Clinical Pathways
Clinical Pathways
Moderate to severe AWS
Moderate to severe AWS

Moderate to severe AWS

View The Full Pathway

Action

  • Administer PO chloradiazepoxide (50 mg), diazepam (10 mg), or phenobarbital (65 mg) (Class I)
  • Send basic laboratory tests, including ethanol level
  • Obtain further workup as clinically indicated
  • Rule out other diagnoses
  • Administer IV fluids, thiamine, glucose, folate, as needed
  • Reassess patient over 1-2 hours
  • Administer another dose of oral medication
  • Repeat CIWA-Ar assessment

Decision

What is the repeat CIWA-Ar score?

icon
9-19 → Admit to monitored bed.

Background

All patients with suspected moderate or severe alcohol withdrawal should have basic laboratory studies obtained, including basic serum chemistries and a complete blood count (CBC). The CBC may show leukocytosis, which may be indicative of a hyperadrenergic state or underlying infection. Thrombocytopenia, anemia, or leukopenia may be indicative of alcohol-induced bone marrow suppression. An elevated mean corpuscular volume may be indicative of megaloblastic anemia secondary to folic acid deficiency. Serum pH and osmolality tests may be indicated based on the results of the patient’s chemistries. Alcoholic ketoacidosis may present with an elevated anion gap; and the serum pH may be low or normal due to concomitant ketoacidosis and contraction alkalosis. Patients with alcohol use disorder commonly have severe electrolyte abnormalities, including hypokalemia, hypomagnesemia, hyponatremia, and alcoholic ketoacidosis. Assessment of serum salicylate and acetaminophen levels are indicated in cases in which the history of presenting illness may suggest drug overdose.

