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alcohol withdrawal syndrome

Etiology: 1) chronic ethanol ingestion 2) isopropanol & methanol less frequently ingested Epidemiology: 1) 5-10% of population have chronic alcoholism - only some will experience withdrawal upon abrupt discontinuation of alcohol 2) increasing age is associated with increasing severity & duration of alcohol withdrawal symptoms [5] 3) 1 in 43 hospitalizations involve alcohol withdrawal (2.3%) [11] Pathology: 1) adaptive responses to long-term use produce tolerance 2) adpative responses persist after discontinuation of alcohol 3) adaptive responses include: a) downregulation of GABA-A receptors b) increase synthesis of excitatory neurotransmitters - norepinephrine, dopamine, serotonin c) upregulation of NMDA receptors d) upregulation of opioid receptors 1] nucleus accumbens & ventral tegmental area 2] results in alcohol craving History: 1) time of last drink 2) how much for how long 3) why did the patient stop drinking 4) previous history of withdrawal (including delirium tremens) 5) AUDIT* [3] useful screen for inpatients at risk of alcohol withdrawal Clinical manifestations: 1) occurs within < 24 hours to 5 days after cessation or significant decrease in alcohol consumption; 6-36 hours [4] 2) severity is generally maximum after 50 hours 3) signs & symptoms a) autonomic hyperactivity b) anorexia c) insomnia d) irritability, generalized tonic-clonic seizure* - within 2 days of last drink - 6-24 hours after last drik e) tremor, anxiety, diaphoresis, palpitations 6-36 hours after last drink f) tachycardia g) hypertension h) fever i) hyperreflexia j) disorientation k) hallucinations 1] auditory, visual, tactile 2] 12-48 hours after last drink 3] hallucinations do not cloud sensorium l) sensation of bugs crawling on skin [10] m) delirium tremens 48-96 (24-48 [4]) hours after last drink 4) signs & symptoms from complications of alcoholism * multiple seizures suggest another disorder [4] Laboratory: 1) blood glucose (finger stick) 2) complete blood count (MCV)* 3) blood alcohol 4) chem 7 5) serum amylase & serum lipase 6) liver function tests,* ALT, AST, GGT [3] 6) urinalysis a) urine ketones b) urine toxicology Special laboratory: - electrocardiogram: a) increased myocardial demand may precipitate myocardial infarction b) prolonged QTc reverts to normal after resolution of withdrawal symptoms Radiology: 1) chest X-ray a) aspiration pneumonia is common b) cardiomyopathy & CHF may be observed 2) head CT - head trauma may result in intracranial bleed Differential diagnosis: 1) pancreatitis 2) alcoholic ketoacidosis 3) anxiety 4) hypoglycemia 5) hypophosphatemia 6) anxiety 7) panic disorder 8) sympathomimetic toxicity Management: 1) hospitalize for a) severe alcohol withdrawal (anticipated) b) lack of social support 2) thiamine 100 mg (IM) PRIOR to food or glucose administration 3) benzodiazepines a) indications: 1] previous alcohol-related seizures - long-acting benzodiazepine on a fixed schedule is indicated even in the absence of symptoms [4] 2] history of delirium tremens 3] significant withdrawal symptoms 4] more severe of longstanding alcohol dependence 5] history of failed or multiple detoxification attempts 6] acute medical illness or surgical illness 7] currently pregnant b) symptom-triggered benzodiazepine for alcohol withdrawal in hospitalized patients results in shorter course of therapy & less benzodiazepine use [4] c) agents of choice [8] 1] chlordiazepoxide in patients without cirrhosis or hepatitis - long 1/2 life 2] oxazepam 15-30 mg PO every 6-8 hours 3] lorazepam 2-4 mg IV every 2 hours PRN 4] lorazepam or oxazepam if cirrhosis or hepatitis d) alternative agents 1] midazolam (Versed) 2] diazepam (non-inferior to lorazepam) [9] e) regimens 1] taper over 5-7 days 2] symptom-triggered dosing (vs taper) [4,6] a] shorter hospital stays (2 vs 3 days) b] lower total benzodiazepine doses (equivalent to 80 mg vs 170 mg of diazepam) f) not all heavy drinkers who stop abruptly will have symptoms of withdrawal & benzodiazepine is not always needed [4] 4) propofol (Diprivan) hospitalized ICU patients with severe withdrawal 5) clonidine 0.1-0.2 mg TID a) can help with attenuation of sympathetic discharge b) allows for sedation with lower doses of sedatives c) monitor blood pressure 6) propranolol - may help control hypertension & tachycardia - may be useful in patients with cirrhosis & esophageal varices - not be use as monotherapy in treatment of alcohol withdrawal 7) carbamazepine, valproate, gabapentin may be used as adjunctive therapy 8) antipsychotics lower the seizure threshold (avoid) [4] 9) dihydropyridines of may be benefit in rodents 19) oral vitamins a) thiamine 100 mg PO QD b) folate 1 mg PO QD

Related

alcoholism (includes binge drinking)

Specific

alcohol withdrawal seizure delirium tremens (DT's)

General

substance withdrawal syndrome

References

  1. McMicken DB & Freeland ES Alcohol-related seizures. Pathophysiology, differential diagnosis, evaluation, and treatment. Emergency Medicine Clinics of North America, 12:1057-1079, 1994 PMID: 7956887
  2. http://www.emedicine.com/emer/topic643.htm
  3. Dolman JM and Hawkes ND. Combining the AUDIT questionnaire and biochemical markers to assess alcohol use and risk of alcohol withdrawal in medical inpatients Alcohol Alcohol 2005 Aug 15. http://dx.doi.org/10.1093/alcalc/agh189
  4. Medical Knowledge Self Assessment Program (MKSAP) 14, 16, 19. American College of Physicians, Philadelphia 2006, 2012, 2021 - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  5. Geriatric Review Syllabus, 7th edition Parada JT et al (eds) American Geriatrics Society, 2010
  6. Cassidy EM et al. Symptom-triggered benzodiazepine therapy for alcohol withdrawal syndrome in the emergency department: A comparison with the standard fixed dose benzodiazepine regimen. Emerg Med J 2012 Oct; 29:802 PMID: 22011975
  7. Amato L, Minozzi S, Davoli M Efficacy and safety of pharmacological interventions for the treatment of the Alcohol Withdrawal Syndrome. Cochrane Database Syst Rev. 2011 Jun 15;(6) PMID: 21678378
  8. NEJM Knowledge+ Question of the Week. Nov 10, 2020 https://knowledgeplus.nejm.org/question-of-week/1330/ - Long D et al. The emergency medicine management of severe alcohol withdrawal. Am J Emerg Med 2017 Jul; 35:1005. PMID: 28188055 - Wong J et al. The ASAM clinical practice guideline on alcohol withdrawal management. J Addict Med 2020 May/Jun; 14:1 PMID: 32511109
  9. Scheuermeyer FX et al. Lorazepam versus diazepam in the management of emergency department patients with alcohol withdrawal. Ann Emerg Med 2020 Dec; 76:774 PMID: 32736932 https://www.annemergmed.com/article/S0196-0644(20)30400-5/fulltext
  10. NEJM Knowledge+ Psychiatry
  11. Steel TL, Matson TE, Hallgren KA et al Incidence of Hospitalizations Involving Alcohol Withdrawal Syndrome in a Primary Care Population. JAMA Netw Open. 2024 Oct 1;7(10):e2438128. PMID: 39378033 Free article.