Alcohol withdrawal syndrome (AWS) is a disease commonly treated in the emergency department, with
~5% of cases leading to delirium tremens.
- In patients with a history of AWS, decreased GABA-A receptor sensitivity to GABA agonists may cause
benzodiazepine (BZD) monotherapy to be ineffective. - Patients may experience increase in morbidity and mortality due to escalated doses of benzodiazepines.
- There are likely a subset of patients that respond poorly to benzodiazepines, therefore requiring alternative
mechanisms to treat AWS. - Phenobarbital (PB) has some theoretical benefits over benzodiazepines alone from a mechanistic
perspective.
a. Chronic alcohol use leads to down regulation of GABA-A receptors and up-regulation of NMDA
receptors.
b. Abrupt withdrawal of alcohol use leads to greater NMDA receptor-mediated excitatory activity,
which may be inhibited more effectively with phenobarbital rather than benzodiazepines.
Pharmacology | |
Dose | Prior to benzodiazepines 5-10 mg/kg over 30 minutes Can split up into multiple doses if concerned about respiratory depression After receiving benzodiazepines • 130-260 mg PRN Q30 minutes to clinical effect(Max ~10-15 mg/kg) |
Mechanism of Action | Bind to the GABA receptor at a different binding site than BZDs, increasing the time the GABA-mediated chloride channels remain open. • inhibitor of excitatory AMPA glutamates receptors |
Formulations | IV/IM/PO |
PK/PD | Onset: IV ~5 minutes Duration: 6-12 hours Half-life: 80-120 hours Renal Excretions: 21% Therapeutic Blood levels: 15-40 ug/mL |
Adverse Effects | Hypotension, respiratory depression, ataxia, lethargy |
Drug Interactions and warnings | Warning with loading doses in patient that are hypotensive and received large doses of benzodiazepines |
Compatibility | Compatible with NS, D5W, and LR |
Overview of Evidence | |||
Author, year | Design/ sample size | Intervention & Comparison | Outcome |
Ibarra, 2019 | Retrospective observational/ n=78 | Lorazepam protocol only (LZP) PB x 1 + LZP protocol (PB+LZP) | No difference in daily lorazepam requirements or hospital LOS PB+LZP group had ↑ pts d/c within 72 hrs No patient in PB group experience intubation or hypotension |
Nisavic, 2019 | Retrospective observational/ n=562 | BZD only fixed dosing PB- Based Protocol (IM load + PO taper) | No difference in AWS-related seizures , ICU admission, over-sedation, LOS, and hallucinations ↑ Delirium in BZP group In BZPà PB crossover pts, PB led to rapid improvement of BZP resistant AWS symptoms |
Nelson, 2019 | Pre-post observational/ n=300 | IV diazepam alone (DZP) IV LZP + IV PB (LZP + PB) IV PB alone (PB) | No difference in ICU admission, ICU LOS, and need for intubation. PB associated with ↑ ED LOS but ↓ BZP requirements |
Tidwell, 2019 | Pre-post observational/ n=120 | BZD only CiWA- Protocol PB Taper ± Benzo PRN | PB ↓ ICU+ Hospital LOS PB↓ total lorazepam requirements PB had less patient intubated |
Sullivan, 2018 | Retrospective observational/ n=209 | BZD only CIWA- Protocol PB + BZD CIWA Protocol | No difference in ICU admission, intubation, hypotension, ED LOS, CIWA score at ED discharge PB group had ↓hospital LOS and Max CIWA score at 24 hrs |
Rosenson, 2013 | RCT/ n=102 | PB 10 mg/kg IV x1 + PRN benzodiazepines Placebo + PRN benzodiazepines | PB had ↓ ICU admission PB had ↓continuous infusion lorazepam PB had ↓ total lorazepam requirements No difference in ICU or hospital LOS |
References
- Phenobarbital. Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved September 28, 2019, from http://www.micromedexsolutions.com/
- Sullivan SM et al. Am J Emerg Med. 2019 Jul;37(7):1313-1316.
- Rosenson J et al. J Emerg Med 2013;44:592–8 [e2].
- Nisavic M et al. Psychosomatics. 2019 Sep – Oct;60(5):458-467.
- Ibarra F Jr et al. Am J Emerg Med. 2019 Jan 30. pii: S0735-6757(19)30075-0
- Nelson AC et al. Am J Emerg Med. 2019 Apr;37(4):733-736.
- Tidwell WP et al. Am J Crit Care. 2018 Nov;27(6):454-460
Related FOAM Posts
ToxCard: Phenobarbital for Alcohol Withdrawal
Podcast: Play in new window | Download
Subscribe: Apple Podcasts | Google Podcasts | Stitcher | RSS | http://pharmsohard.com/