Unusual Complications of Alcohol Withdrawal
- May 14th, 2018
- Mengyang Liu
Authors: Mengyang Liu, MD (EM Resident Physician, Baylor College of Medicine) and Spencer Greene, MD (EM Attending Physician and Director of Medical Toxicology, Baylor College of Medicine) // Edited by: Alex Koyfman, MD (@EMHighAK) and Brit Long, MD (@long_brit)
Clinical case #1
A 35-year-old woman with a history of alcoholism, anxiety, and depression presents to the emergency department with 3 days of generalized nausea, vomiting, and generalized abdominal pains. The patient stopped drinking 5 days. She reports drinking about 5 drinks a day for the past 10 years. She also endorses intermittent chest pain and difficulties breathing when she tries to sleep for the past few days.
Vitals show BP 154/72, HR 108, RR 24, SpO2 92% on room air, T 98.4F. Exam shows patient with respiratory distress and bibasilar rales. Patient improves with non-invasive positive pressure ventilation (NIPPV) and sublingual nitroglycerin. EKG shows sinus tachycardia, right axis deviation, and T-wave inversions in lateral leads. Troponin I is elevated at 0.2. Chest X-ray shows pulmonary edema.
What is the pathophysiology underlying this patient’s acute heart failure and cardiac ischemia?
Clinical case #2
A 58-year-old male with a history of alcohol abuse presents to the ED with 2 days of nausea, vomiting, and epigastric abdominal pain. The patient stopped drinking 3 days ago after his son was recently killed in a drunk driving accident. His symptoms have gradually been worsening since then. He has been consuming 6-8 beers a day for the past 25 years.
Vitals show BP 166/84, HR 110, RR 22, SpO2 98% on room air, T 99.2F. He is alert and oriented to person, place, and time, but needs frequent redirection. Exam shows an anxious patient, mildly diaphoretic, with moderate epigastric tenderness. Labs on presentation reveal Na 140, K 4.0, Cl 100, CO2 10, glucose 65 mg/dL, venous pH 7.14. Lipase is 1,500, and LFT’s show mild elevation in AST/ALT. UA demonstrates glycosuria and ketonuria. Beta-hydroxybutyrate is positive.
What is causing this patient’s acidosis, and how should you manage it?
Withdrawal is a major source of morbidity and mortality in alcoholic patients and accounts for a significant portion of intensive care unit (ICU) admissions . Fortunately, earlier recognition and better management of alcohol withdrawal have reduced the mortality rate of severe alcohol withdrawal to about 1-4% [1,2]. Management is centered on aggressive initial dosing of and symptom-triggered use of benzodiazepines, alongside supportive care and adequate fluid resuscitation. The complications of alcohol withdrawal that are more commonly recognized are autonomic hyperactivity, withdrawal seizures, and withdrawal delirium [1,2]. This article serves to highlight less common and less well studied complications of alcohol withdrawal, many of which are life-threatening. For more on withdrawal itself, see this emDocs post. This article will not look at vitamin deficiencies of other alcohol-associated complications.
Alcohol agonizes GABA receptors and antagonizes NMDA receptors to produce generalized CNS depression. Chronic use causes conformational changes of these receptors that result in desensitization of GABA receptors and upregulation of NMDA receptors . Acute decrease or cessation in alcohol consumption then causes loss of inhibition of GABA and antagonism of NMDA, leading to down-stream surges of catecholamines responsible for increased sympathetic activity [3,4]. Most alcoholics have underlying electrolyte abnormalities secondary to alcohol and malnutrition, and these may be worsened during alcohol withdrawal. Specifically, the catecholamine surge during alcohol withdrawal causes intracellular shifting of potassium, magnesium, and phosphate [5, 6]. Patients in alcohol withdrawal are also in an overall fasting state due to metabolism of alcohol to acetyl-CoA, which inhibits glycolysis and promotes fatty acid metabolism. Many of the complications described below are related to the catecholamine surge, metabolic disturbances, and fasting state accompanying alcohol withdrawal.
