Delirium Tremens (DTs) 

  • Author: Michael James Burns, MD, FACEP, FACP; Chief Editor: Michael R Pinsky, MD, CM, FCCP, FCCM   more...
 
Updated: Jun 29, 2011
 

Background

Delirium tremens (DTs) is the most severe form of ethanol withdrawal; it is manifested by altered mental status (global confusion) and sympathetic overdrive (autonomic hyperactivity), which can progress to cardiovascular collapse. DTs is a medical emergency with a high mortality rate, making early recognition and treatment essential. (See Prognosis, Clinical Presentation, Differentials, Workup, and Treatment.)

Chronic intake of alcohol affects several neurotransmitter systems in the brain. These effects include increased release of endogenous opiates; activation of the gamma-aminobutyric acid-A (GABA-A) receptor and a decrease in GABA-A receptor function, with a resultant influx of chloride ions; inhibition of the N -methyl-D-aspartate (NMDA) type of glutamate receptor (which mediates the postsynaptic excitatory effects of glutamate), with up-regulation of this receptor; and interactions with serotonin and dopamine receptors. (See Etiology.)

During withdrawal from alcohol, the loss of GABA-A receptor stimulation causes a reduction in chloride flux and is associated with tremors, diaphoresis, tachycardia, anxiety, and seizures. In addition, the lack of inhibition of the NMDA receptors may lead to seizures and delirium. Excessive nervous system excitability during periods of abstinence from alcohol is related to the effect of alcohol on the number and function of brain receptors.

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Etiology

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 to 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When ethanol is withdrawn, a functional decrease in the inhibitory neurotransmitter GABA is seen.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 NMDA 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. The clinical manifestations of ethanol withdrawal are due to the combination of effects on the GABA and NMDA receptors. Past episodes of withdrawal lead to increased frequency and severity of future episodes. This is the phenomenon known as kindling.

Risk factors

Risk factors for developing delirium tremens (DTs) include the following:

  • Prior ethanol withdrawal seizures
  • History of DTs
  • Concurrent illness
  • Daily heavy and prolonged ethanol consumption
  • Greater number of days since last drink
  • Severe withdrawal symptoms at presentation
  • Prior detoxification
  • Intense craving for alcohol
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Epidemiology

According to US statistics, fewer than 50% of alcohol-dependent persons develop any significant withdrawal symptoms that require pharmacologic treatment upon cessation of alcohol intake. Only 5% of patients with ethanol withdrawal progress to delirium tremens (DTs).White patients have a higher risk of developing severe alcohol withdrawal, while black patients have a lower risk.[1] Whether or not gender differences exist in the rates of development of severe alcohol withdrawal is not clear.

DTs rarely occurs among pediatric patients, because the physiologic substrate for severe alcohol withdrawal takes time to develop.

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Prognosis

Complications of delirium tremens (DTs) include the following:

  • Oversedation
  • Respiratory depression, respiratory arrest, intubation
  • Aspiration pneumonitis
  • Cardiac arrhythmias

Despite appropriate treatment, the current mortality for patients with DTs ranges from 5-15%. Mortality was as high as 35% prior to the era of intensive care and advanced pharmacotherapy. The most common conditions leading to death in patients with DTs are respiratory failure and cardiac arrhythmias.

Patients at greatest risk for death are those with extreme fever, fluid and electrolyte imbalance, or an intercurrent illness, such as occult trauma, pneumonia, hepatitis, pancreatitis, alcoholic ketoacidosis, or Wernicke-Korsakoff syndrome.

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Contributor Information and Disclosures
Author

Michael James Burns, MD, FACEP, FACP  Health Science Clinical Professor, Department of Emergency Medicine, Department of Internal Medicine, Division of Infectious Diseases, University of California Irvine School of Medicine

Michael James Burns, MD, FACEP, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Emergency Physicians, American College of Physicians, American Society of Tropical Medicine and Hygiene, California Medical Association, Infectious Diseases Society of America, Phi Beta Kappa, Royal Society of Tropical Medicine and Hygiene, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

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.

J Stephen Huff, MD  Associate Professor of Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia School of Medicine

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.

Michael E Lekawa, MD, FACS  Associate Clinical Professor of Surgery, University of California, Irvine School of Medicine; Chief, Department of Surgery, Division of Trauma and Critical Care, Director of Trauma Services, Director of Surgical Intensive Care Unit, Director of Student Critical Care Teaching Program, Medical Director of Surgery Clinics, University of California, Irvine Medical Center

Michael E Lekawa, MD, FACS is a member of the following medical societies: American Association for the Surgery of Trauma, American College of Surgeons, and Society of Critical Care Medicine

Disclosure: Nothing to disclose.

James B Price, MD  Attending Emergency Physician, Mission Hospital; Clinical Faculty, Department of Emergency Medicine, Harbor-UCLA Medical Center

James B Price, MD is a member of the following medical societies: Alpha Omega Alpha and American College of Emergency Physicians

Disclosure: Nothing to disclose.

John T VanDeVoort, PharmD  Regional Director of Pharmacy, Sacred Heart and 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.

Sage W Wiener, MD  Assistant Professor, Department of Emergency Medicine, State University of New York Downstate Medical Center; Assistant 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.

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.

Specialty Editor Board

Lisa Kirkland, MD, FACP, CNSP, MSHA  Assistant Professor, Department of Internal Medicine, Division of Hospital Medicine, Mayo Clinic; ANW Intensivists, Abbott Northwestern Hospital

Lisa Kirkland, MD, FACP, CNSP, MSHA is a member of the following medical societies: American College of Physicians, Society of Critical Care Medicine, and Society of Hospital Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Harold L Manning, MD  Professor, Departments of Medicine, Anesthesiology and Physiology, Section of Pulmonary and Critical Care Medicine, Dartmouth Medical School

Harold L Manning, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and American Thoracic Society

Disclosure: Nothing to disclose.

Barry E Brenner, MD, PhD, FACEP  Professor of Emergency Medicine, Professor of Internal Medicine, Program Director, Emergency Medicine, Case Medical Center, University Hospitals, Case Western Reserve University School of Medicine

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.

Chief Editor

Michael R Pinsky, MD, CM, FCCP, FCCM  Professor of Critical Care Medicine, Bioengineering, Cardiovascular Disease and Anesthesiology, Vice-Chair of Academic Affairs, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center

Michael R Pinsky, MD, CM, FCCP, FCCM is a member of the following medical societies: American College of Chest Physicians, American College of Critical Care Medicine, American Heart Association, American Thoracic Society, Association of University Anesthetists, European Society of Intensive Care Medicine, Shock Society, and Society of Critical Care Medicine

Disclosure: LiDCO Ltd Honoraria Consulting; iNTELOMED Intellectual property rights Board membership; Edwards Lifesciences Honoraria Consulting; Applied Physiology, Ltd Honoraria Consulting; Cheetah Medical Consulting fee Consulting

Acknowledgments

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author William G Gossman, MD, to the development and writing of a source article.

References

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  5. Weinberg JA, Magnotti LJ, Fischer PE, et al. Comparison of intravenous ethanol versus diazepam for alcohol withdrawal prophylaxis in the trauma ICU: results of a randomized trial. J Trauma. Jan 2008;64(1):99-104. [Medline].

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

  7. Hendey GW, Dery RA, Barnes RL, Snowden B, Mentler P. A prospective, randomized, trial of phenobarbital versus benzodiazepines for acute alcohol withdrawal. Am J Emerg Med. May 2011;29(4):382-5. [Medline].

  8. 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].

  9. 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].

 
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