**6. Management**

#### **6.1 Disposition**

Management of alcohol withdrawal occurs in a variety of settings, the most appropriate being a withdrawal management facility, or commonly known as a "detox center," or a hospital (note that "detox" refers to management of withdrawal symptoms, not actual detoxification, which is the removal of an agent). The authors do not generally recommend outpatient alcohol withdrawal management due to the difficulty in assessing mild versus early withdrawal with the risk of worsening, as well as difficulty with patient compliance. Patients may primarily seek withdrawal management and be appropriately placed in a detox facility that meets their level of medical needs or may occur in the hospital setting. Alcohol withdrawal often occurs in the hospital setting when patients present ill from their withdrawal symptoms and require admission, present for complications of alcohol use disorder (e.g., pancreatitis, trauma, etc.) and withdraw, or present for other medical problems requiring admission and have to suddenly discontinue consumption of alcohol. When alcohol use disorder or withdrawal are encountered in the hospital setting, a collaborative approach is recommended to assure patient safety and optimize patient care. This collaborative approach may include internal medicine, critical care, medical toxicology, addiction medicine, psychiatry, and case management.

Although the focus of this chapter is alcohol withdrawal in the hospital setting, it is important to realize there are withdrawal management facilities available to safely discontinue alcohol. The *American Society of Addiction Medicine* has designated four levels (1–4) of withdrawal management. Level 1 refers to ambulatory management with minimal on-site monitoring, and Level 4 corresponds to a medically managed inpatient therapy setting [16]. Generally, patients with a CIWA score < 10 may be managed in Level 1 settings, CIWA score of 10 to 18 in Level 2 or

#### *Improving the Safety of Admitted Patients with Alcohol Use Disorder and Withdrawal DOI: http://dx.doi.org/10.5772/intechopen.110030*

Level 3 settings, and > 19 should be managed in a Level 4, resource rich environment [16]. Independent of a patient's symptoms, additional factors will influence the required treatment setting. Psychosocial factors, such as social support or suicide risk, may require a higher level of care. Additional considerations influencing the level of care include but are not limited to: co-substance dependence (opioids, tobacco, etc..), recent ethanol consumption, personal history of AWS or complicated withdrawal, and co-morbid illness such as cirrhosis, chronic obstructive pulmonary disease, congestive heart failure, epilepsy, or renal disease [16]. Patients who are older or pregnant are at higher risk of complications from AWS and benefit from more highly monitored settings [16]. Ultimately, this decision should be made on a case-by-case basis. If in question, it is always better to err on the side of caution and recommend a higher level of care.

Despite there being detox facilities available, many patients may still ultimately require withdrawal management in an inpatient hospital setting due to the aforementioned reasons. Additionally, patients with severe withdrawal, encephalopathy or additional complications may require intensive care. To assure patient safety, the authors recommend hospitals consider employing and collaborating with addiction specialists for consultation or primary management [16]. While withdrawal management facilities generally involve treatment from addiction specialists, opportunities commonly exist within hospitals to provide expert care from this specialty.

Once a treatment setting has been decided upon, general supportive care management should be followed concurrently with appropriate pharmacotherapy (as will be described in subsequent sections). Non-pharmacological options should be utilized, including a dark, quiet room with minimal stimulation [17]. Efforts should be made to frequently reassure patients. Psychiatric assessments for anxiety, insomnia, or suicidality should be conducted and treated appropriately. General supportive care often includes correction of electrolyte imbalances, hypoglycemia correction, hydration therapy (either oral or via fluid resuscitation), and thiamine and other B-vitamin supplementation. Typical thiamine dosing is 100 mg PO per day for 3 to 5 days and ideally should be given prior to, or in conjunction with, glucose supplementation to prevent precipitating (or worsening) Wernicke's Encephalopathy (this will be further elaborated upon in Section 5.3.3) [16, 17]. Patients should be monitored closely and informed regarding their treatment progress, including whether a higher-level treatment setting is indicated.

#### **6.2 Treatment**

#### *6.2.1 Benzodiazepines (BZD): B*

ZDs have long been considered the "gold standard" pharmacological treatment option for AWS. They act primarily by stimulating GABAA receptors by enhancing the *frequency* of chloride channel opening in the presence of GABA [16, 17]. BZDs have been shown to reduce the incidence of seizures, DT, and mortality in AWS [23]. BZDs may be delivered via intravenous, oral, or intramuscular routes, making it an advantageous drug in a variety of situations. Longer acting agents, such as diazepam or chlordiazepoxide, are preferred to allow for a theoretically smoother clinical course due to a proposed auto-tapering mechanism [16, 17]; however, they are all generally effective if dosed appropriately. Diazepam, when administered intravenously, has both the fastest onset and longest duration of action. Lorazepam, diazepam, and chlordiazepoxide are the most prescribed BZDs in treating AWS [16]. There is never

