Special concern

Special concern

C H A P T E R 31 Special concern: sources of inaccuracy in breath alcohol analysis Amitava Dasgupta Department of Pathology and Laboratory Medicine, ...

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31 Special concern: sources of inaccuracy in breath alcohol analysis Amitava Dasgupta Department of Pathology and Laboratory Medicine, University of Texas McGovern Medical School, Houston, TX, United States

INTRODUCTION Alcohol levels are measured in various body fluids including blood, breath, urine and saliva. In addition, transdermal alcohol sensors are used in the criminal justice system. Blood alcohol as well as breath alcohol are measured both in medical and legal situations. Although breath alcohol measurement is commonly conducted in the roadside for screening drivers suspected of driving under the influence of alcohol, breath alcohol analysis is also conducted in the hospital emergency room in intoxicated patients. Breath alcohol analysis may also be used in workplace drug testing. Breath alcohol analyzers can be classified broadly under two categories; screening devices and evidential breath alcohol analyzers. Result obtained by using an approved evidential breath analyzer is usually accepted in the court of law as evidence. However, for medical breath alcohol testing, evidentiary breath alcohol analyzers may also be used due to better precision and accuracy of such analyzers compared to screening devices. Although DWI (driving while intoxicated) and DUI (driving under the influence) are very similar in nature, in some states DUI may indicate a lesser degree of impairment. Therefore, conviction under a DUI charge may carry a lesser penalty than a DWI charge. Alcohol measurement in blood is discussed in Chapter 17. In this chapter limitations of measuring alcohol in breath are discussed.

ALCOHOL ANALYSIS USING BREATH ANALYZERS: LEGAL ISSUES The legal limit for driving in all states in the US is 0.08% blood alcohol (80 mg/dL). However, personnel

Accurate Results in the Clinical Laboratory, Second Edition https://doi.org/10.1016/B978-0-12-813776-5.00031-5

involved in safety sensitive positions are subjected to more stringent requirements. Usually commercial drivers should have blood alcohol lower than 0.02% which is virtually no alcohol in the body. Breath analysis is often used to ensure that commercial drivers are virtually alcohol free before joining their duties. Commercial drivers with blood alcohol level of 0.04% (40 mg/dL) or higher should be suspended immediately. Those who register a blood alcohol between 0.02 and 0.03% should be removed from their duties for 24 h. In the case of an accident all involved drivers are required to submit to alcohol testing within 2 h [1]. The employee’s refusal to be tested for breath alcohol or not cooperating with such testing is considered as a violation of the rule and appropriate action can be taken against that person. The Federal Aviation Administration (FAA) also has strict guidelines for alcohol consumption for security and safety sensitive personnel involved in the aviation industry. Airline pilots must abide by the current regulations governing alcohol. Moreover, FAA has the authority to take emergency revocation action against a pilot’s airman certificate when a pilot is in violation of the agency’s alcohol and drug policy. The FAA has a longstanding policy of 8 h of prohibition against pre-duty alcohol consumption. Different airlines may have policies where pilots must refrain from consuming alcohol longer than 8 h. Because of extremely low acceptable limits for blood alcohol in pilots it is possible that a pilot may not able to fly the airplane despite not consuming alcohol for 8 h. The current regulation prohibits pilots from performing safety sensitive duties with a blood alcohol level of 0.02% or higher. In addition, alcohol levels between 0.02 and 0.039% may result in grounding of the pilot for an additional 8 h, unless the alcohol level is reduced below the 0.02% limit. Reporting for duty or


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being on duty with a blood alcohol level of 0.04% or higher as measured by a breath analyzer or other method is a serious violation of FAA regulations and the pilot may subject to stiff penalties. The United States Department of Defense also enforces a strict policy to ensure military personnel are not affected by alcohol and drug abuse. Active duty members are not allowed to consume any alcohol if below the age of 21. In addition, alcohol cannot be consumed 12 h prior to joining active duty, while in uniform, within 12 h of operating a motor vehicle, or any other time as restricted by the commander. Evidential breath alcohol analyzers are widely used in military. In one study the authors used breath alcohol analysis to evaluate the effect of a alcohol misconduct prevention program on 10,087 Air Force technical trainees at Lackland Air Force Base in San Antonio, Texas and observed significant reductions in the number of alcohol related incidents after such training. The average rate of alcohol related incidents reduced from 7.30 per 1000 trainees per quarter to 4.06 per 1000 trainees per quarter after implementing the alcohol misconduct prevention program [2].

ALCOHOL MEASUREMENT IN BREATH Breath alcohol is measured using various devices as a reliable estimate of blood alcohol concentrations over the last 50 years. Police may often use any breath alcohol analyzer for screening purpose at the roadside but an initial result is not admissible in the court of law as evidence. Nevertheless initial screening results indicating intoxication may be sufficient grounds for arrest and after bringing that person to the police station breath alcohol is measured again with an evidential breath alcohol analyzer approved by National Highway Traffic Safety Administration. Results obtained by using evidential breath measurement devices are reliable and values are admissible to court as evidence. Though interlock devices in the car also work on the principle of breathalyzers, such devices are not designed for legal alcohol testing.

