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Alcohol Withdrawal Syndrome in the Acute Care Setting: Symptom-based vs. Schedule-based Therapy


Darriel A. Johnson, Pharm. D. Pharmacy Practice Resident Bayfront Medical Center St. Petersburg, Fl * * Subjects were enrolled from April 2001 May 2003 Inclusion ... – PowerPoint PPT presentation

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Title: Alcohol Withdrawal Syndrome in the Acute Care Setting: Symptom-based vs. Schedule-based Therapy

Alcohol Withdrawal Syndrome in the Acute Care
Setting Symptom-based vs. Schedule-based Therapy
  • Darriel A. Johnson, Pharm. D.
  • Pharmacy Practice Resident
  • Bayfront Medical Center
  • St. Petersburg, Fl

Presenter Information
  • Born in Stillwater, Ok
  • Small town that has produced big time talent
  • University of Tulsa
  • Bachelor of Science in Biochemistry
  • Univ. of Tennessee Health Science Center
  • Doctor of Pharmacy
  • Bayfront Medical Center
  • Pharmacy Practice Resident

  • Define alcohol withdrawal syndrome list typical
    signs symptoms
  • Review current treatment options for alcohol
    withdrawal syndrome
  • Compare symptom-based vs. scheduled-based
    treatment of alcohol withdrawal syndrome

Alcohol Abuse
  • Defined as a pattern of use associated with
    dangerous behaviors /or a failure to meet
    obligations at home or work
  • Driving under the influence
  • Physical or verbal altercations
  • Out of character actions or decisions
  • Promiscuous or unsafe sexual activity

Alcohol Abuse
  • Alcohol use, abuse, dependence highly prevalent
  • Occurs in men women as well as all ages of
  • Estimated that 17.6 million Americans have some
    form of alcohol disorder
  • Approximately 30 of adults consume enough
    alcohol to elevate their risk of physical
    psychosocial complications

Alcohol Abuse
  • 15 of patient hospitalizations are a result of
    alcohol-related morbidity
  • 25 of patients admitted to medical or surgical
    services have an alcohol use disorder
  • Patients with alcohol use disorders typically
    have increased length of stays occurrence of

CAGE Questionnaire
  • Have you ever felt you should Cut down on your
  • Have people Annoyed you by criticizing your
  • Have you ever felt bad or Guilty about your
  • Have you ever had a Eye opener to steady your
    nerves or to get rid of a hangover?

CAGE Questionnaire
  • Developed by Dr. John Ewing
  • Director of Bowels Center for Alcohol Studies,
    University of North Carolina at Chapel Hill
  • Internationally used assessment tool
  • Primarily used by primary care givers
  • Used in acute setting as part of health history
  • Scoring patient responses are scored 0 or 1
  • Higher total scores are indication of alcohol
  • Total score of 2 considered clinically

CAGE Questionnaire
  • CAGE Questionnaire introduced in 1970
  • Recognized as a efficient effective screening
  • Clinicians can paraphrase the 4 questions
  • Can make patient specific without compromising
  • Validity of tool questioned due to lack of data
  • Stated that CAGE was not studied in a general
    hospital pop.

CAGE Questionnaire
  • Original CAGE study consisted of 130 subjects
  • Conducted in a general hospital population
  • Randomly selected medical surgical patients
  • 16 of 130 identified as suffering from alcoholism
  • Answered questions designed to detect alcoholism
  • Answers compared to those of the 16 known
  • Determined 4 questions would produce 2 groups
  • Re-ordered to produce CAGE mnemonic

CAGE Questionnaire
  • Interviewed 166 males in alcoholism rehab center
  • Study conducted in response to lack of data
  • Subjects provided self-assessment of consumption
  • Alcoholic vs. Heavy drinker vs. Denial of
  • 68 patients were identified as non-alcoholics
  • General hospital patients who used alcohol but
    not alcoholics
  • Subjects were interviewed using CAGE questions

