What’s on Tap for the
Treatment of Alcohol
Withdrawal?
Andrew Straznitskas, PharmD, BCPS
Clinical Pharmacist, Medical Intensive Care Unit
Bellevue Hospital Center
NYSCHP 2015 Critical Care Program: Downstate
October 2, 2015
Disclosure
• The presenter has no conflicts of interest to
disclose
• UAN# 0134-0000-15-132-L01-P
– Knowledge-based Activity
– 1 contact hour (0.1 CEU)
Objectives
• Describe the pathogenesis and clinical progression of
alcohol withdrawal syndrome.
• Evaluate commonly used monitoring tools for alcohol
withdrawal syndrome and explain their limitations in a
critically ill patient population.
• Compare treatment modalities for alcohol withdrawal
syndrome and outline their benefits and drawbacks.
• Identify adjunctive treatments for alcohol withdrawal
syndrome used in critical care and specify their
appropriate place in therapy.
Incidence of Alcohol Use Disorders in
Hospital Medicine and Critical Care
• Alcohol use disorders are present in more
than 20% of US population
– Heavy alcohol use: 6.3%
• Hospitalized Patients
– 20-40%
• Intensive Care Unit
– 10-30%
CHEST 2010;138:994-1003
Crit Care Clin 2008;24:767-88
Alcohol Dependence and
Development of Alcohol Withdrawal
• Estimated two million patients experience
symptoms of alcohol withdrawal annually
• Mild Symptoms
– > 80%
– Anxiety, tremors, sleep disturbance, sweating, etc.
• Severe Symptoms
– 15-30%
– Delirium tremens, hallucinations, seizures
Am Fam Physician 2004;69:1443-50
Alcohol Health Res World 1998;22:73-9
Complications of Alcohol Dependence
and Withdrawal in Critically Ill
• Associated with worse outcomes
– Increase sedative requirement
– Increased incidence of sepsis
– Increased need for and longer duration of
mechanical ventilation
– Increased length of stay (ICU and hospital)
– Increased mortality
CHEST 2010;138:994-1003
Crit Care Clin 2008;24:767-88
Intensive Care Med 2013;39:16-30
Pathogenesis of Alcohol Withdrawal
Syndrome (AWS)
• Neuromodulation associated with chronic
alcohol use
– GABA-A receptor down-regulation
• Desensitization to GABA mediated stimulation
• Impaired neuronal inhibition
– NMDA up-regulation
• Hyper sensitization to glutamatergic stimulation
• Increased neuronal excitability
J Clin Neurophysiol 2013;30:435-7
Pathogenesis of AWS
• Abrupt cessation of alcohol
– Increase extracellular dopamine
– Dopaminergic hyperexcitability
– Excess catecholamines and hyperadrenergic state
• Repeated episodes of withdrawal amplify
severity of AWS
– Kindling effect
J Clin Neurophysiol 2013;30:435-7
Crit Care Med 2010;38[suppl.]:S494-501
Clinical Progression of AWS
Onset after last
drink
Duration
Autonomic
Hyperactivity
Tachycardia,
diaphoresis,
anxiety, agitation,
tremulousness
6-8 hours
1-2 days
Alcoholic
Hallucinosis
Visual, tactile, and,
auditory
hallucinations
8-48 hours
2-4 days
Withdrawal
Seizures
Generalized tonicclonic seizures
12-48 hours
2-3 days
Delirium Tremens
Severe
sympathetic
activity,
hallucinations,
delirium, agitation
48-96 hours
2-5 days
Stage
Clinical features
Aust Crit Care 2011;24:110-6
Crit Care Med 2013;41:S57-68
Crit Care Clin 2008;24:767-88
Crit Care Med 2010;38[suppl.]:S494-501
Risk Factors for Severe Alcohol
Withdrawal
•
•
•
•
•
•
Previous withdrawal history
Family history
Race
Benzodiazepine dose
Liver disease (protective)
Inconsistent association with alcohol levels
Crit Care Med 2010;38[suppl.]:S494-501
Screening and Monitoring for AWS
