Ethanol and other ‘toxic’ alcohols

Introduction

Alcohols are hydrocarbons that contain a hydroxyl (OH) group. Ethanol, a two-carbon primary alcohol, is the most commonly used recreational drug in Australasia and elsewhere in the western world. Ethanol misuse is a major cause of mortality and morbidity both directly and indirectly, and emergency departments (EDs) deal with the results on a daily basis. It was estimated that 3290 Australians died in 1997 from injury due to high-risk drinking, and that there were 72,302 hospitalizations. In a recent study it was noted that 1 in 10 presentations to EDs in Australia were related to alcohol.

The complications of chronic alcohol consumption contribute to the development of a number of medical and surgical emergencies, many of which are dealt with elsewhere in this text. This chapter confines its discussion to acute ethanol intoxication, ethanol withdrawal and two other important ethanol-specific emergency presentations—Wernicke encephalopathy (WE) and alcoholic ketoacidosis (AKA).

A number of other alcohols, though far less frequently implicated in ED presentation than ethanol, are metabolized to form toxic organic acids and produce life-threatening clinical syndromes. These alcohols include methanol and ethylene glycol and are termed ‘toxic alcohols’. Early recognition of their ingestion and intervention can prevent significant morbidity and mortality due to these alcohols.

Ethanol

Clinical presentation

Ethanol withdrawal syndrome

A withdrawal syndrome usually develops within 6 to 24 hours of cessation or reduction in ethanol consumption in dependent individuals. Symptoms can begin any time after the blood ethanol concentration begins to fall, and blood ethanol is frequently still measurable in withdrawing patients. The duration of the syndrome may be from 2 to 7 days. Although its pathophysiology is not well understood, the syndrome presents as unopposed sympathetic and CNS stimulation. It is associated with a mortality of 5%, and early clinical recognition of this syndrome is important.

Patients may present to the ED already in withdrawal after deliberately abstaining from alcohol or after stopping drinking due to intercurrent illness or lack of funds to buy alcohol. Alternatively, ethanol-dependent patients may begin to withdraw while being treated in the ED, particularly where their stay is prolonged.

Clinical features of mild ethanol withdrawal are those of mild autonomic hyperactivity and include nausea, anorexia, coarse tremor, tachycardia, hypertension, hyperreflexia, insomnia and anxiety. In more severe cases, the patient goes on to develop more pronounced anxiety, insomnia, irritability, tremor, tachycardia, hyperreflexia, hypertension, fever, visual hallucinations, seizures and delirium. Symptoms usually peak by 50 hours. Delirium tremens represents the extreme end of the spectrum of ethanol withdrawal. It is an uncommon but potentially lethal complication.

Wernicke encephalopathy

This is an acute neuropsychiatric syndrome that develops in certain alcohol-dependent individuals as a result of thiamine deficiency. It is a spectrum disorder that is classically described as a triad of

• oculomotor disturbance (usually nystagmus and ocular palsies)

• abnormal mentation (usually confusion)

• ataxia

In up to 20% of cases, the signs and symptoms of the classic triad are not evident at presentation. Less common presentations include stupor, hypothermia, cardiovascular instability, seizures, visual disturbances, hallucinations and alterations in behaviour. In extremis, the condition may present with hyperthermia, hypertonia, spastic paresis, dyskinesias and coma.

WE is a clinical diagnosis and constitutes a medical emergency with significant morbidity and a mortality of 10% to 20% if left untreated. For this reason, the emergency physician must maintain a high index of suspicion in any patient with altered mental status and suspected prolonged heavy ethanol intake.

Alcoholic ketoacidosis

AKA, also termed alcoholic acidosis, is an often unrecognized potentially life-threatening medical condition that develops in the alcoholic patient in response to starvation. The normal response to starvation is increased gluconeogenesis from pyruvate. In the alcoholic patient, pyruvate is preferentially converted to lactate. In response, fatty-acid metabolism is increased as an alternative source of energy, resulting in the production of acetyl-CoA and acetoacetate which, in turn, is reduced to β-hydroxybutyrate (BOHB), producing the ketoacidotic state.

Patients with AKA usually present with a history of prolonged heavy alcohol misuse preceding a bout of particularly excessive intake, which has been terminated several days earlier by nausea, severe vomiting and abdominal pain. There may be a history of previous episodes requiring brief admissions with labels of ‘query pancreatitis’ or ‘alcoholic gastritis’. Examination usually reveals tachypnoea, tachycardia, hypotension and diffuse epigastric tenderness on palpation. In contrast to patients with diabetic ketoacidosis, mental status is usually normal. The presence of an altered mental state should prompt consideration of other causes, especially hypoglycaemia and acute ethanol intoxication.

Toxic alcohol poisoning is an important differential diagnosis. Toxic alcohol acidosis does not produce ketosis and, in contrast, does cause significant alteration to conscious state, visual symptoms (methanol) and renal failure/crystalluria (ethylene glycol).

Clinical investigations

The excretion of ethanol by the lungs, although relatively unimportant in terms of ethanol elimination, obeys the Henry law, that is, the ratio between the concentration of ethanol in the alveolar air and blood is constant. This allows breath sampling of ethanol to estimate reliably blood ethanol concentration.

Most non-tolerant adults would be expected to develop some impairment of higher functions at blood ethanol concentrations in the range of 0.025 to 0.05 mg/dL (5 to 11 mmol/L) and to develop significant CNS depression in the range of 0.25 to 0.4 mg/L (55 to 88 mmol/L).

In a patient presenting with acute intoxication, no investigations may be necessary; however, blood or breath ethanol levels (BALs) are frequently useful to confirm the diagnosis. A BAL of zero is highly significant in a patient with an altered level of consciousness, as ethanol intoxication is excluded and other diagnoses need to be considered. A positive blood ethanol level does not exclude alternative diagnoses.

Other investigations should be performed as clinically indicated in an effort to exclude coexisting pathologies and alternative diagnoses as detailed earlier.

In the patient with AKA, bedside investigations reveal a low/normal glucose, low or absent breath ethanol and urinary ketones (these may be low or absent due to the inability of bedside assays to detect all ketone moieties, especially BOHB). Laboratory investigation will reveal an anion-gap (AG) acidosis (this may be severe with AG >30) and mild hyperlactaemia insufficient to account for the AG.