Prevention is Key
Most patients who drink heavily and daily will have at least mild withdrawal when they stop drinking, e.g., with headache, nausea, tremors, diaphoresis, and anxiety. This usually starts about 12 hours after the last drink and lasts 4 to 5 days. Hospitalization for another problem or inter-current illness are classic precipitating factors so every patient admitted to the hospital should be asked about their alcohol use to ensure appropriate precautions are taken to prevent the development of serious withdrawal states in patients at risk. Severe alcohol withdrawal (seizures and DTs) are preventable if treated early, and are far easier to prevent than to treat.
As with opioids, the care of patients dependent on alcohol begins with detoxification. This is arguable even more important that for opioids because the alcohol withdrawal syndrome is more dangerous: seizures and delirium tremens can result in death. Heavy drinkers usually don’t understand this possibility until they first experience withdrawal, so individuals motivated to stop drinking need to be explicitly guided into detoxification.
Pathophysiology: What’s withdrawal all about?
80% or more who have alcohol withdrawal will not progress past the mild withdrawal stage. However, the more severe withdrawal states are medical emergencies which should be prevented. They are alcoholic hallucinations, alcohol-related seizures, and delirium tremens.
These responses can be understood by understanding the pharmacology of alcohol (and benzodiazepines). GABA is the major inhibitory neurotransmitter in brain. Chronic exposure to alcohol stimulates GABA activity in brain and mediates sedative effects of alcohol. The brain compensates by suppressing GABA activity and simplistically, tolerance to alcohol is a balance of GABA stimulation and suppression that allows person to function. When alcohol is removed, unopposed down-regulation of GABA receptors leads to lack of inhibitor neurotransmission which leads to stimulated state, anxiety, insomnia. Stimulation of sympathetic autonomic system via the locus caeruleus leads to tremors, ↑BP, ↑HR, diaphoresis, and fever.
Alcoholic hallucinosis, typically visual, but occasionally auditory, occur in about one third of those suffering milder withdrawal symptoms, and may be a harbinger of more severe features.
Alcohol withdrawal seizures occur in 10-20% who have alcohol withdrawal. They are usually a single grand mal (generalized) seizure, occurring within 48 hours of last drink. They may occur later, especially if the patient is taking benzodiazepines. The risk for seizures is thought to increase with repeated withdrawals. Rarely, this can lead to status epilepticus. Alcohol withdrawal seizures can be prevented by initiation of benzodiazepine in early withdrawal. There is no indication for phenytoin or any other anticonvulsant prescribed long term in patients who have alcohol withdrawal seizures. Anticonvulsants indicated only if there is history of underlying seizure disorder. If patient stops drinking, he will have further seizures only if there is an underlying seizure disorder.
Delirium tremens is most serious type of alcohol withdrawal. When untreated, this has a mortality of 30-40%. Even with treatment, mortality is approximately 5%. The DTs usually start about 48 hours after the last drink and, as with seizures, this may be delayed if the patient taking benzodiazepines, receiving opiate pain meds, or has been under anesthesia recently. The hallmark of delirium tremens is delirium, but it is a diagnosis of exclusion: all other causes of delirium must be ruled out. One of most common errors in treatment of DTs is missing underlying cause of the delirium.
Reversible Causes of Delirium
meningitis, pneumonia, bacteremia, bacterial peritonitis
Low Na+ or glucose, elevated NH3, calcium, or CO2, acidosis
Benzodiazepines, prednisone, stimulant use, serotonin syndrome, neuroleptic malignant syndrome
Subdural hematoma, cancer, stroke, brain abscess, encephalitis
Thiamine or riboflavin deficiency
The signs of DTs include an acute onset altering of all levels of consciousness, including a reduced ability to focus and sustain/shift attention, disorientation, poor recall and hallucinations. These symptoms and signs can wax and wane throughout the day or night so, at times, the patient appears to be improving. DTs usually last 3 to 5 days. If patient’s delirium does not resolve after several days consider other diagnoses again. Since some patients remain delirious from benzodiazepine being given to treat the DTs, consider stopping this medication once the autonomic overactivity has subsided.
Symptoms of withdrawal can be quantified and monitored using the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale. This scale uses 10 criteria with a range of 0-7 for each (except for orientation). The total score is the sum of these measures, and it is recommended that benzodiazepines be started for patients with a total CIWA-Ar score of 8 or greater, and additional medication should be given on a prn basis for a total CIWA-Ar score > 15. The form allows documentation of vital signs, CIWA scores, and total medication administration. This appears to be the most sensitive tool for assessing alcohol withdrawal and early intervention at a score 8 or greater provides a means of preventing progression of withdrawal.
Ways to Detox Alcohol
To determine the need for detoxification, and inform the patient of the process, you will need a good history (to assess the likelihood that withdrawal could be severe), and you will need to explain why we use a potentially addicting drug (benzodiazepines) for a short term to prevent withdrawal complications. This point may be quite important to some patients, who have decided that “the problems is the use of drugs”, and therefore are resistant to use drugs for detoxification or maintenance of sobriety.
It starts with a History
Take a good alcohol history! Quantity, frequency, pattern (binge drinking). If the patient reports heavy daily consumption and has tremors when not drinking, there is risk. Patients with prior history of seizures or DTs are at particular risk.
