Case
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…
My approach
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.
Extras
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.
Notes
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
EMCrit Podcast 11 – Delirium Tremens
Phenobarbital monotherapy for alcohol withdrawal: Simplicity and power on PulmCrit
CIWA-Ar for Alcohol Withdrawal on MDCalc
Treatment of severe alcohol withdrawal on Pharmacy Joe
References
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]
Lorentzen K, Lauritsen AØ, Bendtsen AO. Use of propofol infusion in alcohol withdrawal-induced refractory delirium tremens. Danish medical journal. 61(5):A4807. 2014. PMID: 24814732 [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
Morgenstern, J. Management of Delirium Tremens, First10EM, April 11, 2016. Available at:
https://doi.org/10.51684/FIRS.1898
7 thoughts on “Management of Delirium Tremens”
Hello! Thank you for an interesting post!
A few questions:
1) Why do not you use phenobarbital monotherapy?
2) Can the use of 5% glucose solution to enhance brain swelling due to the metabolism of glucose and the transition of the remaining water in the brain cells?
Thanks for the questions Gleb
1) Phenobarbital monotherapy is interesting, but I don’t think there is enough evidence for it to be a standard recommendation yet. The benefit seen (generally a decrease in intubation rate) has to be balanced with the potential complications of using a medication people are generally much less familiar with than benzodiazapines. For now, I think that benzos should remain the standard except for teams who manage DTs frequently and have expertise in the use of phenobarb. Good evidence could change that position in the future though.
2) I am not aware of cerebral edema being a large component of delirium tremens. On the other hand, almost all alcoholic patients this sick will be significantly malnourished and are at risk of hypoglycemia. That being said, these all very sick patients and a thorough assessment and guided resuscitation will ultimately take precedence over any empiric management strategy. That being said, while waiting for labs to return, I do not think there is any harm in giving some glucose containing fluids. (It doesn’t have to be D5W if you are worried about the water load – there are solutions of glucose plus saline as well).
What if the patient has associated COPD along with delerium tremens?
Should we still be so aggressive with benzos? May cause respiratory depression and lead to intubation in a COPD guy?
I did encounter this situation sometime bag..
Thanks for the excellent question. I will preface my answer by saying that I am unaware of any evidence that addresses this specific question, so my answer is opinion only.
I think benzos are still the absolute go to in the COPD patient with severe alcohol withdrawal. I know there are some that will suggest going straight to phenobarbital, and there is some limited data that a phenobarbital only approach may decrease intubation. However, where I work this would be an unusual therapy and much more difficult to get done.
In any situation when faced with one real emergency (withdrawal) and another potential complication (COPD), I think your focus has to be on the emergency in front of you. Severe alcohol withdrawal needs benzos. You just have to treat. These patients are really sick, and if they have to be intubated, that is just part of critical care.
However, as long as you are titrating your benzos, I don’t think that COPD is likely to significantly increase the need for intubation. These patients have significant upregulation of their GABA receptors, and need GABA agonists. COPD doesn’t change that. For some DT patients, we are going to overshoot and require intubation, but for the majority we are just putting them back at their usual GABA equilibrium that they have set with chronic alcohol use.