Uncommon complications of alcohol withdrawal
While alcohol abuse precipitates dysrhythmias, most notably atrial fibrillation in the setting of alcoholic cardiomyopathy, alcohol withdrawal can also precipitate potentially life-threatening dysrhythmias. Alcohol withdrawal has been associated with QTc prolongation and increased QTc variability due to increased sympathetic activity and concurrent electrolyte abnormalities (hypokalemia, hypomagnesemia) [7, 8]. Both these changes in the QTc interval have been shown to increase the risk of ventricular dysrhythmias and sudden cardiac death. A retrospective study of EKG changes in 49 patients with severe alcohol withdrawal (seizures or delirium tremens) not on QT prolonging medications showed that 60-70% had QTc prolongation, 2 of which developed torsades . There have been case reports of ventricular fibrillation and ventricular tachycardia being precipitated by alcohol withdrawal [7, 10, 11]. Alcohol withdrawal has also been shown to interact with cardiovascular medications, notably by potentiating the bradycardic effects of beta-blockers .
Patients with alcohol withdrawal without a prior history of coronary artery disease have also been noted to develop ST segment abnormalities , though not all of these were symptomatic. There have been case reports of alcohol withdrawal precipitating non-ST and ST elevation myocardial ischemia in patients with underlying cardiovascular disease [10, 14]. A prospective analysis of EKG changes in 20 admitted patients with alcohol withdrawal syndrome found that 5/20 had chest pain, 2 of which were ischemic in nature . Cardiac ischemia in the setting of alcohol withdrawal is thought to be caused by increased sympathetic activity causing increased myocardial oxygen demand and alcohol-induced structural changes to the heart. It can be refractory to benzodiazepines, as benzodiazepines act on GABA but do not have any effect on upregulated NMDA receptors. Fortunately, coronary ischemia in setting of alcohol withdrawal has not yet been demonstrated in patients without underlying coronary artery disease or structural heart disease.
Stress cardiomyopathy, aka Takotsubo cardiomyopathy, is an acute reversible apical ventricular dysfunction in the absence of obstructive coronary artery disease (CAD). It is thought to be due to a sudden excess catecholamine surge and can present with chest pain, heart failure, ischemic changes on EKG, and elevated troponin. Treatment is supportive, but due to ischemic changes often meeting criteria for STEM, these patients are usually diagnosed in the cath lab. Due to a sudden surge in catecholamines, alcohol withdrawal has been shown to precipitate stress cardiomyopathy [4, 16, 17, 18]. Like cardiac ischemia, stress cardiomyopathy in the setting of alcohol withdrawal can be refractory to benzodiazepines alone and may require adjunctive medications such as dexmedetomidine . Though it is important to recognize and stabilize stress cardiomyopathy due to alcohol withdrawal, it is vital to remember that the diagnosis of stress cardiomyopathy requires the absence of obstructive CAD, as the management of these two pathologies are very different.
Osmotic demyelination syndrome
Osmotic demyelination syndrome (ODS) results from rapid fall in brain volume primarily in the context of rapid correct of hyponatremia. ODS most often involves the pons (central pontine demyelination), but can also involve extrapontine areas such as the basal ganglia, midbrain, and thalamus. It results in variable neurologic deficits ranging from confusion and behavioral disturbances to seizures, comas, and the infamous “locked-in” syndrome (quadriplegia with inability to speak or swallow) [19, 20, 21]. Definitive diagnosis is made by MRI. Management involves prevention of rapid correction of hyponatremia, DDAVP, and possibly D5W in an intensive care setting.
Patients with alcohol withdrawal are at increased risk for ODS due to underlying hyponatremia [19-23]. Changes in the integrity of the blood-brain barrier during alcohol withdrawal and decreased glucose available for cerebral osmotic regulation (increased overall metabolic demand, underlying starvation state) contribute . ODS secondary to alcohol withdrawal has also been seen in patients who are normonatremic, though it is difficult to assess if hyponatremia was present prior to presentation [19, 22]. While hyponatremic ODS has a mortality as high as 50% in the first 2 weeks, ODS associated with alcohol withdrawal without hyponatremia is thought to have a better prognosis .
