Attending Version
Alcohol Withdrawal Module
Created by Dr. Greg Fotieo
Objectives:
1) Understand the biochemical effects of alcohol use and alcohol withdrawal
2) Review the various alcohol withdrawal syndromes
3) Discuss treatment of alcohol withdrawal
References:
1. Kosten TR, O'Connor PG, Management of Drug and Alcohol Withdrawal, N Engl J Med 2003, 348;18, pp 1786-95.
2. : Alcohol withdrawal syndromes.
3. Benzodiazepines for alcohol withdrawal. Cochrane Database Syst Rev 2005.
CASE
HPI: Mr. Johnson is 45 yo man who presents to the ED with c/o purulent cough, fever, malaise, and weight loss for 2 months. He is brought in by his daughter. She has been urging him to come in for weeks but he refused because “I don’t trust doctors”.
Physical Exam-
T 100.7BP 166/98HR 115RR 16RA O2 sat 87%
General- disheveled man who looks older than age, angry but cooperative, mildly tremulous, coughing up purulent sputum
Chest- coarse rhonchi in lower lung fields 1/3 up bilaterally
CV- tachycardic, nl s1 and s2, no murmurs
Abd- benign
Extremities- no edema
Neuro- alert and oriented, CN 2-12 intact, motor and sensory exams wnl, brisk symmetric reflexes
CXR- infiltrates in posterior segments of lower lobes bilaterally
Labs:
WBC 12K, 78% PMN’s
H/H 11/33, MCV 105
Platelets 170 K
Na+ 138 K+ 3.0 Cl- 114 CO2 12 BUN 8 Creat 0.8
You decide to admit the patient to medicine for an aspiration pneumonia. Before heading off the see your other five admissions, the daughter pulls you aside and tells you that her father drinks heavily on a daily basis.
1. What are the different alcohol withdrawal syndromes for which this patient is at risk?
The syndromes are listed in Table 1.
2. What further information would you like to help you assess our patient’s risk for alcohol withdrawal?
The patient and his daughter should be asked about the quantity of alcohol use, the duration of use, time since the last drink, previous alcohol withdrawal syndromes, presence of co-morbid conditions, and abuse of other substances. A careful physical exam should be done with special attention to signs of complicating medical illnesses.
The patient states that he has “a few drinks” a day and has been doing it since he was young. He denies ever having alcohol withdrawal. He states that he has always been healthy and never needed a doctor. The daughter relates that he drinks more that a few drinks each day. He is usually drunk when she sees him. She doesn’t think he has ever been sober long enough to have withdrawal.
3.
A. How should alcohol withdrawal be treated?
The patient should be placed in a quiet, safe environment. Thiamine should be given prior to any glucose containing fluids to prevent precipitating Wernicke-Korsakoff syndrome. Volume and electrolyte deficits should be replaced. Benzodiazepines are the mainstay of therapy. They are safe, treat the psychomotor agitation, and limit the progression to major withdrawal symptoms and seizures. They have been shown to reduce mortality and the duration of symptoms.
B. Should treatment for withdrawal be initiated with a scheduled dosing regimen or a symptom-triggered regimen?
Our patient is in the gray area when deciding on whether to use a fixed schedule or symptom triggered regimen. He has no history of seizures or DTs and is relatively young without significant pre-existing co-morbidities. He might be appropriate for symptom triggered therapy although a fixed dose approach is not unreasonable given the duration and extent of his alcohol use and his underlying pneumonia.
4. How is the severity of withdrawal symptoms assessed?
Typically w/ a scale such as the Clinical Institute Withdrawal Assessment of Alcohol (CIWA-Ar) – Figure 2, which helps divide the patients into the different severity category and guide treatment.
5. What doses of benzodiazipines would be reasonable to use in this patient?
The amount of benzodiazepine required to treat withdrawal varies from patient to patient and varies over time in the same patient. The dosing should be based on the patient’s risk factors and ability to tolerate DTs. Since Mr. Johnson is relatively young without significant co-morbidities, or a h/o DTs, he should be dosed with benzodiazepines to achieve light sedation.
