Exigencies in Management of the Person who Consumes Ethanol

What particularities impact the emergent care of a patient who drinks?

Ethanol is problematic, a socially sanctioned drug that nevertheless causes great harm. Because of its central nervous system (CNS) effects, because of its hepatotoxicity and effect on almost all body systems, and because of widespread use at hazardous and harmful levels, ethanol is a potent social ill. All up, counting acute binge drinking, ethanol withdrawal, and chronic ethanol overuse, not to mention its often far-reaching psychological and social effects, ethanol will account for as many as 15% of Emergency Department visits. Many of these conditions, including the acute binge, can be life-threatening. Chronic alcoholics often consume few calories other than alcohol, resulting in metabolic derangements and vitamin deficiency syndromes that can also be life-threatening. Moreover, there is evidence that both sustained and binge drinking have the same toxic effect on the hepatocytes. ln addition, the toxic effect of alcohol on hepatocytes can result in a chemical hepatitis.

Together, this all means that patients with alcohol related diseases are often unwell and vulnerable. Have a comprehensive approach to these patients so that they come to no harm and so that they get appropriate care.

Broach the history with a matter-of-fact but kind approach, while remaining somewhat guarded, in that, given the complex nature of addiction behaviour, patients often avoid questions pertaining to their drinking habits. A kind word here often goes a long way. Once rapport has been established, however, a non-judgemental execution of the CAGE questionnaire will screen for the presence of ethanol abuse before ascertaining a quantitative account of their ethanol intake, as appropriate:

C. Have you ever felt that you need to Cut down on your drinking?
A. Have people Annoyed you by criticizing your drinking?
G. Have you ever felt bad or Guilty about your drinking?
E. Have you ever had a drink first thing in the morning to steady your nerves or get rid of a hangover [“E” is for the so-called “Eye-opener”, or morning drink)?

Alcohol is primarily a depressant neurotransmitter in the CNS, mimicking GABA neuroregulators. GABA receptors are up-regulated in chronic alcohol abuse while, in alcohol withdrawal, the absence of GABA stimulation results in a hyperadrenergic state, with signs and symptoms of anxiety, tremors, diaphoresis, tachycardia and hypertension.¹ Ethanol metabolism is primarily hepatic via alcohol dehydrogenase and, though typically following zero-order kinetics for most, may follow first-order kinetics in high dose or the chronic user so that alcohol metabolism may be described as non-linear; nevertheless, the average rate of alcohol metabolism in an adult is about 20-30 mg/dL/hr.

Alcohol associated conditions and red-flag presentations:

• GI bleeding: (chronic) liver disease, portal hypertension, splanchnic venous congestion (+/- thromboses), coagulopathy
• Alcoholic pancreatitis
• Alcoholic hepatitis
• Alcoholic ketoacidosis
• Trauma/ Falls
• Vitamin and nutritional deficiency syndromes: malnutrition, starvation, hypoglycemia, hyponatremia
• Withdrawal syndromes: Delirium Tremens; Wernicke-Korsakoff syndrome
• Alcohol substitution: ethylene glycol, methanol, or isopropyl alcohol toxicity, Listerine toxicity
• Dyspnoea: aspiration pneumonia, tuberculosis, pulmonary infection
• Weakness: malnutrition, co-ingestion, liver disease, anemia, muscle atrophy, cachexia
• Tremor, fasciculations: seizure (withdrawal), liver disease, hypoglycemia

Some useful pointed questions to consider, among others, in especially the unwell patient who otherwise volunteers little:

1. Have you been vomiting?
2. Have you had a fever / chills?
3. Have you had any abdominal pain?

Alcohol withdrawal syndromes (in order of increasing severity, symptoms additive)

• mild alcohol withdrawal: tremors, abdominal pain, nausea, vomiting
• alcohol withdrawal seizure: hallucinations; generalised seizures, over a short period occurring at any time following abstinence
• delirium tremens (DTs): hyperthermia, altered mental state, adrenergic instability
  • severe tremor
  • tachycardia
  • hypertension
  • tachypnoea
  • diaphoresis
  • fever
  • profoundly altered mental state

Other drug withdrawal syndromes to particularly consider in the patient that overuses ethanol:

• benzodiazepine withdrawal
• opiate withdrawal

Have a low threshold to obtain diagnostic imaging because of the frequent episodes of blunt trauma that accompany alcohol intoxication and alcohol withdrawal. A good initial approach to evaluating patients with either alcohol intoxication or alcohol withdrawal is to completely expose them and perform a complete examination evaluating for occult injuries.

