Alcohol Withdrawal Assessment and Treatment

1
Alcohol WithdrawalAssessment and Treatment

• Stacy Campbell-Bright, Pharm.D, BCPS
• Clinical Specialist, Medicine ICU
• July 22, 2008

2
Alcohol Abuse Incidence Complications

• 20 of patients in hospitals meet diagnostic
  criteria for alcohol dependence
• 50-60 of pts admitted with trauma are alcoholic
• Alcoholic pts in an ICU have 50 mortality rate
  compared with 26 in non-alcoholic pts
• AWS is often mild doesnt require treatment
• 20 of patients will show signs of withdrawal
• 10 develop seizures
• 5 of pts will develop Delirium tremens
• Mortality 2-10

3
Alcohol Withdrawal Syndrome Complications

• Morbidity Mortality associated with AWS are
  increased by a delay in recognition treatment
• Presence of concurrent medical or surgical
  problems such as pneumonia, cardiac disease,
  pancreatitis, and trauma are associated with
  increased risk of developing major withdrawal

4
Screening Approaches in Medical Settings

• Ask patients about current and past alcohol use
• Family history of alcohol abuse?
• History of type of alcohol ingested,
  quantity,frequency, duration, prior withdrawal
• History of other drug use
• When was last drink?

5
Determine if Patient is Alcohol Dependent

• Daily drinking
• Drinking early in the day
• Rating priority of alcohol in patients life
• Previous medical interventions required in
  relation to drinking
• Establish if problems have arisen in relation to
  drinking
• Social, domestic, emotional occupational,
  financial

6
Screening Pts at high risk for Alcohol Withdrawal

• CAGE Questionnaire
• Have you ever felt you should cut down on your
  drinking?
• Have people annoyed you by criticizing your
  drinking?
• Have you ever felt bad or guilty about drinking?
• Have you ever had a drink first thing in the
  morning to steady your nerves (eye-opener)?
  

7
Screening

• Physical Exam
• Signs of intoxication
• Withdrawal symptoms
• Sequelae of chronic alcohol use
• Signs of liver disease
• Wernickes encephalopathy ( ataxia, amnesia,
  ophthalmoplegia)

8
Screening

• Laboratory
• Blood alcohol concentration
• Urine drug screen
• Electrolyes
• CBC
• LFTs, coags albumin
• In alcohol dependence can see
• ?GGT, ?MCV
• Folate B12 deficiency
• ?homocysteine

9
Pathophysiology

• Alcohol interferes with two neurotransmitters
• Agonizes gamma-aminobutyric acid A
• (GABA A)
• Antagonizes N-methyl-D-asparate ( NMDA)
• Abstinence enhanced NMDA receptor function and
  reduced GABA transmission dysregulation of
  dopaminergic system

10
Diagnosis of Alcohol Withdrawal(DSM-IV)

• Patient has decreased or stopped his/her heavy,
  prolonged ingestion of alcohol
• AND
• Has at least two symptoms of withdrawal which
  must cause clinically significant distress or
  impairment, and not be caused by other disorders

11
Alcohol Withdrawal Symptoms (DSM-IV)

• Autonomic hyperactivity (sweating, pulse gt100)
• Increased hand tremor
• Insomnia
• Nausea or vomiting
• Transient visual, tactile or auditory
  hallucinations or illusions
• Psychomotor agitation
• Anxiety
• Grand- mal seizures

12
Symptoms of Alcohol Withdrawal
13
Goals of Treatment

• Safely reduce severity of withdrawal symptoms
• Prevent seizures and delirium
• Facilitate the transition to alcohol treatment
  and rehabilitation
• Prevent complications

14
NON-DRUG THERAPY

• Supportive Care
• General nursing care in a quiet, well-lit room,
  reassurance and reorientation
• Frequent monitoring of vital signs
• Nutrition and electrolyte replacement as needed

15
MEDICATION TREATMENT OPTIONS

• DRUG CLASS OF CHOICE
• Benzodiazepines

16
PROPERTIES OF BENZODIAZEPINES

• Act on GABA-A receptors, similarly to ETOH
• Low potential for physical dependence and
  tolerance with short courses
• Cross tolerant with ethanol
• Minimal side effects
• Wide safety margin