• Assist in early identification
• Indicate when medication is needed
• Recognize worsening of symptoms and need
to escalate care
• Aid in de-escalation of treatment
• Easy to administer and high inter-evaluator
reliability
Alcohol Alcohol 2001;36:104-8
Screening and Monitoring Tools for
AWS
• Clinical Institute Withdrawal Assessment for
Alcohol (CIWA-Ar)
• Clinical Institute Withdrawal Assessment for
Alcohol revised to DSM
• Alcohol Withdrawal Symptom Checklist
• Glasgow Modified Alcohol Withdrawal Scale
Alcohol Clin Exp Res 2007;31:612-8
Am J Addict 2006;15:85-93
Q J Med 2012;105:649-56
CIWA-Ar
Crit Care Med 2010;38[suppl.]:S494-501
CIWA-Ar
• 10 item scale
– Assessing various symptoms
– 7 items require patient participation
• Can be used as frequently as every 30 minutes
– Most commonly every 1-2 hours
• Score range from 0-67
– Score ≥ 10 prompts treatment
– Score ≥ 20 signifies increased AWS severity
Crit Care Med 2013;41:S57-68
Aust Crit Care 2011;24:110-6
Br J Addict 1989;84:1353-7
Limitations of AWS Assessment Tools
• Lack validation in critically ill patients
• Many items require active patient interaction
• Alternatives
– Richmond Analgesia and Sedation Score (RASS)
– Sedation-Agitation Scale (SAS)
Crit Care Med 2013;41:S57-68
Aust Crit Care 2011;24:110-6
AWS Treatment Goals
• Decrease symptom severity
• Mitigate AWS progression and complications
– Withdrawal seizures
– Delirium tremens
• Minimize adverse treatment effects
– Over-sedation
– Need for mechanical ventilation
Crit Care Clin 2008;24:767-88
Treatment of AWS: Benzodiazepines
• Gold standard for treatment of AWS
• Compared to placebo
– Decreased AWS severity
– Withdrawal seizures
• 0.5% vs. 8% (p < 0.001)
• Number Needed to Treat: 13
– Delirium
• 1.7% vs. 5.9% (p = 0.04)
• Number Needed to Treat: 24
Crit Care Clin 2008;24:767-88
JAMA 1997;278:144-51
Cochrane Database Syst Rev 2010;3:CD005063
Treatment of AWS:
Benzodiazepines vs. Non-Benzodiazepines
• Compared with other medication classes
– No proven benefit of benzodiazepines
• Direct comparison trials limited
– Small patient population
– Low AWS severity
– Heterogeneous interventions
Crit Care Clin 2008;24:767-88
JAMA 1997;278:144-51
Cochrane Database Syst Rev 2010;3:CD005063
Treatment of AWS:
Benzodiazepines vs. Non-Benzodiazepines
Cochrane Database Syst Rev 2010;3:CD005063
Treatment of AWS:
Benzodiazepines vs. Non-Benzodiazepines
Cochrane Database Syst Rev 2010;3:CD005063
Pharmacokinetic Comparison of
Commonly Used Benzodiazepines in AWS
Benzodiazepine
Routes of
Administration
Equivalent
Dosage
Half-life (hours)
Metabolism
Chlordiazepoxide PO
25 mg
Parent: 6-24
Hepatic
Metabolite: 24-96 Active metabolite
Diazepam
PO, IM, IV, PR
5 mg
Parent: 24-48
Hepatic
Metabolite: 72-96 Active metabolite
Lorazepam
PO, IM, IV
1 mg
~12
Glucuronidation
Inactive metabolite
Oxazepam
PO
15 mg
8-12
Glucuronidation
Inactive metabolite
Midazolam
IM, IV
2 mg
2-6
Hepatic
Active metabolite
Chapter 17. Hypnotics and Sedatives
Chlordiazepoxide. In: Lexicomp Online
Diazepam. In: Lexicomp Online
Lorazepam. In: Lexicomp Online
Oxazepam. In: Lexicomp Online
Midazolam. In: Lexicomp Online
Selection of Benzodiazepine
• Comparative data demonstrates similar
efficacy among benzodiazepines
– Long-acting agents suggested to have improved
efficacy in prevention of withdrawal seizures and
delirium tremens
Cochrane Database Syst Rev 2010;3:CD005063
JAMA 1997;278:144-51
