Hospital Medicine

Alcohol withdrawal

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Alcohol withdrawal

I. What every physician needs to know.

Alcohol withdrawal symptoms can vary widely among patients, therefore, it is important to be aware of the range of symptoms that need to be monitored. The first symptoms of alcohol withdrawal can appear as early as 6 hours but can take as long as 36 hours to manifest after the patient’s last drink. Additionally, some patients may start having minor withdrawal symptoms with positive blood alcohol levels. Alcohol withdrawal can be life-threatening and the goal of withdrawal care is to control symptoms and prevent progression to the next level of withdrawal.

Clinicians' delay in identifying patients in withdrawal can result in increased severity and risk of progressing to the next level of alcohol withdrawal. It should be noted that concurrent medical illness is a significant risk factor for triggering alcohol withdrawal and was found to be the single greatest predictor for the development of delirium tremens (DTs). DTs is one of the most serious manifestations of alcohol withdrawal and can be both fatal and difficult to treat.

Please refer to sections below on “History Part I: Pattern Recognition” and “Immediate Management” for withdrawal symptoms and management.

II. Diagnostic Confirmation: Are you sure your patient has alcohol withdrawal?

Rule out other causes of patient’s symptomatology/delirium concurrently.

A. History Part I: Pattern Recognition.

Symptoms of “minor” or “early” alcohol withdrawal occur within 6 to 36 hours after the patient’s last drink and may include the following: tremor, nervousness, headache, sweating, palpitations, anorexia, nausea/vomiting, and mild autonomic dysfunction (increased heart rate, increased blood pressure, low grade fever.)

Withdrawal seizures can occur within 6 to 48 hours after the patient’s last drink and are usually generalized, tonic-clonic seizures. Seizures occur in 3% of patients in alcohol withdrawal. Of those who develop seizures, 3% will develop status epilepticus.

Alcoholic hallucinosis can occur 12 to 48 hours after the patient’s last drink. These hallucinations are usually visual but may be tactile or auditory. It is important to differentiate this from DTs as the patient has a clear sensorium during alcoholic hallucinosis.

”Late" or “major” alcohol withdrawal, also known as delirium tremens (DTs), can occur 48 to 96 hours after the patient’s last drink and can last for days to weeks. DTs can be fatal and difficult to treat. Five percent of patients undergoing withdrawal will experience DTs. Acute medical illness is the greatest risk factor for developing DTs. Symptoms of DTs include hallucinations, disorientation, tachycardia, hypertension, hyperpyrexia, agitation, and diaphoresis.

The clinician should be aware that patients are unlikely to go through all the stages of alcohol withdrawal mentioned. They may experience some of these symptoms but are unlikely to show all the symptoms stated above. Therefore, it is important to be aware of the wide variety of symptoms that alcohol withdrawal can present with, to be able to recognize and quickly and effectively treat to prevent progression of withdrawal.

B. History Part 2: Prevalence.

Up to 20% of medical inpatients qualify for alcohol use disorder and all patients should be screened.

C. History Part 3: Competing diagnoses that can mimic alcohol withdrawal.

Wernicke's encephalopathy and delirium from a general medical condition.

D. Physical Examination Findings.

On physical exam, the clinician should perform a complete exam including a thorough neurological exam. Exam findings suggestive of withdrawal can include disorientation, diaphoresis, agitation, tremulousness, hyper-reflexia, ataxia, and nystagmus.

Review of systems (ROS) should note complaints of nausea, vomiting, palpitations, anxiety, hallucinations and headache.

It is important to trend vital signs for autonomic instability. Note that not all patients in withdrawal will show autonomic instability and this should not be relied upon as a sole marker for alcohol withdrawal. Therefore, it is important to be aware of the wide range of symptoms and signs, withdrawal stages and suspected time of last drink as the patient can have various presentations of alcohol withdrawal. Additionally, the clinician should be aware not all patients are forthcoming about the amount of alcohol used or time since their last drink.

E. What diagnostic tests should be performed?

Electrocardiogram (ECG) to monitor QT interval if giving neuroleptics or if suspected arrhythmia / acute coronary syndrome that can occur with alcohol withdrawal.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Alcohol withdrawal is a clinical diagnosis.

