Ethanol Level

The blood ethanol (alcohol) level measures the concentration of ethanol in serum, plasma or whole blood (or breath), by enzymatic assay (alcohol dehydrogenase, with NAD to NADH detected at 340 nm, the commonest clinical method), gas chromatography with flame ionisation detection (the reference method, used in forensic work, with identification of methanol, isopropanol and acetone), or breath analysers (infrared or fuel cell).

Results are reported in mmol/L, mg/dL or g/L (1 g/L is equal to 100 mg/dL and 21.7 mmol/L). Serum ethanol concentrations are about 10 to 15% higher than whole blood concentrations.

Alcohol is involved in about 3 million deaths worldwide each year (5% of all deaths) and 20 to 40% of emergency attendances after injury. Acute intoxication causes dis inhibition, ataxia, dysarthria, sedation, coma and respiratory depression, and fatalities occur with levels over 4 g/L (400 mg/dL), though tolerant drinkers survive higher levels.

Ethanol is metabolised at a constant rate (zero order kinetics) of 0.10 to 0.25 g/L each hour in occasional drinkers (10 to 25 mg/dL/hour; 2 to 5 mmol/L/hour), and 0.25 to 0.40 g/L each hour in heavy chronic drinkers. Ethanol is also measured to assess coexisting causes of altered consciousness, in medico legal requests, driving offences, and before organ transplantation.

Indications. Altered consciousness, confusion, ataxia, aggression, seizure or coma of unknown cause. Trauma, head injury and road traffic accident victims. Suspected poisoning or overdose with co-ingestants. Unexplained metabolic acidosis with high anion gap and osmolar gap (to calculate the contribution of ethanol).

Monitoring in suspected toxic alcohol ingestion treated with ethanol or fomepizole. Medico legal and workplace testing (with chain of custody). Assessment of fitness for discharge and for procedures. Alcohol withdrawal risk assessment (a low or zero level in a heavy drinker with tremor, sweating and agitation).

Specimen. Venous blood 2 to 5 mL in a sodium fluoride and potassium oxalate tube (grey top), or a lithium heparin tube, collected with a non-alcohol skin cleaner (chlorhexidine or povidone iodine in water, not isopropyl or ethanol based swabs).

The tube is filled completely, capped tightly, mixed, and refrigerated (ethanol evaporates, and is produced by microbial fermentation in unpreserved samples with glucose). Record the time of collection and the time of last drink. For medico legal tests, two samples are collected with witnessed identification and sealed chain-of-custody forms.

Reference values. Not detected or under 0.1 g/L (under 10 mg/dL, 2 mmol/L) in non-drinkers. Legal driving limits vary by jurisdiction, from 0.2 to 0.8 g/L (20 to 80 mg/dL; 0.2 to 0.8 mg/mL).

Interpretation.

• 0.3 to 0.5 g/L: mild euphoria and reduced attention. 0.5 to 1.5 g/L: impaired coordination, judgement and reaction time. 1.5 to 3.0 g/L: ataxia, slurred speech, nausea and vomiting, emotional lability. 3.0 to 4.0 g/L: stupor, hypothermia, hypoglycaemia, aspiration risk. Over 4.0 g/L: coma, respiratory depression and risk of death (non-tolerant).
• Tolerant drinkers may be alert with levels over 3 g/L, and lack of impairment does not exclude significant intoxication.
• Clinical signs out of proportion to the ethanol level (deep coma at 1 to 2 g/L) indicate other causes: head injury, hypoglycaemia, hypoxia, co-ingestion (opioids, benzodiazepines, toxic alcohols, gamma hydroxybutyrate), infection, stroke or hepatic encephalopathy. Alcohol must never be assumed as the sole cause.
• Osmolar gap: ethanol contributes about 1 mOsm/kg for each 4.6 mg/dL (about 1 mmol/L adds 1 mOsm/kg). If the measured osmolality exceeds the calculated osmolality (including ethanol) by over 10 mOsm/kg, toxic alcohols (methanol, ethylene glycol, isopropanol) are suspected.
• Estimate of time to sobriety: divide the level by the elimination rate (0.15 g/L each hour for an average person).
• Zero or low ethanol in a heavy drinker with agitation, tremor, sweating, tachycardia or seizures: alcohol withdrawal.
• High anion gap acidosis with ketones and low or moderate ethanol: alcoholic ketoacidosis, which is also possible after cessation of drinking.
• Positive result in a post-mortem sample must be interpreted with caution for microbial production (comparison with vitreous humour or urine ethanol, and detection of n-propanol).