CAGE Questionnaire
  • Authors examined responses from two view points
  • Total number of yes answers per subject group
  • Questions receiving a yes answer per subject
  • Providing 2 yes answers to CAGE questions
  • Alcoholics 100, Heavy drinkers 97, Denial 92,
    Non 4
  • Annoyed Eye-opener answers varied
  • None of the non-alcoholics responded yes to these
  • Excellent tool for providing insight into
    alcohol use
  • Use to determine index of suspicion of alcoholism
  • Should NOT be used as a alcoholism diagnostic

CAGE Questionnaire
CIWA-Ar Assessment Tool
  • Clinical Institute Withdrawal Assessment for
    Alcohol Scale (revised)
  • Scale consists of 10 signs symptoms
  • Nausea/vomiting, tremor, paroxysmal sweats,
    anxiety, agitation, tactile disturbances,
    auditory visual disturbances, headache,
  • Patients asked questions or evaluated on s/s
  • s/s evaluated on 7-point scale orientation on a
    4-point scale

CIWA-Ar Assessment Tool
  • Scores range from 0 67 points
  • Mild withdrawal 8 points
  • Moderate withdrawal 9 15 points
  • Severe withdrawal gt 15 points
  • Scale should be applied at least 1 3 times a
  • Increase frequency when patient is symptomatic
  • Can be used hourly to make dosing adjustments
  • Applied to determine effectiveness of therapy
  • Allows objective evaluation of patient regarding
    severity of withdrawal

Alcohol Withdrawal Syndrome
  • An event that occurs when a person who frequently
    ingests a large quantity of alcohol (daily)
    abruptly discontinues or rapidly decreases the
    amount he/she is accustomed to consuming
  • Abrupt cessation of alcohol consumption can
    result in a myriad of symptoms classified as
    alcohol withdrawal syndrome (AWS)

Alcohol Withdrawal Syndrome
  • AWS is a heterogeneous syndrome
  • Frequently misunderstood by clinicians as a
    single syndrome
  • Confused with other issues such as electrolyte
    imbalances, pain, infections
  • AWS consists of 3 distinct symptom categories
  • Each group has its own physiologic basis
    treatment agents
  • Symptom categories are labeled as A, B, C
  • Various pharmacologic agents have been used to

Alcohol Withdrawal Syndrome
  • Type A central nervous system excitation
  • Type B adrenergic hyperactivity
  • Type C delirium
  • AWS s/s present within 6 to 24 hours after last
  • Untreated will evolve over 48 72 hrs of
  • Symptoms subside within a few days
  • Severe withdrawal symptoms may persist gt 2 weeks

Alcohol Withdrawal Syndrome
  • Mild AWS tremor, N/V, diaphoresis, hypertension,
    tachycardia, anxiety, irritability insomnia
  • Moderate AWS confusion hallucinations
  • Marked increase of the mild AWS symptoms
  • Severe AWS seizures, uncontrollable tremor,
    profuse diaphoresis, tachypnea, hyperthermia
  • Increases of aforementioned symptoms
  • Formerly known as delirium tremens (DTs)

Alcohol Withdrawal Syndrome
  • AWS s/s related to changes in neurotransmitter,
    neuropeptide, neuroendocrine systems
  • Decreased central inhibition increased
  • Decreased inhibition 2 to decreased
    Gamma-aminobutyric acid (GABA) activity
  • GABA N-methyl-D-aspartic acid (NMDA) are two of
    several neurotransmitters that are of importance
    in AWS

Alcohol Withdrawal Syndrome
  • GABA major inhibitory neurotransmitter
  • GABAa receptor complex regulates Cl- entrance
    into cells
  • Cl- cause hyperpolarization cell becomes less
  • Alcohol is an agonist of GABAa receptors
  • Causes anxiolytic, sedative, anticonvulsant,
    motor impairment
  • Alcohol causes down-regulation of GABAa receptor
  • Decreased central inhibition during withdrawal -

Alcohol Withdrawal Syndrome
  • NMDA important excitatory neurotransmitter in AWS
  • Alcohol inhibits NMDA receptors
  • Controls excitability by increasing
    depolarization of neuronal membrane
  • Regulates the flow of calcium into the neuron
  • Withdrawal causes rebound stimulatory effects
  • Adrenergic hypersensitivity leading to
    irritability, tremors, and seizures

