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ARTICLE
Does Ethanol Explain the Acidosis Commonly Seen inEthanol-Intoxicated Patients?
Shahriar Zehtabchi, M.D., Richard Sinert, D.O., Bonny J. Baron, M.D.,Lorenzo Paladino, M.D., and Kabir Yadav, M.D.
Department of Emergency Medicine, Downstate Medical Center/Kings County Hospital Center,
State University of New York, Brooklyn, New York, USA
Objective. Emergency physicians frequently treat ethanol-intoxicated trauma patients. In patients with apparently minorinjuries, the presence of metabolic acidosis is often attributed toserum ethanol. We tested whether there is justification for thebias that ethanol reliably explains the acidosis commonly seen inalcohol-intoxicated patients. Methods. Prospective, observa-tional. Inclusion criteria: Ethanol-intoxicated patients admittedto the emergency department (ED) following significant traumamechanisms, in whom diagnostic evaluation revealed only minorinjury. Exclusion criteria: Major trauma (blood transfusions,drop in Hct >10 points over 24 h, or Injury Severity Score [ISS]>5) or positive urine toxicology screen. Definitions: EthanolIntoxication: (Blood Alcohol Level (BAL) �80 mg/dl), Acidosis:BD ��3.0 mMol/L; Lactic Acidosis (LAC >2.2 mMol/L). Datawere reported as mean±SD. Data were compared by t-tests orFishers exact test as appropriate (a=0.05, 2 tails) and correlationsby Pearson correlation coefficient. Results. 192 patients werestudied (84% male) with a mean age of 31.7±15.6 years. Acidosiswas observed in 19.3% (CI 95%, 14.5% to 25.0%) of all studypatients. We observed significant (p < 0.001) difference inprevalence of acidosis in ethanol intoxicated (42%) compared tononintoxicated (1%) patients. Comparing the two study groups,patients with ethanol intoxication had lower BD (�2.24±2.74 vs.�0.05±2.35, p<0.001) and higher LAC (2.69±1.48 vs. 2.00±1.78,p=0.02). However, ethanol levels did not correlate significantlywith BD (p= 0.50) or LAC (p=0.14). Conclusion. Ethanolintoxication is associated with acidosis, which does not correlatewith BD or LAC. The complexity of pathogenesis of acidosis inethanol intoxication justifies further diagnostic evaluation ofthese patients in order to rule out other causes of acidosis.
Keywords Ethanol; Lactic acidosis; Injuries; Toxins; Cocaine
INTRODUCTION
Approximately 100,000 alcohol-related deaths are reported
each year (1,2). Ethanol consumption is a major risk factor for
various types of injuries including motor vehicle crashes,
pedestrians struck, cycle injuries, falls, burns, drowning,
suicides, and assaults (2–4). Nearly 50% of trauma patients
have used alcohol prior to their injury (5) and more than half
of fatal motor vehicle crashes are alcohol related (6).
Ethanol-intoxicated patients present to the emergency
department (ED) with a spectrum of conditions ranging from
simple intoxication to complex medical or traumatic illnesses.
ED physicians are faced with the challenge of identifying
potentially life-threatening illnesses in uncooperative, intox-
icated patients with unreliable histories and physical exams.
Adjunctive laboratory tests may provide the only early clue as
to the patient’s degree of illness. These tests may, however,
further confuse an already complicated clinical picture.
Metabolic derangements may reflect illness or injury, or they
may be secondary to alcohol or illicit drugs.
Acid-base disturbances are commonly found in ethanol
intoxicated patients. Lamminpaa et al. documented abnor-
malities in acid-base equilibrium in 49% of 192 adult
alcoholic ED patients (7). Since mild to moderate acidosis
is so commonly seen in the ethanol-intoxicated patient, the
ED physician’s bias is often to ascribe a low base deficit
level to the direct effects of ethanol. This bias is not
completely unfounded since many published case series of
ethanol intoxicated patients have described a coexistent
metabolic acidosis (8,9). Prospective studies using both
healthy human volunteers (10,11) and animals (12,13) have
linked ethanol intake to the development of a metabol-
ic acidosis.