Partition of alcohol between blood and alveolar air The principle of breath alcohol measurement is partition of alcohol between blood and alveolar air (breath) following Henry’s Law, which states that when equilibrium is reached at a fixed temperature the liquid to air solubility coefficient of a gas is expressed by the following equation: Solubility coefficient ¼ concentration in the liquid phase=concentration in the vapor phase

Although original Henry’s Law is applicable to gas, such approach can be adopted for alcohol, which is a volatile substance. The passage of alcohol from blood to breath follows the same process as other volatile gases in the exhaled air such as carbon dioxide and acetone. Alcohol diffuses from the pulmonary blood into the alveolar air at the body temperature of 37  C until equilibrium is reached. The ratio of concentration of alcohol in the blood and in the alveolar air at equilibrium is known as blood/breath partition ratio or Ostwald solubility coefficient. The value selected for the blood/breath ratio is an essential element of breath alcohol analysis because this ratio determines the value of blood alcohol level when measured breath alcohol level is converted into blood alcohol concentration. In the United States, the accepted ratio is 2100:1. Therefore, one liter of blood contains the same amount of alcohol as 2100 litters of breath at 34  C. Although the normal body temperature is 37  C, the temperature of exhaled air is 34  C because the temperature of exhaled air drops from the physiological temperature during passage through the respiratory tract [3]. The concentration of breath alcohol measured as mg/ L should be multiplied by 2100 to calculate blood alcohol concentration in mg/L. In the United States, the driving legal limit is 0.08% whole blood alcohol (80 mg/dL). Therefore, the breath alcohol level measured as mg/L should be multiplied by 210 in order to calculate blood alcohol concentration in mg/dL. As a result, the legal limit of breath alcohol concentration is 0.38 mg/L or 38 mg/dL. However, in the US if breath alcohol concentration is reported as mg/210 L by the device, then that value is equivalent to mg/dL blood alcohol level. For example 80 mg/210 L breath alcohol is equivalent to 80 mg/dL blood alcohol. Although in the United States, Canada, Norway and Sweden, the accepted ratio between blood alcohol and breath alcohol is 2100:1, in Great Britain and Netherland, the ratio is 2300:1. In Austria, the ratio is 2000:1. The legal limit of driving in Great Britain is also 80 mg/dL but due to higher blood/breath partition ratio, the limit of driving is 35 mg/dL of breath alcohol level which is slightly lower than legal limit of breath alcohol in the US [4]. Therefore, if the blood/breath alcohol ratio is lower than 2100:1 in an individual, breath alcohol analysis may overestimate true blood alcohol in the US. In contrast, if the ratio is higher than 2100:1, then breath alcohol analysis may underestimate the true blood alcohol concentration.

Technical aspect of breath alcohol measurement Analyzers used for breath alcohol measurement utilize one of the following technologies: • Color change due to a chemical reaction of a cocktail of chemicals with alcohol is used to determine alcohol level



• Alcohol in breath is measured using principles of infrared spectroscopy • Electrochemical oxidation of alcohol (fuel cell technology) • Analyzer based on mixed technology (infrared and fuel cell) The earliest developed breath alcohol analyzers utilized chemical oxidation of ethanol with potassium permanganate (Drunkometer) or iodine pentoxide (Alcometer). Than another colorimetric method of analysis of alcohol concentration in breath was developed where exhaled air was allowed to pass through a cocktail of chemicals containing sulfuric acid, potassium dichromate, silver nitrate and water. Silver nitrate catalyzes the reaction where alcohol in the presence of sulfuric acid turns orange potassium dichromate solution into green due to conversion of potassium dichromate into chromium sulfate. The intensity of the green color can be used to estimate the amount of alcohol in the exhaled air. Captain Robert Borkenstein of the Indiana State Police used this chemical principle to develop breath analyzers in 1954 and some breath alcohol analyzers still use this principle today. Breathalyzer is the oldest technology of breath alcohol analyzer based on the principle of color change of potassium dichromate solution in the presence of alcohol and then analysis by using spectroscopy after a specified time to ensure complete reaction. The analyzer contains two vials of chemical cocktail. After a subject exhales into the device, the air is passed through one vial and if alcohol is present in the exhale, a color change occurs. A system of photocells connected to a meter measure the color change associated with the chemical reaction by comparing the response from the second vial (where no air is passed through) thus producing an electrical signal proportional to the color change in the reaction vial. This electrical signal can move the meter (more alcohol, more signal and higher reading) and the alcohol level in the subject can be determined. Breathalyzer was the brand name originally developed and marketed by Smith and Wesson and the company then sold that brand to a German Company called Draeger. The old Breathalyzer 900 model was replaced by newer versions such as model 1100 but this technology is subjected to interferences from a variety of substances and because of that other companies focused on developing more robust technologies for breath alcohol analysis [5]. In 1970s, breath alcohol analyzers based on infrared spectrometry, and electrochemical oxidation (fuel cell technology) appeared in the commercial market offering more sensitivity and specificity compared to the original colorimetry based instruments. The infrared spectrum of alcohol shows a distinct absorption band close to 3.4 mm due to CeH bind stretching and also at 9.5 mm