image

‣
References
  1. Bard MR, Goettler CE, Toschlog EA, et al. Alcohol withdrawal syndrome: turning minor injuries into a major problem. J Trauma. 2006;61(6):1441-1445. (Retrospective review of the National Trauma Registry of the American College of Surgeons database; 6431 patients)
  2. Foy A, Kay J, Taylor A. The course of alcohol withdrawal in a general hospital. QJM.1997;90(4):253-261. (Observational study; 539 patients)
  3. Genther DJ, Gourin CG. The effect of alcohol abuse and alcohol withdrawal on short-term outcomes and cost of care after head and neck cancer surgery. Laryngoscope. 2012;122(8):1739-1747. (Retrospective cross-sectional study; 92,312 patients)
  4. Joy PS, Kumar G. Delirium tremens leads to poor outcomes for acute coronary syndrome. Cardiology. 2015;132(3):172-175. (Retrospective cohort study and database review; 2,465,852 patients, 7959 patients with alcohol withdrawal)
  5. Jawa RS, Stothert JC, Shostrom VK, et al. Alcohol withdrawal syndrome in admitted trauma patients. Am J Surg. 2014;208(5):781-787. (Retrospective database review; 159 patients)
  6. Caetano R, Clark CL, Greenfield TK. Prevalence, trends, and incidence of alcohol withdrawal symptoms: analysis of general population and clinical samples. Alcohol Health Res World. 1998;22(1):73-79. (Review)
  7. American Psychiatric Association. DSM-5 Task Force. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. 5th ed. Washington, DC: American Psychiatric Association; 2013. (Medical reference text)
  8. Benedict NJ, Wong A, Cassidy E, et al. Predictors of resistant alcohol withdrawal (RAW): a retrospective case-control study. Drug Alcohol Depend. 2018;192:303-308. (Retrospective cohort analysis; 736 patients)
  9. Nelson L, Goldfrank LR, Hoffman, RS, et al. Goldfrank’s Toxicologic Emergencies. 11th ed. New York, NY: McGraw-Hill Medical; 2011. (Textbook)
  10. Brent J. Critical Care Toxicology: Diagnosis and Management of the Critically Poisoned Patient. 1st ed. St. Louis, MO: Mosby; 2005. (Textbook)
  11. 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(6):CD008537. (Systematic review)
  12. Amato L, Minozzi S, Vecchi S, et al. Benzodiazepines for alcohol withdrawal. Cochrane Database Syst Rev. 2010(3):CD005063. (Systematic review) DOI: 10.1002/14651858.CD005063.pub3
  13. Asplund CA, Aaronson JW, Aaronson HE. 3 regimens for alcohol withdrawal and detoxification. J Fam Pract. 2004;53(7):545-554. (Review)
  14. Holloway HC, Hales RE, Watanabe HK. Recognition and treatment of acute alcohol withdrawal syndromes. Psychiatr Clin North Am. 1984;7(4):729-743. (Review)
  15. Hodges B, Mazur JE. Intravenous ethanol for the treatment of alcohol withdrawal syndrome in critically ill patients. Pharmacotherapy. 2004;24(11):1578-1585. (Review)
  16. Mayo-Smith MF, Beecher LH, Fischer TL, et al. Management of alcohol withdrawal delirium - an evidence-based practice guideline. Arch Internal Med. 2004;164(13):1405-1412. (Systematic review) DOI: 10.1001/archinte.164.13.1405
  17. Muzyk AJ, Leung JG, Nelson S, et al. The role of diazepam loading for the treatment of alcohol withdrawal syndrome in hospitalized patients. Am J Addict. 2013;22(2):113-118. (Review)
  18. Newman JP, Terris DJ, Moore M. Trends in the management of alcohol-withdrawal syndrome. Laryngoscope. 1995;105(1):1-7. (Review)
  19. Sarff M, Gold JA. Alcohol withdrawal syndromes in the intensive care unit. Crit Care Med. 2010;38(9):S494-S501. (Review)
  20. Stehman CR, Mycyk MB. A rational approach to the treatment of alcohol withdrawal in the ED. Am J Emerg Med. 2013;31(4):734-742. (Review)
  21. Chance JF. Emergency department treatment of alcohol withdrawal seizures with phenytoin. Ann Emerg Med. 1991;20(5):520-522. (Prospective randomized double-blind placebo-controlled trial; 55 patients) DOI: 10.1016/s0196-0644(05)81606-3
  22. Hendey GW, Dery RA, Barnes RL, et al. A prospective, randomized, trial of phenobarbital versus benzodiazepines for acute alcohol withdrawal. Am J Emerg Med. 2011;29(4):382-385. (Prospective; randomized trial; 44 patients)
  23. Pizon AF, Becker CE, Bikin D. The clinical significance of variations in ethanol toxicokinetics. J Med Toxicol. 2007;3(2):63-72. (Review)
  24. Klockhoff H, Näslund I, Jones AW. Faster absorption of ethanol and higher peak concentration in women after gastric bypass surgery. Br J Clin Pharmacol. 2002;54(6):587-591. (Prospective cohort study; 24 patients)
  25. Cagetti E, Liang J, Spigelman I, et al. Withdrawal from chronic intermittent ethanol treatment changes subunit composition, reduces synaptic function, and decreases behavioral responses to positive allosteric modulators of GABA receptors. Mol Pharmacol. 2003;63(1):53-64. (Animal study; rats)

