Alcohol Withdrawal

Published on 07/03/2015 by admin

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Chapter 65 Alcohol Withdrawal

Bruce A. Crookes, MD, FACS , William Peery, MD

1 What are alcohol use disorders (AUDs)?

AUDs are a spectrum of disorders that range from excessive use, to abuse, to dependence, to addiction.

image Abuse is defined as being when an individual has adverse socioeconomic or health consequences related to the use of a substance.

image Dependence is manifested when a patient has withdrawal symptoms when the substance is discontinued or when larger amounts are required to obtain the same effect.

image Addiction is present when the individual has a compulsive craving for the substance. It is important to realize that, at any one time, an individual may be experiencing a combination of abuse, dependence, and/or addiction.

2 How much alcohol is too much? How big a problem is it in the intensive care unit (ICU)?

The National Institutes of Health has published guidelines that serve to quantify and define excessive alcohol use. Men aged ≤65 years are thought to have excessive alcohol consumption if they consume more than four drinks per day or more than 14 drinks in a week. For men >65 years and for women, these volumes are halved. It is thought that patients who consume excessive amounts of alcohol are at increased risk for health problems. It has been estimated that AUDs are seen in as many of 15% to 20% of primary care and hospitalized patients, in 10% to 33% of ICU admissions, and in approximately 50% of trauma patients.

3 Are AUDs associated with any alterations in patient outcomes?

The outcomes of patients with AUDs appear to vary by the reason for admission. Trauma patients with AUDs seem to have no difference in mortality or length of stay as compared with controls, although trauma patients with a history of chronic alcohol abuse have a higher incidence of pneumonia and cardiac complications. Burn patients with AUDs have higher mortality and poorer shorter and long-term outcomes. Surgical patients are at greater risk for pneumonia, wound infections, sepsis, poor wound healing, and cardiac complications. In the medical ICU, AUDs increase the need for mechanical ventilation and are independent risk factors for sepsis.

4 How is immune function altered by alcohol ingestion?

Neutrophil and macrophage response is altered by the ingestion of alcohol, and leukopenia may result from depressed levels of granulocyte colony-stimulating factor. In surgical and trauma patients, aberrant cytokine concentrations have been noted, including decreased levels of interleukin (IL)-1, IL-6, IL-12, tumor necrosis factor-α, and interferon-β. Overall, in surgical and trauma patients, an imbalance appears to exist between proinflammatory cytokines and antiinflammatory cytokines.

5 What are the criteria for alcohol withdrawal, and when does it typically occur?

First, the patient must have cessation of (or reduction in) alcohol use that has been heavy and prolonged. In addition, the patient must have two or more of the following, developing several hours to a few days after cessation: autonomic hyperactivity (i.e., sweating or heart rate >100 beats/minute); increased hand tremor; insomnia; nausea or vomiting; transient visual, tactile, or auditory hallucinations or illusions; psychomotor agitation; anxiety; and grand mal seizures, typically tonic-clonic in nature. Alcohol withdrawal typically manifests itself 48 to 96 hours after abstinence from alcohol.

6 What is delirium tremens (DTs)? What is the mortality associated with DTs in the ICU?

According to the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, fourth edition, DTs is alcohol withdrawal and associated with either a:

image Disturbance of consciousness (i.e., reduced clarity of awareness in the environment) with reduced ability to focus, sustain, or shift attention; delirium; confusion; and frank psychosis

image or

image Change in cognition (such as memory deficit, disorientation, language disturbance)

image or

image Development of a perceptual disturbance that is not better accounted for by a preexisting, established, or evolving dementia

ICU patients in whom DTs develop have a mortality rate of 5% to 15%.

7 What are the four clinical states of alcohol withdrawal?

Alcohol withdrawal has four clinical states: autonomic hyperactivity, hallucinations, neuronal excitation, and DTs. Note that these states occur along a timeline relative to time at which alcohol intake was reduced, but patients do not progress linearly from one stage to the next, often skipping one or more of the stages.