Discussion Outline
1. Prevalence/Incidence
- Alcohol use disorders are very common. It is estimated that up to 25% of patients admitted to general medicine inpatient services have alcohol use disorders.
- Each year in the US, there are over 500,000 episodes of alcohol withdrawal severe enough to require pharmacologic treatment.
2. Pathophysiology
The brain maintains a neurochemical balance between the excitatory and inhibitory neurotransmitters. The main inhibitory neurotransmitter is gamma-aminobutyric acid (GABA). One of the major excitatory neurotransmitters is glutamate which acts through N-methyl-D-aspartate (NMDA) receptor. Alcohol is a central nervous system depressant. Alcohol enhances the effects of GABA on its receptor which decreases brain excitation. Chronic exposure the alcohol causes a compensatory decrease in the GABA receptor response. Alcohol also inhibits the excitatory NMDA receptor resulting in an upregulation these receptors. When alcohol is abruptly withdrawn, it unmasks the compensatory increase in excitatory neurotransmitters. The down regulation of the GABA receptor and the upregulation of the NMDA receptor result in brain hyperexcitability and the symptoms of alcohol withdrawal.
3. Distinct alcohol withdrawal syndromes
A. Minor alcohol withdrawal:It is characterized by mild autonomic hyperactivity. The specific withdrawal symptoms are usually the same from one episode to another in an individual.
B. Alcoholic hallucinosis:They are usually visual but may be tactile or auditory. They occur in 10-25% of hospitalized alcoholics. These patients are more likely to be heavy drinkers and to have started drinking heavily at a younger age. Hallucinosis is distinct from DTs. It is not associated with disorientation and occurs much earlier after alcohol cessation than DTs.
C. Withdrawal seizures (“rum fits”):They are short, usually single generalized tonic clonic convulsions. They occur in about 10% of patients who withdraw from alcohol. They occur most commonly in individuals with a prolonged history of chronic alcoholism. If seizures are prolonged, recurrent or focal, then further investigation is warranted with neuroimaging and an LP to evaluate for infectious or structural etiologies since these features are atypical for withdrawal seizures.
D. Delirium tremens (DTs):DTs is the extreme of the alcohol withdrawal spectrum and is a medical emergency. The mortality rate has dropped to less than 5% due to more timely recognition and improved supportive care. Deaths are usually due to arrhythmias or comorbid illnesses. Fortunately, only 5% of patients who have alcohol withdrawal will develop DTs. Risk factors for DTs include a history of sustained drinking, past DTs, age >30, presence of concurrent illness, and a greater period of time since the last drink (DTs are a late manifestation of alcohol withdrawal). Due to the autonomic hyperactivity, DTs are poorly tolerated by older patients with significant comobidities. Before making the diagnosis of DTs, other causes of delirium (sepsis, meningitis, hypoxia, hypoglycemia, hepatic encephalopathy, and intracranial bleeding) need to be ruled out.
4. Factors affecting the severity of alcohol withdrawal
We do not fully understand why some individuals have severe withdrawal and others do not suffer any withdrawal. Alcohol withdrawal symptoms seem to relate to the amount of alcohol intake and the duration of the recent drinking. It appears that most individuals are vulnerable to the effects of abrupt alcohol cessation. However, most patients drink episodically rather than continuously and do not sustain constant elevated alcohol levels. Withdrawal symptoms can occur any time after blood alcohol levels start to fall and even a reduction in alcohol intake may result in withdrawal.
5. Treatment:
It is important to be aware that alcohol withdrawal is a diagnosis of exclusion. Alcohol withdrawal may be confused with thyrotoxicosis, hypoglycemia, anticholinergic drug poisoning, amphetamine or cocaine use, drug induced psychosis, acute schizophrenia, and CNS infections or hemorrhage.
A. Main goals of treatment:
1)Treating comorbid conditions
2)Supplementing vitamins, typically thiamine and folate (thiamine should be given prior to any glucose containing fluids to prevent precipitating Wernicke-Korsakoff syndrome); alcoholics have poor diet and may have B12 deficiency also.