    26. A

  26. Ross DW, Schullek JR, Homan MB. EMS triage and transport of intoxicated individuals to a detoxification facility instead of an emergency department. Ann Emerg Med. 2013:61(2):175-184. (Retrospective cohort study; 718 patients)
  27. Smith-Bernardin SM, Kennel M, Yeh C. EMS Can Safely Transport Intoxicated Patients to a Sobering Center as an Alternate Destination. Ann Emerg Med. 2019;74(1):112-118. (Retrospective case review; 11,596 visits, 3268 patients)
  28. Maldonado JR, Sher Y, Das S, et al. Prospective Validation Study of the Prediction of Alcohol Withdrawal Severity Scale (PAWSS) in Medically Ill Inpatients: a new scale for the prediction of complicated alcohol withdrawal syndrome. Alcohol Alcohol. 2015;50(5):509-518. (Prospective comparative observational study; 403 patients)
  29. Kim DW, Kim HK, Bae EK, et al. Clinical predictors for delirium tremens in patients with alcohol withdrawal seizures. Am J Emerg Med. 2015;33(5):701-704. (Prospective cohort study; 97 patients)
  30. Goodson CM, Clark BJ, Douglas IS. Predictors of severe alcohol withdrawal syndrome: a systematic review and meta-analysis. Alcohol Clin Exp Res. 2014;38(10):2664-2677. (Systematic review; 15 studies)
  31. Kraemer KL, Mayo-Smith MF, Calkins DR. Independent clinical correlates of severe alcohol withdrawal. Subst Abuse. 2003;24(4):197-209. (Retrospective cohort; 284 patients)
  32. Wetterling T, Kanitz RD, Veltrup C, et al. Clinical predictors of alcohol-withdrawal delirium. Alcohol Clin Exp Res. 1994;18(5):1100-1102.
  33. Vinson DC, Menezes M. Admission alcohol level: a predictor of the course of alcohol withdrawal. J Fam Pract. 1991;33(2):161-167. (Retrospective review; 185 patients)
  34. Tsuang JW, Irwin MR, Smith TL, et al. Characteristics of men with alcoholic hallucinosis. Addiction. 1994;89(1):73-78. (Comparison study; 532 patients)
  35. Schuckit MA. Recognition and management of withdrawal delirium (delirium tremens). N Engl J Med. 2014;371(22):2109-2113. (Review)
  36. Kaim SC, Klett CJ, Rothfeld B. Treatment of the acute alcohol withdrawal state: a comparison of four drugs. Am J Psychiatry. 1969;125(12):1640-1646. (Prospective randomized double-blind placebo-controlled trial; 537 patients)
  37. Mayo-Smith MF. Pharmacological management of alcohol withdrawal. A meta-analysis and evidence-based practice guideline. JAMA. 1997;278(2):144-151. (Meta-analysis and practice guideline) DOI: 10.1001/jama.1997.03550020076042
  38. Arendt RM, Greenblatt DJ, deJong RH, et al. In vitro correlates of benzodiazepine cerebrospinal fluid uptake, pharmacodynamic action and peripheral distribution. J Pharmacol Exp Ther. 1983;227(1):98-106. (Animal study)
  39. Gold JA, Rimal B, Nolan A, et al. A strategy of escalating doses of benzodiazepines and phenobarbital administration reduces the need for mechanical ventilation in delirium tremens. Crit Care Med. 2007;35(3):724-730. (Retrospective cohort; 54 patients) DOI: 10.1097/01.CCM.0000256841.28351.80
  40. Lee JA, Duby JJ, Cocanour CS. Effect of early and focused benzodiazepine therapy on length of stay in severe alcohol withdrawal syndrome. Clin Toxicol (Phila). 2019;57(7):624-627. (Pre- and post-protocol cohort study; 113 patients) DOI: 10.1080/15563650.2018.1542701
  41. Wretlind M, Pilbrant A, Sundwall A, et al. Disposition of 3 benzodiazepines after single oral administration in man. Acta Pharmacologica Et Toxicologica. 1977;40 Suppl 1(1):28-39. (Kinetics study; 7 patients)
