Alcohol withdrawal: Difference between revisions

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==Background==
==Background==
*Withdrawal symptoms due to reduced GABA and increased glutamate
*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
*Don’t use [[phenytoin]] or [[fosphenytoin]] to treat seizures caused by drug toxicity or drug withdrawal.<ref>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/</ref>


==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]]
===Seizures===
===Tremulousness===
*Onset after last drink: 6-12h
===[[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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**No delirium
**No delirium
**Normal vital signs
**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==
==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''
 
{{Inpatient management of ETOH withdrawal}}
===[[Benzodiazepines]]===
{{Vitamin prophylaxis for ETOH}}
*[[Diazepam]] (Valium) 5-10mg IV (depending on severity)
**May repeat q5-10min for severe withdrawal (double dose until desired effect achieved)
**Half-life 20-100h (long acting)
*[[Lorazepam]] (Ativan) 1-4mg IV (depending on severity)
**May repeat q15-20min 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>
**Half-life 10-20h (medium acting)
 
===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
 
===[[Barbituates]] ([[Phenobarbital]])===
*Used when refractory to [[benzodiazepines]]
*[[Phenobarbital]] 130-260mg 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>
 
===[[Ketamine]]===
*May have some use in refractory cases
*Blocks the NMDA receptor which is excited an unregulated. <ref>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</ref>
 
===Nutritional supplementation===
*Banana bag
**[[Thiamine]] 100mg IV
**[[Folate]] 1mg IV (cheaper PO)
**Multivitamin 1 tab IV (cheaper PO)
**[[Magnesium sulfate]] 2mg IV
**Normal saline as needed for hydration
 
===Special Situations===
*The propylene glycol diluent in [[lorazepam]], [[phenobarbital]], and [[diazepam]], may induce a hyperosmolar anion gap [[metabolic acidosis]] if given as a drip in high doses ≥ 48hrs.<ref>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.</ref>  Consider alternatives such as [[propofol]] or [[dexmedetomidine]] if patients need long term sedation for [[delirium tremens]].


==Outpatient Management==
==Outpatient Management==
''Don’t use [[phenytoin]] or [[fosphenytoin]] to treat seizures caused by drug toxicity or drug withdrawal.''<ref>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/</ref>
===[[Chlordiazepoxide]]===
===[[Chlordiazepoxide]]===
'''Generally for outpatient treatment of mild cases and as a taper'''
'''Generally for outpatient treatment of mild cases and as a taper'''
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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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**800 mg per day be fixed or tapered over 5-9 days
**800 mg per day be fixed or tapered over 5-9 days


====Example outpatient [[lorazepam]] taper====
===DHS Expected Practice Example Tables (2020)<ref>LA County DHS Expected Practice Example Tables (2020). Available at: https://lacounty.sharepoint.com/sites/dhs-ccl/Addiction%20Medicine/Forms/AllItems.aspx?id=%2Fsites%2Fdhs%2Dccl%2FAddiction%20Medicine%2FOutpatient%20Medication%20Management%20of%20Alcohol%20Use%20Disorder%2Epdf&parent=%2Fsites%2Fdhs%2Dccl%2FAddiction%20Medicine</ref>===
*2 mg tid x3 days
{| {{table}}
*2 mg BID on day 4
| align="center" style="background:#f0f0f0;"|'''Days'''
*2 mg once on day 5
| align="center" style="background:#f0f0f0;"|'''Carbemazepine Montherapy'''
 
|-
====Example outpatient [[gabapentin]] taper====
| 1-3 ||200mg QID
''Similar in efficacy to lorazepam according to one RCT<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>''
|-
*400 mg TID x3 days
| 4-6||200mg TID
*300 mg BID on day 4
|-
*300 mg once on day 5
| 7-9||200mg BID
|-
| 10-11||200mg QHS
|-
|}


====Example outpatient [[carbamazepine]] taper====
{| {{table}}
*200 mg q6hr day 1
| align="center" style="background:#f0f0f0;"|'''Days'''
*200 mg q8hr day 2
| align="center" style="background:#f0f0f0;"|'''Gabapentin Monotherapy'''
*200 mg q12hr day 3
|-
*200 mg QD days 4 and 5
| 1||1,200mg BID plus 1,200mg x 1 PRN
|-
| 2-7||600mg TID plus 600mg x 1 PRN
|-
| 8||300mg TID
|-
| 9||300mg BID
|-
| 10||300mg QHS
|-
|}