A difficult diagnostic question is whether the presence of
ethanol can completely account for the acidosis seen in
ethanol intoxicated patients. Previous studies which looked at
acidosis in acute and chronically ethanol-intoxicated patients
did not exclude coexisting medical or surgical problems and
Address correspondence to Shahriar Zehtabchi, M.D., Depart-ment of Emergency Medicine, Downstate Medical Center, StateUniversity of New York, Box: 1228, 450 Clarkson Ave., Brooklyn,NY 11203, USA; E-mail: [email protected]
161
Clinical Toxicology, 43:161–166, 2005
Copyright D Taylor & Francis Inc.
ISSN: 0731-3810 print / 1097-9875 online
DOI: 10.1081/CLT-200053083
Order reprints of this article at www.copyright.rightslink.com
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did not control for multiple intoxicants in addition to ethanol
(7–9). Healthy volunteers and animals have been used in
models of acute intoxication. Acute ethanol intoxication
combined with chronic ethanol intake, a pattern often seen
in ED patients, has not been extensively studied. In addition,
prospective studies utilizing human volunteers were limited by
ethical concerns which restricted the amount of ethanol
consumed, thus preventing analysis of a dose-response curve
of alcohol causing acidosis.
We designed a prospective study using ethanol-intoxicated
trauma patients who were diagnosed with only minor or no
injuries. After excluding patients with other co-intoxicants,
or additional known causes of acidosis, we attempted to
correlate ethanol level with degree of acidosis, in the
remaining patients. We hypothesized that a dose-response
curve could be produced to predict the expected acidosis for
any given level of ethanol. If ethanol levels could reliably
predict acidosis, then the ED physician could easily
determine if the acidosis in their intoxicated patient could
be attributed to ethanol alone or whether further diagnostic
workup was indicated.
METHODS
Study Design
Patients with significant mechanisms of blunt or pene-
trating trauma, who required laboratory analysis as part of
their diagnostic evaluation, were enrolled in the study. The
determination of significant trauma and the need for labo-
ratory evaluation was at the discretion of the emergency med-
icine attending physician in charge of the trauma resuscitation.
A convenience sample of trauma patients was enrolled by
emergency medicine residents and attendings.
The primary outcome variable was to investigate the
correlation of serum ethanol level with degree of metabolic
acidosis in ethanol-intoxicated trauma patients with only
minor injuries. The study was approved by the joint insti-
tutional review boards (IRB) of State University of New
York, Downstate Medical Center, and Kings County Hos-
pital Center. A policy of waived consent, which adhered
to the principle of implied consent, was approved by
the IRB.
Study Population and Setting
This study was conducted at Kings County Hospital Center
(KCHC) in Brooklyn, New York. KCHC is an urban, level one
trauma center. Data were collected from July 2002 to August
2003. Patients with blunt or penetrating trauma suspected of
having significant injury underwent diagnostic evaluation.
Patients found to have major injuries were excluded from the
data set. Significantly injured patients were excluded in order
to avoid any confounding effect of blood loss and tissue
ischemia on the metabolic acidosis caused by ethanol
intoxication. Patients with major injuries were defined as
those with any of the following: received blood transfusion,
drop in hematocrit (Hct) of greater than 10 points in the first
24 h, or injury severity score (ISS) >5. ISS �5 has previously
been used in the literature to define minor trauma (14). It is
associated with a mortality rate of less than 1% (15). Drop in
Hct and blood transfusions have also been used as indicators
of major trauma in previous studies (16).
Patients with positive urine toxicology (see Measurements)
were also excluded from the data set in order to rule out
additional exogenous causes of metabolic acidosis other
than ethanol.
Measurements
Age, gender, vital signs (systolic blood pressure, pulse
rate), mechanism of injury, and physical findings were
collected for all patients. Shortly after patients’ arrival to the
ED, blood samples were obtained for measurement of arterial
base deficit (BD), lactate (Radiometer ABL 725, Copenhagen,
Denmark), and serum ethanol level (AxSYM System, Abbott
Laboratories, IL). Urine toxicology screen (Utox) and serial
hematocrits were ordered for all the patients. In our institu-
tion urine toxicology screen is performed by using kinetic
interaction of microparticles in solution (KIMS) technique
(Roche Modular ISE1800 and D 2400) and detects the
following components: Opiates, Cannabinoids, Cocaine (Ben-
zoylecguanine), Benzodiazepines, Methadone, Barbiturates,
Methylqualone, Amphetamine, Phencyclidine, and Propoxy-
phene. The results of all diagnostic studies were recorded.
