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Delirium Tremens (DTs)

  • Author: Michael James Burns, MD, FACEP, FACP; Chief Editor: Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM  more...
 
Updated: Apr 14, 2016
 

Background

Delirium tremens (DTs) is the most severe form of ethanol withdrawal 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 (1) increased release of endogenous opiates; (2) activation of the inhibitory gamma-aminobutyric acid-A (GABA-A) receptor producing increased GABA inhibition, with a resultant influx of chloride ions; (3) up-regulation of the postsynaptic N -methyl-D-aspartate (NMDA) type of glutamate receptor, which mediates the postsynaptic excitatory effects of glutamate; and (4) 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When ethanol is withdrawn, a functional decrease in the inhibitory neurotransmitter GABA is seen.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 DTs are inconsistent among studies[1, 2] and include the following:

  • Prior ethanol withdrawal seizures
  • History of DTs
  • Concurrent illness and more medical comorbidities
  • Daily heavy and prolonged ethanol consumption
  • Greater number of days since last drink
  • Severe withdrawal symptoms at presentation
  • Prior detoxification
  • Intense craving for alcohol
  • Older age
  • Hypokalemia
  • Thrombocytopenia
  • Elevated blood level of homocysteine
  • Presence of structural brain lesions
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Epidemiology

Using the diagnostic criteria for alcohol use disorder (AUD) listed in DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th edition), the 12-month and lifetime prevalences of AUD in US noninstitutionalized civilian adults is highest in men (17.6% and 36.0%, respectively), with higher prevalences in whites, Native Americans, younger adults, and previously married and never married adults, as compared with women, African Americans, Asian Americans, and older and married adults.[3] Less than 50% of alcohol-dependent persons develop any significant withdrawal symptoms that require pharmacologic treatment upon cessation of alcohol intake. The lifetime risk for developing delirium tremens (DTs) among chronic alcoholics is estimated at 5-10%. Only 5% of patients with ethanol withdrawal progress to DTs. White patients have a higher risk of developing severe alcohol withdrawal, while black patients have a lower risk.[4] Whether or not sex differences exist in the rates of development of severe alcohol withdrawal is not clear. In any particular alcohol-dependent person, symptoms of withdrawal can differ widely among different withdrawal episodes.

Delirium tremens 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%, but should be closer to 5% with modern ICU management. 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 Geriatrics Society, American Society of Tropical Medicine and Hygiene, Infectious Diseases Society of America, Phi Beta Kappa, Royal Society of Tropical Medicine and Hygiene, American College of Emergency Physicians, American College of Physicians, California Medical Association, Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

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, American College of Emergency Physicians

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, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Chief Editor

Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM Professor of Critical Care Medicine, Bioengineering, Cardiovascular Disease, Clinical and Translational Science and Anesthesiology, Vice-Chair of Academic Affairs, Department of Critical Care Medicine, University of Pittsburgh Medical Center, University of Pittsburgh School of Medicine

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

Disclosure: Received income in an amount equal to or greater than $250 from: Masimo<br/>Received honoraria from LiDCO Ltd for consulting; Received intellectual property rights from iNTELOMED for board membership; Received honoraria from Edwards Lifesciences for consulting; Received honoraria from Masimo, Inc for board membership.

Acknowledgements

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.

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.

William G Gossman, MD Associate Clinical Professor of Emergency Medicine, Creighton University School of Medicine; Consulting Staff, Department of Emergency Medicine, Creighton University Medical Center

William G Gossman, MD is a member of the following medical societies: American Academy of 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.

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.

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.

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

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.

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Average annual deaths from alcohol.
Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar). The CIWA-Ar is not copyrighted and may be reproduced freely. This assessment for monitoring withdrawal symptoms requires approximately 5 minutes to administer. The maximum score is 67 (see instrument). Patients scoring less than 10 do not usually need additional medication for withdrawal. From Sullivan JT, Sykora K, Schneiderman J, et al. Assessment of alcohol withdrawal: The revised Clinical Institute Withdrawal Assessment for Alcohol scale (CIWA-Ar). British Journal of Addiction 1989;84:1353-1357.
 
 
 
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