Introduction To Alcohol Withdrawal: Richard Saitz, M.D., M.P.H
Introduction To Alcohol Withdrawal: Richard Saitz, M.D., M.P.H
Introduction To Alcohol Withdrawal: Richard Saitz, M.D., M.P.H
Withdrawal
Richard Saitz, M.D., M.P.H.
Heavy drinkers who suddenly decrease their alcohol consumption or abstain completely may
experience alcohol withdrawal (AW). Signs and symptoms of AW can include, among others,
mild to moderate tremors, irritability, anxiety, or agitation. The most severe manifestations of
withdrawal include delirium tremens, hallucinations, and seizures. These manifestations
result from alcohol-induced imbalances in the brain chemistry that cause excessive neuronal
activity if the alcohol is withheld. Management of AW includes thorough assessment of the
severity of the patient’s symptoms and of any complicating conditions as well as treatment of
the withdrawal symptoms with pharmacological and nonpharmacological approaches.
Treatment can occur in both inpatient and outpatient settings. Recognition and treatment of
withdrawal can represent a first step in the patient’s recovery process. KEY WORDS: AOD
withdrawal syndrome; biochemical mechanism; neurotransmission; neurotransmitter receptors;
central nervous system; symptom; tremor; anxiety state; delirium tremens; AODR (alcohol and
other drug related) hallucinosis; AODR seizure; AOD abstinence; disease severity; patient
assessment; treatment method; alcohol withdrawal agents; drug therapy; detoxification;
addiction care; literature review
E
very year more than one-and- clinical syndrome that affects people
a-half million people in the accustomed to regular alcohol intake RICHARD SAITZ, M.D., M.P.H., is an
United States either enter alco- who either decrease their alcohol assistant professor of medicine in the
holism treatment or are admitted to consumption or stop drinking com- Clinical Addiction Research and
a general hospital because of medical pletely. In these people, the central Education Unit, Section of General
consequences resulting from alcohol nervous system (CNS) has adjusted to Internal Medicine, Department of
dependence. These patients, as well as the constant presence of alcohol in the Medicine, at Boston Medical Center
a substantial number of other people body and compensates for alcohol’s and Boston University School of Medicine;
who stop drinking without seeking depressive effects on both brain func- a faculty fellow in the Center for
professional treatment, experience tion and the communication among Substance Abuse Prevention Faculty
alcohol withdrawal (AW). AW is a nerve cells (i.e., neurons). Consequently, Development Program; and a generalist
1
when the alcohol level is suddenly physician faculty scholar of the Robert
Clinicians generally distinguish between signs and lowered, the brain remains in a hyper- Wood Johnson Foundation.
symptoms of a disorder or syndrome. “Signs” are
changes in the patient’s condition that can be active, or hyperexcited, state, causing
objectively observed by an examiner (e.g., temperature, withdrawal syndrome. Support for this work was provided
a rash, or high blood pressure). Conversely, symp- AW syndrome varies significantly by National Institute on Alcohol
toms are changes that are subjectively perceived by among alcoholics in both its clinical Abuse and Alcoholism grant
the patient (e.g., irritability or craving for alcohol).
The term “manifestations of alcohol withdrawal,”
manifestations and its severity. These 5RO1–AA–10870 and by Center
which is used in this article, can refer to either signs manifestations1 can range from mild for Substance Abuse Prevention grant
or symptoms. insomnia to severe consequences, 1T15–SPO7773.
percent (Victor and Adams 1953; the first seizure (Victor and Brausch • Abnormal liver function
Saitz et al. 1994). What is the reason 1967). Although multiple seizures are
for this variability? Likely, individual not common, AW is one of the most • Prior detoxification
patients differ in their underlying common causes in the United States
risks for withdrawal symptoms. These of status epilepticus—a medical emer- • Past experience of seizures or DT’s
differences result from factors such as gency characterized by continuous,
the patient’s pattern of alcohol use, the unrelenting seizures. • Intense craving for alcohol
presence of coexisting illnesses, varia- DT’s, which last up to 3 or 4 days,
tions in genetic influences and CNS are characterized by disorientation and • Concomitant acute illness
mechanisms, as well as the neuro- are usually accompanied by autonomic
chemical mechanisms described in signs resulting from the activation of • Older age
the previous section. the nerves responsible for the body’s
Despite the variability in the type response to stress). Those signs include • Use of other drugs in addition to
and severity of symptoms that a person severe agitation, rapid heartbeat (i.e., alcohol
can experience, the clinical syndrome tachycardia), high blood pressure, and
of AW has been well defined. Its symp- fever. (Thus, DT’s are a much more • More severe withdrawal symptoms
toms generally appear within hours of serious condition than the “shakes,” when presenting for treatment.