Urgent and bedside testing

• Point-of-Care BGL
• Serum ethanol: use blood ethanol levels, in conjunction with the patient’s presentation, to differentiate alcohol intoxication from other conditions. A patient able to communicate appropriately, ambulate safely, eat and drink successfully, and understand discharge instructions, is likely ready for discharge, regardless of blood ethanol level. That patient, however, should not be allowed to drive, should have a place to go, and should be released with another adult (who has been given and understands the discharge instructions). Psychiatric facilities may not accept intoxicated patients who require hospitalization for psychiatric purposes until an ethanol level is < 100 mg/ dL.
• CBC: alcoholic patients may have a leukocytosis due to infection, or leukopenia and thrombocytopaenia secondary to chronic bone marrow suppression
• Metabolic panel: apart from the common disturbances of K⁺ and Na⁺, the bicarbonate level should be made note of, because low bicarbonate may indicate the presence of an anion gap acidosis (especially with alcoholic ketoacidosis). In addition, ingesting methanol or ethylene glycol (toxic alcohols that cause significant morbidity) can cause profound anion gap metabolic acidoses.
• LFTs: The aspartate aminotransferase (AST) is typically much greater than the alanine aminotransferase (ALT) in alcoholic liver disease. The gamma-glutamyl transferase (GGT) is a liver enzyme that is elevated in alcoholics.
• Lipase: there may be no elevation of serum lipase, however, where the pancreatitis is chronic
• INR and Coags: chronic liver disease causes both a coagulopathy and thrombophilia
• Urinalysis: infection, ketones, blood, urobilirubin
• Calcium, magnesium, phosphorus: reduced in alcoholism and malnutrition and essential to metabolism; serum hypomagnesemia only occurs in the most severe stages of whole-body hypomagnesemia; i.e. a normal serum magnesium level does not accurately reflect magnesium stores
• Serum osmolality: any great difference between the calculated and measured serum osmolality (Osmolar gap: normal < 10 mOsm/kg) signifies the presence of osmotically active substances, such as methanol, ethylene glycol, isopropanol, acetone or mannitol, in serum.

Principles of Management

Acute ethanol intoxication

Cover the ABCs and provide supportive treatment. Disinhibited or agitated intoxicated patients commonly require sedation, because they may present a safety threat to themselves and others. Use chemical sedation to avoid the use of more harmful physical restraints. Benzodiazepines (e.g., lorazepam, diazepam, and midazolam) are the most commonly used sedative agents in the agitated, alcoholic patient, although large doses may be required in this setting, which may cause significant respiratory depression. The butyrophenone, haloperidol, offers greater sedation with little to no respiratory depression and is as effective as benzodiazepines for chemical restraint with fewer side effects. Butyrophenones, however, are not as effective for the sole treatment of alcohol withdrawal, as they lack GABA effects.

Alcohol-associated conditions

Metabolic and nutritional deficiencies: Patients fail to consume complex carbohydrates and vitamins because ethanol is often the predominant (or only) carbohydrate they ingest. Ketoacidosis from glucose lack and Wernicke’s encephalopathy due to thiamine deficiency are metabolic and nutritional deficiencies commonly seen in alcoholics. Replace vitamins, including thiamine and folate in patients suffering from chronic alcohol abuse. Where appropriate, offer the patient a balanced meal; not only to see if the patient can tolerate it, but it provides calories and carbohydrates needed for metabolism. Otherwise, intravenous glucose should be provided if the patient is unable to eat. Fluids and glucose will rapidly correct alcoholic ketoacidosis. With proper treatment, alcoholic ketoacidosis can resolve within hours. Meanwhile, thiamine deficiency and the resulting altered mental status may take several days and large quantities of vitamin B1 to correct. Patients with severe thiamine deficiency generally require admission. Because of a theoretical risk of precipitating Wernicke’s encephalopathy if glucose is given to a thiamine-deficient patient, thiamine is generally administered simultaneously with the glucose. Alcoholic patients are typically magnesium and phosphate depleted, and these should both be replaced.

