Download ALCOHOL WITHDRAWAL

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ALCOHOL WITHDRAWAL
Cold Turkey Can Land You in Hot Water. . . . . . . . . . Level I
Kevin M. Tuohy, PharmD, BCPS
The patient is a 54-year-old man who is brought to the ED by his
wife for symptoms of confusion and tremors. The patient’s wife
reports that her husband may have already experienced a seizure
1 hour prior to presentation to the ED. She also reports that he has
abused alcohol for the past 25 years. His drinks of choice are beer
and whiskey. It is estimated that he consumes, on average, 16 drinks
per day. He has quit drinking abruptly due to lack of financial
resources secondary to loss of employment. He has not had a drink
in 2 days. His alcohol serum concentration is negative, and he is
experiencing acute alcohol withdrawal. He will need to be treated
with a benzodiazepine-containing regimen in order to control his
current symptoms as well as prevent progression to delirium tremens and further seizures. The patient will also require replacement
of electrolytes and prophylaxis with thiamine in order to prevent
Wernicke’s encephalopathy.
QUESTIONS
Problem Identification
1.a. Create a list of patient’s drug therapy problems.
• Consumption of approximately 16 drinks per day for past
25 years
• History of alcohol withdrawal with seizure 4 years ago.
• GERD may be secondary to erosive esophagitis, as is often seen
in patients with alcohol dependence.
1.d. What laboratory abnormalities may be expected in a patient
with a history of alcohol abuse?
• Increased hepatic transaminases including aspartate aminotransferase/alanine aminotransferase ratio, increased INR in
the absence of warfarin use, decreased albumin—all point
toward liver disease secondary to long-term alcohol use.
• Decreased potassium and magnesium as exhibited in this
patient
Desired Outcome
2.What are the goals of pharmacotherapy in this case?
Short-term goals:
• Control acute symptoms of alcohol withdrawal.
• Prevent progression to delirium tremens.
• Prevent future alcohol withdrawal seizures.
• Correct electrolyte imbalances (potassium and magnesium).
• Start prophylaxis to prevent Wernicke’s encephalopathy.
Long-term goals:
• Enroll patient in a program to help him stop drinking,
followed by long-term abstinence control.
• Work up potential liver disease to prevent further progression.
• Alcohol dependence
• Bring hypertension under control with long-term pharmacologic management in order to reduce the incidence of endorgan damage and cardiovascular events.
• Hypomagnesemia (Mg 1.6 mg/dL) requiring replacement
• Optimize GERD treatment.
• Mild hypokalemia (K 3.2 mEq/L) requiring replacement
• Refer patient to dietitian for assistance with long-term nutritional stability.
• Acute alcohol-withdrawal syndrome, status-post seizure
• Uncontrolled hypertension, treated with hydrochlorothiazide
and amlodipine. Assessment is needed to determine if it is due
to treatment failure or nonadherence.
• History of gastroesophageal reflux disease (GERD), treated
with over-the-counter omeprazole at a less-than optimal dose.
• Laboratory assessment indicative of mild hepatic disease needs
to be worked up further after acute alcohol withdrawal syndrome treatment.
• Malnutrition needs to be addressed in a long-term fashion.
1.b.What information (signs, symptoms, and laboratory values) indicates that this patient is experiencing alcohol
withdrawal?
• Signs: seizure, confusion, tremor, tachycardia, exaggerated
deep tendon reflexes.
• Symptoms: unresponsiveness indicates confusion and possible
postictal state secondary to seizure; sweating, shaking, and
tachycardia.
• Laboratory values: negative ethyl alcohol level and increased
γ-glutamyltransferase are consistent with alcohol withdrawal
syndrome. Increased hepatic transaminases and international
normalized ratio (INR) are indicative of potential liver disease,
which would be expected in a patient with approximately
25 years of alcohol abuse.
Therapeutic Alternatives
3.a. What pharmacotherapeutic alternatives are available for the
treatment of alcohol withdrawal?
• Benzodiazepines are the treatment of choice for alcohol withdrawal. Benzodiazepines are cross tolerant with alcohol, have
anticonvulsant activity, and have been shown to be effective in
the reduction of signs and symptoms related to alcohol withdrawal.1–3 Benzodiazepines are used to treat the psychomotor
agitation as well as neurohormonal activation that occurs
during acute withdrawal and to prevent progression to major
symptoms (delirium tremens).1–3
• All benzodiazepines appear equally efficacious in reducing
signs and symptoms of withdrawal, and the choice among
them can be guided by the following clinical considerations:
✓Long-acting agents (diazepam and chlordiazepoxide) may
be more effective in preventing withdrawal seizures and can
contribute to a smoother withdrawal with fewer rebound
symptoms.1 Loading doses of these long-acting agents will
lead to serum drug concentrations that will auto-taper
through metabolism. There is an increased risk of benzodiazepine toxicity during the early phase of this treatment;
therefore, close clinical monitoring is required. Quick access
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
Alcohol Withdrawal
CASE SUMMARY
• At least a 25-year history of alcohol use
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1.c.What signs, symptoms, and history are consistent with
alcohol dependence in this patient?