Critical values and findings needing immediate action.

• Ethanol over 4 g/L, or coma or respiratory depression at any level: airway protection, ventilation, oxygen, glucose, thiamine, and observation in a monitored setting; haemodialysis in life threatening cases.
• Hypoglycaemia in intoxicated patients: immediate glucose (with thiamine first or at the same time).
• Combined with unexplained high anion gap acidosis or large osmolar gap: suspected methanol or ethylene glycol poisoning, fomepizole, bicarbonate and urgent dialysis.
• Head injury in an intoxicated patient: do not attribute altered consciousness to alcohol; CT head if neurology is impaired or deteriorates.
• Intoxicated patient with suicidal ideation, children, or vulnerable adults: safeguarding, psychiatric and social assessment.
• Alcohol withdrawal (hallucinations, seizures, delirium tremens): benzodiazepines, thiamine and supportive care.

Interferences and pitfalls.

• Enzymatic assays can be falsely high in the presence of lactate and lactate dehydrogenase (in severe lactic acidosis, for example in shock, with ethylene glycol, or in uraemia), because of the reverse reaction; laboratory methods with gas chromatography confirm medico legal samples.
• Alcohol based skin preparations contaminate samples, and leaving tubes uncapped causes loss by evaporation.
• Samples without fluoride can ferment glucose to ethanol, and storage at room temperature for days raises results.
• Whole blood versus serum conversion: divide serum results by 1.15 to estimate whole blood, which matters for legal limits.
• Breath analysers estimate blood levels (partition ratio 2100 to 1) and are affected by mouth alcohol, acetone in diabetic ketoacidosis, and recent drinks.
• Isopropanol and methanol are not detected by enzymatic ethanol assays (alcohol dehydrogenase has low reactivity), and gas chromatography or specific assays are needed.
• Carbohydrate deficient transferrin, gamma glutamyl transferase, mean cell volume, ethyl glucuronide and phosphatidylethanol (PEth) assess chronic drinking, not acute levels. PEth in blood is detectable for 2 to 4 weeks, ethyl glucuronide in urine for 3 to 5 days.
• Medico legal use requires chain of custody, consent or legal authority, and documentation of times.
• Absorption is affected by food, gastric emptying and drugs; peak levels occur 30 to 90 minutes after drinking.
• Intoxication is a risk factor for harm and not an exclusion for assessment, treatment and discharge decisions.

Special groups.

• Children: hypoglycaemia, seizures and coma at low levels from accidental ingestion of hand sanitiser, mouthwash or perfume.
• Pregnancy: alcohol causes foetal alcohol spectrum disorder; screening and brief interventions are indicated.
• Older adults: increased sensitivity and falls at low levels.
• Heavy drinkers: tolerance, withdrawal, thiamine deficiency (Wernicke encephalopathy), liver disease and pancreatitis.
• Co-ingestion patients: opioids, benzodiazepines and sedatives additively depress breathing.
• Regions: alcohol use is a major cause of injury and violence in many countries; informal and illicit alcohol may contain methanol, causing outbreaks of poisoning.

Follow up tests. Blood glucose, venous blood gas, electrolytes with anion gap, serum osmolality and osmolar gap, urea and creatinine, liver function and gamma glutamyl transferase, lipase, magnesium, phosphate and potassium, full blood count, paracetamol and salicylate levels, urine drug screen, toxic alcohol levels, ketones (beta hydroxybutyrate), CT head in trauma,

thiamine and folate, hepatitis serology, phosphatidylethanol or carbohydrate deficient transferrin for chronic use, and psychosocial assessment.