Treatment of AWS
  • The numerous symptoms of AWS effects of alcohol
    on neurotransmitters calls for treatment
  • Alcohol abusers have high rate of malnutrition
  • Poor diet impaired absorption results in
    depletion of B vitamins
  • Require daily thiamine, folate, multivitamin
  • Thiamine to prevent mental status changes from
    Wernickes encephalopathy, or Korsakoffs
  • Folate to treat or prevent anemia
  • Smoking cessation nicotine replacement
  • Should be offered to increase comfort during

Treatment of AWS
  • Benzodiazepines (BZDs) are the treatment of
  • Used to prevent or reduce severity of AWS
  • Reduce agitation, autonomic hyperactivity,
  • Short-acting preferred 2 less active metabolites
  • Adrenergic hyperactivity not controlled by BZDs
    has been treated with alpha-adrenergic agonist
  • Clonidine
  • Neuroleptics have been used for agitation
  • Use cautiously due to ability to lower seizure

Treatment of AWS
  • BZDs dosed as a fixed schedule or as needed
  • Scheduled dosing vs. symptom triggered
  • Administered early to prevent s/s of AWS
  • Dosage should be tailored to patients condition
  • Oxazepam Chlordiazepoxide available PO
  • Used in outpatient detox settings inpatient
    if able to take
  • Lorazepam Diazepam multi administration routes
  • Allows tailoring to individual patients medical
  • Monitor patients for oversedation
  • Goal is minimal sedation patient should be
    easily arousable

Treatment of AWS
  • Antiepileptic medications are being investigated
  • Examining use when benzodiazepines fail to
    prevent seizures
  • Valproic acid carbamazepine studied most
  • Several studies have shown promising results
  • Alcohol to prevent or treat withdrawal symptoms
  • This treatment is not recommended by experts
  • Practiced in some hospitals especially on
    surgical services

Stanley et al
  • Purpose provide standardized treatment of AWS
  • Standardization provided through the use of an
    adult AWS practice guideline
  • Standardized symptom-triggered therapy would
    decrease benzodiazepine usage
  • Increase use of adjunctive medications for
    adrenergic hyperactivity delirium
  • Study compared prospective pilot group to
    retrospective control group

Stanley et al
  • AWS guideline was developed for surgical patients
  • Institution revised protocol for internal med
  • Changes involved the assessment frequency BZD
  • Investigation took place at a university teaching
  • Inclusion internal med admission, 2 on CAGE
    questionnaire, gt 6 drinks daily, history of AWS,
    or AWS-related seizures
  • Controls were patients identified by AWS
    diagnosis or therapy of BZDs, thiamine, folic
    acid, MVI use

Stanley et al
  • Control patients were d/c during 6-month period
    preceding guideline implementation
  • Excluded therapy with alcohol or incomplete med
  • Pilot group received lorazepam, clonidine,
    haloperidol based on guideline criteria
  • Authors compared drugs administered, sitter use,
    physical restraints, LOS, d/c with drug taper

Stanley et al
  • 81 total patients included (32 pilot 49
  • No significant difference in mean age, race, or
  • Significantly more men in control group than
    pilot group (p0.02)
  • Pilot group received significantly less lorazepam
    (p0.001), but significantly more clonidine
    (p0.01) haloperidol (p0.002)
  • More controls (71.4) vs. pilot (18.8)
    discharged with benzodiazepine taper (plt0.01)

Stanley et al
  • 1 pt in each group had an AWS-related seizure
  • 13 of 18 pilot (72) 8 of 29 (28) controls had
    prolonged QTc interval while given haloperidol
  • No patients experienced cardiovascular adverse
  • Sitter required for 1 pilot (3) 6 control
    (12) patients (p0.23)
  • No significant difference seen in restraint use
    or length of stay

