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Alcohol Withdrawal Anthony Worsham, MD Thursday School Division of Hospital Medicine Department of Internal Medicine University of New Mexico Health Sciences Center Thursday, August 7, 2014 The dose makes the poison What is it that is not a poison? All things are poison and nothing is without poison. Solely, the dose determines that a thing is not a poison. --Paracelsus (1493–1541), the Renaissance Father of Toxicology, in his Third Defense Erickson TB, The approach to the patient with an unknown overdose, Emerg Med Clin N Am 25 (2007) 249–281 http://en.wikipedia.org/wiki/Paracelsus What is alcohol? An alcoholic beverage is a drink that typically contains 3% – 40% alcohol (ethanol) • beer • wine • spirits (distilled beverages) http://en.wikipedia.org/wiki/Alcoholic_beverage Alcohol BAC and effects Kelly JF, Renner JA, Alcohol-Related Disorders, Massachusetts General Hospital Comprehensive Clinical Psychiatry http://www.cdc.gov/al cohol/pdfs/excessive_ alcohol_cost.pdf What is excessive EtOH use? 49% Prescription opioids(i.e.,methadone,oxycodone,morphine) 36% heroin 31% cocaine 29% tranquilizers/musclerelaxants 16% antidepressants median age of unintentional drug overdose: 43.7years O’Connor PG, Alcohol Abuse And Dependence, Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 31. CAGE questionnaire 1.Have you ever felt you needed to Cut down on your drinking? 2.Have people Annoyed you by criticizing your drinking? 3.Have you ever felt Guilty about drinking? 4.Have you ever felt you needed a drink first thing in the morning (Eye-opener) to steady your nerves or to get rid of a hangover? CAGE test scores >=2 is positive Excessive drinking: specificity 76%, sensitivity of 93% alcoholism: specificity of 77%, sensitivity of 91% Kitchens JM (1994). "Does this patient have an alcohol problem?". JAMA 272 (22):1782–7. Apply DSM-IV Diagnostic Criteria for Alcohol Withdrawal ICD-10 alcohol withdrawal codes F10.23 Alcohol dependence with withdrawal F10.230 …… uncomplicated F10.231 …… delirium F10.232 …… with perceptual disturbance F10.239 …… unspecified Abuse versus dependence: DSM IV-TR Alcohol abuse Alcohol dependence A. A maladaptive pattern of drinking, leading to clinically significant impairment or distress, as manifested by at least one of the following occurring within a 12-month period: A. A maladaptive pattern of drinking, leading to clinically significant impairment or distress, as manifested by three or more of the following occurring at any time in the same 12-month period: •Recurrent use of alcohol resulting in a failure to fulfill major role obligations at work, school, or home (e.g., repeated absences or poor work performance related to alcohol use; alcoholrelated absences, suspensions, or expulsions from school; neglect of children or household) •Recurrent alcohol use in situations in which it is physically hazardous (e.g., driving an automobile or operating a machine when impaired by alcohol use) •Recurrent alcohol-related legal problems (e.g., arrests for alcohol-related disorderly conduct) •Continued alcohol use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of alcohol (e.g., arguments with spouse about consequences of intoxication). B. No duration criterion separately specified, but several dependence criteria must occur repeatedly as specified by duration qualifiers associated with criteria (e.g., “persistent,” “continued”). •Need for markedly increased amounts of alcohol to achieve intoxication or desired effect; or markedly diminished effect with continued use of the same amount of alcohol •The characteristic withdrawal syndrome for alcohol; or drinking (or using a closely related substance) to relieve or avoid withdrawal symptoms •Drinking in larger amounts or over a longer period than intended. •Persistent desire or one or more unsuccessful efforts to cut down or control drinking •Important social, occupational, or recreational activities given up or reduced because of drinking •A great deal of time spent in activities necessary to obtain, to use, or to recover from the effects of drinking •Continued drinking despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to be caused or exacerbated by drinking. B. Never met criteria for alcohol dependence. American Psychiatric Association. (2000). Diagnostic and statistical manual of mental disorders (4th ed., text rev.). Substance use disorder Diagnostic criteria A. A problematic pattern of __ use leading to clinically significant impairment or distress, as manifested by at least two or the following, occuring within a 12-month period: American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Substance-use disorders Diagnostic criteria • Criteria A – Impaired control (Criteria 1-4) – Social impairment (Criteria 5-7) – Risky use (Criteria 8-9) – Pharmacological criteria (Criteria 10-11) American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Substance use disorder Diagnostic criteria: Impaired control 1. __ is often taken in larger amounts or over a longer period than was intended. 