Beta Blockers and Cocaine: Practice Change?

[docB]

So continuing on with Quinn‘s cocaine in the ED theme we got some new literature in last month’s Annals.

There was a study by Datillo, et al that concludes that patients who present with chest pain and had positive cocaine tests actually do better on beta blockers despite the widely held but possibly erroneous view that beta blockers + cocaine = unopposed alpha and agitation, hyperthermia, seizures and death.

Beta-blockers are associated with reduced risk of myocardial infarction after cocaine use.
Annals of Emergency Medicine - Volume 51, Issue 2 (February 2008)
Abstract:
STUDY OBJECTIVE: Beta-blocker use is associated with coronary artery spasm after cocaine administration but also decreases mortality in patients with myocardial infarction or systolic dysfunction. We conduct a retrospective cohort study to analyze the safety of beta-blockers in patients with positive urine toxicology results for cocaine. METHODS: The cohort consisted of 363 consecutive telemetry and ICU patients who were admitted to a municipal hospital and had positive urine toxicology results for cocaine during a 5-year period (307 patients). Fifteen patients with uncertain history of beta-blocker use before admission were excluded. The primary outcome measure was myocardial infarction; secondary outcome measure was inhospital mortality. Logistic regression analysis using generalized estimating equations models and propensity scores compared outcomes. RESULTS: Beta-blockers were given in 60 of 348 admissions. The incidence of myocardial infarction after administration of beta-blocker was significantly lower than without treatment (6.1% versus 26.0%; difference in proportion 19.9%; 95% confidence interval [CI] 10.3% to 30.0%). One of 14 deaths occurred in patients who received beta-blockade (incidence 1.7% versus 4.5% without beta-blockade; difference in proportion 2.8%; 95% CI -1.2% to 6.7%). Multivariate analysis showed that use of beta-blockers significantly reduced the risk of myocardial infarction (odds ratio 0.06; 95% CI 0.01 to 0.61). CONCLUSION: In our cohort, administration of beta-blockers was associated with reduction in incidence of myocardial infarction after cocaine use. The benefit of beta-blockers on myocardial function may offset the risk of coronary artery spasm.
Citation:
Beta-blockers are associated with reduced risk of myocardial infarction after cocaine use.
Dattilo PB - Ann Emerg Med - 01-FEB-2008; 51(2): 117-25
From NIH/NLM MEDLINE
NLM Citation ID:17583376 (PubMed ID)
Comment:Ann Emerg Med. 2008 Feb;51(2):127-9
PubMed ID: 17889405
Full Source Title:
Annals of emergency medicine
Publication Type:
Journal Article
Language:
English
Author Affiliation:
Department of Medicine, Jacobi Medical Center, Bronx, NY 10461, USA.
Authors:
Dattilo PB; Hailpern SM; Fearon K; Sohal D; Nordin C

But wait! There are some editorials on the subject:

Cocaine and beta-blockers: should the controversy continue?
Hoffman RS - Ann Emerg Med - 01-FEB-2008; 51(2): 127-9
From NIH/NLM MEDLINE
NLM Citation ID:17889405 (PubMed ID)
Comment:Comment On: Ann Emerg Med. 2008 Feb;51(2):117-25
PubMed ID: 17583376
Full Source Title: Annals of emergency medicine
Publication Type: Comment; Editorial
Language: English
Authors: Hoffman RS

Since editorials don’t have abstracts and it would be a copyright violation to post the text I’ll cite and summarize. Hoffman argues that the morbidity and mortality from cocaine induced chest pain is quite low (on the order of 5%) so exposing these patients to a known, deadly if rare drug interaction is unwarranted. He is saying we should stick with the status quo and avoid beta blockers in cocaine users. He goes as far as to say that doing a study to try to figure this out would be “premature” and “dangerous.”

But wait, there’s another editorial:

Cocaine, Myocardial Infarction, and β-Blockers: Time to Rethink the Equation?Annals of Emergency Medicine - Volume 51, Issue 2 (February 2008) - Copyright © 2008 American College of Emergency Physicians
Cocaine, Myocardial Infarction, and β-Blockers: Time to Rethink the Equation?


Kalev Freeman, MD, PhDa,
James A. Feldman, MD, MPHb
a University of Vermont College of Medicine, Department of Surgery, Burlington, VT
b Boston University School of Medicine, Department of Emergency Medicine, Boston, MA.
* Address for correspondence: Kalev Freeman, MD, PhD, University of Vermont College of Medicine, Department of Surgery, Burlington, VT; 802-847-5354, fax 802-847-5579
E-mail address: [email protected]
Supervising editor: Richard C. Dart, MD, PhD
Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article, that might create any potential conflict of interest. The authors have stated that no such relationships exist. See the Manuscript Submission Agreement in this issue for examples of specific conflicts covered by this statement.
Publication date: Available online October 15, 2007.
Earn CME Credit: Continuing Medical Education for this article is available at: www.ACEP-EMedHome.com .
Reprints not available from the authors.
PII S0196-0644(07)01449-7

Freeman and Feldman argue that the traditional view that beta blockers must be avoided in cocaine use is “toxicomythology” and that it is an “entranched but inaccurate” belief. They argue that more study is warranted but they don’t go so far as to say that current practice should change.

So what are we to do with all this? I took note because I routinely give the speech to students and residents about beta blockers + cocaine = unopposed alpha. My first thought was “Have I been talking out of my ***?” Turns out probably not, but the winds of change may be starting to blow and in a few years we may be practicing differently.

Another point for the students and residents in EM is that additional retrospective studies are needed. The Dattilo paper was based on a retrospective chart review of patients admitted for chest pain who and received beta blockers and had positive cocaine tests. They had 363 patients. We need to know if this paper’s findings extend to other centers and greater numbers. Retrospective chart review studies like this are relatively easy to do and are within the reach of resident research projects.

