eMedicine Specialties > Emergency Medicine > Neurology

Delirium Tremens

Author: Anne Yim, MD, Resident Physician, Department of Emergency Medicine, Kings County Hospital and State University of New York Downstate Medical Center
Coauthor(s): Sage W Wiener, MD, Assistant Professor, Department of Emergency Medicine, State University of New York Downstate, Director of Medical Toxicology, Department of Emergency Medicine, Kings County Hospital Center
Contributor Information and Disclosures

Updated: Oct 6, 2009

Introduction

Background

Delirium tremens (DT) is the most severe form of ethanol withdrawal manifested by altered mental status and sympathetic overdrive, which can progress to cardiovascular collapse. The syndrome was first described by Thomas Sutton in 1813, but the link to alcohol abstinence was not made until the 1950s with the work of Victor and Adams.1,2  Delirium tremens is a medical emergency with a high mortality rate, making early recognition and treatment essential.

Pathophysiology

Ethanol interacts with GABA receptors enhancing activity. GABA receptors are a family of chloride ion channels that mediate inhibitory neurotransmission. They are pentameric complexes composed of several glycoprotein subunits. Chronic ethanol abuse seems to modify the GABA receptor via several mechanisms leading to a decrease in GABA activity. Chronic ethanol exposure has been found to alter gene expression and increase cellular internalization of certain subunits affecting the type of GABA receptors that are available at the cell surface and the synapse. Chronic ethanol exposure has also been found to alter phosphorylation of GABA receptors, which may alter receptor function. When ethanol is withdrawn, a functional decrease in the inhibitory neurotransmitter GABA is seen. This leads to a loss of the inhibitory control of excitatory neurotransmitters such as norepinephrine, glutamate, and dopamine. 

Ethanol also acts as an N -methyl D-aspartate receptor antagonist. Withdrawal of ethanol leads to increased activity of these excitatory neuroreceptors, resulting in the clinical manifestations of ethanol withdrawal: tremors, agitation, hallucinations, seizures, tachycardia, hyperthermia, and hypertension. Past episodes of withdrawal lead to increased frequency and severity of future episodes. This is the phenomenon known as kindling.

Frequency

United States

  • Fewer than 50% of ethanol-dependent persons develop significant withdrawal syndrome requiring pharmacologic treatment.
  • Only 5% of patients with ethanol withdrawal progress to delirium tremens (DT).

Mortality/Morbidity

  • The mortality rate for delirium tremens may be as high as 35% if untreated but is less than 5% with early recognition and treatment.
  • Patients at greatest risk for death are those with extreme fever, fluid and electrolyte imbalance, or intercurrent illness such as occult trauma, pneumonia, hepatitis, pancreatitis, alcoholic ketoacidosis, or Wernicke-Korsakoff syndrome.

Race

  • Patients of white race have a higher risk of developing severe alcohol withdrawal.3
  • Patients of black race have a lower risk of severe alcohol withdrawal.3

Sex

  • Prevalence of alcohol abuse is approximately 7% in males and 3% in females.
  • Incidence of withdrawal symptoms is lower in females than in males.

Age

  • Prevalence of alcohol abuse is highest among young adults, but delirium tremens rarely occurs among pediatric patients because the physiological substrate for severe alcohol withdrawal takes time to develop.

Clinical

History

Alcohol withdrawal syndrome occurs when the blood alcohol level falls below a certain threshold in patients with a long history of alcohol consumption. Manifestations progress from mild withdrawal to its most severe and fatal form, delirium tremens (DT). Patients may have any manifestation of mild withdrawal independently (eg, patients may have alcohol withdrawal seizures or alcoholic hallucinosis without alcoholic tremulousness), and any form of mild withdrawal may progress to delirium tremens.

  • Alcoholic tremulousness occurs 6-12 hours after cessation or decrease of alcohol intake and is characterized by autonomic hyperactivity; anxiety, tremors, hypertension, tachycardia, nausea, vomiting, or diarrhea.
  • Alcohol withdrawal seizures or "rum fits" occur at 6-48 hours after last drink, most commonly within the first 24 hours. They are usually generalized tonic clonic, self-limited, and rarely progress to status epilepticus.
  • Alcoholic hallucinosis (formerly known as Kraepelin's hallucinatory insanity) occurs 10-72 hours after the last drink. These hallucinations may often be visual, but they can also be auditory, tactile (formication), or olfactory. Outside of hallucinations, sensorium is intact.
  • Delirium tremens usually occurs 3-7 days after the last drink. It is differentiated from the less severe forms of withdrawal by altered sensorium and autonomic instability. Confusion, obtundation, and delirium are the hallmarks of delirium tremens. Other findings include severe agitation, hyperpyrexia, tachycardia, hypertension, and diaphoresis.

