Alcohol withdrawal: Difference between revisions

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==Background==
==Background==
*Withdrawal symptoms due to reduced GABA and increased NMDA receptors
*Withdrawal symptoms due to reduced GABA and increased NMDA receptors
*[[Benzodiazepines|Benzos]] useful due to cross tolerance at [[Ethanol toxicity|ethanol]] GABA receptor
*[[Benzodiazepines|Benzos]] useful due to cross tolerance at [[Ethanol toxicity|ethanol]] GABA receptor and longer half-life
*Symptom-triggered therapy
*Symptom-triggered therapy
**As effective as fixed dose therapy, but with more rapid detox
**As effective as fixed dose therapy, but with more rapid detox
===Benzodiazepine overview===
{| {{table}}
| align="center" style="background:#f0f0f0;"|'''Agents'''
| align="center" style="background:#f0f0f0;"|'''Equivalent PO dose (mg)'''
| align="center" style="background:#f0f0f0;"|'''Route'''
| align="center" style="background:#f0f0f0;"|'''Onset of Action (min)'''
| align="center" style="background:#f0f0f0;"|'''Half Life (hr)'''
| align="center" style="background:#f0f0f0;"|'''Metabolism'''
|-
| Chlordiazepoxide||25||PO, IV||30 - 120||7-28||CYP; active metabolites
|-
| Diazepam||5||PO, IV, IM||2 - 5||20-120||CYP; active metabolites
|-
| Lorazepam||1||PO, IM, IV||15-20||8-19||Glucuronidation
|}


==Clinical Features==
==Clinical Features==
*Reduction in alcohol use that has been heavy and prolonged
*Reduction in alcohol use that has been heavy and prolonged
*At least 2 of the following
*At least 2 of the following
**Autonomic hyperactivity (e.g., diaphoresis, HR>100)
**Autonomic hyperactivity (e.g., diaphoresis, [[tachycardia|HR>100)
**Increased hand tremor
**Increased hand [[tremor]]
**Insomnia
**[[Insomnia]]
**[[Nausea/vomiting]]
**[[Nausea/vomiting]]
**Transient visual, tactile, or auditory hallucinations
**Transient visual, tactile, or auditory [[hallucinations]]
**Psychomotor agitation
**Psychomotor agitation
**Anxiety
**[[Anxiety]]
**Grand mal [[seizures]]
**Grand mal [[seizures]]
===Tremulousness===
===Tremulousness===
*Onset after last drink: 6-12h
*Onset after last drink: 6-12h
===Seizures===
===[[alcohol withdrawal seizures|Seizures]]===
*Onset after last drink: 6-48h
*Onset after last drink: 6-48h
*Multiple seizures: 60% of patients
*Multiple seizures: 60% of patients
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===[[Delirium tremens]]===
===[[Delirium tremens]]===
*Onset after last drink: 48+hrs
*Onset after last drink: 48+hrs
*Decreased attention and awareness
*Disturbance in attention, awareness, memory, orientation, language, perception, visouspatial ability that fluctuates in severity
*No evidence of coma or other evolving neurocognitive disorders


==Differential Diagnosis==
==Differential Diagnosis==
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==Evaluation==
==Evaluation==
*Consider workup for alternate etiologies if clinical presentation unclear
*Consider workup to evaluate any symptoms that led patient to stop drinking (e.g. did patient stop in setting of feeling unwell due to [[abdominal pain]], [[pneumonia]], etc.?)
{{CIWA score}}
{{CIWA score}}