If we judge possible research projects by the triumvirate of “Is it novel, is it interesting, will it change practice?” such projects would meet 2 out of 3.

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[WallowaWanderer]

Thanks for posting this DocB. In talking with various attendings, it seems that only about 50% believe in the whole unnoposed alpha thing.

I think I read somewhere on this board that the mixed antagonists like carvedilol and labetolol only contain a wisp of alpha blokcker - something like 9 to 1.

So, my question is . . . if a tachy STEMI patient has had cocaine recently, why not give two drugs - an equal amount of an alpha blocker and a beta blocker?

 

[BADMD]

I have two major problems with the Datillo study.

1) Positive urine toxicology. One cannot equate a positive urine toxicology screen with active cocaine intoxication. The metabolites are detectable for 48 hours after a single use or up to a week for someone who is a chronic user.

2) Other causes of ischemia. This was not a cohort of patients with diagnosed cocaine chest pain. There were a number of diagnoses, including sepsis, smoke inhalation and GI bleeding, and betablockers were probably not appropriate for these patients. While chest pain was the number one diagnosis, it only made up about half the patients and was less than half the admitting diagnoses.

I look at this study as really being quite meaningless. I can't say if betablockers are "safe" since I'm unconvinced that the patients in this study were acutely intoxicated. I also don't know if you can really take anything out of the mortality data and try to apply it to chest pain, as the patients who died didn't have have chest pain. As I can tell, there is no benefit in face of cocaine chest pain (and the only guy with a clear cut ACS got betablockers and died). Personally, I'll refrain from betablockers in those who are acutely intoxicated with cocaine and use them, when appropriate, in people who aren't.

 

[BADMD]

So, my question is . . . if a tachy STEMI patient has had cocaine recently, why not give two drugs - an equal amount of an alpha blocker and a beta blocker?

I don't know that other people will say, but here is my take.

I will hit them with two drugs: a nitrate and a benzo. I'll use lots of both. This is a sympathomimetic crisis and not a true "STEMI." When you take someone to cath who has a cocaine related MI, they have clean coronaries. The ST elevations are caused by microvascular spasm and not by a huge clot in one of the large arteries. The treatment is to vasodilate and to block the sympathetic release.

There may be a role for b1 selective betablockers, but I'd start with liberal application of the above two drugs first.

 

[docB]

I don't know that other people will say, but here is my take.

I will hit them with two drugs: a nitrate and a benzo. I'll used lots of both. This is a sympathomimetic crisis and not a true "STEMI." When you take someone to cath who has a cocaine related MI, then have clean coronaries. The ST elevations are caused by microvascular spasm and not by a huge clot in one of the large arteries. The treatment is to vasodilation and to block the sympathetic release.

There may be a role for b1 selective betablockers, but I'd start with liberal application of the above to drugs first.

I'll echo the use of nitro and plenty of benzos. I always say that with sympathomimetics the road to happiness is paved with liberally titrated benzos. It goes without saying that narcs, O2, IVF and all the other stuff helps too.

I would be interested to see more study on this. It just has that feeling of something that we all assume is true and may not be. Look at the changing/diminishing role of AC in OD.

 

[BADMD]

I'll echo the use of nitro and plenty of benzos. I always say that with sympathomimetics the road to happiness is paved with liberally titrated benzos. It goes without saying that narcs, O2, IVF and all the other stuff helps too.

I would be interested to see more study on this. It just has that feeling of something that we all assume is true and may not be. Look at the changing/diminishing role of AC in OD.

I know that I am using/recommending less charcoal. I've seen too much black crap coming up ET tubes to think that it doesn't get aspirated to certain degree. I haven't had any cases where the patient experienced a significant pneumonitis from charcoal, but I'm sure that is only a matter of time. I'd like to see intoxicated patients (and frankly most ED patients) intubated with ET tubes that have subglottic suction ports.

I'd love to see a trial of benzo versus something (but what). Given the low incidence of sympathomimetic crisis and lack of money for such a trial, sadly, opinion will probably be all we have. Unless you know someone at NIH...

 

[Hernandez]

There may be a role for b1 selective betablockers, but I'd start with liberal application of the above two drugs first.

I'm curious about people's views on using a Non-selective blocker like Coreg. You'll get both Beta and alpha-1 blockade, and if you want to get some Alpha 2 blockade, you could just throw in some Remron too.

I'll admit that I'm not fully versed in this aspect of the pathophys, but I've always wondered about that.

 

[BADMD]

I'm curious about people's views on using a Non-selective blocker like Coreg. You'll get both Beta and alpha-1 blockade, and if you want to get some Alpha 2 blockade, you could just throw in some Remron too.

I'll admit that I'm not fully versed in this aspect of the pathophys, but I've always wondered about that.

Carvedilol is a hard medication to use in the acute setting. It has a high volume of distribution, thus making it very difficult to titrate rapidly. It is also only orally available. Labetalol has very little alpha blockade and, when given IV, is essentially pure beta.

Remron? I'm not familiar with this medication. Are you talking about mirtazapine (Remeron)?

Once a sympathomimitic crisis is broken, the patient usually comes down fairly rapidly. So you want to use medications that can be titrated. Phentolamine is only alpha blocker that is really practical to use. It has a very short duration of action and has to be dripped to be of much use. It works for Bp control. However I'm more comfortable using direct acting vasodilators than I am trying to play the competing agonist/antagonist game. Plus I like the nitrates to try and dilate out the arteriole spasm that is the likely cause of the ischemic symptoms.