  42. Hung OR, Dyck JB, Varvel J, et al. Comparative absorption kinetics of intramuscular midazolam and diazepam. Can J Anaesth. 1996;43(5 Pt 1):450-455. (Kinetics study; 11 patients)
  43. Wermeling DP, Miller JL, Archer SM, et al. Bioavailability and pharmacokinetics of lorazepam after intranasal, intravenous, and intramuscular administration. J Clin Pharmacol. 2001;41(11):1225-1231. (Randomized crossover study; 11 patients)
  44. Greenblatt DJ, Joyce TH, Comer WH, et al. Clinical pharmacokinetics of lorazepam. II. Intramuscular injection. Clin Pharmacol Ther. 1977;21(2):222-230. (Kinetics study; 6 patients)
  45. Elliott HW. Metabolism of lorazepam. Br J Anaesth. 1976;48(10):1017-1023. (Review)
  46. Gershkovich P, Wasan KM, Ribeyre C, et al. Effect of variations in treatment regimen and liver cirrhosis on exposure to benzodiazepines during treatment of alcohol withdrawal syndrome. Drugs Context. 2015;4:212287. (Review)
  47. Bird RD, Makela EH. Alcohol withdrawal: what is the benzodiazepine of choice? Ann Pharmacother. 1994;28(1):67-71. (Review)
  48. Hammond DA, Rowe JM, Wong A, et al. Patient outcomes associated with phenobarbital use with or without benzodiazepines for alcohol withdrawal syndrome: a systematic review. Hosp Pharm. 2017;52(9):607-616. (Systematic review; 4 controlled trials, 5 observational studies)
  49. Nisavic M, Nejad SH, Isenberg BM, et al. Use of phenobarbital in alcohol withdrawal management - a retrospective comparison study of phenobarbital and benzodiazepines for acute alcohol withdrawal management in general medical patients. Psychosomatics. 2019;60(5):458-467. (Retrospective chart review; 562 patients)
  50. Ibarra F Jr. Single dose phenobarbital in addition to symptom-triggered lorazepam in alcohol withdrawal. Am J Emerg Med. 2020;38(2):178-181. (Retrospective chart review; 78 patients)
  51. Waldee E, Phan SV. Evaluating the use of phenobarbital for the management of alcohol withdrawal syndrome in psychiatric inpatients. J Pharm Pract. 2020 Aug;33(4):477-480. (Observational prospective study; 122 patients)
  52. Sullivan SM, Dewey BN, Jarrell DH, et al. Comparison of phenobarbital-adjunct versus benzodiazepine-only approach for alcohol withdrawal syndrome in the emergency department. Am J Emerg Med. 2019 Jul;37(7):1313-1316. (Retrospective cohort study; 209 patients)
  53. Tidwell WP, Thomas TL, Pouliot JD, et al. Treatment of alcohol withdrawal syndrome: phenobarbital vs CIWA-Ar protocol. Am J Crit Care. 2018;27(6):454-460. (Retrospective cohort study; 120 patients)
  54. Oks M, Cleven KL, Healy L, et al. The safety and utility of phenobarbital use for the treatment of severe alcohol withdrawal syndrome in the medical intensive care unit. J Intensive Care Med. 2020;35(9):844-850. (Retrospective observational study; 86 patients)
  55. Hjermo I, Anderson JE, Fink-Jensen A, et al. Phenobarbital versus diazepam for delirium tremens--a retrospective study. Dan Med Bull. 2010;57(8):A4169. (Retrospective study; 194 patients)
  56. Rosenson J, Clements C, Simon B, et al. Phenobarbital for acute alcohol withdrawal: a prospective randomized double-blind placebo-controlled study. J Emerg Med.2013;44(3):592-598. (Prospective randomized double-blind placebo-controlled trial; 102 patients)
  57. Korpi ER, Mattila MJ, Wisden W, et al. GABA(A)-receptor subtypes: clinical efficacy and selectivity of benzodiazepine site ligands. Ann Med. 1997;29(4):275-282. (Review)