due to CeO bond stretching frequency. There are many evidential breath alcohol analyzers that are based on the principle of infrared spectroscopy (IR spectroscopy) for quantitative determination of alcohol in exhaled air. The Intoxilyzer was originally developed by Omicron in Palo Alto, CA, and later sold to CMI, Inc., in Owensboro, KY. The earlier models were 4011 A, 4011 S and Intoxilyzer 5000 and more recently the Intoxilyzer 8000 model is available as an evidential breath analyzer. In addition to Intoxilyzer, Data Master cdm (National Patent Analytical System, Mansfield, OH), which is also used in many states as the evidentiary breath alcohol analyzer, is based on IR spectroscopy technology. The newer version of Intoxilyzer (Intoxilyzer 5000) uses a five wavelength filter at 3.36, 3.4, 3.47, 3.52, and 3.8 mm and thus can differentiate between ethanol and common interferences in exhaled air such as acetone, acetaldehyde and toluene. The 3.4 mm wavelength is used to detect alcohol while 3.47 identify interfering substances and 3.8 mm is used as the reference wavelength. The latest model Intoxilyzer 8000 uses a pulsed IR source instead of moving wavelength filter and uses dual wavelengths for measuring alcohol (3.4 and 9.36 mm) in the breath. It also has more advanced computer technology to accurately provide alcohol level results. The Data Master cdm, an evidentiary breath analyzer widely used by police officers in many states is also based on the principle of infra-red (IR) spectroscopy where alcohol is detected using two different wavelengths (3.37 and 3.44 mm). In Sweden, Evidenzer, an evidential breath analyzer, utilizes five wavelengths (3.37, 3.41, 3.47, 3.52 and 3.80 mm). In this instrument wavelengths at 3.37, 3.41, 3.47 and 3.52 are used for measuring alcohol and other volatiles such as acetone in breath while 3.80 mm wavelength is used as a reference wavelength [6]. There are several different brands of evidential breath alcohol analyzers which are based on the principle of fuel cell technology, such as Alcotest Models 6510, 6810, 7410, etc., (National Drager, Durango, Colorado), and Alco-Sensor III and IV (Intoximeters Inc, St. Louis, MO). The fuel cell is a porous disk coated with platinum oxide (also called platinum black) on both sides. The porous layer is impregnated with acidic solution containing various electrolytes so that charged particles such as hydrogen ions can travel through that medium. In addition, both sides of the disk containing platinum oxide are connected through a platinum wire. The manufacturer mounts this fuel cell in a case along with the entire assembly so that when a person blows to the disposable mouthpiece the air can travel through the fuel cell. If any alcohol is present in the exhaled air, then the alcohol is converted into acetic acid, hydrogen ion and electrons on the top surface




by the platinum oxide. Then hydrogen ions travel to the bottom surface (also containing platinum oxide) and are converted into water by combining with oxygen present in the air. In this process, electrons are removed from the platinum oxide. Because there is an electron excess on the top surface and electron deficit on the bottom surface, electrons flow from one surface to another generating an electric current which flows through the platinum wire and the intensity of the current is proportional to the amount of alcohol present in the exhaled air. The microprocessor of the instrument then converts that current to equivalent breath and or blood alcohol. Some evidentiary breath analyzers are based on both fuel cell and infrared spectroscopy technology giving them good sensitivity and specificity. Various models of Intox EC/IR l desktop evidentiary alcohol breath analyzers, also manufactured by Intoximeters, Inc., combine reliable fuel cell analysis with real time analytical advantages of infrared technology. Semiconductor alcohol sensors are utilized in inexpensive breath analyzers marketed to the general public. However, the sensor response is non-specific to alcohol and also non-linear. For example, semiconductor sensors will respond to particles and gases present in cigarette smoke. Gas chromatography technique applied for analysis of blood alcohol may also be used for breath alcohol analysis [7,8]. Various technologies applied in breath alcohol analysis are summarized in Table 31.1.

TABLE 31.1

ISSUES WITH PARTITION RATIO Although in the US blood/breath partition ratio is 2100:1, wide variation of this partition ratio (1300:1 to 2700:1) in different individuals have been reported. Such fluctuations are due to difference between arterial blood and venous blood during the early stage of alcohol absorption by the body. After drinking, alcohol is found in higher concentration in arterial blood transporting newly absorbed alcohol to tissues and as a result the venous alcohol concentration is lower than arterial blood alcohol but after reaching equilibrium, both arterial and venous blood alcohol levels are comparable. Jones et al. compared time course of arterial and venous blood alcohol concentration differences using nine healthy male volunteers and observed that the mean peak arterial blood concentration was 98 mg/dL while the mean peak venous blood alcohol concentration was 84 mg/dL whereas the median time to reach the maximum blood alcohol concentration was the same (35 min). The arterial blood alcohol level was significantly higher than venous blood alcohol level 10 min after the end of drinking (mean difference 20 mg/dL; range: 9e40 mg/dL). At a median time of 90 min after drinking (range: 45e105 min), no difference between arterial and venous blood alcohol was observed [9]. Because alcohol is measured using venous blood, after drinking the blood to breath alcohol ratio is lower during the absorption phase. Nevertheless, in most individual the blood to breath ratio is close to 2100:1

Examples of breathalyzers based on different technologies. Examples of breathalyzers




Cocktail of chemicals containing sulfuric acid, potassium dichromate, silver nitrate and water is used. If alcohol is present, orange color of potassium dichromate is changed to green.

