emDOCs Revamp: Alcohol Withdrawal

Authors: Kyler Osborne (EM-3 Resident Physician; Tacoma, WA); Katey DG Osborne, MD (EM Attending Physician; Tacoma, WA); Rachel Bridwell, MD (EM Attending Physician; Charlotte, NC) // Reviewed by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UTSW / Parkland Memorial Hospital) and Brit Long, MD (@long_brit, EM Attending Physician)

Welcome to emDOCs revamp! This series provides evidence-based updates to previous posts so you can stay current with what you need to know.

A 36-year-old male presents to the emergency department after being found down at home by his spouse. Per the man’s wife, the patient is a heavy drinker – often consuming two to three pints of vodka daily. Upon EMS arrival the male is noted to be anxious and tremulous with a GCS of 14.

Initial vital signs: HR 136 BPM, BP 172/82 mmHg, RR 24, T 37.2°C, SpO2 97% RA

Physical examination:

General: restless, mildly agitated

CV: tachycardic, regularly regular, diaphoretic,

Abdomen: Soft, NT, ND, intermittently dry heaving

Neuro: tremulous in bilateral arms and hands, tongue fasciculations

What do you suspect as the diagnosis? What is the next step in evaluation and treatment?

Answer: Alcohol Withdrawal Syndrome (AWS)^1-14

Epidemiology

• Globally, alcohol use disorder (AUD) is the most prevalent substance use disorder with over 100 million estimated cases in 2016⁷
• Many patients with, or at risk for, AUD access care in the Emergency Department (ED) and often only in the ED⁸
• AUD is a leading cause of worldwide mortality, and many patients with AUD will develop AWS during their ED course⁹
  • Nearly one-third of patients presenting primarily for AUD will experience moderate-to-severe withdrawal during ED stay⁹
• Alcohol-related ED visits are rapidly escalating, and these patients are at high risk for poor outcomes, nearly 1 in 10 of whom will die within 1 year⁸
• Severe complications, including seizures and/or delirium tremens, which may occur in approximately 3-5% of these patients¹⁰

Pathophysiology:

• Acute Alcohol Intoxication:
  • CNS depressant
    • Increases GABA, glutamate neurotransmission à enhances inhibitory tone¹
    • Decreases NMDA neurotransmission à inhibits excitatory tone¹ 
• Chronic Alcohol Intoxication:
  • CNS attempts to achieve homeostasis via:
    • Downregulation of GABA and upregulation of NMDA receptors secondary to confirmational changes⁹
    • Accounts for alcohol tolerance which requires higher blood alcohol levels to achieve the same level of intoxication⁹
• Alcohol Withdrawal:
  • Sudden cessation or acute reduction of alcohol disrupts chronic adaptations, unmasking CNS hyperexcitation and hyperstimulation¹¹
    • Decreased GABA neurotransmission
      • Loss of inhibitory effects
    • Increased NMDA neurotransmission
      • Increased excitatory effects
  • CNS hyperexcitation releases catecholamines causing increased sympathetic activity¹¹

Clinical Presentation:

• Non-sequential progression, significant overlap of signs/symptoms:^2,3
• • 6-12 hours: ^8,9,10
    • Neuropsych: Restlessness, anxiety, agitation, irritability, insomnia, tremors, headache
    • GI: Nausea/vomiting
    • Cardiovascular: Mild tachycardia, mild hypertension, diaphoresis, mild tachypnea
  • 12-24 hours: ^8,9,10
    • Alcohol Hallucinosis
      • Auditory (most common), tactile, visual (least common)
      • Occurs in 2–8% of individuals with chronic, heavy alcohol use, particularly those who began drinking at age 17 or earlier
      • Delusions/paranoia
    • Withdrawal seizures
      • Generalized, tonic-clonic convulsions
      • Occurs in 5–10% of individuals with active AWS⁹
  • 24-72+ hours: ^8,9,10
    • Delirium tremens (DT)
      • Confusion with fluctuating LOC
      • Disturbance in attention, awareness, orientation, language, perception
      • Severe autonomic changes: tachycardia, hypertension, hyperthermia
      • Occurs in approximately 3–5% of patients hospitalized with AWS⁹
• Factors associated with DT development¹⁰
  • History of previous DT
  • History of sustained drinking
  • CIWA scores > 15
  • Patients with SBP > 150, or patients with HR greater than 100
  • Recent withdrawal seizures
  • Prior withdrawal delirium or seizures
  • Older age
  • Recent misuse of other depressants
  • Concomitant medical problems