Crit Care Clin 2008;24:767-88
Crit Care Med 2013;41:S57-68
Selection of Benzodiazepine
Cochrane Database Syst Rev 2010;3:CD005063
Selection of Benzodiazepine
Cochrane Database Syst Rev 2010;3:CD005063
Selection of Benzodiazepine
• Route of administration
– Intravenous generally preferred for critically ill
patients
• Pharmacokinetic differences
– Agents with long half-lives and active metabolites
may accumulate in patients with hepatic failure
• Dosage form considerations
– Lorazepam and diazepam injection formulations
contain propylene glycol diluent
Crit Care Clin 2008;24:767-88
Crit Care Med 2013;41:S57-68
AWS Treatment Modalities
• Fixed dose
– Set, scheduled doses, tapered over several days
– Additional treatment as needed
• Symptom triggered
– Frequent, scheduled patient assessments using
standardized monitoring tool
– Treatment as needed in response to symptoms
– Treatment withheld if no or minimal symptoms
National Clinical Guideline Centre (UK) 2010;Clinical Guideline 100
What is the preferred AWS treatment
modality at your institution?
a. Fixed dose benzodiazepine
b. Symptom triggered benzodiazepine
c. Provider specific; No preferred modality
d. Unsure; Do not know
“Individualized Treatment for Alcohol
Withdrawal”
• Randomized, controlled trial at VA Medical
Center
– Included 101 patients in alcohol detoxification unit
– Symptom triggered vs. fixed dose therapy
• Fixed dose
– Chlordiazepoxide 50 mg Q6hr for 24 hours followed by
25 mg Q6hr for 48 hours
– Additional chlordiazepoxide (25-100 mg) as needed
for CIWA-Ar ≥ 8
• Symptom triggered
– Chlordiazepoxide Q1hr as needed for CIWA-Ar ≥ 8
JAMA 1994;272:519-23
“Individualized Treatment for Alcohol
Withdrawal”
• Primary outcome
– Duration of treatment – 9 vs. 68 hr (p < 0.001)
– Total benzodiazepine – 100 vs. 425 mg (p < 0.001)
• No significant difference in AWS severity or
development of complications
JAMA 1994;272:519-23
“Individualized Treatment for Alcohol
Withdrawal”
• Low acuity patient population
– Alcohol detoxification unit
– Low withdrawal severity
• Staff training
– Participating staff provided adequate training on
use of monitoring tools and treatment protocol
JAMA 1994;272:519-23
Inpatient Management of AWS:
Symptom Triggered vs. Fixed Dose
• Randomized, controlled trial of patients admitted
to an inpatient alcohol detoxification program
– Randomized 117 patients to symptom based vs. fixed
dose
• Fixed dose
– Oxazepam 30 mg Q6hr for 24 hours followed by 15 mg
Q6hr for 38 hours
– Additional medication as needed based on symptoms
• Symptom Triggered
– Oxazepam as needed based on development of
symptoms
Arch Intern Med 2002;162:1117-21
Inpatient Management of AWS:
Symptom Triggered vs. Fixed Dose
• Total benzodiazepine: 38 vs. 231 mg (p < 0.001)
• Treatment duration: 20 vs. 63 hr (p < 0.001)
• No difference in AWS severity or development
of complications
• Subgroup analysis among patients with history
of severe AWS
– Total benzodiazepine: 94 mg vs. 240 mg (p = 0.07)
– Treatment duration: 23 vs. 62 hr (p = 0.04)
Arch Intern Med 2002;162:1117-21
Inpatient Management of AWS:
Symptom Triggered vs. Fixed Dose
• Inpatient population
– Low AWS severity
• Subgroup analysis suggestive that symptom
triggered management may be beneficial in
patients with more severe AWS
• Lack of controlled data in severe AWS or
benzodiazepine resistant AWS
– Is symptom-triggered management appropriate for
these patients?