17
Efficacy of Benzodiazepines

• Six prospective trials, BZDs vs placebo
• Reduce the incidence of seizures
• Risk reduction of 7.7/100 patients
  treated(p0.003)
• CI -12.0 to -3.5
• Reduce the incidence of delirium
• Risk reduction of 4.9/100 (p0.04)
• CI -9.0 to -0.7

18
Long-Acting Benzodiazepines

• Long half-life agents(gt30h)
• Chlordiazepoxide and Diazepam
• Overall smoother withdrawal course
• Less breakthrough or rebound symptoms
• Undergo oxidative metabolism
• Metabolites with long half-lives
• Increased sedation in liver dz and elderly

19
Intermediate Acting Benzodiazepines

• Intermediate half-life agents(10-20h)
• Lorazepam and Oxazepam
• No active metabolites
• Preferred in liver dz and the elderly
• Cyclical variations
• Frequent dosing required

20
DOSING BENZODIAZEPINES

• Fixed Schedule
• Scheduled PRN
• Taper once symptom controlled
• Symptom Triggered
• Medication given every 1-2 hours in the presence
  of symptoms(CIWA-A OR CIWA-Ar)

21
SYMPTOM-TRIGGERED THERAPY

• Withdrawal severity assessment scales
• Objectively quantify severity of withdrawal
• Well documented reliability, reproducibility
  validity based on comparisons with ratings by
  experienced clinicians
• High scores associated with seizures delirium
• Used in detox units, psych wards, general medical
  surgical wards

22
Structured Assessment Forms used in
Symptom-Triggered Therapy

• Clinical Institute Withdrawal Assessment for
  Alcohol Scale (CIWA-A)
• Clinical Institute Withdrawal Assessment for
  Alcohol, revised (CIWA-Ar)
• CIWA-A, modified (Foy, et.al)

23
Clinical Institute Withdrawal Assessment for
Alcohol ( CIWA-Ar) Scale

• 10 item scale
• Clinician gives score for each response (0-7)
• Overall score indicates severity of withdrawal
  and treatment and follow-up required
• Validated, high inter- rater reliability

24
CIWA-Ar Scale

• Nausea and Vomiting
• Tremor
• Paroxysmal sweats
• Anxiety
• Agitation
• Tactile disturbances

• Auditory disturbances
• Visual disturbances
• Headache, fullness in head
• Disorientation

25
CIWA-A, modified

• In addition to objectives characterized by
  CIWA-Ar, the modified CIWA also includes
• Temperature
• Pulse
• RR
• Diastolic BP
• This is the assessment tool used at UNC first
  validated in medically-ill patients

26
Symptom Triggered Approach to Treatment of
Alcohol Withdrawal

• As effective as fixed dose regimens
• Allows earlier identification of patients at risk
  for AWS earlier administration of medication
• Allows objective titration of doses to individual
  need
• Leads to more rapid detoxification
• Reduction in total benzodiazepine dose
• Decreased incidence of over sedation

27
Disadvantages of Structured Assessment Forms
CIWA

• Requires screening to identify appropriate
  patients for use
• Requires trained staff
• Low scores may give false confidence
• High scores may be related to other disorders
• Difficult to use in non-communicative or
  mechanically-ventilated patients

28
Alcohol Withdrawal Pharmacotherapy for Inpatients
with Medical Comorbidity

• Designed to determine if there was a difference
  between symptom-triggered (ST) and fixed-schedule
  (FS) dosing of lorazepam in patients hospitalized
  on general medical wards at a University Medical
  Center

29
Alcohol Withdrawal Pharmacotherapy for Inpatients
with Medical Comorbidity

• Inclusion 21-75yo, daily ETOH intake for 7 days
  or greater, with last use no more than 72 hours
  prior to enrollment. Patients on GIM service
• Exclusion unable to give informed consent,
  chronic sedative-hypnotic use
• Most common comorbid diagnosis were pancreatitis,
  pneumonia, gastrointestinal bleeding, cellulitis
  and chest pain
• Used CIWA-Ar
• Used in conjunction with sedation scale