Stanley et al
  • Internal medicine patients at risk for AWS can be
    managed by a symptom-triggered approach
  • Can see a decrease in benzodiazepine usage when
    adjunctive medications are used
  • Can see an increase in QTc prolongation with
  • Further investigations necessary to determine
    true impact of guidelines on patient outcomes

Weaver et al
  • Prospective clinical study designed to take place
    at Virginia Commonwealth University Medical
  • General internal medicine units of an urban
    teaching hospital
  • Determine if difference exist between
    symptom-triggered (ST) fixed-schedule (FS)
    dosing of lorazepam
  • Authors believed that symptom-triggered therapy
    would result in decreased lorazepam
    administration, protocol errors, withdrawal
    assessment scores

Weaver et al
  • Subjects were enrolled from April 2001 May 2003
  • Inclusion age 21-75, history of daily alcohol
    use for at least 7 consecutive days, last use lt72
    hrs prior
  • Exclusion unable to give IC, lack of surrogate
    to give IC, altered mental status, chronic
    sedative-hypnotic usage
  • Clinical Institute Withdrawal Assessment for
  • Score lt5 minimal withdrawal, 6-19 mild, gt30
    severe risk
  • Nurses residents taught to administer
    assessment tool

Weaver et al
  • Somnolence Scale used prior to lorazepam dose
  • Score gt2 resulted in dose being held
  • Subjects evaluated q4 hrs with CIWA-Ar
  • D/C if score lt6 for 24 hrs performed for 48 hrs
  • ST Protocol score of 10-19 given 1mg, 20-29
    given 2mg, 30-39 given 3mg, gt40 given 4mg
  • FS Protocol 1st 48 hrs give 2mg PO q4 hrs for 12
    doses after 1st 48 hrs dose began to be tapered
    over an additional 48 hrs

Weaver et al
  • Total of 183 subjects enrolled (91 ST 92 FS)
  • Predominance of male subjects enrolled (81 vs.
  • Median length of stay was 3 days for all subjects
  • FS group received more lorazepam than ST group
  • Seen in all CIWA-Ar score ranges 0 - 6, 6 - lt10,
    10 - lt20
  • ST group had statistically significant more
    protocol errors (p0.042)
  • ST therapy resulted in similar withdrawal relief
    to FS

Weaver et al
  • ST therapy allows more flexibility in dosing in
    accordance with fluctuations in CIWA-Ar score
    sedation level
  • FS can result in doses higher than necessary
  • ST therapy is a proactive approach avoiding
    oversedation and allowing dose escalation quickly
  • Increased education in the proper usage as well
    as the principles of ST may result in fewer
    errors when using the protocol in the future

Repper-DeLisi et al
  • Medical or surgical conditions complicate AWS
    treatment diagnosis
  • Conversely AWS s/s can mask underlying illness
  • Symptoms attributed to AWS overlooking comorbid
  • Numerous protocols created to treat AWS
  • Minimal produced tested in medical or surgical
  • Through the creation/implementation of a protocol
    hospital staff would change treatment practices
  • Resulting in improved practice economic outcomes

Repper-DeLisi et al
  • Retrospective medical record review for 80
  • 40 patients pre-protocol/AWS education 40
    post-protocol introduction
  • Pre group Oct 02 May 03 Post group Oct 03
    Jun 04
  • Identified by discharge diagnosis review of
    clinical notes to confirm
  • Inclusion alcohol within 2 weeks of admission,
    /or withdrawal or treatment for AWS during
  • Demographic information, patient characteristics,
    1st three day compliance to pathway was

Repper-DeLisi et al
  • No significant difference between age, or gender
  • Majority were men, mean age 50.4 yrs (pre) 47.1
    yrs (post), admitted through ED
  • Comorbid coditions similar majority being HTN
    or MI
  • Majority had history of alcohol related
  • 68 pre vs. 88 post AWS-related seizures (30
    vs. 35), DTs (15 vs. 7.5)
  • 42.5 (Pre) vs. 30 (Post) arrived to hospital
    experiencing alcohol withdrawal syndrome
  • 12.5 vs. 10 had seizures just prior to or upon