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SECTION 7
to intensive care services is preferred if this loading dose
strategy is employed.2
effect. Bradycardia was a significant adverse reaction experienced by the dexmedetomidine patients.6
✓Short-acting agents (lorazepam and oxazepam) may have a
lower risk of oversedation.1
• β-Adrenergic antagonists, carbamazepine, and neuroleptic
agents may be useful in controlling some of the symptoms
associated with alcohol withdrawal. However, they have not
been shown to reduce delirium or seizures and therefore are
not recommended as monotherapy in patients experiencing
alcohol withdrawal.1
✓Certain benzodiazepines (alprazolam and diazepam) have a
higher liability for abuse.1
Psychiatric Disorders
• When making the choice of which benzodiazepine to choose
for treatment, the clinician should take into account the
pharmacokinetic parameters of the drug. These parameters
include onset of activity, duration of action, and role of active
metabolites.
3.b.How should alcohol withdrawal seizures be managed
pharmacologically?
✓Diazepam and chlordiazepoxide are long-acting drugs that
are preferred by some clinicians because they effectively
control withdrawal symptoms with few rebound effects after
they are discontinued. However, both drugs are metabolized
in the liver to active metabolites, so they have the potential
to accumulate in elderly patients and in patients with hepatic
dysfunction. These problems in the elderly and in patients
with hepatic dysfunction may contribute to side effects such
as oversedation and ataxia.1
• Alcohol-related seizures are typically brief, usually generalized
tonic–clonic seizures that occur 6–48 hours after the last drink.
These seizures usually occur at the time when the blood alcohol
level reaches zero but may also occur when there is still some
alcohol in the blood.7,8
✓Lorazepam and oxazepam are short- to intermediate-acting
drugs that have no active metabolites, are less affected by
liver dysfunction, and have fewer residual sedative effects
after discontinuation than longer acting benzodiazepines.1
• A front-loading dose is used if the patient appears to be experiencing delirium tremens and immediate symptom control is
desirable. It is important to make a clear determination that
delirium tremens is present, to avoid oversedation.1,2
• A fixed-dose regimen uses a standard dose that is not individualized for the patient. Fixed-dose regimens may lead to longer
use of benzodiazepines and more risk of side effects.1
• The symptom-triggered regimen may help reduce the medication dose and duration in the inpatient setting. The symptomtriggered regimen is based on the Clinical Institute Withdrawal
Assessment Scale for Alcohol–Revised (CIWA-Ar) tool.1 The
regimen is based on using the CIWA-Ar tool and treating only
when needed, which allows for more individualized treatment.
Symptom-triggered regimens have been shown to result in the
administration of less total medication and to require a shorter
duration of treatment.1
• Pregabalin at a dose of up to 450 mg/day as monotherapy
has been shown to reduce the signs and symptoms of alcohol
withdrawal. This treatment may be considered for patients by
whom benzodiazepines are not tolerated or not preferred.3
• Baclofen at a dose of 10 mg PO TID in addition to a standardized lorazepam-based alcohol withdrawal protocol resulted
in a statistically significant reduction in the use of high-dose
lorazepam (20 mg or more over a 72-hour period) when
compared with patients who received the lorazepam protocol
alone.4 Baclofen is, therefore, an option to add to a benzodiazepine when high doses of benzodiazepines are not desired.
• Alcohol withdrawal seizures are caused by sudden abstinence
and should be considered a diagnosis of exclusion once other
risk factors have been considered and ruled out.7
• Status epilepticus is an uncommon presentation of alcoholrelated seizures.7
• The management of alcohol withdrawal seizures includes the
treatment of seizures that are in progress, seizure-preventing
medication at the baseline of detoxification, and medication
for the prevention of seizure recurrence and status epilepticus
after an acute alcohol withdrawal seizure has occurred.8
• Benzodiazepines are effective in preventing both initial and
recurrent seizures in alcohol-dependent individuals. These
agents possess excellent anticonvulsant activity with minimal
respiratory and cardiac depression. Benzodiazepines should
be given not only for treatment of active seizures but also for
the short-term prophylaxis within the 6- to 12-hour window
after cessation of drinking when patients are at highest risk
of seizures. This is especially important in patients who are at
higher risk for seizures secondary to preexisting epilepsy, prior
alcohol-related seizures, or multiple previous detoxifications.7,8
• Long-term treatment with nonbenzodiazepine antiepileptic
drugs in alcohol-dependent patients may cause more harm
than benefit. Reasons for this observation include poor compliance, erratic drug taking, drug–alcohol interactions, and
abuse of the sedative antiepileptic drugs.8
3.c. What electrolyte imbalances need to be corrected in this
patient, and what vitamin deficiencies should be corrected?
