Doses vary greatly and should be patient- specific. Patients should be monitored for signs of oversedation and respiratory depression. 171 Benzodiazepines are Schedule IV controlled substances that carry a risk of misuse or diversion. This risk can be mitigated by ordering the minimum amount needed to achieve stability and hold the patient over until their next appointment. Benzodiazepines should be discontinued once alcohol withdrawal treatment is complete. Patients and caregivers should be educated on the risks of combining alcohol with benzodiazepines, the risks of driving or using heavy machinery while taking benzodiazepines, and the interaction between benzodiazepines and other CNS depressants. Patients at a high risk of benzodiazepine abuse or diversion can be prescribed alternative medications or referred for inpatient management, depending on the severity of their case. 171 For patients in hospitals or treatment centers, the preferred dosing method is symptom-triggered dosing administered by trained staff. In this method, patients are given medication only when experiencing significant symptoms of withdrawal, as noted by a symptom severity scale such as the CIWA-Ar, and doses are based on symptom severity. Withdrawal symptoms can be monitored using the CIWA-Ar scale every 1 to 4 hours initially, and can be extended to every 4 to 8 hours once the patient has been stabilized. Symptom triggered treatment allows for individualized dosing based on real time severity of symptoms, reducing the risk of over or under treatment. Patients may require large doses of benzodiazepines initially, with reduced doses over time. Studies have shown that symptom-triggered dosing reduces treatment duration and length of inpatient stay compared to fixed-dose schedules. 171 Fixed dosing is commonly used in ambulatory settings. This method allows for set amounts of benzodiazepines to be administered at regular intervals, and the dose and/or frequency is gradually tapered according to a set schedule. Fixed dosing is easier for patients to self-administer, though it is also easier to over or underestimate the dose needed, leading to oversedation or sub- optimal symptom control. Patients on fixed dose schedules still require frequent monitoring, and should be reassessed regularly to determine if dosage changes are necessary. 171 Front loading with benzodiazepines is recommended for patients in severe alcohol withdrawal, as noted by CIWA-Ar scores greater than 19. Front loading involves giving a moderate or high dose of a long-acting benzodiazepine to ensure withdrawal symptoms are rapidly controlled. Longer-acting agents such as diazepam or chlordiazepoxide are preferred agents for this purpose, to prevent the development of seizures or delirium. Studies have shown that front loading reduces the risk of withdrawal seizures, shortens treatment durations, and reduces the duration of delirium. Patients receiving front-loaded doses should be closely monitored for respiratory depression and signs of oversedation, as these side effects occur more frequently with this type of dosing regimen. 171
Phenobarbital Patients who have a contraindication to benzodiazepine use that are experiencing moderate to severe withdrawal, or are at risk of developing severe or complicated withdrawal, may be treated with phenobarbital. Phenobarbital, a barbiturate, was the first medication used to successfully treat alcohol withdrawal; its use for this purpose began in the 1920s. Phenobarbital is best administered by providers experienced with its use who are able to closely monitor the patient, due to the risk of toxicity when used in high doses or in combination with alcohol. Phenobarbital has a narrow therapeutic window which can create challenges in dosing it appropriately; it can cause respiratory depression and oversedation when used at high doses. Its dosing can also be complicated by its long half-life of up to seven days, and its metabolism by the liver, which can be impaired in patients who chronically abuse alcohol. Phenobarbital is associated with a number of other side effects, including hypotension, pulmonary edema, bradycardia, bradypnea, hypothermia, acute renal failure, and Steven-Johnson syndrome. When the effective use of benzodiazepines for the treatment of alcohol withdrawal was initiated in the 1960s, the use of phenobarbital fell out of favor. 171 Anticonvulsants Anticonvulsants such as carbamazepine, gabapentin, or valproic acid can be used as adjunct therapy with benzodiazepines to improve control of withdrawal. Carbamazepine or gabapentin can also be used as monotherapy if benzodiazepines are contraindicated; valproic acid does not have sufficient evidence to support its use as monotherapy. There is not enough evidence to support the use of anticonvulsants over benzodiazepines, particularly in patients at a high risk of severe withdrawal, delirium, or seizures. Gabapentin may be an effective adjunct bridge therapy between the treatment of alcohol withdrawal and long-term management of alcohol use disorder. Gabapentin has been associated with increased abstinence rates and fewer heavy drinking days compared with placebo in the management of alcohol use disorder. Valproic acid should be avoided in patients with liver disease as well as in women of childbearing potential. 171 Alpha2 Adrenergic Agonists and Beta Blockers Alpha2 adrenergic agonists such as clonidine can be useful as adjunct therapy in patients with anxiety or autonomic hyperactivity that is not controlled by benzodiazepines. Beta-adrenergic antagonists, also known as beta blockers, can also be used in appropriate patients to treat persistent hypertension or tachycardia. Since many alcohol withdrawal patients experience cardiac symptoms such as tachycardia or hypertension, those that are not alleviated by correcting electrolyte imbalances, dehydration, or through the use of benzodiazepines can benefit from the use of alpha2 agonists or beta blockers. These agents should not be used as monotherapy in withdrawal treatment: they can reduce the symptoms of withdrawal without treating
the underlying pathophysiology, increasing the risk of developing more severe withdrawal. They are also not effective when used alone for the treatment of withdrawal seizures or delirium. 171 Managing Complicated Alcohol Withdrawal Seizures Patients who have experienced a seizure during their current withdrawal episode should be admitted to a setting that has close monitoring available for frequent reassessment every 1 to 2 hours for the next 6 to 24 hours. Electrolyte levels should be monitored to determine the need for IV fluids and patients should be closely monitored for delirium. Safety measures such as fall precautions, frequent check-ins, and assistance with activities of daily living can also be implemented to ensure patient safety. 171 Treatment should be initiated immediately with a medication that is effective at seizure prevention; parenteral administration through the intravenous route, or intramuscular if intravenous is unavailable, is preferred. Fast acting benzodiazepines such as lorazepam or diazepam are first line treatment. When compared to placebo in a double-blind clinical trial of emergency department patients, intravenous lorazepam significantly reduced the risk of recurrent seizures. Phenobarbital can be used in patients who are unable to use benzodiazepines; parenteral phenobarbital should only be given in intensive or critical care units due to the risk of oversedation and respiratory depression. 171 Delirium Patients experiencing delirium due to alcohol withdrawal often need to be admitted to intensive or critical care units to receive close nursing observation and supportive care such as regular vital sign monitoring and frequent reassessment. Intravenous access should be established quickly to allow for rapid administration of fluids and medication. CIWA-Ar scores are not recommended to monitor withdrawal symptoms in patients with delirium, since it relies on patient-reported symptoms. Instead, structured assessment scales such as the Confusion Assessment Method for ICU Patients (CAM-ICU) should be utilized. One on one observation should be initiated in patients who are agitated and disoriented. Restraints should be avoided unless necessary to prevent injury or comply with state laws. 171 Benzodiazepines are recommended as first line treatment for alcohol withdrawal delirium. Administration of intravenous benzodiazepines to achieve a light sedation where the patient is awake but tends to fall asleep unless stimulated is recommended to help control agitation and maintain patient safety. High doses of benzodiazepines may be required to control agitation in delirium patients as compared to other populations; providers should not hesitate to use large doses, but should monitor for oversedation and respiratory depression as well. Intermittent use of long and short acting benzodiazepines is recommended; continuous IV infusion has not shown superiority over intermittent dosing and is typically more expensive.
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