Repper-DeLisi et al
  • Increased alcohol amount frequency assessment
    occurred post-protocol
  • CAGE questionnaire infrequently utilized
  • Psych Nursing consult 55 vs. 77.5 (plt0.05)
  • Vital sign assessment increased for first 3 days
  • 20.03 12.52 vs. 25.89 17.13
  • No difference in daily BZD fixed-dose
  • Significant difference seen in percentage of
    fixed vs. PRN dose for the first 3 days (plt0.05)

Repper-DeLisi et al
  • Delirium incident lower 52 vs. 40
  • Difference was not significant
  • lt48 mg/d LOS 5.4 days to 4.0 days (not sig
  • gt48 mg/d had increased LOS
  • 20 of post-protocol patients received BZD doses
    above recommendations of the AWS protocol

Repper-DeLisi et al
  • Assessment of patients remained infrequent
  • Protocols easily changed the ordering of lab
  • Difficult task involved changing the diagnosis,
    treatment, monitoring of AWS
  • Practice change hindered by lack of education

Riddle et al
  • Multidisciplinary committee formed to develop a
    standing order set for treatment of AWS
  • Nurses, dieticians, pharmacist, physicians
  • Standing order to be used in critical
    non-critical patients
  • Order set created as a symptom based protocol
  • CIWA-Ar used for assessment dose selection
  • Provided medication to treat nausea vitamin
  • Treatment of electrolyte imbalances, infections
    fever provided, as well as ability to order
    pertinent labs

Alcohol Withdrawal Standing Order
  • Order set divided into 4 separate areas
  • Nursing Pharmacy orders, Other, Laboratory
  • Nursing area explains how when to use tool
  • Collection of vital signs CIWA-Ar on back of
    order set
  • Pharmacy area based on CIWA-Ar Symptom Scale
  • Mild 8, Moderate 9 15, Severe 15

Alcohol Withdrawal Standing Order
  • Mild No treatment, reassess patient in 4 hours
  • Moderate Chlordiazepoxide 25 50 mg PO q2 hr
    PRN maximum daily dose 300 mg per 24 hours
  • Lorazepam 1 - 2 mg IVP q4 hr PRN maximum 24
    mg/24 hr
  • Severe Chlordiazepoxide 50 100 mg q1 hr PRN
  • Lorazepam 2 4 mg IVP q2 hr PRN reassess in 1
  • Other nausea, vomiting, fever medications
  • IV/PO thiamine, folic acid, multivitamin
  • Labs CBC with Met-C, Urine drug screen, Blood
    alcohol level, Mg2 Phosphorus

Riddle et al
  • Prior to implementation staff education regarding
    protocol use AWS was conducted
  • Training in-servicing was managed by nurse
    educators as well as pharmacist
  • Quality improvement project took place in the ICU
    medical/surgical step-down units of Bayfront
    Medical Center

Riddle et al
  • Quality improvement project comprised of
    prospective retrospective investigation
  • Patients with history of alcohol abuse,
    intoxication on admission, or experiencing DTs
    were identified
  • Chart review conducted to identify patients
    treated for AWS prior to standing order
  • Only PO chlordiazepoxide or IV lorazepam included

Riddle et al
  • Data collected on all study subjects included
  • LOS, patient demographics, days on medication
    with protocol, days on medication without
  • Amount of lorazepam administered, amount of
    chlordiazepoxide administered, reversal agent
  • History of seizures, use of restraints, use of
    sitter, other pertinent medications, blood
    alcohol level

Riddle et al
  • 56 total subjects were examined (80.3 Male)
  • 31 in symptom-based group 25 in comparison
  • Symptom-based 14 non-critical 17 critical care
  • Ave Age 49 yo (non-critical) 51 yo (critical)
    24 male
  • LOS 14.85 days (non-critical) 14 days
  • Ave Protocol Use 3 days (non-critical) 2.69
    days (critical)
  • Comparison Group 16 non-critical 9 critical
  • Ave Age 52 yo (non-critical) 55 yo (critical)
    21 male
  • LOS 6.6 days (non-critical) 6.5 days
  • Ave Med Use 5.4 days (non-critical) 4.8 days