• Magnesium needs to be given because the patient is hypomagnesemic; replacing his deficit may increase the seizure
threshold (thereby preventing seizures) and reduce symptoms
of withdrawal.
• Potassium also needs to be replaced because the patient is
mildly hypokalemic.
• Thiamine is needed in this patient to replace thiamine stores
and to prevent development of Wernicke’s encephalopathy.
• A multivitamin may be given once daily in order to replete
other vitamins that may be deficient because of chronically
poor dietary intake.
• Clonidine, a centrally acting α2-agonist at low doses (0.3–
0.9 mg per day) orally or transdermally, may have a role in
symptom control of alcohol withdrawal secondary to reduction of autonomic hyperactivity (hypertension, tachycardia,
tremor, etc.).5
3.d. What pharmacotherapeutic agent can be recommended to
treat this patient’s acutely elevated blood pressure (BP) and
heart rate?
• Dexmedetomidine, a more specific α2-agonist than clonidine,
has evidence to show sympathetic symptom control with less
sedation than clonidine when used as an adjunctive therapy
to lorazepam in patients with severe alcohol withdrawal. This
included a short-term (24 hours) benzodiazepine sparing
• Clonidine can be safely added to this patient’s acute treatment
regimen. It has been shown to decrease symptoms in patients
experiencing mild-to-moderate alcohol withdrawal. In the
short term, it should also help lower the patient’s BP and heart
rate.1,5
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4.Design an appropriate pharmacotherapy regimen for the
treatment of alcohol withdrawal in this patient. Include recommendations for electrolyte replacement and correction
of vitamin deficiencies as well as for the management of the
patient’s other medical problems.
Alcohol withdrawal:
• An example of an appropriate starting regimen is: lorazepam
2–4 mg PO/IV Q 4–6 H. Additional doses of 2 mg PO/IV should
be given with a CIWA-Ar score >8–10. (CIWA-Ar should be
assessed every hour upon admission then tapered as symptoms
of withdrawal subside.) This dose should be tapered as the
patient becomes stabilized. An example taper schedule is: lorazepam 2 mg PO TID × 2 days, then 2 mg BID × 2 days, then 2 mg
daily × 2 days, then 1 mg daily times × 2 days.
Malnutrition and correction of vitamin deficiencies:
• Thiamine 100 mg PO/IM daily × 3 days
• Multivitamin PO daily
• Obtain consult from dietitian for long-term management of
malnutrition
Electrolyte replacement:
• Potassium chloride 40 mEq PO Q 12 H × 2 doses, then reassess potassium daily and replace as needed to maintain serum
concentration of 3.5–5.0 mEq/L.
• Magnesium sulfate 4 g IV piggyback over 4 hours × 1 dose.
Reassess magnesium in 48 hours and replace as needed to
maintain serum concentration of 1.5–2.5 mEq/L.
Alcohol dependence:
• Obtain consultation from chemical dependency expert for
referral to long-term alcohol abstinence program.
Deep vein thrombosis prophylaxis:
• Assess risk of deep vein thrombosis while patient is hospitalized.
Hypertension:
• Short term: Continue hydrochlorothiazide 25 mg PO daily and
amlodipine 5 mg PO daily. Consider the addition of clonidine
0.1 mg PO TID to decrease withdrawal symptoms as well as
acute elevation in BP and heart rate.
• Long term: Assess adherence to hydrochlorothiazide and
amlodipine because BP is currently above goal of <140/90 mm
Hg. If the patient states that he has been taking medications as
prescribed, consider increasing the amlodipine dose to 10 mg
PO daily.
GERD:
• Assess GERD symptoms. Current omeprazole dose is not
optimal. Patient should be instructed to take omeprazole
20 mg PO daily on a scheduled basis for up to 14 days. Any
further OTC PPI use should be evaluated by a physician.
Outcome Evaluation
5.What clinical and laboratory parameters are necessary to evaluate your therapy for the achievement of desired therapeutic
outcome and to detect or prevent adverse effects?