  58. Ives TJ, Mooney AJ 3rd, Gwyther RE. Pharmacokinetic dosing of phenobarbital in the treatment of alcohol withdrawal syndrome. South Med J. 1991;84(1):18-21. (Case reports; 2 patients)
  59. Long D, Long B, Koyfman A. The emergency medicine management of severe alcohol withdrawal. Am J Emerg Med. 2017;35(7):1005-1011. (Review)
  60. Nelson AC, Kehoe J, Sankoff J, et al. Benzodiazepines vs barbiturates for alcohol withdrawal: Analysis of 3 different treatment protocols. Am J Emerg Med. 2019;37(4):733-736. (Retrospective chart review; 300 patients)
  61. Wong A, Benedict NJ, Kane-Gill SL. Multicenter evaluation of pharmacologic management and outcomes associated with severe resistant alcohol withdrawal. J Crit Care. 2015;30(2):405-409. (Retrospective chart review; 184 patients)
  62. Craft PP, Foil MB, Cunningham PR, et al. Intravenous ethanol for alcohol detoxification in trauma patients. South Med J. 1994;87(1):47-54. (Retrospective study; 37 patients)
  63. DiPaula B, Tommasello A, Solounias B, et al. An evaluation of intravenous ethanol in hospitalized patients. J Subst Abuse Treat. 1998;15(5):437-442. (Retrospective study; 68 patients)
  64. Weinberg JA, Magnotti LJ, Fischer PE, 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(1):99-104. (Prospective randomized trial; 50 patients)
  65. Hayashida M, Alterman AI, McLellan AT, et al. Comparative effectiveness and costs of inpatient and outpatient detoxification of patients with mild-to-moderate alcohol withdrawal syndrome. N Engl J Med. 1989;320(6):358-365. (Prospective randomized trial; 164 patients) DOI: 10.1056/NEJM198902093200605
  66. Barata IA, Shandro JR, Montgomery M, et al. Effectiveness of SBIRT for alcohol use disorders in the emergency department: a systematic review. West J Emerg Med. 2017;18(6):1143-1152. (Systematic review; 35 articles)
  67. Erskine RJ, Murphy PJ, Langton JA, Smith G. Effect of age on the sensitivity of upper airway reflexes. Br J Anaesth. 1993; 70(5):574-575. (Descriptive study; 102 patients)
  68. Alldredge BK, Lowenstein DH, Simon RP. Placebo-controlled trial of intravenous diphenylhydantoin for short-term treatment of alcohol withdrawal seizures. Am J Med.1989;87(6):645-648. (Prospective randomized double-blind placebo-controlled trial; 90 patients)
  69. Rathlev NK, D’Onofrio G, Fish SS, et al. The lack of efficacy of phenytoin in the prevention of recurrent alcohol-related seizures. Ann Emerg Med. 1994;23(3):513-518. (Prospective randomized double-blind trial; 147 patients)
  70. D’Onofrio G, Rathlev NK, Ulrich AS, et al. Lorazepam for the prevention of recurrent seizures related to alcohol. N Engl J Med. 1999;340(12):915-919. (Randomized double-blind trial; 229 patients)
  71. Daniell LC. Effect of anesthetic and convulsant barbiturates on Nmethyl-D-aspartate receptor-mediated calcium flux in brain membrane-vesicles. Pharmacology.1994;49(5):296-307. (Animal study)
  72. Hans P, Bonhomme V, Collette J, et al. Propofol protects cultured rat hippocampal neurons against Nmethyl-D-aspartate receptor-mediated glutamate toxicity. J Neurosurg Anesthesiol. 1994;6(4):249-253. (Animal study)
  73. Irifune M, Takarada T, Shimizu Y, et al. Propofol-induced anesthesia in mice is mediated by gamma-aminobutyric acid-A and excitatory amino acid receptors. Anesth Analg.2003;97(2):424-429. (Animal study)