Breathalyzer 900, Breathalyzer 1100 etc.

Infrared based technology

The infrared spectrum of alcohol shows distinct absorption bands close to 3.4 mm due to CeH bind stretching and 9.5 mm due to CeO bond stretching frequency. The newer version of Intoxilyzer (Intoxilyzer 5000) uses a five wavelength filter at 3.36, 3.4, 3.47, 3.52, and 3.8 mm and thus can differentiate between ethanol and common interferences in exhaled air such as acetone, acetaldehyde and toluene. Some analyzer uses dual wavelengths for measuring alcohol (3.4 and 9.36 mm) levels in the breath

Intoxilyzer 5000, Intoxilyzer 8000, Intoxilyzer 9000, etc. Data Master cdm etc.

Fuel cell based technology

Fuel cell technology is based on electrochemical oxidation of ethanol into acetic acid, hydrogen ion and electrons which generates an electric current proportional to amount of ethanol present in breath.

Alcotest various models, Alco-Sensor III and IV etc.

Mixed technology

Incorporates both infrared and fuel cell technology in one analyzer.

Intox EC/IR, Intox DMT, dual sensors etc.


Breath alcohol analysis based on semiconductor technology utilizes increase in conductance of a tin oxide layer if alcohol is present in breath. Usually less precise than fuel cell or infrared technology.

AlcAlert etc., semiconductor



and as a result values provided by a breath analyzer such as Drager 7110 MKIII IL breathalyzer correlate with blood alcohol analysis with high sensitivity (97%) and specificity (93%). Moreover, mean blood alcohol and breath alcohol 29 min post-consumption were 70.9 mg/dL and 32.57 mg/dL respectively indicating a mean blood/breath alcohol ratio of 2164.1:1 (n ¼ 60) while blood and breath alcohol 58 min post consumption were 82.6 mg/dL and 35.15 mg/dL respectively indicating that the blood/breath alcohol ratio was 2346.9:1 (n ¼ 61) [10]. Breathalyzers can also measure very low alcohol concentrations in breath accurately. In one study involving 62 Intoxilyzer 500-D analyzers (evidential breath analyzer) used for screening suspected drunk drivers, the authors reported that breathalyzers accurately measured low breath alcohol levels of 0e0.059 g/210 L [11]. These values correspond to 0e0.059% blood alcohol (0e59 mg/dL). Sometimes non-evidential breath analyzers (prearrest breath analyzers) are used for roadside screening of suspected drunk drivers and then at the police station evidential breath analyzers are used to verify initial screening results. Polissar et al. evaluated the validity of results obtained by using pre-arrest breath analyzers by comparing results obtained by an evidential breath analyzer using data from 1,779 DUI arrestees and observed excellent correlation between values obtained by using pre-arrest breath analyzers and evidential breath analyzer although values were slightly lower (120 mg/210 L breath) using evidential breath analyzer compared to results obtained by using pre-arrest breath analyzer (127 mg/210 L breath). The values obtained by the evidential breath analyzer were slightly lower because of time elapsed between both measurements (median time: 48 min) where alcohol continued to be eliminated from the body [12]. However, there are some problems in calculating blood alcohol levels from breath alcohol levels. Breath alcohol analyzers may underestimate blood alcohol concentration by an average of 15% which could be beneficial to the person being tested [13]. Nevertheless, over estimation of blood alcohol based on breath alcohol analysis is also possible because blood/breath partition ratio vary widely between different individuals as well as in the same individual during the different phases of alcohol absorption, metabolism and elimination. Dubowski after data analysis of 393 subjects using Gaussian distribution reported that the blood/breath partition ratio varied from 1555:1 to 3005:1 in 99.7% of population studied but the mean blood/breath partition ratio was 2280:1 [14]. Although the mean partition ratio in this study was comparable to 2100:1, in a person with a partition ration of 1555:1, breath alcohol should produce falsely elevated blood alcohol concentration. In contrast in a person with a partition ratio of 3005:1,


breath alcohol analysis should produce falsely lower blood alcohol levels. For example, in a person with partition ratio of 1555:1, true blood alcohol of 0.07% (70 mg/ dL) will be overestimated to 0.95% (95 mg/dL) if breath alcohol analyze is used for estimating blood alcohol. Similarly for a person with 3005:1 partition ratio true blood alcohol of 0.07% will be underestimated as 0.049% (49 mg/dL) using breath alcohol analysis. Hartung et al. performed a controlled drinking experiment involving 78 volunteers and reported that the blood/breath partition ratio varied from 1571.1:1 to 2394.1:1 and increased with increasing blood alcohol levels. The authors used Drager Alcotest 9510 DE breathalyzers for measuring breath alcohol level. The difference between breath and blood alcohol measurements was not more than 10 min. The authors concluded that a blood alcohol measurement is superior to a breath alcohol measurement in legal cases [15].