Labs that may be suggestive of underlying alcohol use disorder include:

  • Elevated transaminases AST > ALT, elevated MCV, leukopenia, anemia, thrombocytopenia, hypomagnesemia, hypophosphatemia, elevated carbohydrate deficient transferrin

  • Hyponatremia in beer potomania

  • Metabolic acidosis with normal to low glucose, elevated anion gap, ketones is suggestive of alcohol ketoacidosis.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Alcohol withdrawal is a clinical diagnosis. If unsure, electroencephalography (EEG) may be helpful in DTs but is not necessary. EEG in DTs can be normal or have increased in excitatory fast frequencies that may help differentiate DTs from other types of delirium.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

Head computed tomography (CT) in prolonged DTs.

III. Default Management.

Regarding monitoring during alcohol withdrawal, the patient should have frequent monitoring of vital signs, particularly heart rate, blood pressure and temperature. Vital sign trends can help indicate uncontrolled withdrawal symptoms. Continuous cardiac monitoring should be strongly considered for patients in alcohol withdrawal as they are at risk for arrhythmias.

Autonomic instability due to alcohol withdrawal should respond to benzodiazepines (BZD.) If the patient is receiving adequate dosing of BZD and is still having autonomic instability, other causes should be investigated. For example, if the patient is sedated on BZD but is still tachycardic, consider other causes of tachycardia that patients with chronic alcohol abuse are also at risk for such as dehydration, fever from aspiration pneumonia, GI bleed, heart failure, etc.

A. Immediate management.

Benzodiazepines (BZDs) have been shown to be the safest and most effective treatment in multiple studies. When deciding what BZD to use, there are a few considerations such as pharmacokinetics, onset of action and abuse potential. Long-acting BZDs are more effective in preventing seizures and contribute to a smoother withdrawal with fewer rebound and breakthrough symptoms. Long acting BZDs can pose a risk of excess sedation in selected groups, especially the elderly and those with liver disease.

Long-acting BZDs can have a slower onset of action but this also results in a lower abuse potential, which is a significant advantage in a patient population that is already struggling with addiction. Examples of long-acting BZDs used for alcohol withdrawal include chlordiazepoxide and oxazepam.

In patients in whom rapid control of symptoms is desired and when other BZDs are not readily available in the ER, the fast onset of action of shorter-acting agents may be preferred to avoid delaying treatment. These agents include lorazepam or diazepam.

Table I shows the most commonly used BZD for alcohol withdrawal with dose equivalents for drug inter-conversion and notation of which BZD is preferred in patients with synthetic liver dysfunction.

Table 1.

Benzodiazepine Dose Equivalents and Pharmacokinetics

Regarding dosing schedule of BZDs for alcohol withdrawal, there are two options: fixed and symptom-triggered dosing.

1. Fixed dosing: refers to placing the patient on a regularly scheduled dose of BZD. Requirements will vary from patient to patient. Therefore, when starting BZD treatment, the patient should be reassessed after receiving their first dose of BZD to determine if they need a higher or lower dose.

They should also have an as needed (PRN) BZD order in addition to the standing order of the fixed BZD dose for breakthrough withdrawal symptoms. Once the patient is stable on a fixed dose of BZD, recommendation for tapering the BZD is to decrease by one-quarter to one-third of the total BZD dose per day while monitoring for breakthrough withdrawal symptoms.

Table II shows an example of a fixed dosing schedule using this tapering method.

Table II.

Example of a Fixed Dosing Schedule using this tapering method

As needed dosing of BZD alone should not be used for alcohol withdrawal unless in conjunction with a standardized, validated alcohol withdrawal scale such as the CIWA-Ar scale, with a clear nursing protocol for its implementation. Nursing staff should also receive specific training on implementation of such withdrawal protocols.

2. Symptom-triggered dosing: should be based on standardized, validated alcohol withdrawal scales such as CIWA-Ar and protocols that require frequent monitoring of the patient's symptoms. This involves having trained nursing staff who are able to assess patients at fixed intervals of no more than every 8 hours and dose BZD based on the patient’s score on the standardized alcohol withdrawal scale at that particular point in time.