  74. Coomes TR, Smith SW. Successful use of propofol in refractory delirium tremens. Ann Emerg Med. 1997;30(6):825-828. (Case report)
  75. McCowan C, Marik P. Refractory delirium tremens treated with propofol: a case series. Crit Care Med. 2000;28(6):1781-1784. (Case series; 4 patients)
  76. Hughes DW, Vanwert E, Lepori L, et al. Propofol for benzodiazepine-refractory alcohol withdrawal in a non-mechanically ventilated patient. Am J Emerg Med. 2014;32(1):112. (Case report)
  77. Corbett SM, Montoya ID, Moore FA. Propofol-related infusion syndrome in intensive care patients. Pharmacotherapy. 2008;28(2):250-258. (Review)
  78. Barrientos-Vega R, Mar Sanchez-Soria M, Morales-Garcia C, et al. Prolonged sedation of critically ill patients with midazolam or propofol: impact on weaning and costs. Crit Care Med. 1997;25(1):33-40. (Prospective randomized open-label trial; 108 patients)
  79. Daeppen JB, Gache P, Landry U, et al. Symptom-triggered vs fixed-schedule doses of benzodiazepine for alcohol withdrawal: a randomized treatment trial. Arch Intern Med.2002;162(10):1117-1121. (Prospective randomized double-blind controlled trial; 117 patients)
  80. Maldonado JR, Nguyen LH, Schader EM, et al. Benzodiazepine loading versus symptom-triggered treatment of alcohol withdrawal: a prospective, randomized clinical trial. Gen Hosp Psychiatry. 2012;34(6):611-617. (Prospective randomized controlled trial; 47 patients)
  81. Saitz R, Mayo-Smith MF, Roberts MS, et al. Individualized treatment for alcohol withdrawal. A randomized double-blind controlled trial. JAMA. 1994;272(7):519-523. (Randomized double-blind controlled trial; 47 patients) DOI: 10.1001/jama.1994.03520070039035
  82. Müller UJ, Schuermann F, Dobrowolny H, et al. Assessment of pharmacological treatment quality: comparison of symptom-triggered vs. fixed-schedule alcohol withdrawal in clinical practice. Pharmacopsychiatry. 2016;49(5):199-203. (Retrospective cohort study; 120 patients) DOI: 10.1055/s-0042-104508
  83. Muzyk AJ, Rogers RE, Dighe G, et al. Impact of an alcohol withdrawal treatment pathway on hospital length of stay: a retrospective observational study comparing pre and post pathway implementation. J Psychiatr Pract. 2017;23(3):233-241. (Retrospective observational study; 582 subjects)
  84. Victor M, Adams RD. The effect of alcohol on the nervous system. Res Publ Assoc Res Nerv Ment Dis. 1953;32:526-573. (Review)
  85. Thomson AD, Baker H, Leevy CM. Patterns of 35S-thiamine hydrochloride absorption in the malnourished alcoholic patient. J Lab Clin Med. 1970;76(1):34-45. (Kinetics study)
  86. Hack JB, Hoffman RS. Thiamine before glucose to prevent Wernicke encephalopathy: examining the conventional wisdom. JAMA. 1998;279(8):583-584. (Editorial comment)
  87. Kotlinska J. NMDA antagonists inhibit the development of ethanol dependence in rats. Pol J Pharmacol. 2001;53(1):47-50. (Animal study)
  88. Fitzgerald GJ, Liu H, Morzorati SL. Decreased sensitivity of NMDA receptors on dopaminergic neurons from the posterior ventral tegmental area following chronic nondependent alcohol consumption. Alcohol Clin Exp Res. 2012;36(10):1710-1719. (Animal study)
  89. Ron D, Wang J. The NMDA receptor and alcohol addiction. In: VanDongen AM, ed. Biology of the NMDA Receptor. Boca Raton, FL: CRC Press; 2009. (Textbook chapter)
  90. Whittington MA, Lambert JD, Little HJ. Increased NMDA receptor and calcium channel activity underlying ethanol withdrawal hyperexcitability. Alcohol Alcohol. 1995;30(1):105-114. (Basic science)