==Inpatient Management==
==Inpatient Management==
''Start aggressive [[Benzodiazepines|Benodiazepine]] therapy at CIWA score of 8. Consider ICU admission with score >20''
''Start aggressive [[Benzodiazepines|Benodiazepine]] therapy at CIWA score of 8. Consider ICU admission with score >20''
===Benzodiazepine overview===
{| {{table}}
| align="center" style="background:#f0f0f0;"|'''Agents'''
| align="center" style="background:#f0f0f0;"|'''Equivalent PO dose (mg)'''
| align="center" style="background:#f0f0f0;"|'''Route'''
| align="center" style="background:#f0f0f0;"|'''Onset of Action (min)'''
| align="center" style="background:#f0f0f0;"|'''Half Life (hr)'''
| align="center" style="background:#f0f0f0;"|'''Metabolism'''
|-
| Chlordiazepoxide||25||PO, IV||30 - 120||7-28||CYP; active metabolites
|-
| Diazepam||5||PO, IV, IM||2 - 5||20-120||CYP; active metabolites
|-
| Lorazepam||1||PO, IM, IV||15-20||8-19||Glucuronidation
|}


===[[Benzodiazepines]]===
===[[Benzodiazepines]]===
*[[Diazepam]] (Valium) 5-10mg IV (depending on severity)
*[[Diazepam]] (Valium) 5-10 mg IV (depending on severity)
**May repeat q5-10min for severe withdrawal (double dose until desired effect achieved)
**May repeat q5-10 min for severe withdrawal (may increase dose by 10 mg every 5-10 min until desired effect achieved, max dose of 200 mg)
**Half-life 20-100h (long acting)
**Half-life 20-100 h (long acting)
*[[Lorazepam]] (Ativan) 1-4mg IV (depending on severity)
*[[Lorazepam]] (Ativan) 1-4mg IV (depending on severity)
**May repeat q15-20min for severe withdrawal (titrated to effect)
**May repeat q15-20 min for severe withdrawal (titrated to effect)
**Rarely causes hepatitis, as opposed to diazepam which may cause a cholestatic hepatitis<ref>National Institute of Diabetes and Digestive and Kidney Diseases. Lorazepam Drug Record. http://livertox.nih.gov/Lorazepam.htm</ref>
**Rarely causes hepatitis, as opposed to diazepam which may cause a cholestatic hepatitis<ref>National Institute of Diabetes and Digestive and Kidney Diseases. Lorazepam Drug Record. http://livertox.nih.gov/Lorazepam.htm</ref>
**Half-life 10-20h (medium acting)
**Half-life 10-20 h (medium acting)
 
===[[Propofol]]===
*If patient does not respond to high doses of [[benzodiazepines]]
*0.3-1.25 mg/kg up to 4 mg/kg/hr (consider intubation), for up to 48 hours


===α-2 agonists ([[Dexmedetomidine]])===
===α-2 agonists ([[Dexmedetomidine]])===
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*Dexmedetomidine drip, start 0.2 mcg/kg/min, likely needing no more than 0.7 mcg/kg/min
*Dexmedetomidine drip, start 0.2 mcg/kg/min, likely needing no more than 0.7 mcg/kg/min


===[[Barbituates]] ([[Phenobarbital]])===
===[[Barbiturates]] ([[Phenobarbital]])===
*Used when refractory to [[benzodiazepines]]
*Used when refractory to [[benzodiazepines]] (consider after patient has received equivalent of 200 mg diazepam)
*[[Phenobarbital]] 130-260mg IV q 15-20 minutes
*[[Phenobarbital]] 130-260 mg IV q 15-20 minutes
*Can also be used as a first line load at 10 mg/kg prior to giving benzodiazepines to decrease benzodiazepine requirements and ICU admissions <ref> Rosenson J, et al. Phenobarbital for acute alcohol withdrawal: a prospective randomized double-blind placebo-controlled study. J Emerg Med. 2013; 44(3):592-598.</ref>
*Can also be used as a first line load at 10 mg/kg prior to giving benzodiazepines to decrease benzodiazepine requirements and ICU admissions <ref> Rosenson J, et al. Phenobarbital for acute alcohol withdrawal: a prospective randomized double-blind placebo-controlled study. J Emerg Med. 2013; 44(3):592-598.</ref>


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*50mg of chlordiazepoxide every 8 hours for two days, then decrease to 25mg every 8 hours for another two days followed by 25mg PRN as needed.
*50mg of chlordiazepoxide every 8 hours for two days, then decrease to 25mg every 8 hours for another two days followed by 25mg PRN as needed.


