Alcohol use disorder is a prevalent medical and psychiatric disease, and consequently, alcohol withdrawal is encountered frequently in the emergency department. Patients commonly manifest hyperadrenergic signs and symptoms, necessitating admission to the intensive care unit, administration of intravenous sedatives, and frequently, adjunctive pharmacotherapy. This issue reviews the pathophysiology of alcohol withdrawal syndrome, describes the manifestations of alcohol withdrawal, and examines the available evidence for optimal treatment of alcohol withdrawal. An aggressive frontloading approach with benzodiazepines is presented, and the management of benzodiazepine- resistant disease is addressed.
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Following are the most informative references cited in this paper, as determined by the authors.
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
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
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
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
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
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
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
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
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
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Keywords: alcohol withdrawal syndrome, alcohol withdrawal seizure, alcoholic hallucinosis, alcoholic hallucinations, tremor, delirium tremens, ethanol, central nervous system hyperexcitation, CNS hyperexcitation, gamma-aminobutyric acid, GABA, N-methyl-D-aspartate, NMDA, ethanol, sobering centers, benzodiazepine, diazepam, lorazepam, midazolam, chlordiazepoxide, barbiturates, phenobarbital, symptom-driven dosing
The Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar) scale provides an efficient and objective means of assessing alcohol withdrawal that can then be utilized in treatment protocols. The CIWA-Ar can be used for patients for whom there is clinical concern for alcohol withdrawal in a variety of settings, including outpatient, emergency, psychiatric, and general medical-surgical units. It is important to note that the CIWA-Ar cannot be used effectively in patients who are intubated and sedated; a sedation scale such as the Richmond Agitation-Sedation Scale would be more appropriate in that setting.
Patients frequently underreport alcohol use, and clinicians often overlook alcohol problems in patients (Kitchens 1994). It is estimated that 1 out of 5 patients admitted to a hospital abuses alcohol (Schuckit 2001). Unrecognized alcohol withdrawal can lead to potentially life-threatening consequences including seizures and delirium tremens.
For a given individual, there is no absolute relationship between alcohol use pattern and risk of physiologic dependence or withdrawal. In general, any suspicion of daily alcohol use over several weeks or more, regardless of quantity, should raise concern for potential alcohol withdrawal. Additional variables that may contribute to risk include age, medical comorbidities (eg, hepatic dysfunction), concomitant medication use, and low seizure threshold (Roffman 2006).
It is important to note that other conditions can mimic or coexist with alcohol withdrawal, including drug overdose, trauma (eg, intracranial hemorrhage), infection (eg, meningitis), metabolic derangements, hepatic failure, and gastrointestinal bleeding. Clinicians should consider additional testing to rule out alternative diagnoses, especially if presentation includes altered mental status and/or fever.
Assessment protocols utilizing the CIWA-Ar scale vary and include medication dosing triggered by symptoms only and combined symptom-triggered and fixed-dose medication dosing.
Benzodiazepines are generally used to control psychomotor agitation and prevent progression to more severe withdrawal. Diazepam, lorazepam, and chlordiazepoxide are the most frequently used benzodiazepines. Clinicians should follow their hospital's alcohol withdrawal protocol; frequently, treatment begins with benzodiazepines when CIWA-Ar scale scores reach 8 to 10, with standing or as-needed dosing for scores of 10 to 20. Some protocols include transfer to the intensive care unit for scores >20. Clinicians should consider additional supportive care, including intravenous fluids, nutritional supplementation, and frequent clinical reassessment including vital signs.
Jonathan Avery, MD
Katherine E. Taylor, MD
Multiple randomized trials and observational studies support the use of symptom-triggered treatment (using CIWA-Ar) over fixed-schedule treatment (in which benzodiazepines are given at fixed intervals) or vitals-triggered treatment. Superior clinical endpoints include:
There is also some evidence for combined symptom-triggered and fixed-schedule treatment utilizing the CIWA-Ar scale (Daeppen 2002).
The original Clinical Institute Withdrawal Assessment for Alcohol (CIWA-A) scale, published by Shaw et al in 1981, was developed to assess the severity of alcohol withdrawal, both to monitor response to treatment and for use in research. The CIWA-Ar scale developed by Sullivan et al (1989) eliminated several redundant and ineffective items to increase the scale’s efficiency while retaining clinical usefulness, validity and reliability. The study proposed using the CIWA-Ar scale as a shortened version of the original CIWA-A scale.
Reoux and colleagues compared routine hospital alcohol detoxification practice with the CIWA-Ar-based as-needed protocol in a retrospective chart review and found fewer total chlordiazepoxide milligram equivalents were used over a shorter duration with utilization of the CIWA-Ar scale.
Edward M. Sellers, MD
Original/Primary Reference
Validation References
Additional References
The Richmond Agitation-Sedation Scale (RASS) is a validated and reliable method to assess patients’ levels of sedation in the intensive care unit (ICU). The RASS is different than the levels of sedation/ analgesia used by the American Society of Anesthesia (minimal, moderate, deep, general), and the two should not be used interchangeably.
As opposed to the Glasgow Coma Scale, the RASS is not limited to patients with intracranial processes. The RASS can be used in all hospitalized patients to describe their level of alertness or agitation. However, it is mostly used in mechanically ventilated patients in order to avoid over- and undersedation. A RASS score of -2 to 0 has been advocated in this patient population in order to minimize sedation. This strategy has been shown to reduce mortality, and to decrease the duration of mechanical ventilation and the length of stay in the ICU.
Mechanically ventilated patients who are deeply sedated (RASS scores of ≤ -3) have been shown to remain intubated and mechanically ventilated for longer periods of time. This in turn leads to longer ICU stays and higher mortality. Similarly, mechanically ventilated patients who are too agitated are at risk of self-extubation and ventilator dyssynchrony.
Patients with a RASS score ≤-3 should have their sedation decreased or modified in order to achieve a RASS of -2 to 0. Patients with a RASS score of 2 to 4 are not sedated enough and should be assessed for pain, anxiety, or delirium. The un-derlying etiology of the agitation should be investigated and appropriately treated to achieve a RASS score of -2 to 0.
A RASS score should be obtained for all hospitalized patients and at regular intervals in all mechanically ventilated patients. Unless a patient meets indications for deep sedation, a protocol for minimal sedation (RASS -2 to 0) should be used.
Kamal Medlej, MD
The interrater reliability of the RASS was demonstrated in a single-center ICU population in 2 phases: before and after implementation of the RASS. In the second phase of the study, the scale was shown to have good interrater reliability (k = 0.80) among trained nurses. This single-center study prospectively assessed the inter-rater reliability of RASS in a medical ICU population. An excellent interrater reliability (k = 0.91) was again demonstrated among nurses.
Curtis Sessler, MD
Original/Primary Reference
Validation References
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