Differential Diagnosis 

• Toxidromes:
  • Sympathomimetic intoxication, anti-cholinergic toxicity, sedative or hypnotic withdrawal, serotonin syndrome, neuroleptic malignant syndrome
• Medical:
  • Thyrotoxicosis, sepsis, meningitis/encephalitis, electrolyte derangement, head trauma, hepatic failure, pulmonary embolism, myocardial ischemia
  • Ketoacidosis: alcoholic, diabetic, or starvation
  • Wernicke or Korsakoff Syndrome

Evaluation:

• Clinical diagnosis and ultimately a diagnosis of exclusion
• Thorough physical exam
  • High risk for necrotizing soft tissue infection (NSTI), Fournier’s gangrene, other skin infections¹²
    • For those with comorbidities, AUD exhibited a 3.55-fold higher risk of NSTI than the control group¹²
    • For those without comorbidities, AUD exhibited a 15.2-fold higher risk of NSTI than did the comparison cohort¹²
• Labs
  • Complete Blood Count –may demonstrate leukocytosis, thrombocytopenia, normocytic or macrocytic anemia
  • Comprehensive Metabolic Panel – may show for electrolyte abnormalities within sodium potassium and magnesium, elevated anion gap metabolic acidosis, liver dysfunction
  • Lipase – assess for pancreatitis
  • Beta-hydroxybutyrate – assess for ketoacidosis or toxic alcohol ingestion
  • PT/INR, PTT – assess for coagulopathy
  • Ethanol Level, Acetaminophen and Salicylate Levels
  • Urine Drug Screen
• EKG
  • Non-specific, may reveal tachycardia
• Imaging
  • Chest Radiograph (CXR) – If ill appearing, may reveal alternative etiology
  • Non-contrasted head computed tomography (CT)
    • Consider if significant altered mental status, evidence of trauma, or focal neurologic examination
• Use of grading scales is recommended:
  • CIWA-Ar: Clinical Institute Withdrawal Assessment – Alcohol, revised.^2-5
    • Objective assessment of withdrawal severity and progression
    • Scoring:
      • < 8 = Absent or minimal withdrawal
        • No treatment recommended
      • 9-19 = Mild-to-moderate withdrawal
        • Treatment recommended
      • > 20 = Severe withdrawal
        • ICU recommended
  • PAWSS: Prediction of Alcohol Withdrawal Severity Scale¹³
    • Identifies those at risk of developing severe AWS
    • Found to be most accurate of predictive tools in inpatient settings
    • Scoring:
      • Negative PAWSS (Score <4) = 0.5% of patients develop severe AWS
      • Positive PAWSS (Score >4) = 93% of patients develop severe AWS

Treatment: (please see charts below for doses and frequencies)

• Address ABCs, with consideration that severe alcohol withdrawal may require advanced airway management
• ED physicians should guide treatment based off adequate symptom control, which requires interval re-evaluation after sequential intervention

• Mild AWS (For CIWA <9)
  • Often safe for outpatient management, low risk of developing severe AWS
    • Supportive care is appropriate
  • Gabapentin (Table 1)
    • Mimics GABA but does not directly interact with GABA neuroreceptors, inhibits voltage-dependent calcium channels and indirectly modulates GABA neurotransmission¹
    • Anxiolytic, sedative and anticonvulsive properties⁸
    • Avoid in renal impairment⁸
  • Carbamazepine (Table 1)
    • A sodium channel blocker that may potentiate GABA neurotransmission¹
    • Studies suggest carbamazepine for use in AWS management, as it decreases the severity of illness and psychiatric distress as well as reducing the likelihood of return to alcohol use⁸