===Anticonvulsants===
===[[Anticonvulsants]]===
*Have less abuse potential but may not prevent seizures<ref>Muncie HL et al. Outpatient Management of Alcohol Withdrawal Syndrome. Am Fam Physician. 2013 Nov 1;88(9):589-595.</ref>
*Have less abuse potential but may not prevent seizures<ref>Muncie HL et al. Outpatient Management of Alcohol Withdrawal Syndrome. Am Fam Physician. 2013 Nov 1;88(9):589-595.</ref>
*[[Gabapentin]] 400mg PO TID<ref>Leung JG, Hall-Flavin D, Nelson S, et al. The role of gabapentin in the management of alcohol withdrawal and dependence. Ann Pharmacother. 2015; 49(8):897-906.</ref>
*[[Gabapentin]] 400mg PO TID<ref>Leung JG, Hall-Flavin D, Nelson S, et al. The role of gabapentin in the management of alcohol withdrawal and dependence. Ann Pharmacother. 2015; 49(8):897-906.</ref>
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===Admit===
===Admit===
*Multiple [[seizures]]
*Multiple [[seizures]]
*DTs
*[[delirium tremens|DTs]]
*Decreased LOC
*[[AMS|Decreased LOC]]
*Inability to control withdrawal after administrating 3-4 doses of benzo's
*Inability to control withdrawal after administrating 3-4 doses of benzo's
*Consider ICU admission with CIWA score >20
*Consider ICU admission with CIWA score >20


===Discharge===
===Discharge===
*Consider discharge [[EBQ:Outpatient use of benzodiazepines for the treatment of acute alcohol withdrawl|with 3 day course of benzodiazepines if patients are attempting to quit alcohol]]
*Two consecutive CIWA scores (two hours apart) <10 with resolution of tremor
*Consider discharge [[EBQ:Outpatient use of benzodiazepines for the treatment of acute alcohol withdrawl|with 3 day course of benzodiazepines if patients are attempting to quit alcohol]] (controversial)
*Consider possible exclusions for outpatient treatment<ref>Myrick et al. A DOUBLE BLIND TRIAL OF GABAPENTIN VS. LORAZEPAM IN THE TREATMENT OF ALCOHOL WITHDRAWAL. Alcohol Clin Exp Res. 2009 Sep; 33(9): 1582–1588. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769515/</ref>:
*Consider possible exclusions for outpatient treatment<ref>Myrick et al. A DOUBLE BLIND TRIAL OF GABAPENTIN VS. LORAZEPAM IN THE TREATMENT OF ALCOHOL WITHDRAWAL. Alcohol Clin Exp Res. 2009 Sep; 33(9): 1582–1588. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769515/</ref>:
**Substance use disorders except alcohol, nicotine, or cannabis
**Substance use disorders except alcohol, nicotine, or cannabis

Revision as of 16:12, 10 October 2019

Background

  • Withdrawal symptoms due to reduced GABA and increased NMDA receptors
  • Benzos useful due to cross tolerance at ethanol GABA receptor and longer half-life
  • Symptom-triggered therapy
    • As effective as fixed dose therapy, but with more rapid detox

Clinical Features

  • Reduction in alcohol use that has been heavy and prolonged
  • At least 2 of the following

Tremulousness

  • Onset after last drink: 6-12h

Seizures

  • Onset after last drink: 6-48h
  • Multiple seizures: 60% of patients
  • Progression to DTs: 33% of patients
  • Treat with benzos (not phenytoin)

Alcoholic Hallucinosis

  • Onset after last drink: 12-24hr
  • Visual hallucinations are most common
  • Different from delirium tremens
    • Resolves within 24-48 from last drink (before onset of DTs)
    • No delirium
    • Normal vital signs

Delirium tremens

  • Onset after last drink: 48+hrs
  • Decreased attention and awareness
  • Disturbance in attention, awareness, memory, orientation, language, perception, visouspatial ability that fluctuates in severity
  • No evidence of coma or other evolving neurocognitive disorders

Differential Diagnosis

Ethanol related disease processes

Sedative/hypnotic withdrawal

Seizure

Evaluation

  • Consider workup for alternate etiologies if clinical presentation unclear
  • Consider workup to evaluate any symptoms that led patient to stop drinking (e.g. did patient stop in setting of feeling unwell due to abdominal pain, pneumonia, etc.?)

