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RAJ:  A 37-year-old man presents to the emergency department with persistent vomiting, retching, and abdominal discomfort. He is highly vocal and agitated. His skin appears flushed.

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This is DDx, a podcast from Figure 1 about how doctors think.

I’m Dr. Raj Bhardwaj.

Today’s case comes from Dr. John Richards

RICHARDS: I am a professor of emergency medicine in Sacramento, California.

RAJ: Dr. Richards was in the middle of an overnight shift in the ER. It was around 4 am and things were just starting to quiet down…

A quick note, the patient in this episode is represented by a professional standardized patient like the ones used in clinical training and exams.

RICHARDS: We had just gotten control of the waiting room and seen the last patient who had been waiting, and we’re feeling pretty good about ourselves.

And then down the hall there was shouting and moaning and yelling. It sounded like someone was dying. And so everyone’s attention was piqued.

And this patient was, was wheeled into our examination room, was basically a very fit, middle aged guy who was screaming out loud and then he would start having these dry heaves. At one point he got up off the gurney and started bending over the gurney and retching and honestly, people thought he was dying. It was very dramatic. And it definitely was not intentional or voluntary, so he had no control over it.

RAJ: On top of the yelling and vomiting, one of the first things Dr. Richards and his colleagues noticed when they saw the patient was the color of his skin.

RICHARDS: All his skin was bright red as if he had just gotten out of a really hot shower or steam room. And I asked him, did you just take a hot shower?

SP: Yeah, I was in there for like an hour.

RAJ: Dr. Richards learned this wasn’t the first time the patient had experienced these kinds of symptoms.

RICHARDS: He had started having these episodes of vomiting and nausea that was uncontrollable, usually in the early morning hours and the only thing that he found would stop it would be to take a hot shower.

And he had gone to several emergency departments with these episodes and been treated and had multiple tests done like cat scans and X-rays of his abdomen and blood tests and urine tests. And they never found anything wrong with him. He even had endoscopy, and that was negative too.

So the patient was never given a diagnosis. Instead he was told we’re not sure what it is, but all we know is that you don’t need to get admitted to the hospital and you don’t need to go to the operating room to have surgery done.

RAJ: That was when Dr. Richards realized there was one key piece of information the previous doctors may have overlooked.

RICHARDS: I asked him, do you smoke marijuana?

SP: Uh, yeah. I smoke pretty much every day.

RICHARDS: And I said, for how long?

SP: I don’t know, I probably started in high school.

RICHARDS: And at that point I realized that it was probably a case of cannabinoid hyperemesis.

RAJ: Cannabinoid hyperemesis is a syndrome that doesn’t yet have a strong body of clinical research behind it. The diagnosis first appeared in the medical literature in 2004. We don’t yet have good data on its prevalence.   But, anecdotally, doctors who work in places where cannabis has been legalized — like Dr. Richards in California — have been diagnosing it more and more.

RICHARDS: So the basis of cannabinoid hyperemesis syndrome is an interesting one and it’s theoretical, but what we think is that certain patients have a genetic predisposition to handle stress in a manner that’s different than others. The reason for that is most patients who smoke marijuana, even daily users, don’t develop this syndrome, and as we all know, cannabis products are used for nausea and vomiting treatment, especially for chemotherapy patients and other disease states. So it’s a bit paradoxical as to why certain patients develop this, but what we feel is there’s a certain genetic component, and as a result of that, their sympathetic nervous system kind of gets out of control.

RAJ: Not every patient Dr. Richards has diagnosed with this syndrome presents with the same symptoms. But he’s observed a few consistent patterns.

RICHARDS: The presentation can be very diverse, but what seems to be underlying is that the patients are quite dramatic, more than just a patient who say had a, a gastroenteritis or maybe a bowel obstruction where they’re trying to kind of keep it on the down-low. The other thing is a lot of them will come in in the early morning hours and that is another signal that this may be related to the sympathetic nervous system, because there’s an early morning sympathetic surge that we all go through with our circadian rhythms and, uh, typically occurs between three and five in the morning, and we used to know about this from patients coming in with acute coronary syndrome in these hours because they were getting a sympathetic surge. So that’s another clue.

RAJ: Diagnosing and treating these kinds of emerging syndromes can be a challenge. But Dr. Richards had seen enough previous cases to recognize some telltale signs and symptoms.

RICHARDS: When the patient came in so symptomatic, I’d only seen this before in patients who had been long-term users of cannabis, so I immediately honed down on two questions. Did he use cannabis daily, and then was he taking hot showers to relieve his symptoms, and really the only syndrome which has those two measures is cannabinoid hyperemesis syndrome.

RAJ: Since he had seen a number of patients with this diagnosis over the past few years, Dr. Richards had been following the research closely.