3)Correcting metabolic derangements (dehydration, hypokalemia, hypomagnesemia, hypophosphatemia) and providing fluids
4)Alleviating symptoms with benzodiazepines
B. Choice of Benzodiazepine:
The choice of agent is based on pharmacokinetics. Diazepam (Valium) and chlordiazepoxide (Librium) have long half lives with active metabolites. These agents result in a smoother course and less chance of rebound withdrawal. Lorazepam (Ativan) and oxazepam have shorter half lives and may be the preferred agents in patients who metabolize medications less effectively such as the elderly and those with advanced liver disease. Oral preparations are preferred. Parenteral therapy must be used in patients unable to take orals and those with seizures or DTs who need immediate therapy.
C. Scheduled dosing vs symptom-triggered dosing
Although physicians are tempted to put patients at risk for alcohol withdrawal on a fixed dosing schedule of benzodiazepines, it is not necessary in many patients. A controlled, double blind trial randomized patients admitted for alcohol withdrawal to receive oxazepam on a q6 hour fixed schedule (with further dosing based on symptoms)or a symptom triggered dosing protocol. There was no difference between the incidence of seizures, DTs or the severity of withdrawal symptoms between the two groups. The symptom triggered group received less oxazepam (38 mg vs. 231 mg) and required a shorter duration of treatment (20 hours vs. 63 hours). Interestingly, 61% of the patients in the symptom triggered group did not require any benzodiazepines during their admission.
However, not all patients are appropriate for symptom based therapy. Most authorities recommended that high risk patients be treated with a fixed dosing schedule. High risk patients include individualswith prolonged alcohol use, a history of seizures or DTs, or those who are not likely to tolerate withdrawal symptoms due to age and comorbidities. These patients should be closely monitored (they may require ICU admission), put on a scheduled benzodiazepine regimen, and given additional benzodiazepines if withdrawal symptoms develop.
D. Assessing severity of withdrawal symptoms
The revised Clinical Institute Withdrawal Assessment of Alcohol (CIWA-Ar) scale is a validated 10-item assessment tool (Figure 2). It is the most commonly used tool to assess the severity of alcohol withdrawal syndromes and guide treatment. CIWA-Ar scores of 8 or less correspond to mild withdrawal, scores of 9-15 correspond to moderate withdrawal, and scores over 15 correspond to severe withdrawal symptoms and an increased risk of DTs and seizures. For treatment purposes, patients are treated with benzodiazepines when a score of 8 is achieved on the CIWA-Ar scale.
E. Dosing of benzodiazepines
A young patient with no comorbidities should be lightly sedated while an older patient with underlying cardiopulmonary disease should be more heavily sedated. Patients with a history of DTs, seizures, or heavy, prolonged alcohol use should be treated with scheduled, relatively high doses of chlordiazepoxide in the range of 50-100 mg (or an equivalent dose of another benzodiazepine) every 6 hrs with additional doses of 25-50 mg each hour based on their CIWA-Ar score. Lower risk patients can be monitored closely and treated with chlordiazepoxide 25-50 mg every hour based on their CIWA-Ar score. If DTs develop, IV diazepam 5-10 mg every 5 minutes should be given until the patient is calm but not obtunded. In patients with refractory DTs despite high doses of benzodiazepines, barbiturates (specifically phenobarbital) or propofol can be effective when used in combination with benzodiazepines.
Review Questions:
Q 1-4: Match each patient to the most appropriate treatment regimen. Each answer is used once.
1. 66 yo man with HTN, heavy recent ETOH, and mild past withdrawal symptoms who presents requesting detoxification.
2. 46 yo man with h/o past DTs and recent heavy ETOH use admitted with a DVT.
3. 82 yo man with Child’s C cirrhosis, CAD, ischemic cardiomyopathy,and a h/o DTs who is admitted for a hip fracture.
4. 21 yo homeless woman with HTN, bipolar disorder,and a history of heavy ETOH use butno past withdrawalwho presents requesting detoxification.