CIWA score

Clinical Institute Withdrawal Assessment – Alcohol – revised (CIWA-Ar)

  • Headache 0-7
  • Orientation 0-4
  • Tremor 0-7
  • Sweating 0-7
  • Anxiety 0-7
  • Nausea (and Vomiting) 0-7
  • Tactile Hallucinations 0-7
  • Auditory Hallucinations 0-7
  • Visual Hallucinations 0-7
  • Agitation 0-7

Maximum Score = 67

  • <8: Typically do not require medication
  • 8-19: Medication
  • ≥20: Medication and admission

Inpatient Management

Start aggressive Benodiazepine therapy at CIWA score of 8. Consider ICU admission with score >20

Benzodiazepine overview

Agents Equivalent PO dose (mg) Route Onset of Action (min) Half Life (hr) Metabolism
Chlordiazepoxide 25 PO, IV 30 - 120 7-28 CYP; active metabolites
Diazepam 5 PO, IV, IM 2 - 5 20-120 CYP; active metabolites
Lorazepam 1 PO, IM, IV 15-20 8-19 Glucuronidation

Benzodiazepines

  • Diazepam (Valium) 5-10 mg IV (depending on severity)
    • May repeat q5-10 min for severe withdrawal (may increase dose by 10 mg every 5-10 min until desired effect achieved, max dose of 200 mg)
    • Half-life 20-100 h (long acting)
  • Lorazepam (Ativan) 1-4mg IV (depending on severity)
    • May repeat q15-20 min for severe withdrawal (titrated to effect)
    • Rarely causes hepatitis, as opposed to diazepam which may cause a cholestatic hepatitis[1]
    • Half-life 10-20 h (medium acting)

Propofol

  • If patient does not respond to high doses of benzodiazepines
  • 0.3-1.25 mg/kg up to 4 mg/kg/hr (consider intubation), for up to 48 hours

α-2 agonists (Dexmedetomidine)

  • Decrease severity of symptoms, but only supplemental to GABA-ergic first-lines
  • Dexmedetomidine drip, start 0.2 mcg/kg/min, likely needing no more than 0.7 mcg/kg/min

Barbiturates (Phenobarbital)

  • Used when refractory to benzodiazepines (consider after patient has received equivalent of 200 mg diazepam)
  • Phenobarbital 130-260 mg IV q 15-20 minutes
  • Can also be used as a first line load at 10 mg/kg prior to giving benzodiazepines to decrease benzodiazepine requirements and ICU admissions [2]

Ketamine

  • May have some use in refractory cases
  • Blocks the NMDA receptor which is excited an unregulated. [3]

Vitamin Prophylaxis for Chronic alcoholics

  • At risk for thiamine deficiency, but no symptoms: thiamine 100mg PO q day
  • Give multivitamin PO; patient at risk for other vitamin deficiencies

Banana bag

The majority of chronic alcoholics do NOT require a banana bag[4][5]

Special Situations

Outpatient Management

Don’t use phenytoin or fosphenytoin to treat seizures caused by drug toxicity or drug withdrawal.[7]

Chlordiazepoxide

Generally for outpatient treatment of mild cases and as a taper

  • 25-50mg of chlordiazepoxide is equivalent to 10mg of diazepam
  • 50mg of chlordiazepoxide every 8 hours for two days, then decrease to 25mg every 8 hours for another two days followed by 25mg PRN as needed.