RICHARDS: I was very puzzled about these patients. It got me very interested in the potential pathophysiology, and more importantly on what were the most effective treatments.

Once we had figured out that this was most likely cannabinoid hyperemesis syndrome, rather than just give him the usual medications that we give for these patients, such as reglan, compazine, phenergan, that we should give him something different and try to attack this from a different direction.

We decided, why don’t we try a beta-blocker?

RAJ: Dr. Richards wanted to try giving the patient propranolol given its effectiveness in children with cyclic vomiting syndrome.

RICHARDS: Many believe that cannabinoid hyperemesis syndrome is a variant of cyclic vomiting syndrome. So there was some precedent, and that’s what guided our choice to use the propranolol to see if it would work as a monotherapy.

I definitely was thinking ahead, and we see these patients often, so I knew there would be an opportunity to treat a patient simply with a beta-blocker and see if that alone would reverse the hyperemesis.

RAJ : As a precaution, Dr. Richards also ran some labs and ordered an abdominal x-ray and CT to rule out other potential causes of his symptoms.

When those came back normal, he and his colleagues gathered in the patient’s room. They wanted to see what would happen when the nurse administered the one-milligram intravenous dose of propranolol.

RICHARDS: After about a minute or two the patient started settling down, his plethora or, you know, very red skin, started to be less red and, he looked like he was just easing up a bit, and the frequency of the hyperemesis started to decrease. We noted that his heart rate started to decrease as well, which was an indication the beta-blocker was working, and after about five minutes he started not having any more episodes of emesis and felt much better. He did remark, he felt very tired and that may have also been a side effect of the beta-blocker. After about 20 minutes he started having more episodes of emesis and we gave him a second dose and that completely terminated any further rounds and he felt much better, back to baseline, and was discharged about four hours later.

RAJ: There are still a lot of questions about what exactly triggers cannabinoid hyperemesis, and about why the usual antiemetics don’t work. We’re not yet sure why certain drugs and therapies are effective. But in the meantime, Dr. Richards will continue to consider beta-blockers as one of the potential treatment options

RICHARDS: This is all theoretical. It’s very difficult to prove, but based on the medications that seem to work, which include not only the propranolol or beta-blockers, but also benzodiazepines and antipsychotics, and all these are very sedating drugs. So we think that there’s a component of sedation that is even more important than just terminating nausea or vomiting. Most people don’t consider beta-blockers to be antiemetic. But in this case, they certainly did arrest the hyperemesis.

RAJ: Dr. Richards explained to the patient that, as far as we know, the only sure-fire way to prevent cannabinoid hyperemesis syndrome, is to simply stop using cannabis.

RICHARDS: A lot of patients have a hard time hearing that because marijuana is their lifestyle. But, uh, he was receptive to that and I don’t have any other follow-up from him.

RAJ: Dr. Richards thinks we’ll probably start seeing more of these cases like this, especially in places where cannabis becomes legalized, and as more potent strains go mainstream.

RICHARDS: Just a little amount of marijuana can have a tremendous effect. I think as long as physicians are aware of it they may have it in the back of their mind when someone presents this way, who’s young has no other comorbidities comes in very dramatic. Normally one would think they have a bowel obstruction or you know, maybe a perforation and that’s why they’re in such pain and discomfort and distress, just asking a couple of directed questions can really narrow down the diagnosis.

RAJ: This means that doctors will have to get more comfortable asking direct questions about cannabis use when taking a patient’s history.

One question is, should we be asking patients upfront if they use marijuana similar to the way we ask them if they drink alcohol or smoke tobacco, and that’s a difficult one because a lot of patients may feel that’s a very intrusive question because marijuana may be illegal in certain states. In California it’s now legal, but it wasn’t not so long ago, so it may have a stigma attached to it that some people would feel would be too intrusive  to comment on.

I personally believe the question should be asked by the physician early on in the interview just to get it out there, because if there’s no other explanation for this vomiting, that may be the one clue that really hones down the diagnosis.

RAJ: Thanks to Dr. John Richards. This is DDX, a podcast from Figure 1, the knowledge-sharing app for doctors.

Figure 1 is an app that  lets doctors share clinical images and knowledge about difficult-to-diagnose cases.

DDX is produced by Earshot Podcasts.

The executive producers are Jesse Brown and Corey Marr.

Our music is by Nathan Burley.

Head to our website figure1.com/ddx where you can find links to Dr. Richard’s research, more cases of cannabinoid hyperemesis syndrome, and a roundup of evidence based cannabis prescribing guidelines.

I’m Dr. Raj Bhardwaj. You can follow me on Twitter at @RajBhardwajMD.

Thanks for listening.