHospitalized for ethanol toxicity.
310
Howard Gershman and Jennifer Steeper
(12-14). The study of Bogusz and colleagues (14) is probably the most applicable to an ED patient population, but is difficult to interpret because the authors found a nonlinear clearance, which is not in agreement with the rest of the literature. The patients in this study also are not an unselected population, but rather only those intoxicated patients requiring hospitalization. In addition, once hospitalized they were treated with intravenous fluids and gastric lavage. Therefore, it is not clear that the rates of clearance obtained from these 28 patients can be used to predict clearance in an unselected population of patients presenting to an innercity ED. The rate of clearance we determined for this population, about 20 mg/dL/h, agrees with the rates cited in original literature (Table 1, references 9-l 1,14-16) as well as in the emergency medicine textbooks (Tintinalli [5] and McMicken [4]) for nonalcoholics. This might mean that the patients in our study were not chronic drinkers. An alternative explanation is that rates of clearance of chronic and nonchronic drinkers are similar. On a practical level, whether the patients in our study were chronic or nonchronic drinkers, they represent an unselected innercity population of patients presenting to the ED with ethanol intoxication and an associated problem such as head trauma, seizure disorder, or organic brain syndrome, and whose mental status examination is rendered equivocal by the presence of ethanol. For example, in our study population, 28% presented with head trauma, 5% with seizures, 17% with other trauma, and 6% with psychiatric illness (Table 1). All of these patients required an evaluation of their mental status. Several studies have attempted to establish either a positive or negative correlation between liver function and rate of ethanol clearance, with variable results. Some of these results are tabulated in Table 2. Theoretically, chronic ethanol use could induce the MEOS component twofold to threefold, while advanced alcoholic liver disease might reduce clearance rates secondary to loss of functional hepatocytes. The studies of Kater and colleagues (9), for example, suggest that chronic alcoholics may clear ethanol up to twice as rapidly as nondrinkers (49.4 & 9.5 and 24.7 ? 10.2 mg/dL/h, respectively). In the same study, alcoholics with advanced liver disease, as evidenced by elevated bilirubin levels, had clearance rates of 24.9 ? 9.3 mgl
dL/h, virtually identical to that of the nondrinkers. In contrast, Keiding and colleagues found no difference between clearance in nonalcoholics and alcoholics without liver disease (16.1 and 15.4 mg/dL/h, respectively). The patients in this study had mildly elevated transaminases, but no elevated bilirubin levels, suggesting relatively normal hepatic function. Analysis of those with elevated AST, ALT, or bilirubin levels, however, did not show either a positive or a negative correlation with clearance rate. This suggests that impairment of hepatic function or biliary function is not correlated with ethanol clearance, or, alternatively, that AST, ALT, or bilirubin levels are not sensitive measures of hepatic or biliary function. In either case, measurements of these levels did not allow us to predict the rate of ethanol clearance. We believe that the patients in this study are an unselected intoxicated innercity population. While it is not known if these patients were alcoholics, patients such as these are often identified in the ED as chronic drinkers on the basis of their clinical presentation, andconsequently an accelerated clearance rate for these patients is often assumed. Based on the data presented here, we suggest that a clearance rate of 20 mg/dL/h should be applied to these patients, rather than assuming a more rapid rate of clearance on the basis of presumed alcoholism. CONCLUSIONS We have determined the rate of ethanol clearance in an intoxicated unselected population presenting to an innercity ED to be 20.43 f 6.86 mg/dL/h. While 20 mg/dL/h is a reproducible mean value, the ED physician should also keep in mind that the variation in clearance rates is considerable (standard deviation of 6.86 mg/dL/h in our study) and that only 68.26% of the population will have clearances between 13.57 and 27.29 mg/dL/h. Therefore, if an accurate prediction of the rate of clearance is required, it will be necessary to draw a second ethanol level after several hours have elapsed. We also find no justification for the measurement of liver, pancreatic, or biliary function tests as a predictor of ethanol clearance in these patients. Dedication - Dedicated to Robert Abeles on the occasion of his 65th birthday.
REFERENCES 1. Lowenfels A, Miller T. Alcohol and trauma. Ann Emer Med. 1984;13:1056-60. 2. Roisen J. Alcohol and trauma. In: Geisbrecht J, Gonazles N,
Gonzales R, et al, eds. Drinking and casualties; accidents, poisonings and violence in an international perspective. London: Routledge; 1988:21-69.