Anticonvulsants

  • Have less abuse potential but may not prevent seizures[8]
  • Gabapentin 400mg PO TID[9]
    • Some protocols call for higher dosing - 600 or 800mg x1
    • Similar efficacy to lorazepam in decreasing craving and anxiety[10]
    • Questionable efficacy in preventing alcohol withdrawal seizures
  • Carbamazepine taper[11]
    • May start when BAL < 150 mg/dL
    • Varying evidence in support of whether agent truly reduces of alcohol withdrawal seizures and delirium tremens
    • 800 mg per day be fixed or tapered over 5-9 days

Example outpatient lorazepam taper

  • 2 mg tid x3 days
  • 2 mg BID on day 4
  • 2 mg once on day 5

Example outpatient gabapentin taper

  • 400 mg TID x3 days
  • 300 mg BID on day 4
  • 300 mg once on day 5

Example outpatient carbamazepine taper

  • 200 mg q6hr day 1
  • 200 mg q8hr day 2
  • 200 mg q12hr day 3
  • 200 mg QD days 4 and 5

Disposition

Admit

  • Multiple seizures
  • DTs
  • Decreased LOC
  • Inability to control withdrawal after administrating 3-4 doses of benzo's
  • Consider ICU admission with CIWA score >20

Discharge

  • Two consecutive CIWA scores (two hours apart) <10 with resolution of tremor
  • Consider discharge with 3 day course of benzodiazepines if patients are attempting to quit alcohol (controversial)
  • Consider possible exclusions for outpatient treatment[12]:
    • Substance use disorders except alcohol, nicotine, or cannabis
    • Major Axis I psych disorder
    • Medication history of benzodiazepines, beta-blockers, calcium-channel blockers, antipsychotics
    • History of head injury, epilepsy, medical instability, ECG abnormality, grossly abnormal lab value

See Also

External Links

References

  1. National Institute of Diabetes and Digestive and Kidney Diseases. Lorazepam Drug Record. http://livertox.nih.gov/Lorazepam.htm
  2. Rosenson J, et al. Phenobarbital for acute alcohol withdrawal: a prospective randomized double-blind placebo-controlled study. J Emerg Med. 2013; 44(3):592-598.
  3. Wong, A et al. Evaluation of adjunctive ketamine to benzodiazepines for management of alcohol withdrawal syndrome. Ann Pharmacother. 2015 Jan;49(1):14-9. PMID: 25325907
  4. Krishel, S, et al. Intravenous Vitamins for Alcoholics in the Emergency Department: A Review. The Journal of Emergency Medicine. 1998; 16(3):419–424.
  5. Li, SF, et al. Vitamin deficiencies in acutely intoxicated patients in the ED. The American Journal of Emergency Medicine. 2008; 26(7):792–795.
  6. Arroliga AC, Shehab N, McCarthy K, Gonzales JP. Relationship of continuous infusion lorazepam to serum propylene glycol concentration in critically ill adults*. Critical Care Medicine. 2004;32(8):1709–1714. doi:10.1097/01.CCM.0000134831.40466.39.
  7. Choosing Wisely. American College of Medical Toxicology and The American Academy of Clinical Toxicology. http://www.choosingwisely.org/clinician-lists/acmt-and-aact-phenytoin-or-fosphenytoin-to-treat-seizures/
  8. Muncie HL et al. Outpatient Management of Alcohol Withdrawal Syndrome. Am Fam Physician. 2013 Nov 1;88(9):589-595.
  9. Leung JG, Hall-Flavin D, Nelson S, et al. The role of gabapentin in the management of alcohol withdrawal and dependence. Ann Pharmacother. 2015; 49(8):897-906.
  10. Myrick, H et al. A double-blind trial of gabapentin versus lorazepam in the treatment of alcohol withdrawal. Alcohol Clin Exp Res. 2009 Sep;33(9):1582-8. PMID: 19485969
  11. Barrons R et al. The role of carbamazepine and oxcarbazepine in alcohol withdrawal syndrome. J Clin Pharm Ther. 2010 Apr;35(2):153-67.
  12. Myrick et al. A DOUBLE BLIND TRIAL OF GABAPENTIN VS. LORAZEPAM IN THE TREATMENT OF ALCOHOL WITHDRAWAL. Alcohol Clin Exp Res. 2009 Sep; 33(9): 1582–1588. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769515/