stopping or even just lowering alco- which often are also colloquially referred
hol intake and, thus, BAC. The most to as DT’s.) DT’s can develop between
common symptoms include tremor, 1 and 4 days after the onset of with-
craving for alcohol, insomnia, vivid drawal and are generally preceded by Management of Alcohol
dreams, anxiety, hypervigilance,2 additional autonomic signs, such as Withdrawal
agitation, irritability, loss of appetite sweating and tremors. About five percent
(i.e., anorexia), nausea, vomiting, of the patients who experience DT’s die
headache, and sweating. Even without from metabolic or cardiovascular com- Assessment
treatment, most of these manifesta- plications, trauma, or infections (Victor
tions will usually resolve several hours and Adams 1953; Cutshall 1964). Before initiating any interventions,
to several days after their appearance. the first step in managing a patient’s
The most severe manifestations of withdrawal is to assess thoroughly the
AW include hallucinosis, seizures, and
Risk Factors for DT’s and Seizures patient’s condition. This assessment
DT’s (see also the figure on pp. 63, Given the wide range of potential mani- should include an evaluation of the
from Victor and Adams’ classic paper). festations associated with withdrawal, presence of coexisting medical and
Hallucinosis, which may occur within is it possible to predict their develop- psychiatric conditions, the severity of
1 or 2 days of decreasing or abstaining ment in individual patients? Currently, the withdrawal symptoms, and the
from alcohol intake, is a complication the answer is “no.” To date, most studies risk of withdrawal complications.
distinct from DT’s. Patients with alcohol of predictors of severe or complicated Moreover, reassessment of the with-
hallucinosis see, hear, or feel things that withdrawal have been too limited method- drawal symptoms at regular intervals
are not there even though they are fully ologically to allow clinically accurate until they have resolved can help
conscious and aware of their surround- prognoses for individual patients. Based guide treatment as well as encourage
ings. Moreover, hallucinosis is not on current understanding of the with- the clinician to monitor the patient
necessarily preceded by various physio- drawal syndrome, as well as on some for the development of complications
logical changes (i.e., autonomic signs). clinical research results, however, clini- that might require more intensive
AW seizures also can occur within 1 cians have identified some patient charac- observation or treatment.
or 2 days of decreased alcohol intake, teristics that likely confer a risk of more The symptoms of withdrawal are
even in the absence of other withdrawal severe withdrawal symptoms; prolonged not specific and easily can be con-
signs and symptoms. The patient usu- symptoms; or withdrawal-specific com- fused with other medical conditions.
ally experiences only one generalized plications, such as DT’s or seizures. Consequently, the clinician’s initial
convulsion, which involves shaking of These factors include the following: assessment also serves to exclude other
the arms and legs and loss of conscious- conditions with symptoms similar to
ness. If a second convulsion occurs, it • More severe alcohol dependence, those of AW. Examples of such condi-
generally happens within 6 hours of including prior development of tions include subdural hematoma (i.e.,
withdrawal symptoms the collection of blood in the space
2
The term “hypervigilance” refers to a state of between the membranes surrounding
being overly concerned with everything (e.g., • Higher levels of alcohol intake, the CNS), pneumonia, meningitis,
one’s surroundings), of being “on edge.” This resulting in higher BAC’s and other infections. Similarly, seizures
state manifests itself, for example, by continually
looking around and moving one’s head in abrupt, and DT’s may be confused with other
jerky movements. • Longer duration of alcoholism conditions that should be excluded
during initial assessment. For example, Once a diagnosis of AW has been riencing severe withdrawal symptoms,
DT’s, which represent an acute confu- made, the clinician must assess the proven benefits of treatment include
sional state, can mimic delirium from severity of withdrawal and the risk amelioration of symptoms, preven-
other medical causes, such as encephali- for associated complications. The tion of both seizures and DT’s, and
tis, meningitis, adverse effects of some best validated tool for such an assess- treatment of DT’s. Treatment also
medications, or Wernicke’s encephalopa- ment is the Clinical Institute may prevent increasing severity of
thy.3 Likewise, AW seizures must be dis- Withdrawal Assessment for Alcohol, withdrawal during subsequent with-
tinguished from seizures resulting from revised (CIWA–Ar) (Sullivan et al. drawal episodes and encourage the
other causes, such as mineral or electrolyte 1989; Foy et al. 1988) (see figure 1). patient to enter alcoholism treatment
abnormalities, strokes, brain tumors, This instrument, which rates 10 for relapse prevention.