Alcoholic ketoacidosis (AKA) presents with gastrointestinal symptoms and volume depletion, and patients are usually less altered or confused than in diabetic ketoacidosis (DKA) . Patients with alcoholic ketoacidosis are also more likely to be eu- or hypo-glycemic than in DKA. AKA typically occurs in the setting of withdrawal rather than during active alcohol consumption. Active ethanol ingestion promotes fatty acid metabolism by the liver but inhibits peripheral lipolysis [3, 24]. It is the corresponding catecholamine surge during alcohol withdrawal that creates a marked increase in hepatic and peripheral lipolysis leading to often profound ketoacidosis. Furthermore, alcohol may be the main source of caloric intake for many chronic alcoholics, leading to increased starvation and worsening of ketoacidosis during the withdrawal period . Management of AKA involves careful consideration of other causes of anion gap acidosis, electrolyte repletion, thiamine, and dextrose containing fluids to stimulate insulin release and glucose metabolism.
Alcohol consumption is a common cause of pancreatitis. Interestingly, a prospective analysis in 2005 of 100 patients with first episode of alcoholic pancreatitis demonstrated that about 70% of patients actually developed symptoms during the first day of cessation or later . Though not likely to change ED management, it is important to consider that though the patient may have stopped drinking alcohol, pancreatitis may actually worsen during the withdrawal phase. For more on pancreatitis, see this emDocs post.
There have also been cases of marked catatonia associated with alcohol withdrawal . Catatonia is characterized by mutism, negativism, immobility, and overall social withdrawal. Catatonia secondary to alcohol withdrawal likely represents a type of alcohol withdrawal delirium as opposed to its own distinct disease process. Support for this comes from observation that both alcohol withdrawal catatonia and delirium occur 3-6 days after discontinuation, are responsive to benzos, and are characterized by lack of significant EEG abnormalities . As the typical patient with alcohol withdrawal demonstrates positive psychiatric symptoms such as agitation or hallucinations, it is paramount to remember that patients with negative symptoms may be experiencing alcohol withdrawal delirium.
Clinical case #1 resolution
Due to concern for acute coronary syndrome, aspirin was given and a heparin drip started. The patient was admitted to the ICU where her symptoms of alcohol withdrawal were appropriately managed with symptom triggered doses of valium. Cardiology was consulted. A transthoracic echocardiogram (TTE) showed hypokinesis of the left ventricular apical walls and an ejection fracture of 35-40%. Cardiac catheterization was performed showing no significant obstruction of the coronary arteries, and troponins down-trended during hospitalization. She was diagnosed with stress cardiomyopathy, heparin was stopped, and the patient was treated supportively. Her symptoms of withdrawal resolved during her hospital stay. She was subsequently discharged, and TTE at a follow up clinic visit showed complete resolution of wall motion abnormality.
Clinical case #2 resolution
The patient was diagnosed with alcohol withdrawal, alcoholic ketoacidosis, and pancreatitis. He was given fluid boluses, started on dextrose containing maintenance fluids, and admitted to an intermediate care unit. His symptoms of alcohol withdrawal were managed with symptom-triggered doses of valium. His metabolic acidosis and pancreatitis improved within the next 2-3 days. He was subsequently discharged with a 5 day course of valium.
- The fundamental pathophysiology of alcohol withdrawal stems from an excess of catecholamines that can cause a wide array of complications outside of tremors, autonomic hyperactivity, delirium, and seizures.
- Alcohol withdrawal involves both desensitization of GABA and upregulation of NMDA. Benzodiazepines only work on GABA receptors, and the remaining NMDA activity may explain benzo-resistant cases of alcohol withdrawal.
- These complications are often exacerbated by underlying electrolyte abnormalities and starvation metabolism that may acutely worsen during withdrawal.
- Be vigilant for cardiovascular complications of alcohol withdrawal. The hyperadrenergic state can serve as a cardiac stress test.
- Alcoholic patients have starving brains and poor blood brain barriers leaving them highly sensitive to changes in sodium and subsequent osmotic demyelination. ODS can even occur during alcohol withdrawal in normo-natremic patients.
- Alcoholic ketoacidosis and diabetic ketoacidosis have similar symptoms and underlying anion gap acidosis. Differentiation relies on careful history taking, though patients with AKA are more likely to be alert and oriented (unless they are in severe withdrawal) and are usually eu- or hypo-glycemic (though you can also have euglycemic DKA).
- Catatonia is a known complication of alcohol withdrawal. A patient that appears calm and withdrawn as opposed to agitated and anxious may still be experiencing alcohol withdrawal.
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