Physical

  • Physical examination findings in delirium tremens (DT) are generally nonspecific. A thorough physical examination should be performed to assess for level of consciousness, other serious illnesses, signs of trauma, and stigmata of chronic liver disease.
  • Physical examination findings may include the following:
    • Tachycardia
    • Hyperthermia
    • Hypertension
    • Tachypnea
    • Diaphoresis
    • Tremor
    • Mydriasis
    • Altered mental status
    • Severe psychomotor agitation

Causes

Risk factors for developing delirium tremens (DT):

  • Prior ethanol withdrawal seizures
  • History of delirium tremens
  • Concurrent illness
  • Daily heavy and prolonged ethanol consumption
  • Greater number of days since last drink

More on Delirium Tremens

Overview: Delirium Tremens
Differential Diagnoses & Workup: Delirium Tremens
Treatment & Medication: Delirium Tremens
Follow-up: Delirium Tremens
References
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References

  1. Sutton T. Tracts on delirium tremens, on peritonitis, and on some other inflammatory affections, and on the gout. 1813.

  2. Victor M, Adams RD. The effect of alcohol on the nervous system. Res Publ Assoc Res Nerv Ment Dis. 1953;32:526-73. [Medline].

  3. Chan GM, Hoffman RS, Gold JA, Whiteman PJ, Goldfrank LR, Nelson LS. Racial variations in the incidence of severe alcohol withdrawal. J Med Toxicol. Mar 2009;5(1):8-14. [Medline].

  4. [Guideline] Mayo-Smith MF. Pharmacological management of alcohol withdrawal. A meta-analysis and evidence-based practice guideline. American Society of Addiction Medicine Working Group on Pharmacological Management of Alcohol Withdrawal. JAMA. Jul 9 1997;278(2):144-51. [Medline].

  5. Daeppen JB, Gache P, Landry U, et al. Symptom-triggered vs fixed-schedule doses of benzodiazepine for alcohol withdrawal: a randomized treatment trial. Arch Intern Med. May 27 2002;162(10):1117-21. [Medline].

  6. Jaeger TM, Lohr RH, Pankratz VS. Symptom-triggered therapy for alcohol withdrawal syndrome in medical inpatients. Mayo Clin Proc. Jul 2001;76(7):695-701. [Medline].

  7. Hayner CE, Wuestefeld NL, Bolton PJ. Phenobarbital treatment in a patient with resistant alcohol withdrawal syndrome. Pharmacotherapy. Jul 2009;29(7):875-8. [Medline].

  8. Caetano R, Clark CL, Greenfield TK. Prevalence, trends, and incidence of alcohol withdrawal symptoms: analysis of general population and clinical samples. Alcohol Health Res World. 1998;22(1):73-9. [Medline].

  9. Chiang C. Withdrawal Syndromes. In: Ford MD, et al. Clinical Toxicology. 1. WB Saunders Company; 2001.

  10. Coomes TR, Smith SW. Successful use of propofol in refractory delirium tremens. Ann Emerg Med. Dec 1997;30(6):825-8. [Medline].

  11. Ferguson JA, Suelzer CJ, Eckert GJ, Zhou XH, Dittus RS. Risk factors for delirium tremens development. J Gen Intern Med. Jul 1996;11(7):410-4. [Medline].

  12. Fiellin DA, O'Connor PG, Holmboe ES, Horwitz RI. Risk for delirium tremens in patients with alcohol withdrawal syndrome. Subst Abus. Jun 2002;23(2):83-94. [Medline].

  13. Girard DE, Kumar KL, McAfee JH. Alcohol intoxication and withdrawal. Med Rounds. 1988;1:158-164.

  14. Grant BF et al. The 12-Month Prevalence and Trends in DSM–IV Alcohol Abuse and Dependence: United States, 1991–1992 and 2001–2001. Drug and Alcohol Dependence. 2004;74 (3):223-234.

  15. Hamilton RJ. Substance Withdrawal. In: Goldfrank LR, et al. Goldfrank's Toxicologic Emergencies. 7. McGraw-Hill Professional Publishing; 2002:1059-1073.

  16. Hodges B, Mazur JE. Intravenous ethanol for the treatment of alcohol withdrawal syndrome in critically ill patients. Pharmacotherapy. Nov 2004;24(11):1578-85. [Medline].

  17. Isbell H, Fraser HF, Wikler A, Belleville RE, Eisenman AJ. An experimental study of the etiology of rum fits and delirium tremens. Q J Stud Alcohol. Mar 1955;16(1):1-33. [Medline].

  18. Klijn IA, van der Mast RC. Pharmacotherapy of alcohol withdrawal delirium in patients admitted to a general hospital. Arch Intern Med. Feb 14 2005;165(3):346. [Medline].