Clearance of Ethanol in Intoxicated Patients
3. Jagger J, Fife D, Vemberg K, Jann JJ. Effect of alcohol intoxication on the diagnosis and apparent severity of brain injury. Neurosurg. 1984; 15:303-6. 4. McMicken DE. Alcohol-related disease. In: Rosen P, Baker FJ, Barkin RM, Braen GR, Dailey RI-I, Levy C. eds. Emergency medicine: concepts and clinical practice, 2nd ed. St. Louis: Mosby, 1988:2065-86. 5. Tintinalli JE. Alcohols. In: Tintinalli JE, Krome RL, Ruiz E, eds. Emergency medicine: a comprehensive study guide. 2nd ed. New York: McGraw-Hill, 1988:705-10. 6. Olsen KR, Becker CE. Poisoning. In: Mills JM, Ho T, Salber PR, Trunkey DD, eds. Current emergency diagnosis and treatment 2nd ed. Los Altos, California: Lange Medical Publications; 1989:451-82. 7. Schuckit MA. Peak blood alcohol levels in men at high risk for the future development of alcoholism. Alcoholism: Clin and Exp Res. 1972;5:64-6. 8. Keiding SN, Christiensen NJ, Damgaard SE, et al. Ethanol metabolism in heavy drinkers after massive and moderate alcohol intake. Biochem Pharmacol. 1983;32:3097-102. 9. Kater RMH, Carulli N, Iber FL. Difference in the rate of ethanol metabolism in recently drinking alcoholic and non-drinking subjects. Am J Clin Nutr. 1969;22:1608-17.
311
10. Misra PS, Lefevre A, Ishii H, Rubin E, Lieber CS. Increase of ethanol, meprobamate and pentobarbital metabolism after chronic ethanol administration in man and in rats. Am J Med. 1971;5 1: 347-5 1. 11. Salaspuro MP, Lieber CS. Non-uniformity of blood ethanol elimination; its exaggeration after chronic consumption. Ann Clin Res. 1976;10:294-7. 12. Hammond KB, Rumack BH, Rodgerson DO. Blood ethanol: a report of unusually high levels in a living patient. JAMA. 1973;226:63-4. 13. O’Neill S, Tipton KF, Prichard JS, Quinlan A. Survival after high blood alcohol levels: association with first-order elimination kinetics. Arch Int Med. 1984;144:641-2. 14. Bogusz M, Path J, Stasko W. Comparative studies on the rate of ethanol elimination in acute poisoning and in controlled conditions. J Forensic Sci. 1977;22:44&51. 15. Nagoshi CT, Wilson JR. Long-term repeatability of human alcohol metabolism, sensitivity and acute tolerance. J Stud Alcohol. 1989;50:162-9. 16. Adachi J, Mizoi Y, Fukunaga T, Ogawa Y, Imamichi H. Comparative study on ethanol elimination and blood acetaldehyde between alcoholics and control subjects. Alcoholism; Clin Exp Res. 1989;13:601+.
Printed in the USA. Copyright 0 1991 Pergamon Press plc
RATE OF CLEARANCE OF ETHANOL FROM THE BLOOD OF INTOXICATED PATIENTS IN THE EMERGENCY DEPARTMENT Howard Gershman,
MD, PhD,
and Jennifer Steeper,
MD
Department of Emergency Medicine, Mt. Sinai Medical Center, One Mt. Sinai Drive, University Circle, Cleveland, Ohio Reprint address: Howard Gershman, MD, MetroHealth Medical Clsnter, Department of Emergency Medicine, 3395 Scranton Rd., Cleveland. OH 44109
uation of possible head trauma can be complicated considerably by the presence of elevated blood ethanol that can render mental status and neurological examinations unreliable. In addition, psychiatric examinations may not be legally valid in a patient with an elevated blood ethanol level. The emergency department physician evaluating intoxicated, patients is often obligated to wait for serum ethanol levels to fall sufficiently to allow an accurate neurologic or psychiatric evaluation. An accurate prediction of the rate of clearance of ethanol from blood would greatly aid this process. The studies presented in this report are an attempt to derive a mean rate of ethanol clearance in an unselected population of intoxicated patients presenting to an innercity ED. We also attempted to establish whether or not demographic data (age, race, sex) or serum levels of liver or pancreatic enzymes or bilirubin were correlated with rates of clearance in such a way as to allow prediction of clearance rates.
IJ Abstract - One hundred and three patients presenting to the Mt. Siii Medical Center emergency department (ED), who appeared on clinical grounds to be acutely intoxicated, were studied to determine the rate of clearance of ethanol from blood. The mean presenting serum ethanol level was 299 mg/dL. The rate of clearance was found to be 20.43 mg/dL/b with a standard deviation of 6.86 mg/dL/h. No correlation was found between rate of ethanol clearance and serum levels of amylase, alkaline phosphatase, glutamate-oxaloacetate or glutamate-pyru vate transaminase, lactic dehydrogenase, or total bilirubin. Similarly, no correlation was found between rate of clearance and race, sex, age, or time of day. We conclude that although the average patient presenting to the emergency department will clear ethanol at about 20 mg/dL/h, a standard deviation of 6 mg/dL/h means that only 83% of these patients will have clearance rates between 8 and 32 mg/dL/b, and that if accurate estimates are necessary, serial determinations of two or more levels are needed.
