Description

• Alcohol withdrawal syndrome (AWS) develops after the cessation of chronic alcohol use/abuse, generally within 6–48 hours. Alcohol abuse is characterized by impaired control over drinking, preoccupation with alcohol, use of alcohol despite adverse consequences, and denial.
• AWS exists as a spectrum of presentations:
  • Mild: Cravings and psychomotor agitation
  • Severe: Hallucinations, autonomic instability (sweating, tachycardia, hypertension), fever, and disorientation. This constellation of symptoms is known as delirium tremens (DT).
• If withdrawal symptoms are not present within a week after the last alcohol consumption, future development is unlikely.

Epidemiology

Incidence

In general, outpatient estimates are between 4% and 15%, whereas 15–40% of all inpatients are thought to have abuse or withdrawal. Of those who experience withdrawal symptoms, 5% have severe symptoms characterized as DT.

Morbidity

• AWS: Dysrhythmias, myocardial ischemia, delirium, and seizures
• Chronic alcohol abuse: Immunosuppression, wound infections, malnutrition, and the complications of cirrhosis and liver failure

Mortality

• Has decreased over time; historical estimates from severe AWS or DT reached levels as high as 40%, but the current rate is probably under 5%.
• Results from dysrhythmia, aspiration pneumonia, or underlying illness that may have been the cause of alcohol cessation in the first place (e.g., infection, pancreatitis, etc.).

Etiology/Risk Factors

• Alcohol use and abuse are obvious risk factors for developing AWS. Use and abuse are associated with a number of demographic characteristics, including:
  • Male sex
  • Lower socioeconomic status
  • White or Native American ethnicity
  • Certain psychiatric conditions (e.g., depression, anxiety disorders)
• Risk factors for the development of DT include:
  • Previous history of DT
  • Presence of AWS despite elevated level of blood alcohol
  • History of sustained drinking

Physiology/Pathophysiology

• The pathophysiology of AWS is probably related to the neurophysiologic changes thought to be caused by chronic alcohol use. Although the functional consequence of receptor-mediated effects of alcohol remain to be elucidated, ingested ethanol has a number of receptor targets:
  • NMDA-related transmission is reduced.
  • GABA function is enhanced.
  • Glycine transmission (complex and location specific) are enhanced
  • Cholinergic and serotonergic activities are enhanced.
• In order to maintain a normal arousal state, an adaptive response to chronic alcohol exposure yields decreased GABA_A sensitivity and increased NMDA sensitivity. When ethanol is acutely withdrawn, reduced central inhibition (via GABA_A) and aberrant activation of excitatory NMDA receptors appear to be responsible for the acute withdrawal symptoms, including altered mental state and noradrenergic overdrive during AWS.

Prevantative Measures

• Prevention of AWS is a crucial aspect of treatment in the clinical arena, whereas public health efforts to curb alcohol abuse are necessary to prevent AWS on a societal level.
• Perioperatively, prevention of AWS starts with an early identification of patients at risk for this condition.
  • The duration of potential abstinence from alcohol should be discussed with the primary care physician and the patient, and possible management solutions must be negotiated with the patient.
  • Nutrition including multivitamin administration should be optimized preoperatively.
  • Optimal medical management can be organized according to the degree of risk going into withdrawal, including additional invasive monitoring intraoperatively and appropriate designation (ICU, TCU) postoperatively.
  • Long-acting benzodiazepines (e.g., chlordiazepoxide) administered preoperatively may reduce the severity of AWS.

Outline

• Description
• Epidemiology
• Etiology/Risk Factors
• Physiology/Pathophysiology
• Prevantative Measures

• AWS is a clinical diagnosis and requires a detailed history and physical examination.
  • Key elements of the history include chronic alcohol use, recent cessation, and determining whether cessation was caused by some other illness.
  • Screening tools like the PAT (Paddington Alcohol Test) and AUDIT (Alcohol Use Disorders Identification Test) questionnaires can identify patients at risk for AWS.
• Clinical manifestations of alcohol withdrawal often follow a timely schedule after the last consumption of alcohol:
  • Early symptoms, including anxiety, tremulousness, palpitations, nausea, anorexia, typically begin after 6–8 hours.
  • Generalized seizures typically occur after 6–48 hours.
  • Alcoholic hallucinations after 12–48 hours
  • Delirium tremens after 48–96 hours
• The latest edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) provides more precise diagnostic criteria that can be summarized as 2 or more of the following signs and symptoms occurring (1) in the context of cessation or reduction of previously heavy alcohol use and (2) not due to some other medical or mental disorder:
  • Sweating or tachycardia
  • Hand tremor
  • Insomnia
  • Nausea or vomiting
  • Hallucinations
  • Agitation
  • Anxiety
  • Generalized tonic–clonic seizure
• It is important to note that in an anesthetized patient, symptoms may be obscured and limited to sympathetic surge (i.e., tachycardia, hypertension).