Most protocols require nursing to administer one of the following medications every hour when the CIWA-Ar score is 8-10: chlordiazepoxide 50-100mg, diazepam 10-20mg, lorazepam 2-4mg. Nursing staff repeats the CIWA-Ar score 1 hour after every dose of BZD given to assess the need for further medication decreased. Patients should be monitored every 4-8 hours, once stable, by means of the CIWA-Ar scale until their score has been less than 8-10 for at least 24 hours.

Symptom-triggered dosing, when used properly by trained nursing staff using an alcohol withdrawal scale with frequent patient monitoring, has been shown to be safe and effective. Additionally, under these monitored circumstances, symptom-triggered dosing may result in lower amounts of BZD being given and shorter duration of therapy based on studies. Furthermore, there is no need for a BZD taper with symptom-triggered dosing, which is an advantage.

Non-BZD medications can be used in conjunction with BZD for alcohol withdrawal but these should not be used in lieu of BZDs. The most commonly used medications are beta-blockers, clonidine and neuroleptics.

1. Beta-blockers have been shown to reduce the autonomic manifestations of withdrawal but have no anticonvulsant activity and may precipitate delirium if using beta-blockers with significant CNS penetration, such as propranolol. There is concern that beta-blockers can mask the symptoms of alcohol withdrawal making it more difficult to use symptom-triggered dosing or to determine if a patient needs a higher fixed dose of a BZD. If using beta-blockers for autonomic dysfunction, the clinician should ensure the patient has received adequate doses of BZD first.

2. Clonidine, an alpha-2 adrenergic agonist, can help ameliorate the autonomic effects of alcohol withdrawal but has its own risks, including rebound tachycardia and hypertension. As with beta-blockers, the clinician should ensure the patient has received adequate doses of BZD first prior to using clonidine as an adjuvant to BZD.

3. Neuroleptics, most commonly haloperidol, may also be used to help control delirium and agitation associated with alcohol withdrawal. Neuroleptics are contraindicated in withdrawal patients with QTc greater than 500msec and in those showings signs of QTc instability as they can prolong QT interval as well. Patients should have an ECG prior to receiving any neuroleptics and after. Electrolytes should be repleted, especially magnesium, if using neuroleptics given the risk of prolonged QT interval and arrythmias.

Additionally, neuroleptics can decrease seizure threshold and alcohol withdrawal patients are already at increased risk for seizures. Therefore, neuroleptics should not be used prior to or in lieu of BZDs in the withdrawing patient. The clinician should ensure the patient has received adequate doses of BZD first prior to using neuroleptics for treating alcohol withdrawal symptoms and only as an adjuvant to BZD treatment.

Supplemental treatment: Thiamine should be administered to all patients suspected of alcohol abuse whether or not they are in withdrawal. There is speculation on the best delivery method for thiamine: intravenously (IV) versus orally. Administering thiamine intravenously ensures adequate absorption of the medication in patients who may have altered mental status impairing swallowing or nausea/vomiting as part of their withdrawal syndrome. Given this, and the lost cost of IV thiamine, consider administering thiamine IV to ensure adequate absorption. Patients with alcohol use disorder are often nutritionally deplete and would benefit from a daily multivitamin including B-vitamins (B12, folic acid) as well as electrolyte repletion discussed.

Patients with alcohol use disorder are often overall volume deplete on admission due to chronic diuresis from alcohol and require intravenous fluids (IVF). Choice of IVF should be based on the patient’s serum sodium as large volume beer drinkers can develop hyponatremia from potomania. Additionally, after thiamine has been administered, consider adding dextrose to IVF as patients can have alcohol ketoacidosis even with normal or slightly low serum glucose levels and this can be easily missed. Low serum bicarbonate, elevated anion gap and presence of serum or urine ketones can aid in the diagnosis of alcohol ketoacidosis.

Delirium Tremens: Patients with DTs experience increased myocardial workload, increased oxygen demand and electrolyte abnormalities from renal losses and transcellular shifts. If they are not supported adequately, they can have complete cardiovascular collapse and should be monitored in an ICU or step down bed on telemetry. Patients with DTs need supportive care with IVF and daily repletion of electrolyte abnormalities.