?? Keywords - ethanol intoxication; ethanol clearance; ethanol metabolism
INTRODUCTION
METHODS
It is well-established that there is an association between ethanol intoxication and trauma (l-3). The eval-
All patients presenting to the Medical Center emergency department (ED) between October 1986 and July 1987 during ED shifts when the authors and several other participants were present, and who appeared by clinical criteria to be intoxicated, were entered into the study, provided they did not meet exclusion criteria.
Dr. Steeper’s current address is Kern Valley Hospital District, 6412 Laurel Ave., P.O. Box 1628, Lake Isabella, CA 93240-1628.
=
Original Contributions presents articles of interest to both academic and practicing physicians.
-
is coordinated
RECEIVED: 25 ACCEPTED: 12
This section of JEM
by John A. Marx, MD, of Denver General Hospital.
June 1990; FINALSUBMISSIONRECEIVED: 16 November 1990; December 1990 8’07
0736-4679/91 $3.00 + .OO
308
Howard Gershman
The exclusion criteria were 1) an initial blood ethanol level 30 20 “increased” 24.7 49.4 24.9
10 10 10
13.6 13.8 18.5
10
23.8
11
22.6*
11
25.7’
14 15 15 16 16
17.9 19.5 19.79 21 .o 20.0*
Patient population nonalcoholics alcoholics nonalcoholics alcoholics nonalcoholics alcoholics alcoholics with jaundice alcoholics nonalcoholics alcoholics, one month drinking nonalcoholics, one month drinking single volunteer, not drinking single volunteer, 2 weeks drinking unspecifiedt nonalcoholics nonalcoholics alcoholics nonalcoholics
‘Calculated from published clearance curves or tables. tHospitalized for ethanol toxicity.
310
Howard Gershman and Jennifer Steeper
(12-14). The study of Bogusz and colleagues (14) is probably the most applicable to an ED patient population, but is difficult to interpret because the authors found a nonlinear clearance, which is not in agreement with the rest of the literature. The patients in this study also are not an unselected population, but rather only those intoxicated patients requiring hospitalization. In addition, once hospitalized they were treated with intravenous fluids and gastric lavage. Therefore, it is not clear that the rates of clearance obtained from these 28 patients can be used to predict clearance in an unselected population of patients presenting to an innercity ED. The rate of clearance we determined for this population, about 20 mg/dL/h, agrees with the rates cited in original literature (Table 1, references 9-l 1,14-16) as well as in the emergency medicine textbooks (Tintinalli [5] and McMicken [4]) for nonalcoholics. This might mean that the patients in our study were not chronic drinkers. An alternative explanation is that rates of clearance of chronic and nonchronic drinkers are similar. On a practical level, whether the patients in our study were chronic or nonchronic drinkers, they represent an unselected innercity population of patients presenting to the ED with ethanol intoxication and an associated problem such as head trauma, seizure disorder, or organic brain syndrome, and whose mental status examination is rendered equivocal by the presence of ethanol. For example, in our study population, 28% presented with head trauma, 5% with seizures, 17% with other trauma, and 6% with psychiatric illness (Table 1). All of these patients required an evaluation of their mental status. Several studies have attempted to establish either a positive or negative correlation between liver function and rate of ethanol clearance, with variable results. Some of these results are tabulated in Table 2. Theoretically, chronic ethanol use could induce the MEOS component twofold to threefold, while advanced alcoholic liver disease might reduce clearance rates secondary to loss of functional hepatocytes. The studies of Kater and colleagues (9), for example, suggest that chronic alcoholics may clear ethanol up to twice as rapidly as nondrinkers (49.4 & 9.5 and 24.7 ? 10.2 mg/dL/h, respectively). In the same study, alcoholics with advanced liver disease, as evidenced by elevated bilirubin levels, had clearance rates of 24.9 ? 9.3 mgl
dL/h, virtually identical to that of the nondrinkers. In contrast, Keiding and colleagues found no difference between clearance in nonalcoholics and alcoholics without liver disease (16.1 and 15.4 mg/dL/h, respectively). The patients in this study had mildly elevated transaminases, but no elevated bilirubin levels, suggesting relatively normal hepatic function. Analysis of those with elevated AST, ALT, or bilirubin levels, however, did not show either a positive or a negative correlation with clearance rate. This suggests that impairment of hepatic function or biliary function is not correlated with ethanol clearance, or, alternatively, that AST, ALT, or bilirubin levels are not sensitive measures of hepatic or biliary function. In either case, measurements of these levels did not allow us to predict the rate of ethanol clearance. We believe that the patients in this study are an unselected intoxicated innercity population. While it is not known if these patients were alcoholics, patients such as these are often identified in the ED as chronic drinkers on the basis of their clinical presentation, andconsequently an accelerated clearance rate for these patients is often assumed. Based on the data presented here, we suggest that a clearance rate of 20 mg/dL/h should be applied to these patients, rather than assuming a more rapid rate of clearance on the basis of presumed alcoholism. CONCLUSIONS We have determined the rate of ethanol clearance in an intoxicated unselected population presenting to an innercity ED to be 20.43 f 6.86 mg/dL/h. While 20 mg/dL/h is a reproducible mean value, the ED physician should also keep in mind that the variation in clearance rates is considerable (standard deviation of 6.86 mg/dL/h in our study) and that only 68.26% of the population will have clearances between 13.57 and 27.29 mg/dL/h. Therefore, if an accurate prediction of the rate of clearance is required, it will be necessary to draw a second ethanol level after several hours have elapsed. We also find no justification for the measurement of liver, pancreatic, or biliary function tests as a predictor of ethanol clearance in these patients. Dedication - Dedicated to Robert Abeles on the occasion of his 65th birthday.