ALCOHOL MEASUREMENT IN BREATH: COOPERATIVE VERSUS NONCOOPERATIVE PERSON Performance of a breath alcohol analyzer depends on level of cooperation from the person being tested. Gibb et al. measured breath alcohol (Alco-Sensor III breath alcohol analyzer) and blood alcohol in 55 patients and observed that the mean blood alcohol level was 217 ng/dL but when blood alcohol was calculated based on breath alcohol analysis, the mean estimated blood alcohol was 187 mg/dL, which was substantially lower than the measured blood alcohol level. Interestingly, the mean blood alcohol level of uncooperative patients was 243 mg/dL compared to the calculated mean blood alcohol level of 183 mg/dL from breath alcohol analysis. In contrast, in cooperative patients, the mean blood alcohol was 194 mg/dL and the mean blood alcohol calculated from breath alcohol analysis was also 194 mg/dL. The authors concluded that in uncooperative individuals breath alcohol analysis may significantly underestimate true blood alcohol concentration [16]. Currier et al. investigated the relative accuracy of breath and serum alcohol readings in the psychiatric emergency service. Breath alcohol and serum alcohol were measured in 55 patients. However, the time of measurements was documented only in 32 patients and the authors analyzed these data. The authors reported that the mean breath alcohol concentration in these patients was 0.15 g per 210 L which was equivalent to 150 mg/ dL of blood alcohol concentration. In contrast, the mean blood alcohol level in these patients was 230 mg/dL. The authors concluded that underestimation of blood alcohol based on breath alcohol analysis




was due to lack of cooperation from patients during breath alcohol analysis [17].

LUNG FUNCTION AND BREATH ALCOHOL ANALYSIS The breath alcohol test involves a single exhalation maneuver where a subject is asked to inhale air (preferably a full inhalation to total lung capacity) and then exhale (preferable a full exhalation to residual volume) into the breathalyzer instrument. The assumption is that the alcohol concentration in exhaled breath is equal to that in alveolar air. In general, the alcohol level in endexhaled air is always lower than in alveolar air. When performing a breath alcohol test, the subject is asked to inhale ambient air and exhale into the analyzer (usually 1.1e1.5 L of exhaled air is needed for the test). Therefore, a smaller subject with smaller lung capacity must exhale a greater fraction of air in their lung to fulfill the minimum volume requirement of the analyzer and as a result, the alcohol breath test may overestimate the blood alcohol level in smaller subjects compared to larger subjects with larger lung capacity [18]. Chronic obstructive pulmonary disease (COPD) may affect breath alcohol analysis. In one study based on 10 normal volunteers and 10 volunteers with COPD, the authors observed that the mean blood/breath partition ratio was significantly higher in subjects with COPD compared to normal subjects. Therefore, the blood alcohol calculated from breath analysis was significantly lower than true blood alcohol concentration. In addition, the authors further observed that breath analyzers also significantly underestimated the blood alcohol level as a function of age. For example in a 52 year old female subject, the blood/breath partition ratio was 2753:1 while in a 66 year old subject, the blood/breath ratio was 3504:1. Therefore, in older subjects breath analyzers may significantly underestimate true blood alcohol [19]. Although most patients with lung disease are able to supply an evidential breath sample (75% subjects with interstitial lung disease and 92% patients with COPD), some subjects with very severe lung disease (vial capacity below 1.5 L) may not be able to provide a specimen for breath alcohol analysis [20].

EFFECT OF HEMATOCRIT AND BODY TEMPERATURE ON BREATH ALCOHOL ANALYSIS The average hematocrit is 46.2% in males and 40.6% in females. Because alcohol is water soluble, for two individuals with the same concentration of alcohol in

whole blood, a person with a higher hematocrit will have a slightly higher alcohol concentration in serum as well as in breath. In addition, body temperature also has an effect on breath alcohol concentration. Usually the temperature of human breath varies between 33.3 to 34.4  C and in the US it is assumed that the breath temperature is 34  C whereas the blood/breath ratio is 2100:1. An in vivo study showed that the blood/breath alcohol ratio increased on average by 5.7% per 1  C increase in body temperature. Lowering body temperature has the opposite effect. Therefore a drop in core temperature works as an advantage for the subjects with hypothermia because breath alcohol analysis should provide falsely lower values [4]. Rinsing the mouth with water reduces breath alcohol concentration determined using Lion AE-D2 alcolmeter but the magnitude of reduction was greater after rinsing mouth with cold water [21]. Fox and Hayward studied the effect of hyperthermia on breath alcohol analysis by submerging alcohol intoxicated subjects in hot water bath thus inducing mild hyperthermia to the extent of 2.5  C increase above normal body temperature. Hyperthermia did not influence the blood alcohol decay curve in these subjects but hyperthermia did cause a significant distortion of the breath alcohol decay curve, up to as much as a 23% increase above the blood alcohol concentration. The authors calculated that for each 1  C increase in body temperature, the breath alcohol concentration may increase by up to 8.62% over the blood alcohol concentration. The author suggested that mouth temperatures must be recorded prior to breath alcohol measurements to allow for potential use of a temperature correction factor [22].