  91. Nagy J, Horvath C, Farkas S, et al. NR2B subunit selective NMDA antagonists inhibit neurotoxic effect of alcohol-withdrawal in primary cultures of rat cortical neurones. Neurochem Int. 2004;44(1):17-23. (Animal study)
  92. Hoffman PL, Tabakoff B. The contribution of voltage-gated and NMDA receptor-gated calcium channels to ethanol withdrawal seizures. Alcohol Alcohol Suppl. 1991;1:171-175. (Review)
  93. Sass H, Soyka M, Mann K, et al. Relapse prevention by acamprosate. Results from a placebo-controlled study on alcohol dependence. Arch Gen Psychiatry. 1996;53(8):673-680. (Randomized double-blind placebo-controlled trial; 272 patients)
  94. Krystal JH, Petrakis IL, Krupitsky E, et al. NMDA receptor antagonism and the ethanol intoxication signal: from alcoholism risk to pharmacotherapy. Ann N Y Acad Sci.2003;1003:176-184. (Review)
  95. Bouza C, Angeles M, Munoz A, et al. Efficacy and safety of naltrexone and acamprosate in the treatment of alcohol dependence: a systematic review. Addiction. 2004;99(7):811-828. (Review)
  96. Staner L, Boeijinga P, Danel T, et al. Effects of acamprosate on sleep during alcohol withdrawal: a double-blind placebo-controlled polysomnographic study in alcohol-dependent subjects. Alcohol Clin Exp Res. 2006;30(9):1492-1499. (Double-blind placebo-controlled trial; 24 patients)
  97. Whitworth AB, Fischer F, Lesch OM, et al. Comparison of acamprosate and placebo in long-term treatment of alcohol dependence. Lancet. 1996;347(9013):1438-1442. (Double-blind placebo-controlled; 455 patients)
  98. Pizon AF, Lynch MJ, Benedict NJ, et al. Adjunct ketamine use in the management of severe ethanol withdrawal. Crit Care Med. 2018;46(8):e768-e771. (Retrospective observational cohort study; 63 patients) DOI: 10.1097/CCM.0000000000003204
  99. Wong A, Benedict NJ, Armahizer MJ, et al. Evaluation of adjunctive ketamine to benzodiazepines for management of alcohol withdrawal syndrome. Ann Pharmacother. 2015;49(1):14-19. (Retrospective review; 23 patients)
  100. Shah P, McDowell M, Ebisu R, et al. Adjunctive use of ketamine for benzodiazepine-resistant severe alcohol withdrawal: a retrospective evaluation. J Med Toxicol. 2018;14(3):229-236. (Retrospective review; 30 patients)
  101. Soto E, Stewart DR, Mannes AJ, et al. Oral ketamine in the palliative care setting: a review of the literature and case report of a patient with neurofibromatosis type 1 and glomus tumor-associated complex regional pain syndrome. Am J Hosp Palliat Care.2012;29(4):308-317. (Case report and review)
  102. Enarson MC, Hays H, Woodroffe MA. Clinical experience with oral ketamine. J Pain Symptom Manag. 1999;17(5):384-386. (Retrospective study; 21 patients)
  103. Moncini M, Masini E, Gambassi F, et al. Gamma-hydroxybutyric acid and alcohol-related syndromes. Alcohol. 2000;20(3):285-291. (Open double-blind placebo-controlled trial; 321 patients)
  104. Addolorato G, Balducci G, Capristo E, et al. Gamma-hydroxybutyric acid (GHB) in the treatment of alcohol withdrawal syndrome: a randomized comparative study versus benzodiazepine. Alcohol Clin Exp Res. 1999;23(10):1596-1604. (Randomized controlled single-blind trial; 60 patients)
  105. Leone MA, Vigna-Taglianti F, Avanzi G, et al. Gamma-hydroxybutyrate (GHB) for treatment of alcohol withdrawal and prevention of relapses. Cochrane Database Syst Rev. 2010(2):CD006266. (Cochrane review)