TABLE 1
Comparison of baseline predictor variables in ethanol-
intoxicated and nonintoxicated patients
Variable ETOH� ETOH+ p
n 147 45 –
BAL (mg/dl)+ 4±16 205±81
Age 31±17 34±13 0.31*
Gender (% male) 78 98 <0.001**
D Hematocrit (%) 2.19±2.76 2.97±2.75 0.09*
SBP$ (mmHg) 138±23 135±15 0.41*
Shock index
(HR/SBP)
0.65±0.18 0.72±0.13 0.01*
Lactate (mMol/L) 2±1.78 2.69±1.48 0.02*
Base deficit
(mMol/L)
�0.05±2.35 �2.24±2.74 <0.001*
+Blood alcohol level.
*Student’s t-test.
**Fisher’s exact test.$Systolic blood pressure.
S. ZEHTABCHI ET AL.162
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Units of transfused PRBCs and change in Hct over the initial
24 h were documented. ISS scores were calculated. Shock
Index was calculated by dividing the patients’ heart rate by
systolic blood pressure.
Ethanol Intoxication (ETOH+) was defined as blood
alcohol level �80 mg/dl, the legal definition for alcohol
intoxication in many states. Acidosis was determined by
analysis of BD. BD is defined by the amount of bicar-
bonate required to titrate a sample of blood to a pH of 7.40
with a PCO2 of 40 mmHg at 37�C (17). We chose a level
of BD ��3.0 mmol/L as the cutoff to define acidosis
based on previous studies of trauma patients (18). BD
��3.0 mmol/L is associated with an increase in serious
injury. A lactate level (LAC) >2.2 mmol/L was used to
define lactic acidosis, the cutoff value for normal lactate in
our laboratory.
Data Analysis
Data were reported as means±standard deviation. Student’s
t-tests or Fishers exact test were used for comparing the means
as appropriate. All tests were two-tailed, with a set at 0.05.
Pearson correlation coefficient was used for analysis of
covariants. Calculations were done using SPSS for Windows,
Rel. 11.0 1997. Chicago: SPSS Inc.
A sample size analysis was calculated assuming a
correlation between ETOH and BD of 0.40. This effect was
selected as the smallest effect that would be important to
detect, in the sense that any smaller effect would not be of
clinical significance. The criterion for significance (alpha) was
set at 0.050. The test was two-tailed, which means that an
effect in either direction would be interpreted. With the
proposed sample size of 44 ethanol-intoxicated patients, the
study would have power of 80.1% to yield a statistically
significant result. Sample size was calculated using Sample-
Power Re. 2.0. 2003, Chicago: SPSS Inc.
RESULTS
A total of 192 patients were enrolled. Study subjects
consisted of 156 males (81%) and 36 females (19%) with
mean age of 32±16 (range of 13 to 89 years old). Comparison
of baseline predictor variables in patients in two categories of
ethanol-intoxicated and nonintoxicated is presented in Table 1.
A total of 147 patients (77%) were classified as non-
intoxicated. Forty-five patients (23%) were ethanol-intoxicat-
ed with a mean BAL of 205±81 mg/dl. No significant
difference was observed between the intoxicated and non-
intoxicated groups when comparing age, systolic blood
pressure, and change in hematocrit over 24 h. A greater per-
centage of ethanol-intoxicated patients were male (p<0.001).
Although the mean shock index (heart rate divided by systolic
TABLE 2
Prevalence of ketonuria, low serum bicarbonate, increased anion gap, and elevated arterial lactate in
intoxicated vs. nonintoxicated patients
Ethanol+
P*
Ethanol�
P*BD<�3
mMol/L (n=19)
BD>�3
mMol/L (n=26)
BD<�3
mMol/L (n=14)
BD>�3
mMol/L (n=133)
Ketonuria 2 (10%) 1 (0.4%) 0.56 1 (0.7%) 15 (11%) 1.00
HCO3
<20 mMol/L
9 (47%) 3 (12%) 0.01 7 (50%) 8 (6%) <0.001
Anion gap >15 16 (89%) 11 (42%) 0.002 8 (54%) 37 (28%) 0.10
Lactate
>2.2 mMol/L
11 (58%) 8 (31%) 0.12 8 (54%) 17 (13%) 0.00
Ethanol+: Blood alcohol level �80 mg/dl.
*Fisher’s exact test.