Arch Intern Med 2002;162:1117-21
Symptom Triggered Management of
AWS in Critical Care
• Retrospective study of 40 patients requiring ICU
admission for severe AWS
• Pre-protocol management
– Non-protocol based
– Standard practice: continuous midazolam infusion
• Protocol based care
–
–
–
–
Frequent patient assessments using MINDS
As needed lorazepam boluses (2-8 mg)
Initiation of infusion if symptoms remain uncontrolled
Protocol based down-titration of infusion
Pharmacotherapy 2007;27:510-8
Symptom Triggered Management of
AWS in Critical Care
• Mean time to symptom control
– 19.4 vs. 7.7 hours (p = 0.002)
• Total benzodiazepine dose
– 1677 mg vs. 1044 mg (p = 0.014)
• Time receiving continuous infusion
– 122.1 vs. 52 hr (p = 0.001)
• No significant difference in length of stay
outcomes
Pharmacotherapy 2007;27:510-8
Symptom Triggered Management of
AWS in Critical Care
• Treatment-related complications (non-significant)
– Pre-protocol: 44% (n = 7)
• Three required intubation (19%)
• Two aspiration pneumonia
• Two diazepam extravasation
– Post-implementation: 25% (n = 6)
•
•
•
•
Two required intubation (8%)
One health-care associated pneumonia
One myocardial infarction
Two propylene glycol toxicities
Pharmacotherapy 2007;27:510-8
Protocol Based Dose Escalation for
Benzodiazepine Resistant AWS
• Retrospective study of patients admitted to ICU
for severe AWS
• Included 95 patients with severe AWS
– Delirium tremens: 98%
– Withdrawal seizures: 34%
• Evaluated impact of protocol implementation
emphasizing escalating doses of diazepam
– Doses escalated to 100-150 mg
– Escalating doses of phenobarbital if refractory
– Propofol infusion for rescue
Crit Care Med 2007;35:724-30
Protocol Based Dose Escalation for
Benzodiazepine Resistant AWS
• Mechanical ventilation: 47% vs. 21% (p =
0.008)
– Pre-protocol: Inadequate sedation with standard
benzodiazepine doses
– Post-implementation: over-sedation (n = 1);
protocol non-compliance (n = 2)
• Mean diazepam dose
– Initial 24 hours: ~250 mg vs. ~500 mg (p = 0.001)
– Maximum dose: ~30 mg vs. ~ 90 mg (p < 0.001)
• Phenobarbital use: 17% vs. 58% (p < 0.001)
Crit Care Med 2007;35:724-30
Which of the following has not been
associated with protocol based,
symptom-triggered benzodiazepine
use in the management of AWS?