30
Alcohol Withdrawal Pharmacotherapy for Inpatients
with Medical Comorbidity

• CIWA-Ar
• lt 5 minimal withdrawal
• 6-19 mild withdrawal
• gt 30 severe withdrawal
• Assessments q4h for a minimum of 48h
• Then if CIWA-Ar lt6 for 6 consecutive
  assessments(24h), assessments stopped

31
ST Protocol
Scores gt30 Assess q1hr and give drug until
score lt30 for 2 consecutive assessments Then
return to q4h assessments
32
Fixed Dose Protocol

• Lorazepam 2mg IV/PO q4h x48hrs then 1mg IV/PO
  q4hr x 24hrs then 0.5mg IV/PO q4h for 6 doses
  then discontinue
• If CIWA-Ar score gt30, additional lorazepam q1hr
  until score lt30 x2 assessments
• If gt6mg additional lorazepam required, then total
  dose over previous 24hrs divided q4hr and tapered
  by 20 over 5days
• Doses held for sedation

33
Alcohol Withdrawal Pharmacotherapy for Inpatients
with Medical Comorbidity

• 209 patients eligible for enrollment
• 183 patients enrolled( 91 ST 92 FS)
• No difference in groups based on age, sex, race,
  drinking history or CIWA-Ar score on Day1
• 81 male, 19 female
• Median length of stay 3 days
• Median drinks per day 7.3 (ST) 9 (FS)
• Years of drinking 23.6(ST) vs. 24.4(FS)
• Mean average CIWA-Ar 4.5(ST) vs 4(FS)

34
Average Total Lorazepam by Protocol and CIWA-Ar
Score
35
Results

• No statistically significant difference in change
  of CIWA-Ar scores for first 2 days between FS and
  ST groups
• ST group received half the amount of lorazepam
  compared to FS group for similar CIWA-Ar scores
• No difference in length of stay
• ST group had greater than 2 times the incidence
  of protocol errors
• No serious adverse effects in either group(
  seizures or respiratory depression)

36
Conclusions

• ST resulted in similar withdrawal relief relative
  to FS with less lorazepam required
• ST allows more flexibility in dosing with
  fluctuations in CIWA-Ar score and level of
  sedation, so less medication can be given if
  withdrawal signs resolve rapidly
• Ability to give lower doses of benzodiazepines in
  the ST group may lead to less side effects such
  as over sedation, paradoxical agitation,
  delirium, respiratory depression

37
Alcohol Withdrawal DeliriumDSM-IV Criteria

• Disturbance of consciousness( reduced clarity of
  awareness of environment) with reduced ability to
  focus, sustain or shift attention
• A change in cognition ( such as memory deficit,
  disorientation, or language disturbance) or
  development of a perceptual disturbance that is
  not better accounted for by a preexisting,
  established or evolving dementia

38
Alcohol Withdrawal Delirium- DSM IV Criteria

• C. The symptoms develop in a short period (
  usually hours to days) and tends to fluctuate
  during the day
• D. There is evidence from the history , PE or
  laboratory findings that the symptoms in criteria
  A and B developed during or shortly after a
  withdrawal syndrome

39
Alcohol Withdrawal Delirium

• This diagnosis is made only when the cognitive
  symptoms are in excess of those usually
  associated with the withdrawal syndrome and when
  the symptoms are sufficiently severe to warrant
  independent clinical attention

40
Delirium Tremens

• Mortality up to 15
• Symptoms delayed 48 hrs after last drink
• Symptoms peak after 4 days
• May last two weeks in severe cases
• Sedative-hypnotics are the treatment of choice in
  fixed dosed method
• Parenteral administration preferred

41
Prediction of Withdrawal Severity

• Type of alcohol, quantity ,frequency and drinking
  pattern
• Past withdrawal seizure
• Past delirium
• Number of previous detoxification's
• Medical comorbidity
• Other addictions
• Advanced age