FIG. 1. Scatterplot of serum ethanol level and arterial base deficit in
intoxicated patients.
163ACIDOSIS SEEN IN ETHANOL-INTOXICATED PATIENTS
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BP) was higher in the intoxicated group, there was no
difference (6.7% vs. 7.4%, p=1.00) in the percentage of
patients with an index greater than 0.9 in either group.
Comparing the two study groups, patients with ethanol
intoxication had lower BD (mean difference: 2.19 mMol/L,
95% CI, 1.37 to 3.01 mMol/L) and higher LAC (mean
difference: 0.69 mMol/L, 95% CI, 0.11 to 1.27 mMol/L).
We observed significant statistical difference (p<0.001) in
the prevalence of acidosis (BD ��3 mmol/L) when com-
paring intoxicated (42%) to nonintoxicated (1%) patients. Of
the 45 patients with ethanol intoxication, 19 (42%) were
acidotic. Among the intoxicated acidotic patients, anion gap
was elevated (AG �15) in 16 patients (84%) and arterial
lactate was elevated in 11 patients (58%). Prevalence of
ketonuria, low serum bicarbonate, high anion gap, and
elevated arterial lactate in intoxicated vs. nonintoxicated
patients are summarized in Table 2.
We tested the correlation (Pearson Correlation Analysis)
between the serum ethanol level, BD, and arterial lactate level
in the study subjects. We detected no significant (p=0.50)
correlation between BD and serum ethanol level in ethanol-
intoxicated patients (see Fig. 1). The correlation between
serum ethanol level and arterial lactate in ethanol-intoxicated
patients was also not statistically significant (p=0.14) (Fig. 2).
DISCUSSION
In our study, 42% of ethanol intoxicated patients (19/42)
had pure metabolic acidosis (BD ��3 mMol/L). This
association between ethanol consumption and metabolic
acidosis has been previously reported in several other studies.
Lamminpaa et al. (7), MacDonald et al. (14), and De Marchi
et al. (19) observed metabolic acidosis in 7.9%, 11.7%, and
33%, respectively, of ethanol-intoxicated patients treated in
their emergency departments. The difference in the prevalence
of metabolic acidosis can be explained by the various
definitions of acidosis used in each study. Lamminpaa (7)
used decreased pH (<7.35) and MacDonald (14) used lactate
level in excess of 2.4 mMol/L as the cutoff for defining
metabolic acidosis. De Marchi (19) compared means of serum
bicarbonate levels and arterial pH in intoxicated vs. non-
intoxicated patients. In our study, BD was used to identify
patients with metabolic acidosis. In contrast to pH, BD is not
affected by changes in PCO2. Changes in BD reflect multiple
causes of acidosis in addition to lactic acidosis.
In our study, although we observed a statistical difference
in BD between the ethanol-intoxicated and nonintoxicated
groups, this difference does not appear to be clinically
significant, as both means fall in the normal range. We also
did not detect a significant (p=0.50) correlation between
serum ethanol levels and arterial BD. Therefore, a dose-
response curve could not be generated between BD and BAL.
Dunham et al. (16) detected a significant but weak correlation
between BD and blood alcohol level (BAL). Unlike our study
population which only consisted of minor trauma patients,
Dunham’s analysis included both minor and major trauma.
Studying a group of hospitalized, acutely alcohol-intoxicated
patients, MacDonald et al. (14) found no significant
correlation (p=0.26) between serum lactate concentration
and BAL. Lamminpaa et al. studied the correlation between
BAL and metabolic acidosis in both ethanol-intoxicated adults
(7) and teenagers (20). Statistically significant correlation was
detected between the serum pH and BAL in adults (r=�0.45,
r2=0.20, p=0.0013) (7) but not in teenagers (r=�0.31,
p=0.16) (24). However, these studies included a significant
number of patients with respiratory acidosis secondary to
CNS depression from alcohol intoxication. In contrast to all
the studies mentioned previously, we specifically excluded
patients with major injuries or intoxications other than
ethanol in order to avoid additional potential causes of
metabolic acidosis.