epilepsy, or subdural hematoma. Thus, a withdrawal features, can be adminis- Patients with mild withdrawal symp-
tered in only a few minutes and toms (i.e., CIWA–Ar scores of 8 or
diagnosis of DT’s and AW seizures
repeated when necessary. A total less) and no increased risk for seizures
should be made only after other reason- score of 15 or more points indicates can be managed without specific phar-
able causes for these complications have that the patient is at an increased risk macotherapy (Mayo-Smith 1997;
been excluded. for confusion and seizures. Saitz and O’Malley 1997). Successful
A thorough assessment also should nonpharmacological treatments include
anticipate health problems that fre- frequent reassurance and monitoring
quently occur in patients withdrawing Treatment of Alcohol Withdrawal by treatment staff in a quiet, calm
from alcohol. These complications Based on the patient’s score on the environment. Most patients with mild
may include the following: CIWA–Ar, the physician determines withdrawal symptoms, whether they
the appropriate treatment (see table). are treated or not, do not develop
• Gastritis (i.e., an inflammation For all patients, especially those expe- complications.
of the stomach lining, which often
is associated with bleeding)
• Gastrointestinal bleeding (e.g., from Examples of Specific Regimens Used in the Treatment of Alcohol Withdrawal
the esophagus, stomach, or intestines)
• Liver disease Treatment Approach Treatment Component
• Cardiomyopathy (i.e., any disorder
of the heart muscle) Monitoring • Monitor the patient by administering the CIWA–Ar1
test every 4 to 8 hours until the score has been
• Pancreatitis (i.e., an inflammation lower than 8 to 10 points for 24 hours
of the pancreas) • Use additional assessments as needed
• Disturbances in the electrolyte
balance (e.g., alcohol ketoacidosis— Symptom-triggered regimens • Perform the CIWA–Ar every hour to assess the
patient’s need for medication
a metabolic derangement that
results in too much acid in the • Administer one of the following medications every
hour when the CIWA–Ar score is at least 8 to 10
bloodstream—and abnormally low
points:
levels of magnesium in the blood) —Chlordiazepoxide (50–100 milligrams [mg])
• Deficiency of the vitamin folate, —Diazepam (10–20 mg)
—Lorazepam (2–4 mg)
which can cause lower-than-normal
numbers of blood cells Fixed-schedule regimens • Administer one of the following medications every
• Deficiency of the vitamin thiamine, 6 hours:
—Chlordiazepoxide (4 doses of 50 mg, then 8
which can lead to serious neurological
doses of 25 mg)
problems, such as Wernicke’s enceph- —Diazepam (4 doses of 10 mg, then 8 doses of 5 mg)
alopathy (accordingly, thiamine should —Lorazepam (4 doses of 2 mg, then 8 doses of 1 mg)
be administered to all patients under- • Provide additional medication if these regimens do
going AW to prevent the development not control the symptoms (i.e., the CIWA–Ar score
of this syndrome). remains at least 8 to 10 points)
3
Wernicke’s encephalopathy is an acute condition 1
CIWA–Ar = Clinical Institute Withdrawal Assessment for Alcohol, revised. For further information see figure 1.
characterized by general confusion, abnormal eye SOURCE: Mayo-Smith 1997.
movements, and difficulty walking or keeping
one’s balance.
or whose withdrawal symptoms that the medication may prevent phenobarbital probably can prevent
cannot be adequately assessed. This seizures. Moreover, it does not inter- AW seizures, although insufficient
includes patients who receive general fere with mental processes, such as data exist in humans to confirm this
anesthesia or who take medications learning, whereas other agents (e.g., hypothesis. In contrast, phenyotin,
that block the sympathetic nervous benzodiazepines) can cause amnesia, an anticonvulsant medication used
system (e.g., beta blockers, which are mental dullness, and sleepiness (i.e., for treating seizures caused by epilepsy
used to treat hypertension and other somnolence). Carbamazepine also and other disorders, is ineffective for
cardiovascular disorders). For these does not potentiate alcohol-induced treating AW seizures. Because a diag-
patients, the traditional fixed-sched- depression of the CNS, nor does it nosis of AW-related seizures may
ule dosing regimens may be more affect respiratory function. In addi- require further evaluation, however,
appropriate. tion, unlike the benzodiazepines, the agent is sometimes administered
Many agents other than benzodi- carbamazepine does not have the until other causes of seizures have
azepines have been used for managing potential for abuse. Finally, carba- been ruled out.