• Essential elements of therapy include:
  • Excluding alternate diagnoses (see above)
  • Seizure prophylaxis
  • Correcting metabolic and hemodynamic derangements
  • Treating symptoms such as anxiety and hallucinations
  • Managing complications (e.g., aspiration pneumonia and malnutrition)
  • Appropriate monitoring
• Benzodiazepines bind to GABA receptors and are cross-tolerant with alcohol; they remain the cornerstone of treatment for AWS. They are effective at reducing anxiety, agitation, and the incidence of seizures; and they often reduce tachycardia and hypertension. They can also be dosed prophylactically, in a scheduled fashion, or in response to symptom severity. The latter has been associated with decreased complications and lower doses of administered drug.
• Propofol in intubated, mechanically ventilated patients produces results similar to those of benzodiazepines (e.g., anxiolysis, seizure prophylaxis, etc.). Patients receiving propofol rarely need additional benzodiazepines to treat agitation or seizures associated with AWS.
• Other agents have been used, but none have completely replaced benzodiazepines:
  • Antipsychotics, such as haloperidol or quetiapine, may reduce agitation and hallucinations but may also reduce the seizure threshold.
  • Antiepileptics, such as carbamazepine, may decrease the development of seizures but have little effect on the other manifestations of AWS.
  • Intravenous infusion of ethanol can precipitate a metabolic acidosis.
  • Alternative sedatives, such as clonidine and dexmedetomidine, almost certainly reduce benzodiazepine requirements but provide no seizure prophylaxis. Dexmedetomidine reduces ICU delirium and may reduce delirium associated with AWS.
• The Clinical Institute for Withdrawal Assessment (CIWA) provides a symptom-driven dosing scheme that calculates a score based upon signs and symptoms of withdrawal (e.g., tremor, sweats, delirium). Higher scores signify more severe withdrawal and would trigger administration of benzodiazepine.
• Bed acuity: The appropriate level of monitoring for patients with AWS has never been defined. The frequent assessments required suggest that general ward care may be inadequate. Additionally, managing hemodynamic abnormalities requires active monitoring of hemodynamics, such as in a telemetry, step-down, or ICU unit. The presence of the following may necessitate ICU care:
  • Coexisting cardiac, pulmonary, or renal disease
  • Having a history of or being at high risk for DTs
  • Requiring propofol or a continuous infusion of sedatives to control symptoms during past admissions
• Thiamine deficiency: Common in patients who abuse alcohol. Thiamine is critical in order to avoid Wernicke's encephalopathy, and must be administered prior to initiating glucose or nutritional therapy. Further treatment should target specific nutritional deficiencies identified by serology.

1. Tetrault JM , O’Connor PG. Substance abuse and withdrawal in the critical care setting. Crit Care Clin. 2008;24:767–788.
2. De Wit M , Jones DG , Sessler CN , et al. Alcohol-use disorders in the critically ill patient. Chest. 2010;138(4):994–1003.
3. Kosten TR , O’Connor PG. Management of drug and alcohol withdrawal. N Engl J Med. 2003;348:1786–1795.

• Spanagel R. Alcoholism: A systems approach from molecular physiology to addictive behavior. Physiol Rev. 2009;89:649–705.
• Sullivan JT , Sykora K , Schneiderman J , et al. Assessment of alcohol withdrawal: The revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). Brit J Addict. 1989;84:1353–1357.

ICD9

291.81 Alcohol withdrawal

ICD10

F10.239 Alcohol dependence with withdrawal, unspecified

Outline

• ICD9
• ICD10

• Cessation of receptor-mediated activity during alcohol abstinence is likely at the root of AWS. It may be that chronic exposure to ethanol decreases sensitivity of GABA receptors, and that cessation reduces GABA output, leading to a state of generalized CNS arousal.
• Seizure may be an early symptom of AWS ("rum-fit") which can occur as early as 2 hours after the last consumption of ethanol.
• Alcohol-dependent, ambulatory patients may never exhibit AWS syndromes during the hospital stay.
• Whenever AWS is suspected, thiamine should be given intravenously. The administration of glucose in thiamine deficiency can precipitate Wernicke's encephalopathy.