Ethanol

GENERAL PRINCIPLES

Pathophysiology

• Ethanol enhances inhibitory signaling through the GABA-A receptor and suppresses excitatory signaling through the NMDA glutamate receptor.

• Over time, patients with chronic heavy ethanol use will develop profound tolerance to the effects of ethanol.

This occurs via qualitative changes in GABA-A receptors which render them less sensitive to activation, and via quantitative upregulation of NMDA receptors.

• Ethanol is eliminated primarily by the alcohol dehydrogenase pathway; elimination follows zero-order kinetics.

• Acute and chronic heavy ethanol use have many deleterious health effects that are outside the scope of this chapter (e.g., alcoholic hepatitis, pancreatitis, cardiomyopathy, peptic ulcer disease, cancers).

DIAGNOSIS

Clinical Presentation

• Alcohol intoxication produces mental status changes, slurred speech, and motor impairment, with prominent cerebellar dysfunction.

• In cases of severe intoxication, airway protective reflexes and respiration may be impaired (although this is much more common in mixed ingestions with other sedatives such as benzodiazepines or opioids).

• Tolerance for ethanol varies considerably; a patient with a history of chronic heavy ethanol consumption may show no clinically obvious signs of intoxication.

Diagnostics

LABORATORIES

• Obtain a blood glucose. Hypoglycemia may mimic ethanol intoxication, and patients with chronic heavy ethanol use are at risk of hypoglycemia.

• It may be reasonable to check a blood ethanol concentration in a patient with mental status changes of unclear etiology.

TREATMENT

• Treatment for ethanol intoxication is exclusively supportive, with clinical monitoring for recovery to

baseline and airway support in the rare patient with airway compromise.

• Clinical reassessment for clinical sobriety is a key component of treatment.

• It is unusual for patients to require intubation and mechanical ventilation for ethanol intoxication alone.

• Patients with any evidence of Wernicke encephalopathy (confusion or mental status changes not improving with time, ataxia or gait changes not improving with time, oculomotor abnormalities) should be treated with high-dose intravenous thiamine (500 mg IV tid ?3-5 days).

SPECIAL CONSIDERATIONS

Alcohol Withdrawal

• Alcohol withdrawal is a potentially life-threatening syndrome of central nervous system hyperexcitation that may occur when an alcohol-tolerant patient abruptly discontinues alcohol intake.

î Not all patients with chronic heavy ethanol use will experience alcohol withdrawal.

î The most important risk factor for alcohol withdrawal in the hospitalized patient is previous episodes of alcohol withdrawal.

• Alcohol-tolerant patients develop significant qualitative and quantitative changes in their GABAergic and glutamatergic signaling pathways that allow for significant alcohol tolerance, as described above. When the alcohol is removed, the patient's underlying unbalanced excitatory-inhibitory state is unmasked.

• Ethanol withdrawal may occur anytime from hours to 4 or 5 days after the patient's last drink.

• There are four primary manifestations of alcohol withdrawal:

î Acute uncomplicated alcohol withdrawal presents with tremulousness, anxiety, nausea, flushing, tachycardia, and hypertension.

î Alcoholic hallucinosis presents with visual and auditory disturbances that are more accurately termed illusions since patients typically retain reality testing.

î Alcohol withdrawal seizures may occur seemingly at random, even in the absence of any other signs of withdrawal.

î Delirium tremens, which is life-threatening, presents with significant dysautonomia (including hyperthermia), seizures, agitation, and psychosis.

• The treatment of alcohol withdrawal should consist of protocol-based, symptom-triggered administration of GABAergic sedatives typically benzodiazepines or phenobarbital.

î Scheduled, fixed-dose treatment regimens are comparatively ineffective and may lead to undertreatment or overtreatment.

î Sedatives may be given by mouth for mild symptoms; moderate and severe symptoms require intravenous treatment.

• Dexmedetomidine is generally not helpful; it does not target the GABAergic or glutamatergic systems, it may mask autonomic signs of alcohol withdrawal without preventing seizures, and it has generally not proven to improve patient-centered outcomes or length of stay in clinical trials. ³¹

Alcohol Use Disorder

• AUD is a problematic pattern of alcohol use leading to clinically significant impairment or distress. Patients with AUD may have overwhelming cravings for alcohol, use alcohol in dangerous situations or despite the knowledge that it is harming them, suffer social and legal consequences from alcohol use, and experience tolerance and withdrawal.

• Pharmacotherapy for AUD may be helpful in reducing drinking days, reducing the amount of alcohol

consumed, and controlling cravings for alcohol.

î Psychotherapy and social support are also key components of AUD treatment for many patients.

î The goal of AUD treatment is not always complete abstinence.

• Naltrexone 50 mg daily may help reduce heavy drinking and cravings by interfering in the endorphin reward pathways that incentivize alcohol consumption.

î Long-acting injectable naltrexone (Vivitrol) may enhance compliance compared to oral naltrexone; this should be administered only after the patient has tolerated oral naltrexone for at least 1 week.

î Naltrexone is contraindicated in patients with a need for opioid therapy (including patients with comorbid OUD who benefit from treatment with buprenorphine or methadone) and in patients with hepatic impairment.

• Gabapentin may help reduce heavy drinking, although the existing evidence is somewhat equivocal.

Various dosing regimens have been studied; 1200 mg daily in divided doses is reasonable. ³²

• Other agents including acamprosate, topiramate, and baclofen may be helpful.

• Disulfiram is ineffective and potentially dangerous and should not be used.