• Efficacy parameters: The CIWA-Ar is a validated tool for the
measurement of symptom severity in alcohol withdrawal.9 The
CIWA-Ar is a rating system that assesses 10 parameters associated with alcohol withdrawal:
1. Nausea and vomiting
2. Tremor
3. Paroxysmal sweating
4. Anxiety
5. Agitation
6. Tactile disturbances
7. Visual disturbances
8. Auditory disturbances
9. Headache or head fullness
10. Orientation
✓ The severity of each of the first nine items is scored as follows:
0 = no symptoms; 1 = mild; 4 = moderate; and 7 = severe.
The severity of the last item (orientation) is scored from 0 to
4 points. Consequently, the maximum (worst) possible score
is 67 points. The CIWA-Ar can be completed in <2 minutes
and is particularly useful because BP and heart rate have not
been found to correlate with severity of withdrawal.
✓Monitor using the CIWA-Ar frequently initially while the
patient is symptomatic such as every hour. As the symptoms
come under control, monitor less frequently such as three
times a day.9
• In addition to the signs and symptoms of withdrawal included
in the CIWA-Ar, monitor overall mental status, BP, pulse,
temperature, and seizure activity. Vital signs and the signs and
symptoms of withdrawal should improve within 48–72 hours.
Worsening of withdrawal symptoms may be exhibited as
increased BP, pulse, and temperature; and increased hallucinations, agitation, and tremors.
• Monitor for the following possible adverse effects of benzodiazepines: drowsiness, lethargy, ataxia, confusion, dizziness,
amnesia, and respiratory depression.
Patient Education
6.What information should be provided to the patient to
enhance adherence, ensure successful therapy, and minimize
adverse effects?
• You are currently being treated with medications that are
designed to relieve your symptoms of alcohol withdrawal.
These symptoms include seizure, confusion, shakiness, sweating, and rapid heart rate. It may take a few days before these
medications completely relieve your symptoms, so please be
patient.
• It is recommended that you speak with your primary care physician so that he or she can refer you to an expert in addiction
medicine. In order to fully recover from alcohol dependence, it
is also highly recommended that you seek the support of people who have had similar difficulties with alcohol. A support
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
Alcohol Withdrawal
• It is assumed that this patient has already experienced an
alcohol-related seizure prior to presentation to the ED. Therefore, it is imperative to start him on a scheduled fixed-dose
regimen of a benzodiazepine. Lorazepam is a good choice for
this patient secondary to its rapid onset and relatively long
duration of activity against seizure. This patient also appears
to be exhibiting signs of hepatotoxicity. Lorazepam is not
metabolized to active metabolites in the liver, which can be
advantageous for this patient.
• If he desires to only take medication on an as-needed basis, an
OTC H2 blocker, such as famotidine 10–20 mg or ranitidine
75–150 mg, can be chosen.
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Optimal Plan
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SECTION 7
group or a 12-step program such as Alcoholics Anonymous can
be very helpful on the road to recovery.
• It is very important to take your medications as directed. Possible side effects include drowsiness and confusion. If you stop
taking the medication you may experience side effects such as
anxiety and agitation.
• If you do experience any of these or other side effects thought
to be caused by your new medication, do not hesitate to contact your physician or pharmacist.
Psychiatric Disorders
REFERENCES
1. Mayo-Smith MF. Pharmacological management of alcohol withdrawal:
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Society of Addiction Medicine Working Group on Pharmacological
Management of Alcohol Withdrawal. JAMA 1997;278:144–151.
2. Muzyk AJ, Leung JG, Nelson S, Embury ER, Jones SR. The role of
diazepam loading for the treatment of alcohol withdrawal syndrome
in hospitalized patients. Am J Addict 2013;22:113–118.
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
3. Martinotti G, diNicola M, Frustaci A, et al. Pregabalin, tiapride, and
lorazepam in alcohol withdrawal syndrome: a multi-centre, randomized, single-blind comparison trial. Addiction 2010;105:288–299.
4. Lyon JE, Khan RA, Gessert CE, Larson PM, Renier CM. Treating
alcohol withdrawal with oral baclofen: a randomized, double-blind,
placebo-controlled trial. J Hosp Med 2011;6:469–474.
5. Muzyk AJ, Fowler JA, Norwood DK, Chilipko A. Role of α2-agonists
in the treatment of acute alcohol withdrawal. Ann Pharmacother
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6. Mueller SW, Preslaski CR, Kiser TH, et al. A randomized, double-blind,
placebo-controlled dose range study of dexmedetomidine as adjunctive therapy for alcohol withdrawal. Crit Care Med 2014;42:1131–1139.
7. Rathlev NK, Ulrich AS, Delanty N, D’Onofrio G. Alcohol-related seizures. J Emerg Med 2006;31:157–163.
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patients. Epidemiology, pathophysiology and management. CNS
Drugs 2003;17:1013–1030.
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Assessment of alcohol withdrawal: the revised clinical institute
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