A 58 year old man is brought into the emergency department by his girlfriend because she thinks he had a seizure at home. He has a long history of alcoholism, and usually drinks about 1 litre of Newfoundland Screech rum every day. However, he had to stop drinking 3 days ago because of a brief stint in jail. He is tremulous, diaphoretic, confused, and complaining of visual hallucinations. His vital signs are a temperature of 37.8°C, heart rate 155, blood pressure 166/99, respiratory rate 22, and oxygen saturation 99% on room air…
Walking up to the patient, I always start with a rapid assessment of the ABCs to consider the need to immediate intervention. In the agitated patient, my first priority is to calm the room and the patient down. Verbal de-escalation is valuable, but frequently fails in patients with medical or toxicologic agitation. Therefore, it is essential to ensure you have the appropriate people present to ensure that both the patient and staff are safe. (EMCrit has a good review of the management of the violent agitated patient here.)
If possible, I like to check a sugar early. Sugar is always important in patients with altered mental status. Alcoholic patients have multiple reasons to be hypoglycemic, and benzodiazepines don’t do anything to treat hypoglycemia.
Benzos, and lots of benzos
The treatment for alcohol withdrawal is a benzodiazepine. I honestly don’t think the benzo you choose matters that much. I use diazepam because its maximal effect intravenously is seen at about 5 minutes, so it is easily and safely titrated and its long half life provides some degree of auto-taper. My first dose is 10mg, and this dose is repeated once at 5 minutes if response is not adequate. (It won’t be in this patient.) I then double the dose to 20mg and continue with 20mg, 30mg, 30mg, 40mg, then 40mg every 5 minutes as needed.
What is the benzodiazepine target?
You have to balance the risks of undertreatment (such as seizure) with the risks of oversedation (aspiration or loss of airway). In mild alcohol withdrawal, titration is usually done by nurses following the CIWA score. However, severe alcohol withdrawal requires rapid titration of very high doses of benzodiazepines that will often make nurses uncomfortable. Therefore, I take charge of the titration. My target is a calm and cooperative, or mildly sedated patient. This would be the equivalent of a Richmond Agitation Sedation Scale of 0 or -1, or a Riker Sedation Analgesia Scale of 3-4. (I don’t have these scales memorized, so my target really is “calm and cooperative”.)
What is the diagnosis?
Once I have started titrating my benzodiazepines, I take some time to consider the wider differential diagnosis. Often, alcohol withdrawal will be obvious. However, in delirium tremens, the patients will have altered mental status, abnormal vital signs, and often a fever. The differential is quite large, including infection, trauma, endocrine and electrolyte abnormalities. A CT of the head is likely on the table, as well as a number of labs. I would also consider empiric antimicrobials to cover meningitis and possibly herpetic encephalitis.
Benzo resistant? Intubate and propofol
If the patient has not responded after my second or third 40mg dose of diazepam (over 200mg total), I will move on to second line agents. One option is to add phenobarbital 65-130mg IV q30min. Dexmedetomidine and ketamine have also been discussed as options. However, my plan at this point is to intubate using propofol as an induction agent and start a propofol infusion (as well as my normal post-intubation fentanyl infusion.) The ideal choice of second line agent probably depends on the familiarity you and your team have with the various options.
There isn’t a rush, but all these patients will get thiamine 100mg IV. Also, almost all of these patients will benefit from IV fluids containing glucose, as well as magnesium.
There is evidence (see Gold 2007 below) that you can limit intubation by using a protocol that uses high doses of phenobarbital. There is even an argument to abandon the benzodiazepines altogether, and use phenobarbital as a sole agent (see a brilliant post by Josh Farkas on PulmCrit here.) However, in my community setting, severe alcohol withdrawal is rare and phenobarbital is almost never used. As always, evidence based medicine is a balance between the literature with what you think is best for your patients in your practice environment. That being said, as more evidence on this topic emerges, I would not be surprised if I had to update this post to include phenobarbital sometime in the future.
Of course, if you are in a remote setting without access to the above medications, alcohol is an effective treatment for alcohol withdrawal, but with more side effects.
Phenytoin is not effective in preventing alcohol withdrawal seizures. Seizure management should focus on benzodiazepines and other gaba agonists.
Other FOAMed Resources
McMicken D, Liss JL. Alcohol-related seizures. Emergency medicine clinics of North America. 29(1):117-24. 2011. PMID: 21109108
Pitzele HZ, Tolia VM. Twenty per hour: altered mental state due to ethanol abuse and withdrawal. Emergency medicine clinics of North America. 28(3):683-705. 2010. PMID: 20709249
Gold JA, Rimal B, Nolan A, Nelson LS. A strategy of escalating doses of benzodiazepines and phenobarbital administration reduces the need for mechanical ventilation in delirium tremens. Critical care medicine. 35(3):724-30. 2007. PMID: 17255852 [free full text]
Finnell JT. Chapter 185. Alcohol-Related Disease. In: Marx JA et al. eds. Rosen’s Emergency Medicine, 8e. Philadelphia: Elsevier Saunders; 2014.
Stern TA, Gross AF, Stern TW, Nejad SH, Maldonado JR. Current approaches to the recognition and treatment of alcohol withdrawal and delirium tremens: “old wine in new bottles” or “new wine in old bottles”. Primary care companion to the Journal of clinical psychiatry. 12(3):. 2010. PMID: 20944765 [free full text]
McCowan C, Marik P. Refractory delirium tremens treated with propofol: a case series. Critical care medicine. 28(6):1781-4. 2000. PMID: 10890619
Hjermø I, Anderson JE, Fink-Jensen A, Allerup P, Ulrichsen J. Phenobarbital versus diazepam for delirium tremens–a retrospective study. Danish medical bulletin. 57(8):A4169. 2010. PMID: 20682133 [free full text]
Hendey GW, Dery RA, Barnes RL, Snowden B, Mentler P. A prospective, randomized, trial of phenobarbital versus benzodiazepines for acute alcohol withdrawal. The American journal of emergency medicine. 29(4):382-5. 2011. PMID: 20825805