[PLEASE NOTE: This post has been updated with a new post describing our current approach to alcohol withdrawal. The material here is still correct, but it does not represent our current practice. If you have time you may read the entire sequence of phenobarb posts: Part 1, Part 2, Part 3, & Part 4.]
Neuropharmacology of alcohol withdrawal, phenobarbital and diazepam
Phenobarbital and diazepam both bind to the GABA receptor in different locations. Benzodiazepines increase the frequency of GABA-receptor channel opening, whereas phenobarbital increases the duration of channel opening. Therefore, these drugs may act synergistically.
Is phenobarbital or diazepam better?
What is the best treatment target?
Treatment algorithm for delirium tremens
(a) Load the patient with 10 mg/kg phenobarbital IV over 30 minutes.
|Relationship between cumulative phenobarbital dose and plasma phenobarbital concentration among patients treated for alcohol withdrawal (Tangmose 2010). We have added green lines indicating the plasma therapeutic range for phenobarbital (64-172 micromol/L = 15-40 ug/ml), an orange line indicating the level at which mild signs of toxicity are usually noted such as ataxia and nystagmus (225 micromol/L = 50 ug/ml), and a red line indicating the lowest level which has been associated with stupor or coma (>280 micromol/L = 65 ug/ml)(Lee 2013).|
(b) Titrate IV diazepam to effect
(c) Additional phenobarbital
Avoidance of propylene glycol toxicity
|Propylene glycol concentration as a function of lorazepam infusion rate (Horinek 2009). We have added a line indicating 100 mg/dL propylene glycol, the level at which propylene glycol may potentially cause clinical deterioration (Zar 2007).|
Too early for phenobarbital-first approach? Or too late?
- Consider initiating treatment for alcohol withdrawal with 10 mg/kg phenobarbital infused over 30 minutes. This is proven to be safe. It may provide a nice baseline level of sedation, blunting the severity of the disease.
- Although phenobarbital is extremely effective, some patients may require very high doses. Rather than a patient “failing” to respond to phenobarbital, it is more likely that we are failing to provide an adequate dose of phenobarbital.
- Lorazepam infusions may cause oversedation (due to accumulation of lorazepam) or propylene glycol toxicity. IV bolus diazepam is probably the best benzodiazepine for management of alcohol withdrawal.
- Consider targeting treatment to achieve an awake and calm state. CIWA scales and vital signs may be confounded by a variety of other factors.
[PLEASE NOTE: This post has been updated with a new post describing our current approach to alcohol withdrawal. The material here is still correct, but it does not represent our current practice. If you have time we would recommend reading this post first, and then reading our newer post.]
Coauthored with neurointensivist colleague and drinking buddy Ryan Clouser (@NeuroCritGuy).
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