8 Is there a methodology to predict the severity of alcohol withdrawal?

The severity of alcohol withdrawal may be predicted by the severity of previous detoxifications or the presence of a history of detoxification-related seizures. The Clinical Institute Withdrawal Assessment for Alcohol revised 10-item scale is a validated, 10-item assessment tool that can be used to monitor and medicate patients, while functioning as a predictor of severe withdrawal symptoms. It examines several symptoms, including nausea or vomiting, tremors, agitation, anxiety, paroxysmal sweats, orientation, tactile and auditory disturbances, visual disturbances, and headache.

9 What is the pathophysiology of alcohol use?

Acutely, alcohol ingestion inhibits excitatory N-methyl-D-aspartate (NMDA) receptors, which leads to a reduction in the release of the neurotransmitter glutamate. Activation of the inhibitory γ-aminobutyric acid A (GABA-A)–type receptor during alcohol exposure leads to anxiolytic and sedative effects, as well as impairment of motor coordination. As alcohol ingestion becomes chronic, GABA-A receptor function is decreased, and the NMDA receptors are up-regulated, leading to tolerance.

10 What is the pathophysiology of alcohol withdrawal?

When alcohol is abruptly discontinued, NMDA receptor function is increased, and the tonic inhibition provided by GABA-A receptors is reduced. This phenomenon of increased excitation and loss of suppression results in the clinical manifestations of autonomic excitability and psychomotor agitation.

11 What class of medications are primarily used to treat alcohol withdrawal?

Benzodiazepines enhance GABA transmission, thereby balancing the surge of glutamate that is responsible for the effects of alcohol withdrawal. Current recommendations in the United States and Europe favor the use of benzodiazepines for the treatment of severe to moderate alcohol withdrawal symptoms, including seizures and DTs. In a recent Cochrane review, it was thought that benzodiazepines showed a protective benefit against alcohol withdrawal symptoms, in particular seizures.

12 What are the advantages and disadvantages of symptom-triggered benzodiazepine therapy?

Short-acting benzodiazepines (i.e., lorazepam, oxazepam) are typically used in a symptom-triggered capacity, in response to the severity of withdrawal. The downside of this approach is that it requires frequent patient assessment, and many of the symptoms of alcohol withdrawal (i.e., agitation) are not uncommon in the typical ICU population. The advantage to this approach is that patients generally receive a lower total dose of benzodiazepines over the course of their ICU stay and generally have fewer days using the ventilator.

13 What are the advantages and disadvantages of fixed-dose benzodiazepine therapy?

Longer-acting benzodiazepines (i.e., diazepam, chlordiazepoxide) are usually used in a “fixed-dose” strategy and may afford a smoother withdrawal. Unfortunately, this strategy may result in patients receiving too much or too little of the benzodiazepine, resulting in uncontrolled symptoms or oversedation. Generally, in the ICU, lorazepam (Ativan) is preferred because of a lack of active metabolites, because it can be administered intravenously, and because it does not need to be adjusted in renal failure. No specific benzodiazepine has been shown to be superior to another when used in the ICU setting.

14 Are there any risks to lorazepam use?

Lorazepam is suspended in propylene glycol, and continuous infusions of lorazepam could result in elevated levels of propylene glycol. Accumulation of propylene glycol is associated with hyperosmolar metabolic acidosis, lactic acidosis, acute tubular necrosis, intravascular hemolysis, central nervous system depression, seizures, cardiac arrhythmias, and hypotension.

15 Is intravenous alcohol safe in the treatment of alcohol withdrawal?

Intravenous alcohol has been used to treat withdrawal and was shown in one trial to be as effective as diazepam for the management of withdrawal. Unfortunately, in the group that received the alcohol infusion, the majority of patients did not have detectable levels of alcohol in their blood, and the patients had wide fluctuations in their level of sedation. This would suggest that dosing is difficult, at best. Most authors recommend that intravenous alcohol not be used to treat withdrawal in the ICU, because of the risks of intoxication, delirium, and gastritis.