42
Adjunctive Agents

• Thiamine
• 100mg IV or IM prior to dextrose then daily x2
• Prevents Wernickes encephalopathy
• Multivitamins and Folate
• Prevents alcohol related deficiencies
• Magnesium
• Patients often deficient
• Requires replacement over 3-5 days
• Usual doses 0.5meq/kg/day ( IBW)
• Add to IVF to minimize urinary losses

43
Adjunctive Agents

• Haloperidol
• May be useful in combination with benzodiazepines
  for agitation and hallucinations
• 0.5-5mg po q4h or IV q30 minutes
• Decrease seizure threshold when used alone so use
  in combination with benzodiazepine
• Monitor QT interval minimize use if QT gt450

44
Adjunctive Agents

• Beta Blockers and Clonidine
• Decrease autonomic symptoms
• No effect on decreasing seizures
• No effect on delirium ( propranolol has been
  associated with increased delirium)
• Use in combination with benzodiazepines
• Beta blockers may be useful in patients with
  ischemic heart disease
• Clonidine may be helpful in opioid addiction

45
CPOE Order Entry for CIWA

• CIWA Score lt10
• Assessments q4h x24h. If CIWA lt10 on 3
  consecutive assessments advance to q6h
• CIWA 10-14
• Assess q2h. After 24h if CIWA lt10 on 3
  consecutive assessments advance to q4h
• CIWA gt14
• Assess q2h and administer diazepam or lorazepam
  per MD order
• Assess for 72hr or until detoxification complete

46
CPOE Order Entry for CIWA

• If CIWA gt14 eligible for medication
• Choose diazepam OR lorazepam
• Choose IV OR PO administration
• Patients initially receive doses q2hr as long as
  CIWA gt10 AND RASS gt-2
• Maximum of 6 doses of either medication and then
  reassess
• If symptoms still consistent with AWS frequency
  of drug administration is increased to q1hr for
  maximum of 6 more doses .
• Doses are held if CIWA lt10 or RASS lt-2

47
CPOE CIWA Order Entry

• CIWA should be discontinued after patient
  receives 12 doses of either lorazepam or
  diazepam.
• If symptoms are still consistent with AWS then
  patients should be placed on a fixed schedule
  taper of lorazepam or diazepam
• Once symptoms controlled taper dose by 20-25 per
  day

48
Monitoring CIWA

• CIWA scores are documented by nursing in E-Chart
• Doses of medication, sedation score and CIWA
  scores are also documented on MAR

49
Summary

• Screen and identify patients early
• Benzodiazepines are drug of choice for treating
  AWS DTs
• All efficacious
• Diazepam and chlordiazepoxide may be preferred
• Substitute lorazepam in elderly pts with liver
  dx

50
SUMMARY

• Symptom-triggered protocols are preferred in
  patients at risk for alcohol withdrawal who are
  identified before severe withdrawal symptoms have
  developed and if trained staff are available
• At UNC patients with CIWA scores lt10 may be
  admitted to floor with q4h assessments
• Floor patients whose CIWA scores become gt10 may
  be treated with PRN or fixed doses of
  benzodiazepines if symptoms remain mild to
  moderate

51
Summary

• Patients with severe withdrawal or DTs should be
  transferred to the MPCU or ICU
• Fixed dose regimens are recommended for patients
  already in severe withdrawal or in
  non-communicative or mechanically ventilated
  patients.

52
Summary

• All patients being treated for alcohol withdrawal
  or DTs should have sedation assessed prior to
  receiving sedative-hypnotics, and doses should be
  held for excessive sedation

53
Richmond Agitation Sedation Scale (RASS)
4 Combative Overtly combative, violent,
immediate danger to staff 3 Very agitated Pulls
or removes tube(s) or catheter(s) aggressive 2
Agitated Frequent non-purposeful movement, fights
ventilator 1 Restless Anxious but movements not
aggressive vigorous 0 Alert and calm -1 Drowsy
Not fully alert, but has sustained
awakening (eye-opening/eye contact) to voice (gt10
seconds) -2 Light sedation Briefly awakens with
eye contact to voice (lt10 seconds) -3 Moderate
sedation Movement or eye opening to voice (but no
eye contact) -4 Deep sedation No response to
voice, but movement or eye opening to physical
stimulation -5 Unarousable No response to voice
or physical stimulation