a need to mix benzodiazepines and it can cloud the clinical picture and increase risk of rebound symptoms. Several different dosing strategies are available, including "fixed-dose", "loading-dose", and a "symptoms-triggered" strategies [17]. In fixed dosing, the chosen drug (e.g.10 mg Diazepam QID) is given regularly and then can be subsequently tapered by 25% on days 4 through 7 with liberal dosing as needed for breakthrough symptoms [17]. In a "symptom-triggered" plan (which is preferred), a chosen BZD (e.g. diazepam, lorazepam, chlordiazepoxide) is prescribed based on a patient's hourly CIWA or SEWS score, and doses are escalated as needed [24]. Tapering occurs through smaller doses as scoring decreases. Finally, in a "loadingdose" strategy, higher doses of a chosen BZD are administered until symptoms improve (e.g. Diazepam 20 mg, 40 mg, 60 mg, …100 mg) to allow for a self-taper effect [25]. Regardless of strategy, when utilizing benzodiazepines, close monitoring is necessary to assure no recurrence of symptoms in the short term, and consideration of duration of action of chosen benzodiazepine should be considered in monitoring time. Prescribing BZDs in a symptom triggered fashion has been shown to reduce the total amount of BZD administered and shortens total therapy time, however no specific strategy is clearly superior [17, 24].

#### *6.2.2 Barbiturates*

Barbiturates, primarily phenobarbital, provide another valuable and safe option for effectively treating alcohol withdrawal. They act by stimulating GABAA but, unlike BZD, they increase *duration* of chloride channel opening and they do not require the presence of GABA [26]. Being able to directly stimulate the GABAA receptor without the presence of GABA may provide increased effectiveness over benzodiazepines in controlling symptoms [26]. Additionally, phenobarbital can decrease glutamate activity which thereby assists in treating the hyperdynamic state that results from upregulated NMDA receptor activity [27]. Phenobarbital also has a more predictable pharmacological profile, is more effective for preventing seizures than benzodiazepines, has less incidence of delirium, results in less progression of symptoms, decreases critical care utilization, [26, 28–31]. Phenobarbital does not need to be tapered as it is very long acting and self-tapers over the course of three to five days, thus generally outlasting the AWS disease process. There are various dosing regimens for phenobarbital. Initial doses of phenobarbital 10 mg/kg IV over thirty minutes may be utilized prior to a benzodiazepine regimen or continued phenobarbital monotherapy. When phenobarbital is utilized as a symptom-triggered monotherapy, a loading dose can be followed by subsequent smaller doses (e.g. 130–260 mg IV, 65 mg PO) until symptoms subside, with a total cumulative dose of over 2–2.5 grams rarely being necessary. As patients approach doses over 2.5 grams they can be prone to additional side effects from phenobarbital, including CNS depression, ataxia, and nystagmus. Due to phenobarbital's various benefits over benzodiazepines, many clinicians prefer utilizing this treatment option.

#### *6.2.3 Adjunctive additional treatments*

While GABA-agonist therapy is the mainstay of treatment for AWS, other adjunctive agents may be useful. These medications should only be considered once a patient with AWS has had sufficient GABA-agonist therapy or as an adjunct for safety purposes in the agitated or encephalopathic patient. These adjunctive agents include ketamine, dexmedetomidine, and propofol. Ketamine and propofol are mechanistically

#### *Improving the Safety of Admitted Patients with Alcohol Use Disorder and Withdrawal DOI: http://dx.doi.org/10.5772/intechopen.110030*

therapeutic as ketamine acts as an NMDA receptor antagonist and propofol, like barbiturates, directly stimulates the GABAA receptor [26]. Dexmedetomidine, a central alpha2 agonist, can be used adjunctively to treat delirium, agitation, but should never be used as a sole, primary agent to treat alcohol withdrawal, as it does not address the underlying physiology. When utilizing dexmedetomidine alone, patients are at risk for decompensating while symptoms are otherwise masked. Airway protection is not necessary for the use of ketamine or dexmedetomidine. While propofol is unnecessary for the patient who is protecting his or her airway, it may be an optimal agent for the intubated patient [18].

Thiamine should also be administered along with concurrent assurance of euglycemia. If patient has no evidence of malabsorption and symptoms are mild to moderate, oral supplementation of 100 mg is sufficient. If any evidence of malabsorption or inability to take medications orally, then thiamine should be given intravenously. If patient is encephalopathic, consider high dose thiamine supplementation out of concern for Wernicke's Encephalopathy or Wernicke-Korsakoff Syndrome (see Complications).

Other than benzodiazepines and barbiturates, there is no role for antiepileptic drugs in treating alcohol withdrawal syndrome or alcohol withdrawal seizures. However, gabapentin may be of some utility in treating the symptoms associated with Post-Acute Withdrawal Syndrome [32]. Upon completion of withdrawal, additional agents, such as naltrexone or acamprosate, should be offered for medication assisted therapy, along with psychosocial and rehabilitative services.