SOURCES OF ERRORS IN BREATH ALCOHOL MEASUREMENT There are several sources of errors in breath alcohol analysis. Sometimes a driver stopped by the police may use mouthwash to hide any alcoholic breath. Because some mouthwashes contain alcohol, use of a mouthwash prior to taking a breath alcohol analysis may cause falsely elevated breath alcohol result. However, residual alcohol evaporates from the mouth rapidly and this is the reason for waiting for 15 min in a police station under supervision so that the suspect cannot take anything by his or her mouth during the waiting period. Fessler et al. studied the effect of alcohol based substances such as mouthwash, cough mixture and breath spray just prior to breath alcohol measurement using Drager Evidential portable breath alcohol analyzer and twenty five volunteers. The authors concluded that 15 min waiting period was necessary to



ensure that there was no residual alcohol in the mouth after using mouthwash and other alcohol containing products. Otherwise alcohol from mouthwash may interfere in breath alcohol analysis causing falsely elevated values [23]. Harding et al. studied the effect of dentures and denture adhesives on mouth alcohol retention using Intoxilyzer 5000 and concluded that dentures had no significant effect on breath alcohol test results as long as a waiting period of 20 min was observed prior to testing [24].

Case report A 37 year old man who was breath tested after following a traffic accident showed a breath alcohol concentration of 70 mg/dL using Lion Intoximeter which was twice as high as legal limit of driving in UK (limit breath alcohol: 35 mg/dL; blood alcohol 80 mg/dL; blood/breath ratio in UK is 2300:1). The defendant protested vigorously that he did not consume that much alcohol but no malfunction was found in the breath analyzer. Alcohol loading test was conducted in the laboratory in two different occasions and the results indicated that breath alcohol analysis significantly overestimated blood alcohol concentration. The observed breath alcohol concentration was 140 mg/dL where calculated breath alcohol concentration should be 35 mg/dL based on the amount of alcohol consumed. A blood sample was taken at a point when breath alcohol concentration was 70 mg/dL (calculated blood alcohol: 80 mg/dL) which was significantly higher than the actual blood alcohol concentration of 54 mg/ dL. Dental examination of the defendant showed that he had extensive dental work carried out including three bridges. The author concluded that possible explanation of significantly elevated breath alcohol level might be due to retention of alcohol in the bridges and periodontal spaces [25]. Logan et al. evaluated the effect of asthma inhalers and nasal decongestant sprays on breath alcohol test and observed that the only product which had any effect on the breath alcohol test was Primatene Mist containing 34% ethyl alcohol but alcohol was eliminated from the breath within 5 min. The authors concluded that inclusion of a 15 min deprivation period when no food or drink could be consumed prior to an evidential breath test was adequate safeguard against interference in the test caused by alcohol containing inhalers [26]. Some mouthwashes contain alcohol. Based on a study using 40 young adult volunteers, the authors in one study showed that immediately after rinse using an alcohol containing mouthwash, a significant amount of alcohol was detected in breath due to the presence of residual alcohol in the mouth cavity but within 10 min after rinsing values were significantly reduced. In addition,


20 min after rinsing no alcohol was detected in the breath. For example, the mean blood alcohol value calculated from breath alcohol analysis was 375 mg/dL immediately after rinsing mouth with a mouthwash containing 21.6% alcohol but 10 min after the value was reduced to 7 mg/dL and finally after 20 min no alcohol was detected in the breath. As expected blood alcohol analysis did not detect any alcohol in these subjects [27]. In another study, the authors demonstrated that rinsing mouth with a mouthwash containing 18% alcohol, the mean time required for breath alcohol level to go back to zero in healthy volunteers was 11.32 min [28]. Drinking an energy drink while driving a car is legal but some energy drinks contain very low levels of alcohol. When volunteers drank various energy drinks, 11 out of 27 drinks gave positive results using evidentiary breath analyzers when testing was done just after drinking. However, after a 15 min waiting period all breath alcohol analysis reports were negative. The authors concluded that a 15 min waiting period eliminates the possibility of testing false positive after consuming an energy drink with low alcohol content [29]. In a hospital setting medical staff may wash hands using alcohol hand gel following World Health Organizations (WHOs) “five moments of hand hygiene” recommendation. Such alcohol hand gel contains 70% alcohol. In one study, the authors observed positive breath alcohol test results in some subjects when breath alcohol analysis was performed within 2 min of using hand gel (highest value: 0.064% blood alcohol calculated from breath alcohol analysis but blood alcohol measurement was negative). However, 62.5% of positive breath analyzer test results returned to zero in less than 7 min. The authors speculated that positive test results may be due to inhalation of alcohol vapor into the respiratory dead space following gel application. The authors concluded that for workplace breath alcohol analysis, a 15 min waiting period after hand ashing with alcohol containing gel is needed to avoid false positive breath test. Moreover, positive results must be confirmed using a direct blood alcohol measurement [30]. Mother tinctures used in homeopathic medicine often contain alcohol. In some countries where homeopathic medicines are commonly used and the legal limit of driving is 0.05% blood alcohol (50 mg/dL), defendants often claim that positive breath alcohol test results are due to use of homeopathic medicine. Boatto et al. based on a study of 30 subjects demonstrated that within 1 min of drinking homeopathic mother tincture, breath alcohol test may be positive (9 out of 30 subjects showed measurable breath alcohol levels) but after 15 min no alcohol was detected in breath. The authors concluded that mandatory 15 min waiting period prior to blood alcohol analysis eliminates possibility of false positive results due to use of homeopathic medicine [31].