Many patients are discovered to have alcohol withdrawal when admitted to the hospital for other reasons but some patients seek care specifically for the alcohol dependence. The majority of these patients do not require inpatient admission for detox. The following is a partial list of criteria for inpatient alcohol detox.
- Current symptoms of severe alcohol withdrawal
- Known history of DTs or withdrawal seizures
- Unable to tolerate oral meds
- Multiple past detoxes
- Significant co-morbid psychiatric or medical conditions such as active psychosis or severe cognitive impairment
- Recent high levels of alcohol consumption
- Poor social support
Inpatient v Outpatient: When and why?
Several factors impact the venue in which a patient is treated for alcohol dependence including patient preference, program availability, insurance and individual patient factors such as co-morbid conditions that could increase the risk of poor patient outcomes (e.g.., cardiovascular disease, cerebrovascular disease, serious mental illness, etc.) the ability to complete close follow-up during the outpatient detox process, social support and the patient’s level of understanding of the process.
Several regimens for detox exist. In the gradually tapering regimen, patients receive a predetermined dose of medication that is gradually weaned over a few days. In the fixed dose regimen, patients received a specified dose of medication several times daily for 2 to 3 days. These 2 regimens can be given in either the inpatient or outpatient setting. A symptom-triggered regimen utilizes the patients symptoms, assessed at frequent intervals (i.e., every 1-2 hours), to help determine the dose and frequency of the medication. This approach may yield less sedation as it is responsive rather than pre-emptive in its approach but it requires close monitoring by experienced personnel.
In motivated patients who are at low risk for complications, detox can be managed by daily dispensing of one-day supply of medication such as chlordiazepoxide at a fixed or tapering dose. Giving alcohol-dependent patients prescription for several days benzodiazepine with expectation they can “wean” themselves off is unrealistic for many patients who may have no greater control over benzodiazepines than alcohol.
Alcohol Detox: Pharmacological Tools
When symptoms and signs of DTs do develop, benzodiazepines are the treatment of choice because they are GABA agonists and thus restore GABA-ergic inhibitory tone. All are equally efficacious. Choice is based on: onset of action, half-life of drug, presence of active metabolites, functional status of patient’s liver, route of administration. Two of the most common medications used for alcohol detox are lorazepam and chlordiazepoxide.
Lorazepam has intermediate half-life (about 12 hours), is easier to titrate upwards rapidly, and can be given IV, IM, or PO. It has no active metabolites and has less potential for over-sedation. Lorazepam is less dependent on liver metabolism, so is a better choice for patients with severe liver disease. However, it can still cause over-sedation and should be used cautiously in patients with liver disease.
Chlordiazepoxide is longer acting and its active metabolite has a half-life of 24-48 hours which allows for a smoother taper and less fluctuation in blood concentration. This drug is metabolized in liver and should be used with caution in patients with liver disease.
The benzodiazepines are the first line choice to prevent and treat alcohol withdrawal. Other drugs, such as anti-epileptics, have been studied in selected patient populations. Anti-epileptics are efficacious in preventing seizures as well as limiting the amount of benzodiazepines required for control of multiple symptoms of withdrawal. Carbamazepine has well-documented anticonvulsant activity and can prevent alcohol withdrawal seizures. The drug does not carry the same abuse potential as benzodiazepines and is less sedating. The major limitation of this drug is the likelihood of interaction with other medications. Valproic acid also limits seizure activity but its use is largely limited by GI and CNS side effects such as nausea, confusion and somnolence.
Social and Behavioral Support
Few patients with alcohol dependence will successfully maintain long-term abstinence without support. There are several structured programs that exist that focus on similar aspects of aftercare, including education about addiction for patients and their families, exploration of the risk factors that led to the aberrant coping mechanisms that patients develop, development of better coping mechanisms to deal with current and future stressors and building new social support systems to ensure long-term abstinence. This learning and re-learning process often takes months in a more formal setting (dedicated addictions program) and years in a less formal setting (group sessions at a mental health clinic or other facility or Alcoholics Anonymous meetings). The addition of aftercare in a more formal program has been shown to increase the rates of abstinence over self-care (“I can do it on my own”) alone.
A Team Approach
The decision of when, where and how to treat should be managed by an addiction specialist working in conjunction with a multidisciplinary team with expertise in detox and care transitions from detox to the next stages of treatment. Both inpatient and outpatient detox can be efficacious and successful long-term recovery after either requires that a patient engage in aftercare that includes education regarding their disease and the necessary coping skills needed to remain abstinent. As with any substance dependence, they must also obtain the support needed that is not often available from family and friends that do not understand their disease.
Alcohol Detox: Key Issues and Conclusions
When your patient decides that alcohol abstinence is their goal and they wish to stop completely and abruptly, the first step will be detoxification. As with opioid detox, there are several ways this can be done: the choice may depend on the patient’s social support, insurance coverage, and the presence of additional medical or psychiatric problems. Again, it is important for you as their primary care provider to understand the detox process so that you can support the patient in their continued recovery after the initial detox. This may come in the form of avoiding writing prescriptions for benzodiazepines, answering patient’s questions about the risks involved with alcohol detox or providing ongoing encouragement and assurance to the patient in follow-up.