a. Reduction in benzodiazepine requirement
b. Shortened duration of treatment
c. Decreased need for mechanical ventilation
d. Increased incidence of progression of AWS
Benefits of Individualized Standard
AWS Treatment Protocols
• Reduction in benzodiazepine use
• Decreased treatment complications
– Over-sedation
– Need for mechanical ventilation
• Shortened duration of treatment and length
of stay
• Reduction in need for ICU admission
• Decreased treatment costs
Intensive Care Med 2013;39:16-30
Adjunctive Treatments for AWS
• Propofol
• α-adrenergic agonists
– Dexmedetomidine
– Clonidine
• Antipsychotics
– Haloperidol
• Anticonvulsants
– Valproic acid
– Carbamazepine
Crit Care Clin 2008;24:767-88
Crit Care Med 2013;41:S57-68
Intensive Care Med 2013;39:16-30
Aust Crit Care 2011;24:110-6
Symptom Oriented AWS Treatment
• Observational study of 38 surgical patients
who developed AWS
– Compared cohorts before and after
implementation of standard treatment protocol
– Patient evaluation classified symptoms into three
types
– Protocol emphasized treatment directed by AWS
symptom type
Arch Otolaryngol Head Neck Surg 2008;134:865-72
Symptom Oriented AWS Treatment
Arch Otolaryngol Head Neck Surg 2008;134:865-72
Symptom Oriented AWS Treatment
• Type A symptoms (CNS Excitation)
– Lorazepam 1-2 mg IV Q1hr as needed
• Type B symptoms (Adrenergic Hyperactivity)
– Clonidine 0.2 mg Q3hr x 2 as needed
• Type C symptoms (Delirium)
– Haloperidol 2-5 mg IV Q2hr as needed
Arch Otolaryngol Head Neck Surg 2008;134:865-72
Symptom Oriented AWS Treatment
• No significant change in length of stay after
protocol implementation
• Decreased rates of escalation in care
– 29% vs. 4% (p = 0.03)
• Lower rates of delirium and violence
– 79% vs. 29% (p=0.004)
– 36% vs. 8 % (P=0.04)
• No significant difference in medication use
Arch Otolaryngol Head Neck Surg 2008;134:865-72
Impact of Symptom Oriented Bolus
vs. Continuous Adjunctive Treatment
• Randomized, controlled trial of 48 surgical
patients who developed AWS
– Randomized to adjunctive medication via
symptom oriented bolus vs. continuous infusion
– All patients received continuous infusion
benzodiazepines
Intensive Care Med 2003;29:2230-8
Impact of Symptom Oriented Bolus
vs. Continuous Adjunctive Treatment
Intensive Care Med 2003;29:2230-8
Impact of Symptom Oriented Bolus
vs. Continuous Adjunctive Treatment
• Increased medication with continuous
infusion
– Clonidine: 1,270 vs. 61,098 mcg (p < 0.001)
– Haloperidol: 180 vs. 1,713 mg (p < 0.001)
– Flunitrazepam: 69.7 vs. 162 mg (p < 0.001)
Intensive Care Med 2003;29:2230-8
Impact of Symptom Oriented Bolus
vs. Continuous Adjunctive Treatment
• Decreased need for mechanical ventilation
with symptom oriented bolus treatment
– Incidence: 90% vs. 65% (p = 0.05)
– Duration: 12 vs. 6 days (p < 0.001)
• Decreased treatment duration with symptom
oriented bolus treatment
– 6 vs. 2 days (p < 0.001)
Intensive Care Med 2003;29:2230-8
Impact of Symptom Oriented Bolus
vs. Continuous Adjunctive Treatment
Intensive Care Med 2003;29:2230-8
Use of Symptom Oriented Adjunctive
Treatment for AWS
• Decrease in benzodiazepine requirement
• Decreased severity of withdrawal and need for
care escalation
• May be due to symptom oriented treatment
or timely management guided by protocol
• Most benefit observed when used as needed
guided by symptom oriented protocol
Propofol in Refractory AWS