Breath alcohol analysis and GERD Studies have shown that breath alcohol analysis provides reliable results in patients suffering from gastroesophageal reflux disease (GERD). Kechagias et al. compared blood alcohol values with values obtained by breath alcohol analyzer (Data Master) in patients suffering from GERD and concluded that breath alcohol analyzers overestimating the true blood alcohol value due to eruption of alcohol from the stomach to the mouth due to gastric reflux is highly improbable [32]. In another study, the authors concluded that people with GERD can provide bias free end-expiratory breath alcohol result provided 15 min waiting period is followed [33].

Interferences of volatiles in breath alcohol analysis Volatile organic compounds are produced in the body as a result of various metabolic processes. These endogenous volatiles are transported in the blood and can be exchanged across the alveolar-blood capillary membrane into exhaled air. Over 1,000 volatile compounds have been identified in exhaled air of healthy humans and also in various diseases. Some of these compounds which are present in extremely low amounts can also be used as biomarkers of various diseases such as lung cancer [34]. In general high concentration of carbon dioxide (approximately 4%) and water vapor are present in exhaled air but other organic compounds such as hydrocarbons, alcohols, ketones, and aldehydes are present in human breath as parts per million to parts per billion concentration. The major volatiles in human breath include isoprene (12e580 ppb), acetone (1.2e1,880 ppb), ethanol (13e1,000 ppb), methanol (160e2,000 ppb) and other alcohols [35]. In another study, the authors also identified many volatile organ compounds in human breath. These compounds include hydrocarbons (isoprene, 2-pentene, 2-methyl-1pentene, benzene, toluene, p-cymene, limonene, 2,4dimethylheptane, n-butane), ethers (dimethyl ether, 1, 3-dioxolane), esters (ethyl acetate), aldehydes and various alcohols including ethanol [36]. Laakso et al. studied the potential interference of volatile solvents with breath alcohol analysis using Drager 7110 evidential breath analyzer using a procedure stimulating a human breathing. The authors concluded that most of the compounds studied had either a negligible effect on breath alcohol analysis (acetone, methyl ethyl ketone, and methyl isobutyl ketone) or were detected in very low concentration (methanol, ethyl acetate and diethyl ether) with little effect on breath alcohol analysis. However, n-propyl alcohol and isopropyl alcohol

showed significant interference [37]. Logan et al. also presented a case report where a person consumed both ethanol and isopropyl alcohol. The authors observed interference of isopropyl alcohol in breath alcohol analysis using Datamaster infrared breath alcohol instruments. Blood analysis using gas chromatography/ mass spectrometry showed the presence of ethanol (76 mg/dL), isopropyl alcohol (23 mg/dL) and acetone (metabolite of isopropyl alcohol; 57 mg/dL). The breathalyzer recorded alcohol levels of 90e170 mg/210 L over a period of 3 h [38]. Jones and Rossner described a case where a 59-yearold man undergoing a weight loss program using a ketogenic diet attempted to drive a car which was fitted with an alcohol ignition interlock device, but the vehicle did not start. Because he completely stopped drinking, he was surprised and upset. Ketogenic diet used for treating obesity and controlling seizure in some epileptic children is high in fat, very low in carbohydrate and also has adequate protein. The goal is to burn fat to get energy rather than getting it from glucose which is formed by carbohydrate metabolism. However, consuming the ketogenic diet lead to a stage called ketonemia where concentrations of acetone, acetoacetic acid, and beta hydroxybutyric acid are high. This high amount of acetone may be found in the exhaled air. The interlock device in the car determines alcohol by electrochemical oxidation method and acetone does not interfere with the process. However, acetone is known to be converted into isopropyl alcohol by the action of liver alcohol dehydrogenase and isopropyl alcohol can be falsely identified as ethanol by the ignition interlock device. In addition, methanol and propanol can also be falsely identified as alcohol. The authors concluded that side effects of ketogenic diets need further evaluation by authorities especially for people involved in safety sensitive positions such as airline pilots and bus drivers who are subjected to much tougher alcohol tolerance policies [39]. Glue sniffing may cause false positive breath alcohol test result because glue contains aliphatic hydrocarbons, ethyl acetate and toluene [40]. Methanol poisoning is dangerous because it may cause death or blindness. Methanol poisoning may cause false positive test results with breath analyzers. In one report the authors observed that toluene, xylene, methanol and isopropyl alcohol in exhaled air can be mistakenly identified as breath alcohol by the Intoxilyzer 5000 evidentiary breath alcohol analyzer [41]. Diethyl ether is a common organic solvent used in laboratories. Prolonged exposure to this solvent (1 h) may cause false positive test results with breath analyzers [42]. Common interferences in breath alcohol analyzers are summarized in Table 31.2.




