Alcohol Withdrawal Syndrome: Improving Outcomes in the Emergency Department With Aggressive Management Strategies - Pharmacology EXTRA Supplement - (Pharmacology CME)

Table of Contents

 

About This Issue

Alcohol use disorder is a prevalent medical and psychiatric disease, and consequently, alcohol withdrawal is encountered frequently in the emergency department. Patients commonly manifest hyperadrenergic signs and symptoms, necessitating admission to the intensive care unit, administration of intravenous sedatives, and frequently, adjunctive pharmacotherapy. This issue reviews the pathophysiology of alcohol withdrawal syndrome, describes the manifestations of alcohol withdrawal, and examines the available evidence for optimal treatment of alcohol withdrawal. An aggressive front-loading approach with benzodiazepines is presented, and the management of benzodiazepine-resistant disease is addressed.

How can an understanding of the pathophysiology of alcohol withdrawal aid the emergency clinician in prompt recognition of AWS?

What are the signs/symptoms of AWS and the risk factors for progression to severe AWS?

How does the emergency clinician determine optimal treatment, and what are the treatment options?

Are any adjunctive or other therapeutic interventions beneficial in the management of AWS?

1. Abstract
2. Case Presentations
3. Introduction
4. Critical Appraisal of the Literature
5. Etiology and Pathophysiology
   1. Ethanol Pharmacology
   2. Pathophysiology of Alcohol Withdrawal
6. Differential Diagnosis
7. Prehospital Care
   1. Sobering Centers
8. Emergency Department Evaluation
   1. History
   2. Physical Examination
      1. Autonomic Hyperactivity
      2. Alcohol Withdrawal Tremor
      3. Alcohol Withdrawal Hallucinosis
      4. Seizures
      5. Delirium Tremens
9. Diagnostic Studies
10. Treatment
    1. GABAA Agonists
       1. Benzodiazepines
       2. Barbiturates
       3. Ethanol
    2. Treatment of Uncomplicated Alcohol Withdrawal Syndrome
    3. Treatment of Severe Alcohol Withdrawal Syndrome
       1. Alcohol Withdrawal Seizures
       2. Alcoholic Hallucinosis
       3. Delirium Tremens and Benzodiazepine-Resistant Alcohol Withdrawal
    4. The Intubated Patient
    5. Symptom-Driven Dosing Versus Fixed Dosing
    6. Prevention And Prophylaxis of Alcohol Withdrawal Syndrome
    7. Adjunctive Therapy
11. Controversies and Cutting Edge
    1. N-methyl-D-aspartate-Receptor Antagonists
    2. Neuromodulators
       1. Gamma-Hydroxybutyric Acid
       2. Baclofen
       3. Adrenergic Antagonists
    3. Antiepileptic Agents
    4. Nonpharmacologic Therapies
12. Disposition
13. Must-Do Markers of Quality Care in the Emergency Department
14. Summary
15. Time- and Cost-Effective Strategies
16. Risk Management Pitfalls for Alcohol Withdrawal Syndrome in the Emergency Department
17. Case Conclusions
18. Clinical Pathway for Emergency Department Management of Alcohol Withdrawal Syndrome
19. Tables and Figures
    1. Table 4. Pharmacologic Properties of Diazepam, Lorazepam, Midazolam, And Chlordiazepoxide
    2. Table 1. Differential Diagnoses of Alcohol Withdrawal Syndrome
    3. Table 2. Risk Factors for the Development of Alcohol Withdrawal
    4. Table 3. Signs and Symptoms of Alcohol Withdrawal Syndrome
    5. Table 5. Disposition Criteria for Patients With Alcohol Withdrawal Syndrome
    6. Figure 1. Alcohol Withdrawal Syndrome Timeline
    7. Figure 2. Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar)
20. References

Abstract

Alcohol use disorder is a prevalent medical and psychiatric disease, and consequently, alcohol withdrawal is encountered frequently in the emergency department. Patients commonly manifest hyperadrenergic signs and symptoms, necessitating admission to the intensive care unit, administration of intravenous sedatives, and frequently, adjunctive pharmacotherapy. This issue reviews the pathophysiology of alcohol withdrawal syndrome, describes the manifestations of alcohol withdrawal, and examines the available evidence for optimal treatment of alcohol withdrawal. An aggressive frontloading approach with benzodiazepines is presented, and the management of benzodiazepine- resistant disease is addressed.

Case Presentations

A 56-year-old woman presents to the ED seeking detoxification from alcohol...

• Her reported consumption is 750 mL of vodka daily. Her last drink was 15 hours prior. The patient denies any history of illicit drug use and states that she has no history of alcohol withdrawal seizures or delirium tremens.
• Upon presentation to the ED, her vital signs are as follows: heart rate, 139 beats/min, and blood pressure, 172/84 mm Hg. She is diaphoretic and has a severe tremor. She is unable to hold a glass of water without spilling it.
• She is given 1 L IV normal saline and 5 mg of IV diazepam. Fifteen minutes later, her tremor is worsening and her vital signs have failed to improve. What treatment modalities should you employ for her worsening symptoms?