REFERENCES 1. Lowenfels A, Miller T. Alcohol and trauma. Ann Emer Med. 1984;13:1056-60. 2. Roisen J. Alcohol and trauma. In: Geisbrecht J, Gonazles N,
Gonzales R, et al, eds. Drinking and casualties; accidents, poisonings and violence in an international perspective. London: Routledge; 1988:21-69.
Clearance of Ethanol in Intoxicated Patients
3. Jagger J, Fife D, Vemberg K, Jann JJ. Effect of alcohol intoxication on the diagnosis and apparent severity of brain injury. Neurosurg. 1984; 15:303-6. 4. McMicken DE. Alcohol-related disease. In: Rosen P, Baker FJ, Barkin RM, Braen GR, Dailey RI-I, Levy C. eds. Emergency medicine: concepts and clinical practice, 2nd ed. St. Louis: Mosby, 1988:2065-86. 5. Tintinalli JE. Alcohols. In: Tintinalli JE, Krome RL, Ruiz E, eds. Emergency medicine: a comprehensive study guide. 2nd ed. New York: McGraw-Hill, 1988:705-10. 6. Olsen KR, Becker CE. Poisoning. In: Mills JM, Ho T, Salber PR, Trunkey DD, eds. Current emergency diagnosis and treatment 2nd ed. Los Altos, California: Lange Medical Publications; 1989:451-82. 7. Schuckit MA. Peak blood alcohol levels in men at high risk for the future development of alcoholism. Alcoholism: Clin and Exp Res. 1972;5:64-6. 8. Keiding SN, Christiensen NJ, Damgaard SE, et al. Ethanol metabolism in heavy drinkers after massive and moderate alcohol intake. Biochem Pharmacol. 1983;32:3097-102. 9. Kater RMH, Carulli N, Iber FL. Difference in the rate of ethanol metabolism in recently drinking alcoholic and non-drinking subjects. Am J Clin Nutr. 1969;22:1608-17.
311
10. Misra PS, Lefevre A, Ishii H, Rubin E, Lieber CS. Increase of ethanol, meprobamate and pentobarbital metabolism after chronic ethanol administration in man and in rats. Am J Med. 1971;5 1: 347-5 1. 11. Salaspuro MP, Lieber CS. Non-uniformity of blood ethanol elimination; its exaggeration after chronic consumption. Ann Clin Res. 1976;10:294-7. 12. Hammond KB, Rumack BH, Rodgerson DO. Blood ethanol: a report of unusually high levels in a living patient. JAMA. 1973;226:63-4. 13. O’Neill S, Tipton KF, Prichard JS, Quinlan A. Survival after high blood alcohol levels: association with first-order elimination kinetics. Arch Int Med. 1984;144:641-2. 14. Bogusz M, Path J, Stasko W. Comparative studies on the rate of ethanol elimination in acute poisoning and in controlled conditions. J Forensic Sci. 1977;22:44&51. 15. Nagoshi CT, Wilson JR. Long-term repeatability of human alcohol metabolism, sensitivity and acute tolerance. J Stud Alcohol. 1989;50:162-9. 16. Adachi J, Mizoi Y, Fukunaga T, Ogawa Y, Imamichi H. Comparative study on ethanol elimination and blood acetaldehyde between alcoholics and control subjects. Alcoholism; Clin Exp Res. 1989;13:601+.