Thiamine is a co-factor in numerous enzymatic reactions involved in energy metabolism. The consequences of thiamine deficiency include an accumulation of lactate and excess production of glutamate, which may lead to excessive excitatory neurotransmission in the brain. This can cause vasogenic and cytotoxic edema.

The daily requirement of thiamine is about 1-2 mg. Thiamine is absorbed only inefficiently by the jejunum and some 30 mg is stored in the liver, but lower amounts in those with liver disease. With inadequate intake, a previously healthy person can become thiamine deplete in as little 2-4 weeks. In the context of acute or chronic illness, deficiency can occur more rapidly still. Magnesium is a cofactor for thiamine activity and magnesium promotes cellular thiamine uptake.²

The classic triad of encephalopathy, ophthalmoplegia, and ataxia is present in only 15% of cases of Wernicke’s encephalopathy. Delirium is the most consistent clinical characteristic of encephalopathy. Horizontal nystagmus is the most common ophthalmoparesis, and may improve within hours of receiving intravenous thiamine. Ataxia predominantly affects the the legs (gait) more than the arms, and speech usually remains unaffected. Other clues for a Wernicke’s encephalopathy include hypothermia (hypothalamic involvement) and hypotension. (More chronic thiamine deficient states present as beriberi: peripheral neuropathy or “dry”; high-output heart failure or “wet”, a medical emergency.) Where uncertainty exists, a whole-blood thiamine diphosphate level might help. A CT brain scan will not usually reveal Wernicke encephalopathy.  The primary role of CT brain in this setting is to exclude alternative causes for the patient’s condition. MRI is about 50% sensitive and 90% specific for diagnosing thiamine deficiency; however, MRI may normalize within days of thiamine initiation. Classically, distribution of MRI abnormalities is paraventricular and symmetric. A variant of dry beriberi, Wernicke encephalopathy presents in well-defined steps: starting with nausea and vomiting, followed by horizontal nystagmus, ocular nerve palsy, fever, ataxia, and progressive mental impairment, eventually leading to the Korsakoff syndrome. With thiamine replacement, ocular abnormalities usually begin to improve within about one day; ataxia and confusion usually begin to improve within a week; and confusion generally resolves over a month. But less than 50% of patients show significant recovery after treatment. An irreversible Korsakoff’s psychosis (marked by confabulation) may occur where treatment with thiamine is delayed.²

Thiamine supplementation is appropriate for all at-risk patients, those with alcoholism or malnutrition. Give 100 mg IV or IM thiamine daily, for a few days. Give also, acutely, Magnesium sulfate 2 g IV over 30-60 min. Where renal function permits, continue magnesium oxide 400 mg PO BID during hospitalisation. A switch to oral thiamine requires increasing the dose to account for inefficient jejunal absorption: 200 mg BID, until discharge. Ensure the patient stays on 100 mg oral daily thiamine after discharge.²

Alcohol withdrawal syndromes

Ethanol withdrawal leads to CNS excitation from GABA-ergic withdrawal. Administration of a GABA agonist will re-open chloride channels and reduce CNS excitation. Mild alcohol withdrawal can often be treated as an outpatient after initial stabilization in the ED, especially if the patient has good support systems in place. The treatment of alcohol withdrawal is based on the degree of withdrawal the patient is experiencing. Consider adopting the Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA) protocol. Patients scoring less than 10 on the CIWA do not usually need additional medication for withdrawal:

• Nausea and vomiting: 0 (nil) to 7 (constant)
• Tremor: examine with arms extended and fingers spread apart: 0 to 7 (severe, even without arms extended)
• Paroxysmal sweats: 0 to 7 (drenching)
• Anxiety: 0 to 7 (acute panic state)
• Agitation: 0 (normal activity) to 7 (paces back and forth during most of the interview
• Tactile disturbances: 0 (nil) to 1-3 (itching) to 7 (continuous hallucinations)
• Auditory disturbances: 0 to 7 (continuous)
• Visual disturbances: 0 to 7 (continuous)
• Headache, fullness in head: 0 to 7 (extremely severe)
• Orientation and Clouding of Sensorium: 0 (oriented and performs serial additions) to 4 (disoriented for person or place)