• Moderate-to-severe AWS (CIWA >9)
  • May be safe for discharge, consider admission for those at higher risk of severe AWS
    • (See disposition recommendations below)
  • Benzodiazepines (Table 2)
    • Historically, are first line therapies for AWS¹¹
      • Act as GABA agonists by increasing frequency of channel opening

• No single benzodiazepine has been shown to be superior¹⁰

• • Phenobarbital
    • A barbiturate, has emerged as an alternative or adjunct therapy⁸
      • Acts as GABA agonists by increasing duration of channel opening, and inhibits glutamate receptor activity
    • GRACE-4 suggests using phenobarbital in addition to benzodiazepines compared to using benzodiazepines alone⁷

• Refractory AWS
  • Ketamine
    • NMDA antagonist, some studies suggest its use in refractory AWS
    • Low/ pain-dose Ketamine may reduce total benzodiazepines requirements¹⁰
  • Dexmedetomidine
    • Central alpha-2-agonist, may be beneficial as adjunct
    • May reduce short-term benzodiazepine requirement and provide sedation; though it does not target the underlying mechanism of AWS and as such, does not treat DTs, withdrawal seizures, or prevent the progression of AWS⁹
  • Propofol
    • Potentiates GABA-A receptor activity and can inhibit NMDA receptors
    • Use in refractory DT and severe AWS, particularly in patients requiring intubation¹⁰

• Other Considerations^8,10
  • Thiamine:
    • Alcohol Withdrawal:
      • 100 mg IV/ PO daily
    • Wernicke’s Encephalopathy:
      • 500mg IV over 30 min TID for 2-3 days, then 250-500mg IV/IM QD for 3-5 days, then 100mg PO QD
  • Folate: 1 mg IV/ PO
  • Multivitamin: PO preferred
  • Electrolyte Derangements
    • Hypomagnesemia: Replete with Magnesium Sulfate 2-4 grams IV
    • Hypokalemia: Replete with Potassium-Chloride 20-40 meq IV/ PO
    • Hyponatremia: Replete according to clinical presentation

Disposition

• Determining which patients can be safely managed in an outpatient setting can be challenging
• Outpatient / Discharge Considerations:
  • Consider for initial CIWA-Ar scores <15 (mild-to-moderate) who are not currently intoxicated may be considered for discharge¹⁰
  • Some studies suggest patients with two sequential (two hours apart) CIWA-Ar scores < 10 and there are no concerning risks for deterioration after initial ED management, consider discharging the patient from the emergency department¹⁴
  • Safety Factors in Outpatient Management⁸
    • In good physical and mental health
    • Supportive social network and stable living environment
      • Able to be monitored at home by family or friends and return to care if worsening symptoms
    • No previous withdrawal episodes; if previous AWS, no severe AWS
    • Mild AWS in ED and control of withdrawal symptoms over a period of ED or hospital-based observation
    • Not also dependent on benzodiazepines or opioids
    • Able to acquire and take oral medications
• Admission:
  • Consider for initial CIWA-Ar > 15 (moderate-to-severe)
  • The American Society of Addiction Medicine recommends that patients with CIWA-Ar score ≥ 19 should receive inpatient treatment⁸
  • ED Observation Units or Clinical Decision Units may be appropriate for those not warranting admission but requiring prolonged observation¹¹
• ICU:
  • Consider for CIWA-Ar >20
  • Patients with severe AWS or medical comorbidities will need ICU admission
  • Factors lending to ICU Admission
    • History of prior alcohol withdrawal complications (e.g. DT, seizure, intubation)
    • Hemodynamic instability, or persistent hyperthermia
    • Severe electrolyte derangements – hypokalemia, hypomagnesemia, hyponatremia
    • Signs of end organ damage including respiratory insufficiency, acute renal failure, infection, infarction, rhabdomyolysis
    • Underlying cardiac disease