16 Can I use carbamazepine or oxcarbazepine to treat alcohol withdrawal?

Carbamazepine and oxcarbazepine are nonbenzodiazepine anticonvulsants that possess GABA-nergic activity and have been used to treat alcohol withdrawal in Europe for more than 30 years. Both of these drugs are nonaddictive, have no sedating effects, and seem to promote a reduction in withdrawal symptoms. Although carbamazepine has demonstrated efficacy, safety, and tolerability in the treatment of moderate to severe alcohol symptoms, the literature is inconclusive in its ability to prevent DTs or seizures relative to benzodiazepines.

17 Are any other new therapies available for the treatment of alcohol withdrawal?

Pregabalin, a newer anticonvulsant drug, has been examined in two small studies and was found to be safe and efficacious in alcohol withdrawal. Unfortunately, not enough evidence exists to develop a recommendation for its use over benzodiazepines. The prototype GABA B receptor antagonist baclofen may also represent an effective alternative in the treatment of alcohol withdrawal, but evidence recommending it in the treatment of alcohol withdrawal is insufficient at this time.

Key Points Alcohol withdrawalimage

1. AUD in trauma patients is associated with higher morbidity but not a higher mortality in the ICU.

2. DTs is associated with a 5% to 15% mortality.

3. Alcohol withdrawal manifests 48 to 96 hours after cessation.

4. Benzodiazepines are the drug of choice for treating alcohol withdrawal.

Bibliography

1 Amato L., Davoli M., Vecchi S., et al. Cochrane systematic reviews in the field of addiction: what’s there and what should be. Drug Alcohol Depend. 2011;113:96–103.

2 American Psychiatric Association. Diagnostic and statistical manual of mental disorders, Text revision, 4th ed. Washington, D.C: American Psychiatric Association. 2000.

3 Baldwin W.A., Rosenfeld B.A., Breslow M.J., et al. Substance abuse-related admissions to adult intensive care. Chest. 1993;103:21–25.

4 Delgado-Rodriguez M., Gomez-Ortega A., Mariscal-Ortiz M., et al. Alcohol drinking as a predictor of intensive care and hospital mortality in general surgery: a prospective study. Addiction. 2003;98:611–616.

5 de Wit M., Jones D.G., Sessler C.N., et al. Alcohol-use disorders in the critically ill patient. Chest. 2010;138:994–1003.

6 Jurkovich G.J., Rivara F.P., Gurney J.G., et al. The effect of acute alcohol intoxication and chronic alcohol abuse on outcome from trauma. JAMA. 1993;270:51–56.

7 Mariani J.J., Levin F.R. Pharmacotherapy for alcohol-related disorders: what clinicians should know. Harv Rev Psychiatry. 2004;12:351–366.

8 Moss M., Burnham E.L. Chronic alcohol abuse, acute respiratory distress syndrome, and multiple organ dysfunction. Crit Care Med. 2003;31:S207–S212.

9 National Institute on Alcohol Abuse and Alcoholism. Helping patients who drink too much: a clinician’s guide. Rockville, Md: Department of Health and Human Services, National Institutes of Health, updated 2005 ed. (rev. Jan. 2007).; 2007.

10 Sarff M., Gold J.A. Alcohol withdrawal syndromes in the intensive care unit. Crit Care Med. 2010;38:S494–S501.

11 Spies C., Tonnesen H., Andreasson S., et al. Perioperative morbidity and mortality in chronic alcoholic patients. Alcohol Clin Exp Res. 2001;25:164S–170S.

12 Turner R.C., Lichstein P.R., Peden J.G.Jr., et al. Alcohol withdrawal syndromes: a review of pathophysiology, clinical presentation, and treatment. J Gen Intern Med. 1989;4:432–444.

13 Weinberg J.A., Magnotti L.J., Fischer P.E., et al. Comparison of intravenous ethanol versus diazepam for alcohol withdrawal prophylaxis in the trauma ICU: results of a randomized trial. J Trauma. 2008;64:99–104.

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