2. There is a persistent desire or unsuccessful efforts to cut down or control __ use. 3. A great deal of time in spent in activities necessary to obtain __, use __, or recover from its effects. 4. Craving, or a strong desire or urge to use __. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Substance use disorder Diagnostic criteria: Social impairment 5. Recurrent __ use resulting in a failure to fulfill major role obligations at work, school, or home 6. Continued __ use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of __. 7. Important social, occupational, or recreational activities are given up or reduced because of __ use. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Substance use disorder Diagnostic criteria: Risky use 8. Recurrent __ use in situations in which it is physically hazardous. 9. Alcohol use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by __. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Substance use disorder Diagnostic criteria: Pharmacology 10. Tolerance, as defined by either of the following: – a. A need for markedly increased amounts of __ to achieve intoxication or desired effect. – b. A markedly diminished effect with continued use of the same amount of __. 11. Withdrawal, as manifested by either of the following: – a. The characteristic withdrawal syndrome for __ – b. __ (or a closely related substance) is taken to relieve or avoid withdrawal symptoms. Substance use disorders Diagnostic criteria • Specifiers – In early remission: no criteria met at least 3 months but less than 12 months – In sustained remission: no criteria met for 12 months or longer – In a controlled environment – Severity • Mild: presence of 2-3 symptoms • Moderate: presence of 4-5 symptoms • Severe: presence of 6 or more symptoms American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). What is alcohol withdrawal? Camí J, Farré M, Drug Addiction, N Engl J Med, 2003;349:975-86. Mechanism of action of alcohol http://thebrain.mcgill.ca/flash/i/i_03/i_03_m/i_03_m_par/i_03_m_par_alcool.html Alcohol Intoxication Withdrawal (2+ within hrs-days) B. Inappropriate sexual or aggressive behavior, mood lability, impaired judgment •Autonomic hyperactivity C. 1 or more of: •Insomnia •Slurred speech •Incoordination •E.g., sweating or pulse rate >100 bpm •Increased hand tremor •Nausea or vomiting •Unsteady gait •Transient visual, tactile, or auditory hallucinations or illusions •Nystagmus •Psychomotor agitation •Impairment in attention or memory •Anxiety •Stupor or coma •Generalized tonic-clonic seizures American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Alcohol withdrawal syndrome progression Haber P et al. Guidelines for the Treatment of Alcohol Problems. Australian Government Department of Health and Ageing. 2009. Signs and symptoms of alcohol withdrawal Haber P et al. Guidelines for the Treatment of Alcohol Problems. Australian Government Department of Health and Ageing. 2009. Alcohol withdrawal spectrum Alcohol Abuse And Dependence: Patrick G. O’Connor. UpToDate Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar) • nausea/vomiting • anxiety • paroxysmal sweats • tactile disturbances • visual disturbances • tremors • agitation • orientation and clouding of sensorium • auditory disturbances • headache Alcohol withdrawal syndrome admission management goals 1. Monitor course of syndrome, ensuring patient safety 2. Use methods to abort progression and treat symptoms 3. Manage comorbid medical, surgical, toxicologic, and psychiatric problems 4. Anticipate need for intensive care monitoring and therapy 5. Ensure multidisciplinary approach to management, including preparation for rehabilitation Carlson RW et al, Alcohol Withdrawal Syndrome, Crit Care Clin 28 (2012) 549–585 Admission studies for patients with moderate to severe alcohol withdrawal syndrome 1. Complete blood cell count 2. Baseline metabolic panel with serum electrolytes (including magnesium), glucose, renal function tests 3. Blood alcohol, and urine and blood toxicology studies 4. Serum calcium, phosphate, lipase, CPK activity 5. Liver function tests, including INR and serum AST, ALT, bilirubin, ammonia 6. Chest radiograph 7. Electrocardiogram, cardiac biomarkers, echocardiogram 8. Urinalysis 9. Arterial blood gas analysis 10. Blood, urine, and sputum cultures Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; CPK, creatine phosphokinase; INR, international normalized ratio. Laboratory, imaging, and clinical evaluations must be individualized. Carlson RW et al, Alcohol Withdrawal Syndrome, Crit Care Clin 28 (2012) 549–585 Moeller KE, Urine Drug Screening: Practical Guide for Clinicians, Mayo Clin Proc. 2008;83(1)66-76 Alcohol labs Blood alcohol level Alcohol-use disorders Marc A Schuckit, Lancet 2009; 373: 492–501 Osmolar Gap Levine M et al, Toxicology in the ICU: Part 1: General Overview and Approach to Treatment. Chest 2011; 140( 3 ): 795 – 806 MKSAP question A 39-year-old man is admitted to the