The most frequently used agents to control alcohol withdrawal are benzodiazepines, especially diazepam and lorazepam. Alcohol withdrawal peaks in 2-3 days and can last 5-7 days; therefore, longer-acting agents are generally preferred to prevent frequent re-dosing. In addition, long-acting agents wear off slowly, leading to a smoother, more predictable, experience for the patient. This allows patients to take subsequent doses of medication before significant withdrawal symptoms recur.

Parenteral benzodiazepines are generally used to treat moderate to severe alcohol withdrawal in the ED, especially if the patient is vomiting or not willing to take oral medication.

The half-life of diazepam is 10-50 hours and active metabolite have a half-life of up to 100 hours, which makes it a much better choice than lorazepam, with a half-life of only 10-20 hours, for oral outpatient use. Oxazepam, with a half-life of 4-15 hours, is also commonly used.

Severe alcohol withdrawal includes significant vital sign changes, CNS excitation, and seizures. Except for the obvious–i.e., treating the seizure–medical therapy is similar to mild alcohol withdrawal. Lorazepam is the preferred parenteral agent to stop an actively seizing patient.

Delirium tremens (DT) is an uncommon but life-threatening condition characterized by severe alterations in mental status and abnormal vital signs. Mortality is usually due to decompensation from adrenergic instability.

Treatment of Delirium Tremens:

1. aggressive GABAergic therapy:
   1. benzodiazepines: large doses and frequently continuous benzodiazepine infusions, but watch for respiratory depression and prolonged sedation
   2. barbiturates: a single intravenous dose of phenobarbital in the ED, typically between 130 and 260 mg, followed by repeated doses of 65-130 mg as necessary, to control tremulousness and withdrawal symptoms and, because of its long half-life (80-120 hours), will remain in the patient’s system for as long as the patient is at risk for alcohol withdrawal symptoms
   3. propofol: in severe cases requiring intubation, propofol is a strong GABA agonist and may be more effective than benzodiazepines and barbiturates
2. volume replacement
3. correction of any electrolyte abnormalities¹

Other medications that may have a therapeutic role in alcohol withdrawal include haloperidol, gabapentin, and clonidine.³ Despite aggressive therapy and modern intensive care, the mortality rate of Delirium Tremens remains approximately 20-30%.

Alcoholic patients not infrequently present with an acute abdomen. The approach here is to consider the life-threatening conditions, inclusive of alcoholic ketoacidosis, first:

• Occult infection
• Gastrointestinal Tract Bleeding (GITB)
• Pancreatitis
• Hepatitis
• Perforated ulcer
• Trauma

These are managed according to standard protocol.

In some patients, the consumption of alcohol comes at the cost of consuming something far more nutritious. These patients invariably suffer from some amount of metabolic, neuropsychiatric, and hepato-synthetic functional deficiency. The hospitableness of bringing them in, providing them warmth, and offering them a plate of food, are the simple acts of human kindness that go a long way in providing not only resolution to the person’s acute medical, but also their long-term situational, crises. By all means, know that you can give propofol to a seizing alcoholic, and know also the dose to give of intravenous lorazepam. But otherwise, do not underestimate the value of warmly offering a plate of food and glass of water. Not only is it the decent thing to do, it is also good medicine.

References

1. Rose, John S. and Laurin, Erik G. “Alcohol-related emergencies.” In (Eds.) S.V. Mahadevan and Gus M. Garme. An Introduction to Clinical Emergency Medicine. 2nd Edn. Cambridge: Cambridge University Press, 2012: 163-175.
2. Farkas, Joshua. “Wernicke encephalopathy.” The Internet Book of Critical Care. Oct 14, 2020. Available at https://emcrit.org/ibcc/wernicke/.

Further:

• University of Michigan Alcohol Withdrawal Guidelines. Available at https://www.med.umich.edu/clinical/images/ETOHCompleteTeachingPacket_FINAL082509.pdf.