  19. Kumar S, Fleming RL, Morrow AL. Ethanol regulation of gamma-aminobutyric acid A receptors: genomic and nongenomic mechanisms. Pharmacol Ther. Mar 2004;101(3):211-26. [Medline].

  20. [Guideline] Mayo-Smith MF, Beecher LH, Fischer TL, et al. Management of alcohol withdrawal delirium. An evidence-based practice guideline. Arch Intern Med. Jul 12 2004;164(13):1405-12. [Medline].

  21. McCowan C, Marik P. Refractory delirium tremens treated with propofol: a case series. Crit Care Med. Jun 2000;28(6):1781-4. [Medline].

  22. Moore M, Gray MG. Delirium tremens: A study of cases at the Boston City Hospital, 1915-1936. N Engl J Med. Feb 14 2005;220:953-956.

  23. Roffman JL, Stern TA. Alcohol withdrawal in the setting of elevated blood alcohol levels. Prim Care Companion J Clin Psychiatry. 2006;8(3):170-3. [Medline].

  24. Saitz R, Mayo-Smith MF, Roberts MS, Redmond HA, Bernard DR, Calkins DR. Individualized treatment for alcohol withdrawal. A randomized double-blind controlled trial. JAMA. Aug 17 1994;272(7):519-23. [Medline].

  25. Schuckit MA. Alcoholism and drug dependency. In: Harrison's Principles of Internal Medicine. 1991:2146-2151.

  26. Shabbir HF, Ilksoy N, Greenwald JL. Alcohol Withdrawal Syndromes. In: Williams MV, et al. Comprehensive Hospital Medicine: An Evidence Based Approach. 1. WB Saunders; 2007.

  27. Tan CY, Weaver DF. Molecular pathogenesis of alcohol withdrawal seizures: the modified lipid-protein interaction mechanism. Seizure. Aug 1997;6(4):255-74. [Medline].

  28. Trevisan LA, Boutros N, Petrakis IL, Krystal JH. Complications of alcohol withdrawal: pathophysiological insights. Alcohol Health Res World. 1998;22(1):61-6. [Medline].

  29. Tsai G, Gastfriend DR, Coyle JT. The glutamatergic basis of human alcoholism. Am J Psychiatry. Mar 1995;152(3):332-40. [Medline].

  30. Wasilewski D, Matsumoto H, Kur E, et al. Assessment of diazepam loading dose therapy of delirium tremens. Alcohol Alcohol. May 1996;31(3):273-8. [Medline].

  31. Wax PM. Withdrawal syndromes. In: The Clinical Practice of Emergency Medicine. 2nd ed. 1996:1434-1439.

  32. Wright T, Myrick H, Henderson S, Peters H, Malcolm R. Risk factors for delirium tremens: a retrospective chart review. Am J Addict. May-Jun 2006;15(3):213-9. [Medline].

  33. Zaloga GP. Alcohol withdrawal syndrome medications. In: The Critical Care Drug Handbook. 1991:40-45.

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Further Reading

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Keywords

DT, delirium tremens, delirium tremens symptoms, alcohol withdrawal delirium, alcohol withdrawal hallucinosis, ethanol abstinence, rum fits, ethanol withdrawal, ethanol alcohol withdrawal, ethanol withdrawal seizures

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Contributor Information and Disclosures

Author

Anne Yim, MD, Resident Physician, Department of Emergency Medicine, Kings County Hospital and State University of New York Downstate Medical Center
Anne Yim, MD is a member of the following medical societies: American College of Emergency Physicians
Disclosure: Nothing to disclose.

Coauthor(s)

Sage W Wiener, MD, Assistant Professor, Department of Emergency Medicine, State University of New York Downstate, Director of Medical Toxicology, Department of Emergency Medicine, Kings County Hospital Center
Sage W Wiener, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Medical Toxicology, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Medical Editor

William K Chiang, MD, Associate Professor, Department of Emergency Medicine, New York University School of Medicine; Chief of Service, Department of Emergency Medicine, Bellevue Hospital Center
William K Chiang, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Medical Toxicology, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

John T VanDeVoort, PharmD, Regional Director of Pharmacy, Sacred Heart & St. Joseph's Hospitals
John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists
Disclosure: Nothing to disclose.

Managing Editor

J Stephen Huff, MD, Associate Professor, Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia Health Sciences Center
J Stephen Huff, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Academy of Neurology, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Barry E Brenner, MD, PhD, FACEP, Professor of Emergency Medicine, Professor of Internal Medicine, Program Director, Emergency Medicine, University Hospitals, Case Medical Center
Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Chest Physicians, American College of Emergency Physicians, American College of Physicians, American Heart Association, American Thoracic Society, Arkansas Medical Society, New York Academy of Medicine, New York Academy of Sciences, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

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