A. Admission to the MICU, treatment with a scheduled dosing regimen of lorazepam with additional lorazepam dosing based on CIWA-Ar scores.
B. Admission to the general medical ward,treatment with supportive care, and symptom triggered treatment with chlordiazepoxide based on CIWA-Ar scores.
C. Admission to the general medical ward and treatment with a scheduled dosing regimen of chlordiazepoxide with additional chlordiazepoxide dosing based on CIWA-Ar scores.
D. Outpatient detoxification with a small quantity of chlordiazepoxide provided and scheduledreturn to clinic the following day.
Answers:
1 -D. He can be managed as an outpatient as he is relatively healthy, has had mild withdrawal symptoms, and has no known complicating social or psychiatric issues.
2 - C. Although he is young and healthy, he has a history of past DTs and is appropriate for fixed dosing rather than symptom based therapy.
3 - A. This elderly patient with significant co-morbidities is at high risk for complications of withdrawal. He should be admitted to the MICU for monitoring and treatment. He should be heavily sedated to limit the autonomic hyperactivity. He should be managed with a short acting agent since he will metabolize benzodiazepines poorly given his age and advanced liver disease.
4 - B. Although the patient is young, healthy and has no history of withdrawal, her social and psychiatric problems necessitate that she be monitored and treated as an inpatient.
5. Which clinical presentation is most consistent with alcoholic hallucinosis?
A. A 45 yo patient admitted to the General Surgery service for an emergent cholecystectomy who develops visual hallucinations, fever, tachycardia, and disorientation on post op day 3.
B. A 32 yo patient admitted with a community acquired pneumonia who develops auditory hallucinations upon transfer to the medicine floor from the ER. He states that he hears voices telling him to escape from the jail so he can stop the alien invasion.
C. A 42 yo patient admitted to the General Surgery service for an emergent appendectomy who develops visual hallucinations on post op day 1.
D. A 79 yo patient admitted for a community acquired pneumoniawho is disoriented andreports seeing his deceased mother in the room on the 2nd night of his hospitalization.
The correct answer is C. The 42 yo man presents with visual hallucinationswithin 24 hours of admission without disorientation which is typical of alcoholic hallucinosis. The 45 yo man admitted for an emergent cholecystectomy is suffering from DTs. His hallucinations are occuring later in the hospitalization and are associated with systemic symptoms and disorientation. The 32 yo man most likely has a primary psychiatric disorder or a drug induced psychosis. The 79 yo man is suffering from an acute delerium due to his age, unfamiliar environment and comorbid illness.
FIGURE 1Symptoms of Alcohol Withdrawal Syndrome
Symptoms / Time of appearance after
cessation of alcohol use
Minor withdrawal symptoms: insomnia, tremulousness, mild anxiety, gastrointestinal upset, headache, diaphoresis, palpitations, anorexia / 6 to 12 hours
Alcoholic hallucinosis: visual, auditory, or tactile hallucinations / 12 to 24 hours*
Withdrawal seizures: generalized tonic-clonic seizures / 24 to 48 hours†
Alcohol withdrawal delirium (delirium tremens): hallucinations (predominately visual), disorientation, tachycardia, hypertension, low-grade fever, agitation, diaphoresis / 48 to 72 hours‡
*--Symptoms generally resolve within 48 hours.
†--Symptoms reported as early as two hours after cessation.
‡--Symptoms peak at five days.
Post Module Evaluation
Please place completed evaluation in an interdepartmental mail envelope and address to Dr. Wendy Gerstein, Department of Medicine, VAMC (111).
1) Topic of module:______
2) On a scale of 1-5, how effective was this module for learning this topic? ______
(1= not effective at all, 5 = extremely effective)
3) Were there any obvious errors, confusing data, or omissions? Please list/comment below:
______
4) Was the attending involved in the teaching of this module? Yes/no (please circle).
5) Please provide any further comments/feedback about this module, or the inpatient curriculum in general:
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Attending Resident (R2/R3)Intern Medical student