  106. Addolorato G, Leggio L, Abenavoli L, et al. Baclofen in the treatment of alcohol withdrawal syndrome: a comparative study vs diazepam. Am J Med. 2006;119(3):276. (Prospective randomized trial; 37 patients)
  107. Lyon JE, Khan RA, Gessert CE, et al. Treating alcohol withdrawal with oral baclofen: a randomized, double-blind, placebo-controlled trial. J Hosp Med. 2011;6(8):469-474. (Prospective randomized double-blind placebo-controlled trial; 79 patients)
  108. Beg M, Fisher S, Siu D, et al. Treatment of alcohol withdrawal syndrome with and without dexmedetomidine. Perm J. 2016;20(2):49-53. (Retrospective cohort study; 77 patients)
  109. Lizotte RJ, Kappes JA, Bartel BJ, et al. Evaluating the effects of dexmedetomidine compared to propofol as adjunctive therapy in patients with alcohol withdrawal. Clin Pharmacol. 2014;6:171-177. (Retrospective chart review; 41 patients)
  110. VanderWeide LA, Foster CJ, MacLaren R, et al. Evaluation of early dexmedetomidine addition to the standard of care for severe alcohol withdrawal in the ICU: a retrospective controlled cohort study. J Intensive Care Med. 2016;31(3):198-204. (Retrospective controlled cohort study; 42 patients)
  111. Mueller SW, Preslaski CR, Kiser TH, et al. A randomized, double-blind, placebo-controlled dose range study of dexmedetomidine as adjunctive therapy for alcohol withdrawal. Crit Care Med. 2014;42(5):1131-1139. (Randomized blinded placebo-controlled; 24 patient) DOI: 10.1097/CCM.0000000000000141
  112. Muzyk AJ, Fowler JA, Norwood DK, et al. Role of alpha(2)-agonists in the treatment of acute alcohol withdrawal. Ann Pharmacother. 2011;45(5):649-657. (Review)
  113. Linn DD, Loeser KC. Dexmedetomidine for alcohol withdrawal syndrome. Ann Pharmacother. 2015;49(12):1336-1342. (Systematic review)
  114. Wong A, Smithburger PL, Kane-Gill SL. Review of adjunctive dexmedetomidine in the management of severe acute alcohol withdrawal syndrome. Am J Drug Alcohol Abuse. 2015;41(5):382-391. (Systematic review)
  115. Minozzi S, Amato L, Vecchi S, et al. Anticonvulsants for alcohol withdrawal. Cochrane Database Syst Rev. 2010;(3):CD005064. (Cochrane review)
  116. Koethe D, Juelicher A, Nolden BM, et al. Oxcarbazepine--efficacy and tolerability during treatment of alcohol withdrawal: a double-blind, randomized, placebo-controlled multicenter pilot study. Alcohol Clin Exp Res. 2007;31(7):1188-1194. (Randomized double-blind placebo-controlled pilot; 50 patients)
  117. Aliyev ZN, Aliyev NA. Valproate treatment of acute alcohol hallucinosis: a double-blind, placebo-controlled study. Alcohol Alcohol. 2008;43(4):456-459. (Randomized double-blind placebo-controlled trial; 40 patients)
  118. Eyer F, Schreckenberg M, Hecht D, et al. Carbamazepine and valproate as adjuncts in the treatment of alcohol withdrawal syndrome: a retrospective cohort study. Alcohol Alcohol. 2011;46(2):177-184. (Retrospective cohort; 827 patients)
  119. Karst M, Passie T, Friedrich S, et al. Acupuncture in the treatment of alcohol withdrawal symptoms: a randomized, placebo-controlled inpatient study. Addict Biol. 2002;7(4):415-419. (Prospective randomized placebo-controlled trial; 34 patients)
  120. Perry EC. Inpatient management of acute alcohol withdrawal syndrome. CNS Drugs.2014;28(5):401-410. (Review)

CIWA-Ar score >19
CIWA-Ar score >19
FacebookTwitterLinkedInInstagramYouTubePinterest

EB Medicine

FOAMed

Podcast

© EB Medicine. All rights reserved