The lack of correlation between ethanol and BD can be
explained by the complexity of the acid-base disturbances
induced by ethanol intoxication. Ethanol contributes to
metabolic acidosis by producing a high anion gap as well as
a non-anion gap acidosis (loss of bicarbonate in the urine)
(21–24). In our study 20% of acidotic ethanol-intoxicated
patients had a non-anion gap, and 80% had a high anion gap
metabolic acidosis. The high anion gap acidosis caused by
ethanol is due to increased production of lactic acid, aceto-
acetate, and beta hydroxybutyric acid (24–28). In addition, the
severity of acidosis in ethanol intoxication can be affected
by other acid-base disorders commonly observed in these
patients. Ethanol consumption can cause vomiting, resulting in
a metabolic alkalosis (29). Ethanol is capable of increasing the
respiratory rate (respiratory alkalosis) at low doses and
decreasing the respiratory rate (respiratory acidosis) at higher
FIG. 2. Scatterplot of serum ethanol level and arterial lactate in intoxicated
patients.
S. ZEHTABCHI ET AL.164
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doses (26,30). A study using rats given fixed doses of ethanol
intraperitoneally revealed that the degree of acidosis, reflected
by decreased arterial pH, was very variable (31). Study
investigators (Gilliam et al.) concluded that differences in
sensitivity to ethanol might be related to endogenous
variations in respiratory and cardiovascular regulatory mech-
anisms. Multiple mechanisms for production of acidosis,
combined with additional confounding factors such as chronic
consumption vs. acute intoxication make the occurrence and
severity of acidosis variable and unpredictable. In addition, the
rate of absorption and metabolism of ethanol varies in an
uncontrolled setting such as an emergency department and
provides another explanation for the poor correlation between
ethanol level and degree of acidosis. In a previous study (32),
we showed that ethanol intoxication did not affect the base
deficit and lactate even in patients with major trauma.
The contribution of lactate to the metabolic acidosis from
ethanol is controversial. Studies of normal volunteers have
shown a predictable rise in plasma lactate after ethanol
ingestion (24,33). However, other studies have reported that
clinically significant lactic acidosis is uncommon in ethanol
intoxicated patients (14,23). Lactate levels in excess of 2.4
mmol/L were associated with a significant increase in
mortality in critically ill patients (35,36). Investigators have
suggested that presence of severe lactic acidosis in ethanol
intoxicated patients warrants diagnostic work-up to investigate
other possible causes of increased lactate production such as
hypoxemia or hypoperfusion (34,35), thiamine deficiency
(36), seizure (37), renal dysfunction (38), sepsis (38–40), and
toxins (39).
We selected our study population to overcome many of the
methodological problems found in earlier studies, correlating
ethanol levels with acidosis. We chose to study trauma
patients because this population tends to be young and healthy.
This enabled us to control for additional metabolic derange-
ments that may occur in patients with acute medical illnesses.
We excluded patients with major trauma to eliminate the
metabolic effects of injury. Finally, in order to study the
metabolic effects of ethanol alone, we excluded any patients
with co-intoxications. This allowed us to study a representa-
tive group of ethanol-intoxicated patients who did not have
any obvious medical or trauma-related metabolic acidosis.
LIMITATIONS
Our study analyzed a convenience sample of trauma
patients, and our data represents only a portion of our
institution’s total trauma admissions. A further limitation
involves our definition of intoxication secondary to illicit
drugs. A urine toxicology screen qualitatively measures the
presence of a drug or its metabolites. A positive Utox may not
necessarily indicate an acute intoxication. The Utox for
cocaine, for example, can be positive for up to three days
postingestion and may not be an indicator of intoxication at the
point of testing. Exclusion of patients with positive Utox could
be a source of selection bias, since some of these patients may
not have acute intoxication. Similarly, we also did not obtain
information about the drinking history of our patients, and the
intoxicated group may have been a mixture of naive and
chronic drinkers. We only measured a single ethanol level and
thus we could not relate this to total volume and time of ethanol
ingestion. Finally, our definition of ethanol intoxication as a
blood alcohol level of 80 mg/dl uses a legal definition. This
may not represent a significant physiological cutoff.
CONCLUSION
We reject our research hypothesis that a dose-response
curve could be produced to predict the expected acidosis for
any given level of ethanol. Patients may exhibit a metabolic
acidosis as a result of ethanol intoxication. The degree of
acidosis, however, cannot be reliably predicted by the serum
ethanol level. Severe metabolic or lactic acidosis in intoxi-
cated patients cannot be safely attributed to ethanol consump-
tion alone. Diagnostic work-up is warranted in such patients to
search for causes of acidosis, other than ethanol intoxication.
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