As you consider treatment options, a nurse asks for your assistance in an adjacent room where EMS has brought in a 62-year-old man with agitated delirium...

• The paramedics tell you he’s a local man with known severe alcohol use disorder. He has a history of pancreatitis, and his wife told the paramedics that he has complained of abdominal pain and has been vomiting for the past 2 or 3 days. The paramedics were initially called for seizure-like activity.
• You find a disheveled man who appears to be malnourished being restrained by 2 security guards. His vital signs are as follows: heart rate, 162 beats/min, and blood pressure, 165/92 mm Hg. He is attempting to sit up in the stretcher and appears to be miming turning a key in a car ignition, repeating over and over, “I have to go.” He is diaphoretic and tremulous.
• What are your priorities in the initial diagnosis and management of this patient?

How would you manage these patients? Subscribe for evidence-based best practices and to discover the outcomes.

Clinical Pathway for Emergency Department Management of Alcohol Withdrawal Syndrome

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Tables and Figures

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Key References

Following are the most informative references cited in this paper, as determined by the authors.

12. * Amato L, Minozzi S, Vecchi S, et al. Benzodiazepines for alcohol withdrawal. Cochrane Database Syst Rev. 2010(3):CD005063. (Systematic review) DOI: 10.1002/14651858.CD005063.pub3

16. * Mayo-Smith MF, Beecher LH, Fischer TL, et al. Management of alcohol withdrawal delirium - an evidence-based practice guideline. Arch Internal Med. 2004;164(13):1405-1412. (Systematic review) DOI: 10.1001/archinte.164.13.1405

21. * Chance JF. Emergency department treatment of alcohol withdrawal seizures with phenytoin. Ann Emerg Med. 1991;20(5):520-522. (Prospective randomized double-blind placebo-controlled trial; 55 patients) DOI: 10.1016/s0196-0644(05)81606-3

37. * Mayo-Smith MF. Pharmacological management of alcohol withdrawal. A meta-analysis and evidence-based practice guideline. JAMA. 1997;278(2):144-151. (Meta-analysis and practice guideline) DOI: 10.1001/jama.1997.03550020076042

39. * Gold JA, Rimal B, Nolan A, et al. A strategy of escalating doses of benzodiazepines and phenobarbital administration reduces the need for mechanical ventilation in delirium tremens. Crit Care Med. 2007;35(3):724-730. (Retrospective cohort; 54 patients) DOI: 10.1097/01.CCM.0000256841.28351.80

40. * Lee JA, Duby JJ, Cocanour CS. Effect of early and focused benzodiazepine therapy on length of stay in severe alcohol withdrawal syndrome. Clin Toxicol (Phila). 2019;57(7):624-627. (Pre- and post-protocol cohort study; 113 patients) DOI: 10.1080/15563650.2018.1542701

65. * Hayashida M, Alterman AI, McLellan AT, et al. Comparative effectiveness and costs of inpatient and outpatient detoxification of patients with mild-to-moderate alcohol withdrawal syndrome. N Engl J Med. 1989;320(6):358-365. (Prospective randomized trial; 164 patients) DOI: 10.1056/NEJM198902093200605

81. * Saitz R, Mayo-Smith MF, Roberts MS, et al. Individualized treatment for alcohol withdrawal. A randomized double-blind controlled trial. JAMA. 1994;272(7):519-523. (Randomized double-blind controlled trial; 47 patients) DOI: 10.1001/jama.1994.03520070039035

82. * Müller UJ, Schuermann F, Dobrowolny H, et al. Assessment of pharmacological treatment quality: comparison of symptom-triggered vs. fixed-schedule alcohol withdrawal in clinical practice. Pharmacopsychiatry. 2016;49(5):199-203. (Retrospective cohort study; 120 patients) DOI: 10.1055/s-0042-104508

98. * Pizon AF, Lynch MJ, Benedict NJ, et al. Adjunct ketamine use in the management of severe ethanol withdrawal. Crit Care Med. 2018;46(8):e768-e771. (Retrospective observational cohort study; 63 patients) DOI: 10.1097/CCM.0000000000003204

111. *Mueller SW, Preslaski CR, Kiser TH, et al. A randomized, double-blind, placebo-controlled dose range study of dexmedetomidine as adjunctive therapy for alcohol withdrawal. Crit Care Med. 2014;42(5):1131-1139. (Randomized blinded placebo-controlled; 24 patient) DOI: 10.1097/CCM.0000000000000141

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Keywords: alcohol withdrawal syndrome, alcohol withdrawal seizure, alcoholic hallucinosis, alcoholic hallucinations, tremor, delirium tremens, ethanol, central nervous system hyperexcitation, CNS hyperexcitation, gamma-aminobutyric acid, GABA, N-methyl-D-aspartate, NMDA, ethanol, sobering centers, benzodiazepine, diazepam, lorazepam, midazolam, chlordiazepoxide, barbiturates, phenobarbital, symptom-driven dosing