AW. For example, other cross-tolerant mazepine may prevent kindling. This Benzodiazepines also prevent DT’s.
medications, such as barbiturates, agent has not been shown, however, However, no known treatments exist
would be expected to relieve with- to prevent withdrawal-specific com- to shorten the course of DT’s once
drawal symptoms and prevent with- plications, and it can cause substantial this complication has been established.
drawal seizures and DT’s. In fact, a side effects, including nausea and dizzi- Nonetheless, diazepam can improve
few studies have demonstrated that ness. (For more information on other outcome by rapidly inducing a calm,
long-acting barbiturates can ease medications used in the treatment of awake state, thereby avoiding the
withdrawal symptoms. However, withdrawal symptoms, see the article traumatic complications associated
controlled studies have not provided by Myrick and Anton, pp. 38–43.) with severe agitation (Thompson et
sufficient data to demonstrate that Other medications can serve as al. 1975). Constant monitoring is
these agents can prevent seizures or effective adjuncts to care. For exam- essential for patients experiencing this
DT’s. Furthermore, barbiturates have ple, beta-blockers (e.g., propranolol serious complication.
a narrow therapeutic index—that is, and atenolol) can ameliorate some
the difference between the minimum manifestations of withdrawal, such as
dose required for a therapeutic effect tachycardia, high blood pressure, and Treatment Settings
and the dose at which the agents even anxiety, but they increase the
become toxic is small. likelihood of delirium when used by Traditionally, patients undergoing
Alcohol itself also would be themselves (i.e., as monotherapy). AW have been treated in hospitals
expected to improve withdrawal Consequently, these agents should be and inpatient alcohol and other drug
symptoms, and alcoholic patients used only in combination with benzo- (AOD) abuse treatment programs.
know that alcohol consumption diazepines. In general, the use of General hospitals and even intensive
can relieve their symptoms. Alcohol beta-blockers for treating withdrawal care units are appropriate for patients
should not be used, however, to treat should be considered primarily for whose withdrawal is severe and/or
withdrawal for several reasons. First, patients with coexisting coronary who suffer from comorbid medical,
using alcohol as a treatment would artery disease. Antipsychotic medica- surgical, or psychiatric conditions
promote its acceptability to the alco- tions such as haloperidol can treat that require hospitalization. For
holic. Second, alcohol has known hallucinations and agitation that are patients without severe withdrawal
toxic effects (e.g., impairing the unresponsive to adequate doses of or complicating illnesses, inpatient or
function of the liver, pancreas, and benzodiazepines. Because antipsy- outpatient AOD treatment settings
bone marrow) that are not shared chotic medications can increase the are appropriate. Some initial reports
by the safer benzodiazepines. Third, risk of seizures, however, these agents even indicate that detoxification can
in one clinical study, alcohol was should be used only in combination be completed successfully in the
inferior to the benzodiazepine with benzodiazepines. patient’s home (Stockwell et al. 1991).
chlordiazepoxide. Withdrawal in settings that offer less
Clonidine—an antihypertensive intensive monitoring, however, should
medication—also may have a role
Management of Withdrawal- be considered with caution. For exam-
in the management of withdrawal
Specific Complications ple, as noted previously, the risk fac-
symptoms, although it has not been AW seizures generally can be pre- tors for more severe withdrawal still
shown to affect the occurrence of vented by medications that are need to be better defined. Further-
withdrawal-specific complications. cross-tolerant with alcohol. For more, although numerous studies of
Another agent that has shown example, benzodiazepines have been diverse treatment settings have reported
promise for managing AW is the shown to prevent both initial and favorable outcomes, many of these
anticonvulsant carbamazepine. recurrent seizures. Similarly, carba- studies have included patient groups
Animal studies have demonstrated mazepine and the barbiturate that were referred specifically to the