TABLE 31.2

Interferences in breath alcohol test.

Interfering substance


Propyl alcohol

Propyl alcohol interferes with breath alcohol analysis.

Isopropyl alcohol

Endogenously produced isopropyl alcohol has no effect on breath alcohol analysis due to very low concentration in breath but isopropyl alcohol if consumed interferes with breath alcohol measurement.


Endogenously produced methanol has no effect on breath alcohol analysis due to very low concentration in breath but methanol if consumed interferes with breath alcohol measurement.


Endogenously produced toluene has no effect on breath alcohol analysis due to very low concentration in breath but toluene if consumed interferes with breath alcohol measurement.


Xylene is an industrial solvent and prolonged exposure to this compound may cause false positive results in breath alcohol analysis.

Diethyl ether

Only prolonged exposure to this common organic solvent commonly used in laboratories may cause false positive breath alcohol test results.

Ketogenic diet

Ketogenic diet lead to a stage called ketonemia where concentrations of acetone, acetoacetic acid, and beta hydroxybutyric acid are high. Acetone is converted into isopropyl alcohol by the action of liver alcohol dehydrogenase and isopropyl alcohol can be falsely identified as ethanol during breath alcohol analysis.

Glue sniffing

Glue aliphatic hydrocarbons, ethyl acetate and toluene and some of these compounds interfere with breath alcohol analysis.

Case report A 47-year-old man who was found at a public park and acting intoxicated was given a breath analyzer test in the police station using Intoxilyzer 5000 EN which showed a concentration corresponding to 288 mg/dL blood alcohol. The subject admitted that he was suicidal and was transported to a hospital. In the emergency room, the patient admitted drinking gas line antifreeze which contains 99% methanol. The serum drug screen for alcohol showed a negative result indicating that the positive ethanol level determined by the breath analyzer was false positive due to interference of methanol. As expected, the patient’s serum methanol level was 589 mg/dL. The patient was initially treated with fomepizole and then with ethanol infusion to reduce

metabolism of methanol to toxic formaldehyde metabolite. Hemodialysis was initiated 9 h after ingestion and after 44 h of ingestion his serum methanol level was reduced to 22 mg/dL. The visual activity of the patient was not affected by methanol intoxication and finally he was transferred to a psychiatric facility [43].

CAN ALCOHOL BE PRODUCED ENDOGENOUSLY? Endogenous production of alcohol (auto-brewery syndrome) is a common defense strategy adopted by some individuals charged with driving under the influence of alcohol. A small amount of alcohol is produced endogenously but it should not alter blood alcohol level. Jones et al. reported that endogenous alcohol level varied from none detected to 1.6 mg/mL (0.16 mg/dL) which is negligible [44]. Madrid et al. studied eight patients with liver cirrhosis and observed that during fasting no patient showed any endogenous ethanol level but after a meal two patients showed serum alcohol level of 11.3 and 8.2 mg/dL while another four patients showed negligible values [45]. In general healthy individuals as well as patients with metabolic disease such as diabetes, hepatitis or cirrhosis showed blood alcohol levels ranged from 0 to 0.08 mg/ dL due to endogenous production of alcohol which is negligible. Hafez et al. investigated endogenous production of alcohol in healthy volunteers, patients with diabetes mellitus, liver cirrhosis as well as patients suffering from both diabetes mellitus and liver cirrhosis. Blood alcohol concentrations were measured using gas chromatography/mass spectrometry. In control group, the blood alcohol concentrations varied from 0.01 to 0.3 mg/dL, in patients with diabetes mellitus, the mean blood alcohol concentration was 4.85 mg/dL (maximum value: 12.90 mg/dL), in patients with liver cirrhosis, the mean value was 3.45 mg/dL (maximum value: 9.7 mg/dL) and in patients suffering from both diabetes mellitus and liver cirrhosis, the mean value was 10.88 mg/dL (maximum value: 22.3 mg/dL) [46]. The dermal absorption of alcohol is usually negligible after washing hands with alcohol containing hand gel.

CONCLUSIONS Breath alcohol analysis is useful for screening drivers suspected of driving under the influence of alcohol but initial screening result must be confirmed in a police station using evidential breath analyzer. Although the result obtained by using an evidential analyzer is accepted in legal situation, there are many limitations




of breath alcohol analysis. The gold standard is blood alcohol measurement by using head space gas chromatography or gas chromatography/mass spectrometry. Breath analyzers are also used as a point of care device in the emergency room in evaluating intoxicated patients but a blood alcohol level determined in a clinical laboratory is recommended if the breath alcohol level is inconsistent with the clinical picture.

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