Pearls/Pitfalls:

• Prior to assigning a diagnosis of AWS, consider concomitant structural CNS pathology, metabolic abnormalities, infection, and toxicologic etiologies
• Additionally, consider reasons for the patient’s cessation of alcohol consumption, which may allow for identification of preceding medical condition (MI, pancreatitis, etc.)
• Early symptoms of AWS may be mild, especially in those with history of severe withdrawal
• The range of electrolyte and vitamin deficiencies can be extreme, identification and early repletion can prevent further clinical deterioration
• The use of grading scales (CIWA-Ar, PAWSS) should guide AWS management and disposition
• GRACE-4 recommends the use and/or addition of Phenobarbital to reduce overall benzodiazepine requirements
• Consider the development of hospital-based protocols for those presenting with AWS
• ED observation units or clinical decision units (CDUs) may be highly benefit those who require extended observation periods but may not necessitate hospital admission

References:

1. Kosten T, O’Connor P. Management of drug and alcohol withdrawal. N Engl JMed. 2003; 348:1786-1795.
2. Gortney J, Raub J, Patel P, et al. Alcohol withdrawal syndrome in medical patients. Cleve Clin J Med. 2016; 83(1): 67-79.
3. Muncie H, Yasinian Y, Oge L. Outpatient management of alcohol withdrawal syndrome. Am Fam Physician. 2013; 88(9): 589-595.
4. Perry E. Inpatient management of acute alcohol withdrawal syndrome. CNS Drugs. 2014; 28(5): 401-410.
5. Sullivan J, Sykora K, Schneiderman J, et al. Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). Br J Addict. 1989; 84(11): 1353-1357.
6. Yanta J, Swartzentruber G, Pizon A. Alcohol withdrawal syndrome: improving outcomes through early identification and aggressive treatment strategies. Emerg Med Pract. 2015; 17(6): 1-19.
7. Borgundvaag B, Bellolio F, Miles I, et al. Guidelines for Reasonable and Appropriate Care in the Emergency Department (GRACE-4): Alcohol use disorder and cannabinoid hyperemesis syndrome management in the emergency department. Acad Emerg Med. 2024;31(5):425-455.
8. Strayer RJ, Friedman BW, Haroz R, et al. Emergency Department Management of Patients With Alcohol Intoxication, Alcohol Withdrawal, and Alcohol Use Disorder: A White Paper Prepared for the American Academy of Emergency Medicine. J Emerg Med. 2023;64(4):517-540.
9. Wolf C, Curry A, Nacht J, Simpson SA. Management of Alcohol Withdrawal in the Emergency Department: Current Perspectives. Open Access Emerg Med. 2020;12:53-65.
10. Long D, Long B, Koyfman A. The emergency medicine management of severe alcohol withdrawal. Am J Emerg Med. 2017;35(7):1005-1011.
11. Yancey J, Micciche D, Phillips T, Koyfman A. Alcohol Withdrawal Syndrome: Identification and Management – emDOCs.net – Emergency Medicine Education. https://www.emdocs.net/alcohol-withdrawal-syndrome-identification-and-management/.
12. Yii YC, Hsieh VC, Lin CL, Wang YC, Chen WK. Alcohol use disorder increases the risk of necrotizing fasciitis: A nationwide retrospective cohort study. Medicine (Baltimore). 2017;96(32):e7509.
13. Maldonado JR, Sher Y, Ashouri JF, et al. The “Prediction of Alcohol Withdrawal Severity Scale” (PAWSS): systematic literature review and pilot study of a new scale for the prediction of complicated alcohol withdrawal syndrome. Alcohol. 2014;48(4):375-390.
14. Helman A. 4-Step Approach to Treating Alcohol Withdrawal. ACEPNow. https://www.acepnow.com/article/4-step-approach-to-treating-alcohol-withdrawal/.