==Disposition==
==Disposition==
===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
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==External Links==
==External Links==
*[http://www.mdcalc.com/ciwa-ar-for-alcohol-withdrawal/#about-calculator MDCalc - CIWA-AR Calculator]
*[http://www.mdcalc.com/ciwa-ar-for-alcohol-withdrawal/#about-calculator MDCalc - CIWA-AR Calculator]
*Link to [https://lacounty.sharepoint.com/sites/dhs-ccl/Addiction%20Medicine/Forms/AllItems.aspx?id=%2Fsites%2Fdhs%2Dccl%2FAddiction%20Medicine%2FOutpatient%20Medication%20Management%20of%20Alcohol%20Use%20Disorder%2Epdf&parent=%2Fsites%2Fdhs%2Dccl%2FAddiction%20Medicine DHS Expected Practice]
*LA County Substance Abuse Service Helpline: 844-804-7500


==References==
==References==

Revision as of 09:27, 24 October 2020

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
  • Don’t use phenytoin or fosphenytoin to treat seizures caused by drug toxicity or drug withdrawal.[1]

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[2]
    • Half-life 10-20 h (medium acting)

Other Agents

For use in cases refractory to benzodiazepine treatment

  • 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
  • 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 [3]
  • α-2 agonists (Dexmedetomidine)
    • Decrease severity of symptoms, but only supplemental to GABA-ergic first-lines
    • Dexmedetomidine drip, start 0.2 mcg/kg/hr, likely needing no more than 0.7 mcg/kg/hr[4]
  • Ketamine
    • May have some use in refractory cases
    • Blocks the NMDA receptor which is excited an unregulated. [5]

Special Situations

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[7][8]

Outpatient Management

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[9]
  • Gabapentin 400mg PO TID[10]
    • Some protocols call for higher dosing - 600 or 800mg x1
    • Similar efficacy to lorazepam in decreasing craving and anxiety[11]
    • Questionable efficacy in preventing alcohol withdrawal seizures
  • Carbamazepine taper[12]
    • 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

DHS Expected Practice Example Tables (2020)[13]

Days Carbemazepine Montherapy
1-3 200mg QID
4-6 200mg TID
7-9 200mg BID
10-11 200mg QHS
Days Gabapentin Monotherapy
1 1,200mg BID plus 1,200mg x 1 PRN
2-7 600mg TID plus 600mg x 1 PRN
8 300mg TID
9 300mg BID
10 300mg QHS

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[14]:
    • 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. 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/
  2. National Institute of Diabetes and Digestive and Kidney Diseases. Lorazepam Drug Record. http://livertox.nih.gov/Lorazepam.htm
  3. 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.
  4. Rayner SG, et al. Dexmedetomidine as adjunct treatment for severe alcohol withdrawal in the ICU. Ann Intensive Care. 2012; 2: 12. Published online 2012 May 23. doi: 10.1186/2110-5820-2-12.
  5. 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
  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. Krishel, S, et al. Intravenous Vitamins for Alcoholics in the Emergency Department: A Review. The Journal of Emergency Medicine. 1998; 16(3):419–424.
  8. Li, SF, et al. Vitamin deficiencies in acutely intoxicated patients in the ED. The American Journal of Emergency Medicine. 2008; 26(7):792–795.
  9. Muncie HL et al. Outpatient Management of Alcohol Withdrawal Syndrome. Am Fam Physician. 2013 Nov 1;88(9):589-595.
  10. 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.
  11. 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
  12. Barrons R et al. The role of carbamazepine and oxcarbazepine in alcohol withdrawal syndrome. J Clin Pharm Ther. 2010 Apr;35(2):153-67.
  13. LA County DHS Expected Practice Example Tables (2020). Available at: https://lacounty.sharepoint.com/sites/dhs-ccl/Addiction%20Medicine/Forms/AllItems.aspx?id=%2Fsites%2Fdhs%2Dccl%2FAddiction%20Medicine%2FOutpatient%20Medication%20Management%20of%20Alcohol%20Use%20Disorder%2Epdf&parent=%2Fsites%2Fdhs%2Dccl%2FAddiction%20Medicine
  14. 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/