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Resident 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. www.uptodate.com: 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 ExamT 100.7 BP 166/98 HR 115 RR 16 RA 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? 2. What further information would you like to help you assess our patient’s risk for alcohol withdrawal? 3. A. How should alcohol withdrawal be treated? B. Should treatment for withdrawal be initiated with a scheduled dosing regimen or a symptom-triggered regimen? 4. How is the severity of withdrawal symptoms assessed? 5. What doses of benzodiazipines would be reasonable to use in this patient? 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 WernickeKorsakoff 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 individuals with 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. A. Admission to the MICU, treatment with a scheduled dosing regimen of lorazepam with additional lorazepam dosing based on CIWA-Ar scores. 2. 46 yo man with h/o past DTs and recent heavy ETOH use admitted with a DVT. B. Admission to the general medical ward, treatment with supportive care, and symptom triggered treatment with chlordiazepoxide based on CIWA-Ar scores. 3. 82 yo man with Child’s C cirrhosis, CAD, ischemic cardiomyopathy, and a h/o DTs who is admitted for a hip fracture. 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. 4. 21 yo homeless woman with HTN, bipolar disorder, and a history of heavy ETOH use but no past withdrawal who presents requesting detoxification. D. Outpatient detoxification with a small quantity of chlordiazepoxide provided and scheduled return to clinic the following day. 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 pneumonia who is disoriented and reports 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 hallucinations within 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 1 Symptoms 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: 6) Please circle one: Attending Resident (R2/R3) Intern Medical student