• Commonly used as a “rescue” medication
• GABA-A agonist and NMDA antagonist
• Short half-life and predictable metabolism
• Bolus and continuous infusion
• Adverse Effects
–
–
–
–
Respiratory suppression
Hemodynamic depression
Hypertriglyceridemia
Propofol-related infusion syndrome
Crit Care Med 2010;38[suppl.]:S494-501
Crit Care Med 2013;41:S57-68
Am J Emerg Med 2013;31:734-42
Propofol in Refractory AWS
• Several case reports describing use of propofol
in benzodiazepine resistant AWS
– Prevented further seizures and successfully
sedated patient refractory to > 150 mg diazepam
– Provided successful sedation in four patients
refractory to > 1,000 mg lorazepam over 3-4 days
– Provided successful sedation in three patients
refractory to lorazepam > 10 mg/hr
Ann Emerg Med 1997;30:825-8
Crit Care Med 2000;28:1781-4
Emerg Med J 2004;21:632-4
Propofol in Refractory AWS
• Retrospective, single-cohort study of propofol in
15 patients with benzodiazepine resistant AWS
– Persistent agitation and delirium after diazepam 1-2 g
• Propofol infusion titrated to deep sedation
– Mean awakening time after discontinuation: 3.4 days
• 80% of patients symptom free after awakening
– Three patients with persistent delirium for 5-11 days
• No progression of AWS after initiation of propofol
Dan Med J 2014;61:A4807
Propofol vs. Benzodiazepines in
Benzodiazepine Resistant AWS
• Retrospective study of 64 patients with AWS
requiring mechanical ventilation
– Propofol: 72%
• 83% with supplemental benzodiazepine
– Benzodiazepine monotherapy: 28%
Ann Pharmacother 2014;48:456-61
Propofol vs. Benzodiazepines in
Benzodiazepine Resistant AWS
• No significant difference in outcomes
– Duration of withdrawal: 8 vs. 7 days
– Hospital length of stay: 9 vs.10 days
– Duration of mechanical ventilation: 4 vs. 3 days
• Post-hoc analysis of propofol monotherapy
demonstrated no difference in outcomes
Ann Pharmacother 2014;48:456-61
Propofol vs. Benzodiazepines in
Benzodiazepine Resistant AWS
• Retrospective study of 66 patients in
benzodiazepine resistant AWS
– Comparison of benzodiazepine monotherapy vs.
propofol infusion
• Benzodiazepine requirement 7 days postresistant AWS designation
– 576.7 vs. 743.3 mg diazepam equivalents (NS)
• Incidence of mechanical ventilation
– 42.4% vs. 100% (p < 0.001)
Drug Alcohol Depend 2015;154:296-9
Propofol vs. Benzodiazepines in
Benzodiazepine Resistant AWS
• Length of stay
– ICU: 4 vs. 10 days (p < 0.001)
– Hospital: 6.7 vs. 16.2 days (p < 0.001)
• Duration of AWS
– 5 vs. 7 days (p = 0.025)
• Nosocomial pneumonia
– 3% vs. 36.4% (p = 0.001)
• No complications of AWS after initiation of
propofol
Drug Alcohol Depend 2015;154:296-9
Which of the following is true
regarding the use of propofol in
patients with refractory AWS?
a. Successful treatment with propofol has been
described in benzodiazepine refractory patients
b. In mechanically ventilated patients, propofol has
not been shown to improve patient outcomes
c. The use of propofol may be limited by the need
for mechanical ventilation
d. All of the above
Propofol vs. Benzodiazepines in
Benzodiazepine Resistant AWS
• Propofol may provide alternative to
benzodiazepines among patients requiring
mechanical ventilation
– No documented progression of AWS
• Propofol associated with worse outcomes
when compared to benzodiazepines in nonmechanically ventilated patients
– Selection bias for higher AWS severity?