Riddle et al
  • Symptom-Based ave amount of drug used varied
  • Lorazepam 14.79 mg (non-critical) 10.94 mg
    (critical care)
  • Chlordiazepoxide 164 mg (non-critical) 142 mg
  • Control Group lorazepam similar,
    chlordiazepoxide varied
  • Lorazepam 6.5 mg (non-critical) 6.7 mg
  • Chlordiazepoxide 372 mg (non-critical) 303 mg
  • Reversal agent used once in control group
  • Symptom-based 5 required restraints 2 required
  • Control group 3 required restraints 1 required

Riddle et al
  • Lorazepam usage greater in symptom-based group
  • Critical care patients less able to take PO
  • Chlordiazepoxide used less in symptom-based group
  • PO intake a factor lorazepam used if symptoms
    not controlled
  • Symptom-based required less time to treat
  • Protocol use allows for fewer days on medication
  • Less costly complicated hospitalizations
  • LOS greater in symptom-based group
  • Numerous factors outside of AWS could contribute
    to length

  • Alcohol abuse is a large part of our society
  • Source of numerous hospital admissions in various
  • AWS is a dynamic complication
  • Can result in life-threatening side effects if
  • Benzodiazepines nutrition/electrolyte
    management is key
  • Symptom-based therapy provides better therapy
  • Less drug usage, decreased sedation adverse
  • Successful implementation requires education of

(No Transcript)
Question 1
  • AWS can be defined as all of the following
  • A) homogenous complication easily identified by
  • B) heterogeneous complication effecting multiple
  • C) syndrome misunderstood by healthcare
  • D) a medical problem see in adults of all ages

Question 2
  • AWS produces adverse effects within this time
    frame after the patients last drink?
  • A) 5 7 days
  • B) 1 3 hours after admission
  • C) 6 24 hours
  • D) Time frame data unknown, but studies pending

Question 3
  • AWS causes all of the following except
  • A) Delirium
  • B) Pneumonia
  • C) Central nervous system excitation
  • D) Hypertension

Question 4
  • Implementation of AWS protocol is more effective
  • A) The protocol use is restricted to ICUs only
  • B) Patients experience DTs prior to
    administration of the protocol
  • C) Patient states willingness to treat underlying
  • D) Hospital staff receives education regarding
    AWS use of protocol

Question 5
  • Patients who are abusers of alcohol
  • A) Rarely engage in dangerous activities (i.e.
    driving under the influence)
  • B) Are generally men from poor educational
  • C) Frequently have increased hospital LOS
  • D) Easily identified by hospital staff

Question 6
  • Utilization of a AWS protocol has demonstrated
  • A) To be ineffective in the acute care setting
  • B) An increase in deleterious side effects of
    alcohol abuse
  • C) Treatment should be reserved for only severe
  • D) Overall decrease in treatment medication usage

Question 7
  • Nutrition evaluation electrolyte replacement is
    important secondary to all of the following
  • A) Hospitals can reduce cost by determination of
    patients with minimal PO intake
  • B) Abusers of alcohol frequently experience
    impaired absorption
  • C) Alcohol abusers have a high rate of
  • D) Thiamine, Folate, multivitamins may be
    required to prevent additional complications

Question 8
  • All of the following are treatments of AWS
  • A) IV/PO Alcohol
  • B) Librium
  • C) Propofol
  • D) Ativan

Question 9
  • Lorazepam (short-acting benzodiazepine) is the
    drug of choice in AWS treatment because of the
  • A) Ability to lower seizure threshold
  • B) Concomitant use with phenytoin shows improved
  • C) Single route of administration
  • D) Lacks active metabolites

Question 10
  • Haloperidol use not recommended because of all of
    the following except
  • A) Neuroleptics decrease seizure threshold
  • B) Benzodiazepines provide better alternative to
    agitation control
  • C) Can cause QTc prolongation
  • D) FDA banned usage in AWS patients due to
    increased electrolyte imbalances in this patient