hospital for new-onset agitation, fluctuating level of consciousness, and tremors. He is diagnosed with acute alcoholic hepatitis. MKSAP Question On physical examination, temperature is 38.8°C (101.8°F), blood pressure is 95/55 mm Hg, pulse rate is 130/min, and respiration rate is 30/min. Jaundice is noted. The abdomen is protuberant with ascites but is soft, with no abdominal rigidity or guarding. There is no blood in the stool. The patient is agitated and disoriented, is unable to maintain attention, and appears to be having visual hallucinations. He believes that the nurse has stolen his wallet (which is in his bedside drawer) in order to obtain his identity. He is diaphoretic and tremulous. Asterixis is absent, and the remainder of the neurologic examination is normal. MKSAP Question Q: Which of the following is the most appropriate management? A. Ceftriaxone B. CT of the head C. Haloperidol D. Lactulose enema E. Lorazepam What is delirium tremens? What is delirium tremens? Delirium Diagnostic Criteria A. A disturbance in attention (i.e., reduced ability to direct, focus, sustain, and shift attention) and awareness (reduced orientation to the environment). B. The disturbance develops over a short period of time (usually hours to a few days), represents a change from baseline attention and awareness, and tends to fluctuate in severity during the course of a day. C. An additional disturbance in cognition (e.g., memory deficit, disorientation, language, visuospatial ability, or perception). D. The disturbances in Criteria A or C are not better explained by another preexisting, established, or evolving neurocognitive disorder and do not occur in the context of a severely reduced level of arousal, such as coma. E. There is evidence from the history, physical examination, or laboratory findings that the disturbance is a direct physiological consequence of another medical condition, substance intoxication or withdrawal (i.e., due to a drug of abuse or to a medication), or exposure to a toxin, or is due to multiple etiologies. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Differentiate delirium tremens from other alcohol withdrawal syndromes • 5% of patients with alcohol withdrawal • Constellation of symptoms: confusion, hallucinations, fever (with or without evidence of infection), and autonomic hyperresponsiveness with hypertension and profound tachycardia • Suspect in any agitated patient withdrawing from alcohol with BP >140/90 mm Hg, HR > 100/min, T > 101 Fahrenheit • Mortality 5-15% Erwin WE et al, Delirium tremens, Southern Medical Journal (May 1998, 91:5), 425-432. MKSAP Question Correct answer: E. Lorazepam. The most appropriate treatment is lorazepam for delirium tremens syndrome. The term delirium tremens is nearly universally used to refer to delirium due to alcohol withdrawal syndrome. The syndrome usually presents 48 to 96 hours after cessation of drinking, can last up to 2 weeks, and is usually exacerbated at night. The syndrome is characterized by impaired level of consciousness and disorientation (which may fluctuate significantly), reduced attention and global amnesia, impaired cognition and speech, and often hallucinations (usually tactile and/or visual) and delusions (persecutory). The condition can be rapidly fatal if not treated appropriately and aggressively. Seizure activity can occur. Benzodiazepines are the treatment of choice, with doses given as needed based on exhibited signs and symptoms consistent with alcohol withdrawal. Delirium tremens Key Points Delirium tremens is characterized by fluctuating level of consciousness, disorientation, reduced attention, global amnesia, impaired cognition and speech, and often hallucinations and delusions. Risk factors for severe course of AWS, including seizures and delirium 1. Prior episodes of AWS requiring detoxification, including seizures or delirium (kindling) 2. Grade 2 severity or higher on presentation (CIWA-Ar Score >10) 3. Advanced age 4. Acute or chronic comorbid conditions, including alcoholic liver disease, co-intoxications, trauma, infections, sepsis 5. Detectable blood alcohol level on admission 6. Use of “eye opener,” high daily intake of alcohol, or number of drinking days/month 7. Abnormal liver function (serum aspartate aminotransferase activity >80 U/L) 8. Prior benzodiazepine use 9. Male sex Abbreviation: CIWA-Ar, Clinical Institute of Withdrawal Assessment for Alcohol, revised. Carlson RW et al, Alcohol Withdrawal Syndrome, Crit Care Clin 28 (2012) 549–585 Potential indications for ICU management 1. Advanced Stage 2 or greater alcohol withdrawal syndrome 2. Critical comorbid conditions including: trauma; severe sepsis; respiratory failure; acute respiratory distress syndrome; hemodynamic instability; gastrointestinal bleeding; hepatic failure; pancreatitis; rhabdomyolysis; co-intoxication; coagulopathies; acute CNS process; cardiac arrhythmias, ischemia, or congestive failure; severe fluid or electrolyte defects; renal failure; persistent fever; or complex acid-base defects 3. Escalating intravenous bolus or continuous-infusion sedation therapy 4. Persistent fever >39 C Carlson RW et al, Alcohol Withdrawal Syndrome, Crit Care Clin 28 (2012) 549–585 Alcohol treatment medications O’Connor PG, Alcohol Abuse And Dependence, Goldman L, Ausiello D, eds. Cecil Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier; 2007:chap 31. Criteria for different withdrawal settings Haber P et al. Guidelines for the Treatment of Alcohol Problems. Australian Government Department of Health and Ageing. 