BZDs are used for behavioral and autonomic control in DTs. Additional medications may be needed with BZD but should not be used in lieu of BZD to control symptoms of DTs. BZDs are generally administered intravenously as the patient is altered and cannot reliably take oral medications. An advantage of IV lorazepam and midazolam over diazepam and chlordiazepoxide is their shorter half-life. This allows more control over titration with potentially fewer adverse effects with shorter half-life medications. BZD cost is also something to consider when selecting choice of BZD. The goal of treatment with BZD during DTs is to maintain a light sedation and control autonomic instability. Patients may require high doses of BZD and may need continuous IV drips to achieve this.

If the patient is no longer responding to IV BZD, propofol can be considered if there is concern for BZD receptor saturation with high dose IV BZD during DTs treatment. IV neuroleptics can also be used as an adjuvant to BZD for behavioral control of DTs with the same caveats described previously that need to be closely monitored. DTs can last for days to weeks.

Consider heparin (LMWH) or equivalent, for deep vein thrombosis prevention as DT patients are often on bed rest due to altered mental status.

Barbiturates, most commonly phenobarbital, have been used for alcohol withdrawal as an alternative to BZDs. One possible advantage of barbiturates over BZDs is their anti-glutamate activity in addition GABA-A agonism. However, barbiturates are less studied than BZDs for alcohol withdrawal, have safety concerns with respiratory depression, a lower therapeutic index than BZDs with no reversal agent and an unclear role in liver patients with decreased clearance. Therefore, BZDs are currently considered the drug of choice for treatment of alcohol withdrawal.

B. Physical Examination Tips to Guide Management.

Trend vital signs for autonomic instability. Monitor for disorientation, diaphoresis, agitation, tremulousness, hyper-reflexia, ataxia, and nystagmus.

C. Laboratory Tests to Monitor Response to, and Adjustments in, Management.

  1. Daily serum chemistry panels with magnesium and phosphorus: Patients with alcohol use disorder frequently have low magnesium and phosphorus levels. Serum magnesium may be in normal range on admission but can be low on subsequent lab draws during their admission and should be checked daily. Patients with alcohol use disorder will usually need several grams of magnesium repleted for days to achieve normal serum magnesium levels.

  2. IVF and sodium: Patients are often overall volume deplete on admission due to chronic diuresis from alcohol and require IVF. Choice of IVF should be based on the patient’s serum sodium as large volume beer drinkers can develop hyponatremia from potomania.

  3. Low serum bicarbonate, elevated anion gap, serum/urine ketones: can aid in the diagnosis of alcohol ketoacidosis which should be treated with supplemental glucose (dextrose in IVF drip) after patient has been administered thiamine.

D. Long-term management.

N/A

E. Common Pitfalls and Side-Effects of Management.

Not reassessing the patient frequently enough for appropriate BZD dosing and the patient progresses into DTs.

Not assessing synthetic liver function (bilirubin, PT, PTT) to determine BZD choice. See liver insufficiency section below.

IV. Management with Co-Morbidities.

N/A

A. Renal Insufficiency.

No change in standard management.

B. Liver Insufficiency.

Lorazepam (Ativan) or oxazepam (Serax) are the preferred BZD in liver insufficiency. Prescribing BZDs other than lorazepam or oxazepam may result in prolonged somnolence and toxicity due to decreased hepatic clearance.

C. Systolic and Diastolic Heart Failure.

Patients in withdrawal are often given IVF for supportive care. Need to assess daily volume status as patients with alcohol use disorder are at risk for alcohol cardiomyopathy and can get volume overloaded on IVF.

D. Coronary Artery Disease or Peripheral Vascular Disease.

Alcohol withdrawal and DTs can be associated with electrolyte abnormalities and increased cardiac demand potentially leading to arrhythmias and myocardial infarction.

E. Diabetes or other Endocrine issues.

No change in standard management.

F. Malignancy.

No change in standard management.

G. Immunosuppression (HIV, chronic steroids, etc.).

No change in standard management.

H. Primary Lung Disease (COPD, Asthma, ILD).

No change in standard management.

I. Gastrointestinal or Nutrition Issues.

Replete vitamin and electrolyte deficiencies associated with alcohol abuse.

