Levels of recommendation (A-C) and Levels of Evidence (I-V) are defined at the end of the "Major Recommendations" field.
Choice of Pharmacologic Agent
The initial therapeutic goal in patients with alcohol withdrawal delirium (AWD) is control of agitation, the symptom that should trigger use of the medication regimens described in this guideline. Rapid and adequate control of agitation reduces the incidence of clinically important adverse events. Sedative-hypnotic drugs are recommended as the primary agents for managing AWD (grade A recommendation). These drugs reduce mortality, reduce the duration of symptoms, and are associated with fewer complications compared with neuroleptic agents in controlled trials.
Current evidence does not clearly indicate that a specific sedative-hypnotic agent is superior to others or that switching from one to another is helpful. Benzodiazepines are most commonly used and recommended by addiction specialists because of a favorable therapeutic/toxic effect index. Examples of commonly used regimens are shown in the original guideline document. However, reported clinical experience indicates that barbiturates may be considered an option. Owing to difficulties in administration and titration of dose, paraldehyde is not recommended (grade A recommendation). Choice among benzodiazepines may be guided by the following considerations: (1) agents with rapid onset control agitation more quickly, for example, oral or intravenous (IV) diazepam has a more rapid onset than other agents (level II evidence); (2) agents with long duration of action (e.g., diazepam) provide a smooth treatment course with less breakthrough symptoms; (3) agents with shorter duration of activity (e.g., lorazepam) may have lower risk when there is concern about prolonged sedation, such as in patients who are elderly or who have substantial liver disease or other serious concomitant medical illness (level III evidence); and (4) the cost of different benzodiazepines can vary considerably.
If a patient demonstrates agitation that is not controlled with extremely large doses of benzodiazepines, use of pentobarbital or propofol can be considered (grade C recommendation).
Determination of Dose and Route of Administration
It is recommended that the dose be determined specifically for each individual patient and that medications be given in doses sufficient to achieve and maintain light somnolence as the recommended therapeutic end point (grade C recommendation). Light somnolence is characterized by a state in which the patient is awake but tends to fall asleep unless stimulated or is sleeping but easily aroused. The amount of medication required for adequate sedation varies greatly from patient to patient and over time in the same patient. Sedative-hypnotic drug doses needed to suppress AWD are commonly much higher than doses used to treat severe anxiety or to sedate patients presurgically. Tolerance, age, severity of signs and symptoms, and medical comorbidity affect the quantity of medication needed for adequate control. When using shorter-acting agents, medication should be tapered carefully even after AWD resolves to prevent the development of breakthrough symptoms or the occurrence of withdrawal seizures.
The medication should be administered by a route that supports achievement of rapid control of agitation and maintenance of appropriate sedation (light somnolence). Intravenous administration has the quickest onset compared with other routes. Intramuscular injection of most benzodiazepines is not recommended owing to erratic absorption (grade C recommendation). Lorazepam, however, is an option in patients with stable cardiovascular status, as it has good intramuscular absorption. Intermittent IV administrations of long-acting medications and continuous IV infusion of short-acting medications seem effective and thus are acceptable. However, continuous IV infusion is considerably more expensive, and there is no existing evidence of therapeutic superiority.
Other Agents
Neuroleptic agents are not recommended as the sole pharmacologic agents in the treatment of AWD because they are associated with higher mortality, longer duration of delirium, and more complications compared with sedative-hypnotic agents in controlled trials (grade A recommendation). Neuroleptic agents may be considered for use in conjunction with benzodiazepines when agitation, perceptual disturbances, or disturbed thinking are not adequately controlled by benzodiazepine therapy (grade C recommendation).
Beta-adrenergic antagonists may be considered for use in conjunction with benzodiazepines in selected patients for control of persistent hypertension or tachycardia (grade C recommendation). They are not recommended for routine use in all patients with AWD, however, as there is no evidence that they improve outcomes in AWD, and beta-adrenergic antagonists, particularly propranolol, may worsen delirium (level V evidence).
Ethyl alcohol is not recommended because there are no controlled trials and there are well-known adverse effects (grade C recommendation).
There is no evidence that magnesium therapy specifically benefits the delirium in alcohol withdrawal. However, magnesium deficiency is common in patients with AWD. Magnesium should be provided for demonstrated hypomagnesemia, and it is also safe and reasonable to include it in IV fluids given for volume repletion provided renal function is normal and levels are monitored (grade C recommendation).
Parenteral administration of thiamine (100 mg daily for at least 3 days, IV or intramuscularly) is recommended to prevent or treat Wernicke-Korsakoff syndrome (grade C recommendation).
Settings and Services
The following recommendations are based on the clinical experience of recognized experts; they have not been the subject of controlled studies (grade C recommendations).
Evaluation
On admission or transfer of a patient from one setting to another, a thorough medical evaluation is needed to determine appropriate diagnostic tests, monitoring, and medication. Elderly patients and those with concurrent medical conditions, acute and chronic, are at higher risk of complications. Concurrent medical conditions are common and may include dehydration, unrecognized head trauma, electrolyte abnormalities, infections (including meningitis), gastrointestinal hemorrhage, pancreatitis, liver disease, and myocardial infarction. These conditions may not be obvious or self-reported in delirious patients.
Monitoring
- Close monitoring by nursing personnel is critical in providing protection for the patient and for maintaining accurate information to guide ongoing medical management. In many cases, continuous, one-to-one observation and monitoring may be required to ensure safe and adequate management of agitated and disoriented patients.
- Vital signs should be monitored regularly in all patients. The appropriate frequency of monitoring depends on the frequency of medication administration, concurrent medical conditions, and the degree of abnormality of the vital signs.
When high doses of benzodiazepines are needed, or when continuous infusions of medication are used, or when patients have significant concurrent medical conditions, cardiac monitoring and oximetry should be in place and resuscitative equipment should be readily available.
Management
- A quiet room with good lighting and environmental cues (e.g., a clock and a calendar) may help reduce confusion.
- Physical restraints may be needed temporarily to protect agitated patients from injuring themselves and to protect staff. Guidelines have been formulated on the appropriate use of restraints to ensure patient safety. If patients cannot take oral medications or maintain adequate oral intake, or if more rapid sedation is needed, IV fluids and medications are recommended. Fluid and electrolyte balance should be maintained, and monitoring of fluid input and output and laboratory variables may be required. Occasionally, endotracheal intubation and ventilatory support may be required.
Definitions:
Strength of the Recommendations
Grade A: Supported by level I studies or by a meta-analysis in which the lower limit of the confidence interval for the effect of treatment exceeds the minimally clinically significant benefit
Grade B: Supported by level II studies or by a meta-analysis in which the estimate of treatment effect exceeds the minimal clinically significant benefit but the lower limit of the confidence interval does not
Grade C: Supported by data other than prospective controlled trials, including secondary analyses of level I or II studies
Levels of Evidence
Level I studies: Randomized trials with low false-positive and low false-negative errors
Level II studies: Randomized trials with high false-positive or high false-negative errors
Level III studies: Nonrandomized, concurrent cohort comparisons
Level IV studies: Nonrandomized, historical cohort comparisons
Level V studies: Case series without controls