2009. Literature review 1 RCT; 3 cohort studies (2 retrospective) Stephens JR, et al. Who Needs Inpatient Detox? Development and Implementation of a Hospitalist Protocol for the Evaluation of Patients for Alcohol Detoxification. J Gen Intern Med. Published online 07 January 2014. Task Force: 3 MD, 1 NP, 1 RN case manager Clinical questions Is inpatient or outpatient treatment superior for alcohol detoxification? What factors should guide decisions on inpatient versus outpatient treatment? Literature search PubMed (years 1980 to 2011) utilizing combinations of the search terms “alcohol detoxification,” “inpatient,” “outpatient,” and “ambulatory” review of reference sources Stephens JR, et al. Who Needs Inpatient Detox? Development and Implementation of a Hospitalist Protocol for the Evaluation of Patients for Alcohol Detoxification. J Gen Intern Med. Published online 07 January 2014. Stephens JR, et al. Who Needs Inpatient Detox? Development and Implementation of a Hospitalist Protocol for the Evaluation of Patients for Alcohol Detoxification. J Gen Intern Med. Published online 07 January 2014. Asplund CA et al. Regimens for alcohol withdrawal and detoxification. J Fam Pract 53:7. (2004) Stephens JR, et al. Who Needs Inpatient Detox? Development and Implementation of a Hospitalist Protocol for the Evaluation of Patients for Alcohol Detoxification. J Gen Intern Med. Published online 07 January 2014. Results Alcohol detoxification admissions: 15.9 v. 18.9/month, p=0.037 Average LOS: 3.4 versus 2.7 days, p=0.09 26.5 Readmission rate: 28.4% v. 26.5%; p=0.33 7-day repeat ED visit: 10.8% v. 8.8% AMA discharges: 18 (1.0/month) v. 16 (2.7/month) Protocol adherence: 15/18 cases (83.3%) Cost savings: $8742 /case, $315,000/yr Stephens JR, et al. Who Needs Inpatient Detox? Development and Implementation of a Hospitalist Protocol for the Evaluation of Patients for Alcohol Detoxification. J Gen Intern Med. Published online 07 January 2014. Weaknesses Unable to definitively tell if protocol is sole reason for decreasing alcohol withdrawal admissions Cannot determine safety because patients not admitted not followed Stephens JR, et al. Who Needs Inpatient Detox? Development and Implementation of a Hospitalist Protocol for the Evaluation of Patients for Alcohol Detoxification. J Gen Intern Med. Published online 07 January 2014. Metropolitan Assessment And Treatment Services (MATS) http://www.bernco.gov/news/139305/ http://www.bernco.gov/mats-faq/ Metropolitan Assessment And Treatment Services (MATS) Qualifications ◦Bernalillo County resident or homeless. ◦18 years of age or older. ◦ In need of detoxification from alcohol or dual substances. If methadone and more than 30 mgs, the person cannot be admitted. If heroin, alcohol, cocaine, etc., not used within the last three days, cannot admit unless symptoms are presenting. ◦If the person is on any life-sustaining prescription medications (such as insulin for diabetes), must have the prescription medication with them. (Note: If the person is on psychiatric drugs but does not have the medication with them, the person can be admitted if not presenting and seems stable.). ◦ Must not have any restraining orders or warrants for arrest. ◦Must not have any appointments within the next 24 hours and up to the next 3 - 5 days. Admission to these services would most likely prevent the person from making that appointment. ◦Individuals must be mobile or able to move without assistance from others. http://www.bernco.gov/mats-faq/ http://www.bernco.gov/news/139305/ UNM Alcohol Withdrawal Powerplan UNM Alcohol Withdrawal Powerplan Arch Intern Med. 2002 May 27;162(10):1117-21. Symptom-triggered vs fixed-schedule doses of benzodiazepine for alcohol withdrawal: a randomized treatment trial. Daeppen JB1, Gache P, Landry U, Sekera E, Schweizer V, Gloor S, Yersin B. prospective, randomized, double-blind, placebo controlled P: adult ED pts admitted to Alameda Co. Medical Center/Highland Hospital, CA w/ alcohol withdrawal I: phenobarbital 10 mg/kg in 100 mL NS + “CIWA” C: 100 mL NS + “CIWA” O: primary: initial level of hospitalization other: lorazepam gtt, LOS, lorazepam total dose, adverse events Rosenson J, Clements C, Simon B, et al. Phenobarbital for acute alcohol withdrawal: a prospective randomized doubleblind placebo-controlled study. J Emerg Med. 2013;44(3):592-598.e2. doi:10.1016/j.jemermed.2012.07.056. UNM CIWA protocol Strategies for Cutting Down from Helping Patients Who Drink Too Much: A Clinician’s Guide. 2005.