J. Hematologic or Coagulation Issues.

No change in standard management.

K. Dementia or Psychiatric Illness/Treatment.

Consider screening for dual diagnosis with alcohol abuse disorder.

V. Transitions of Care.

A. Sign-out considerations While Hospitalized.

Patients may need BZD dose adjusted up or down depending on clinical response.

B. Anticipated Length of Stay.

Variable depending on if the patient goes into DTs, which can last from days to weeks.

C. When is the Patient Ready for Discharge?

Once withdrawal is completed.

D. Arranging for Clinic Follow-up.

Once treatment of withdrawal is complete, it is strongly recommended prior to discharge, the patient be referred to an alcohol treatment center for ongoing treatment of their alcohol use disorder.

1. When should clinic follow up be arranged and with whom?

Substance abuse treatment (either inpatient or outpatient) immediately upon hospital discharge.

2. What tests should be conducted prior to discharge to enable best clinic first visit?

N/A

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit?

N/A

E. Placement Considerations.

Given immobility during DTs treatment, patients often become deconditioned, in addition to the risk of ataxia from chronic alcohol abuse, and may require physical therapy prior to safe discharge home.

F. Prognosis and Patient Counseling.

Risk for relapse is high. Recommended the patient is referred to an alcohol treatment center (either inpatient or outpatient) for ongoing treatment of their alcohol use disorder once detoxification is completed.

VI. Patient Safety and Quality Measures.

A. Core Indicator Standards and Documentation.

N/A

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

It is strongly recommended that prior to discharge, the patient is referred to an alcohol treatment center in their area for ongoing treatment of their alcohol use disorder once detoxification is completed.

VII. What's the evidence?

Mayo-Smith, MF. "Pharmacological Management of Alcohol Withdrawal: A Meta-Analysis and Evidence Based Practice Guideline". JAMA. vol. 278. 1997. pp. 144-51.

Mayo-Smith, MF. "Management of Alcohol Withdrawal Delirium: An Evidence-Based Practice Guideline". Arch Int Med. vol. 164. 2004. pp. 1405-12.

Sullivan, JT, Sykora, K, Schneiderman, J, Naranjo, CA, Sellers, EM. "Assessment of Alcohol Withdrawal: The revised Clinical Institute Withdrawal Instrument for Alcohol Scale (CIWA-Ar)". British Journal of Addiction. vol. 84. 1989. pp. 1353-1357.

Ferguson, JA. "Risk Factors for Delirium Tremens Development". Journal of General Internal Medicine. vol. 11. 1996. pp. 410-414.

Daeppen, JB. "Symptom-Triggered versus Fixed-Schedule Doses of Benzodiazepines for Alcohol Withdrawal". Arch Int Med. vol. 162. May 27, 2002. pp. 1117-1121.

Sullivan, JT. "Benzodiazepine Requirements During Alcohol Withdrawal Syndrome: Clinical Implications of Using a Standardized Withdrawal Scale". J of Clinical Psychopharmacology. vol. 11. Oct 1991. pp. 291-295.

Saitz, R. "Individualized Treatment for Alcohol Withdrawal: A Randomized Double-Blind Controlled Trial". JAMA. vol. 272. Aug 17, 1994. pp. 519-523.

Jaeger, TM. "Symptom-Triggered Treatment for Alcohol Withdrawal Syndrome in Medical Inpatients". Mayo Clin Proc. vol. 76. Aug 2001. pp. 695-701.

Duffens, K, Marx, J. "Alcoholic Ketoacidosis - A Review". The Journal of Emergency Medicine. vol. 5. 1987. pp. 399-406.

DeCarolis, DD, Rice, KL, Ho, L. "Symptom-Driven Lorazepam Protocol for the Treatment of Severe Alcohol Withdrawal Delirium in the Intensive Care Unit". Pharmacotherapy. vol. 27. 2007. pp. 510-518.

Varelas, Panayiotis. "Seizures in Critical Care: A Guide to Diagnosis and Therapeutics". 2010. pp. 284.

O'Conner, Patrick. "Medical Progress: Patients with Alcohol Problems". NEJM. vol. 338. 1998. pp. 592-602.

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