– Likely associated with need for mechanical
ventilation
Dexmedetomidine in Refractory AWS
• Several reports of use for adjunctive sedation
• Centrally acting α2 agonist
– Sympatholytic
– Anxiolytic
– No respiratory depression
– No GABA-A activity
• Short half-life and easily titratable
Crit Care Med 2013;41:S57-68
Dexmedetomidine in Refractory AWS
• Case report of control of agitation after persistent
agitation with benzodiazepine infusion
– Rapid discontinuation of benzodiazepine infusion after
dexmedetomidine started
– Transferred out of ICU on day 3
• Case series of ten patients with refractory AWS
– Three treatment failures
– Three patients required mechanical ventilation
– No patients with significant hemodynamic instability
or development of withdrawal seizures
Ann Pharmacother 2008;42:1703-5
J Anesth 2012;26:601-5
Dexmedetomidine in Refractory AWS
• Retrospective descriptive studies evaluating
use of dexmedetomidine in severe AWS
– Reduction in benzodiazepine requirement by 6070%
– Reduction in AWS severity by ~20%
– Normalization of hemodynamics
• ~80% increase in time with HR < 100
• ~40% decrease in time with SBP < 140
– Mechanical ventilation required in four patients
– Significant hemodynamic depression in ~10%
Ann Intensive Care 2012;2:12
J Crit Care 2014;29:298-302
Dexmedetomidine in Refractory AWS
• Retrospective study of 61 non-intubated patients with
severe AWS
– Compared benzodiazepine infusion vs. dexmedetomidine
• Median cumulative dose of benzodiazepine
– 105 vs. 3.5 mg (p < 0.01)
• No significant difference in outcomes
– Development of withdrawal seizures
– Need for mechanical ventilation
– Length of stay
• Hemodynamic adverse effects
– ~15% vs. ~45% (p < 0.01)
Pharmacotherapy 2014;34:910-7
Dexmedetomidine in Refractory AWS
• Randomized, controlled of 24 patients with
severe AWS
– Assessed adjunct dexmedetomidine to symptomtriggered treatment with benzodiazepines
– Randomized to one of three groups:
• Placebo
• Low dose (0.4 mcg/kg/hr)
• High dose (1.2 mcg/kg/hr)
Crit Care Med 2014;42:1131-9
Dexmedetomidine in Refractory AWS
• Reduction in benzodiazepine dose post-initiation
– -8 vs. -56.4 mg (p = 0.037)
• Post-initiation total benzodiazepine requirement
– 109.1 vs. 58.1 (NS)
• No dose-response relationship identified
• Adverse effects
– Bradycardia: 0% vs. 25% (NS)
– Hypotension: 0% vs. 19% (NS)
• No patients required mechanical ventilation after
initiation of study drug
Crit Care Med 2014;42:1131-9
All of the following benefits have
been seen with dexmedetomidine use
in AWS except:
a. Decrease in benzodiazepine requirement
b. Decreased need for mechanical ventilation
c. Improvement in adrenergic symptoms of
AWS
d. Reduction in AWS severity score
Dexmedetomidine in Refractory AWS
• Potential benefits for use as adjunct
– Decreased benzodiazepine requirement
– Improved hemodynamics among patients with
significant hyperadrenergic symptoms
– No respiratory depression
• No data demonstrating improved outcomes
compared with benzodiazepines
– Impact on length of stay
– Impact on need for mechanical ventilation
Dexmedetomidine in Refractory AWS
• On-going randomized controlled trial
– Patients requiring ICU admission for severe AWS
• Dexmedetomidine vs. placebo
• Goal enrollment: 150 patients
• Primary outcome
– ICU length of stay
• Anticipated completion: 2017
ClinicalTrials.gov. NCT01362205
Summary
• Benzodiazepines are the gold standard
intervention for treatment of AWS
– No single benzodiazepine has demonstrated
superiority over another
• Symptom-triggered benzodiazepines have
shown significant improvements in outcomes
– Decreased benzodiazepine requirement
– Decreased treatment duration and length of stay
Summary
• Standard protocols, validated monitoring
tools, and staff education are essential for
symptom-triggered management
• Management of AWS in critical care is often
complicated by benzodiazepine resistance
Summary
• Propofol may provide alternative in refractory
patients
– Primary limitation is requirement for mechanical
ventilation
• Dexmedetomidine shows promise as adjunct
– No data showing improvements in important
clinical endpoints compared with benzodiazepines
– Future studies may elucidate role in management
of AWS in critically ill
Questions?
What’s on Tap for the Treatment of
Alcohol Withdrawal?
Andrew Straznitskas, PharmD, BCPS
Clinical Pharmacist,
Medical Intensive Care Unit
Bellevue Hospital Center
NYSCHP 2015 Critical Care Program: Downstate
October 2, 2015
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•
•
•
•
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•
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Williams ST. Pathophysiology of encephalopathy and delirium. J Clin
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Awissi DK, Lebrun G, Fagnan M, Skrobik Y. Alcohol, nicotine, and iatrogenic
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