Evidence Based Charm:
Purging the Haze: Cannabinoid Hyperemesis Syndrome

Dr. Kade Goepferd: This is Talking Pediatrics, a clinical podcast by Children’s Minnesota, home to the Kid Experts, where the complex is our every day. Each episode, we bring you intriguing stories and relevant pediatric health care information as we partner with you in the care of your patients. Our guests, data, ideas and practical tips will surprise, challenge, and perhaps change, how you care for kids.

Welcome to Talking Pediatrics. I’m your host, Dr. Kade Goepferd. On today’s segment, Evidence Based Charm Guidelines with Courtney, hospitalist Dr. Courtney Herring informs us of the latest evidence-based, expert-driven clinical practice guidelines. Alongside her informative guest, she takes us through all the steps of care, from ambulatory to inpatient and back again – with a sizeable dose of Southern charm.

Dr. Courtney Herring: Welcome everyone. Today’s episode of Evidence-Based Charm, Guidelines with Courtney, I’m your host Courtney Herring. So we will meander through the murky maze of a malevolent menace of cannabis use. Cannabis use in adolescence has been on the rise for the past two decades, and over the past decade the perceived risk of harm of weekly cannabis use has decreased by nearly half. The CDC published this year that in a survey of 2022, over 30% of 12th graders reported using cannabis in the past year, and 6% reported using cannabis daily in the past 30 days.

With discreet methods of delivery such as vaping and edibles being widely available, prediction models continue to forecast increasing trends of adolescent cannabis use, alongside a sociopolitical push to liberate barriers to legalize cannabis, such as the federal government’s move to reclassify cannabis as a Schedule 3 controlled substance. With a shifting paradigm around cannabis and its use, it continues to be integral to public health that we collectively evaluate the dangers of such products.

Cannabinoid hyperemesis syndrome is a specific potential comorbid of cannabis use, with overall prevalence thought to be around 0.1% with higher rates in young adults. To give us perspective on one such, danger is Dr. Nadia Maccabee-Ryaboy, Children’s Minnesota hospitalist and University of Minnesota, Assistant Program Director of the Pediatric Hospital of Medicine Fellowship. Nadia, again, it’s so lovely to be in person with you and to share a voice with you today.

Dr. Nadia Maccabee-Ryaboy: Thank you so much. It’s an honor to be back, Courtney.

Dr. Courtney Herring: Well, let’s get into it. In your perspective, Nadia, what is cannabinoid Hyperemesis syndrome?

Dr. Nadia Maccabee-Ryaboy: So cannabinoid hyperemesis syndrome, sometimes called CHS, is a disorder characterized by cyclic episodes of nausea and vomiting that’s seen in some people with chronic cannabis use. So, there are three criteria in the Rome IV Criteria for a formal diagnosis. Those criteria are, one, these stereotypical episodes of vomiting that kind of resemble cyclic vomiting syndrome, so periods of unremitting, paroxysmal vomiting, lasting hours to days, and then symptom free periods between those episodes of vomiting. And usually patients should have at least three episodes in the past year.

Secondly, the CHS diagnosis is made in a patient who’s had chronic cannabis use, so at least six months of cannabis use. And then thirdly is relief of vomiting episodes once the patient completely ceases cannabis use.

Dr. Courtney Herring: There is different pathophysiology here with a toxidrome part of having cannabis use is a big part of the history, so just to call out for our pediatricians and people caring for children, that cyclical vomiting is separate and specifically you called out the Rome Criteria for CHS.

Dr. Nadia Maccabee-Ryaboy: Yeah. And the literature does show that it can be hard to distinguish cyclic vomiting syndrome from cannabinoid hyperemesis syndrome. Cyclic vomiting syndrome can be seen in infants as young as six months, versus CHS where we’re seeing that really in teenagers. There are some other things that can help distinguish one versus the other. A lot of it is a really good history.

Patients with CHS are more likely to have this pathognomonic hot showering or hot bathing that can relieve symptoms. It’s less common in cyclic vomiting syndrome. If one were to do a gastric emptying study, which we don’t always do in these patients, it would be normal or accelerated gastric emptying time in cyclic vomiting syndrome, but actually it’s often slowed in CHS. These are different entities though they often present similarly.

And also the International Headache Society characterizes cyclic vomiting syndrome actually as a migraine variant. So, you’ll often see that migraine personal history, migraine family history in patients with CVS, with cyclic vomiting syndrome, and that’s not necessarily associated with CHS.

Dr. Courtney Herring: I feel like we’re foreshadowing some management opportunities here. Moving on, we talked about how CHS can be diagnosed, but when you were developing the guideline, what were the leveling pieces you wanted to make sure were being published?

Dr. Nadia Maccabee-Ryaboy: Thinking about why make a guideline about CHS? There were two big reasons. One is that it can be hard to diagnose. Cannabinoid hyperemesis syndrome, it takes a really good history that’s done confidentially with a patient, and excluding alternative diagnoses, but there’s no one test that confirms this is CHS. Then also the treatment can be tough, because typical antiemetics like Zofran and Compazine are notoriously ineffective in CHS. So, we knew we had to develop this guideline to guide clinicians in how can we appropriately treat these patients who come in often suffering quite a bit? So, that’s what was the impetus for this guideline.

Dr. Courtney Herring: And who did you feel was important to collaborate with while building this guideline?

Dr. Nadia Maccabee-Ryaboy: So, it was a multidisciplinary effort. As those Rome IV criteria are classically GI criteria, we definitely involved our pediatric gastroenterologists, also our pediatric toxicologists, our adolescent medicine specialists, psychology and social work were also involved, as well as emergency department providers who are often the first line when patients come in with severe vomiting, as well as our primary care doctors.

Dr. Courtney Herring: What a beautiful spectrum of expertise. Grateful for all of those. As we understand as we continue to care for kids, it is truly not one person doing all the work.

Dr. Nadia Maccabee-Ryaboy: Absolutely.

Dr. Courtney Herring: A lot of times in our emergency departments, locally and across the nation, what are you looking for and how are you working up CHS?

Dr. Nadia Maccabee-Ryaboy: Our guideline recommends that the CHS workup is a targeted approach. So, first starting with that confidential history, asking the parent to step out of the room and making sure to figure out is this a patient who has chronic cannabis use? And then also a really good exam and history to try to eliminate other potential causes of paroxysmal vomiting. And then taking a targeted lab and imaging workup once that go-to-history and physical has been completed. So, we suggest workup to consider would be a complete metabolic panel, a lipase, a urinalysis, maybe a urine pregnancy test, a CBC, and then considering imaging, again, based on one’s exam. So there isn’t a one size fits all. And then I should add also, a urine quick drug screen should also be considered for these patients.

Dr. Courtney Herring: And what do you feel like the role of the drug screen is? Because we get a lot of different chatter around the use of urine drug screens, especially in our department of Hospital of Medicine. What is your take in regards to CHS of how helpful it is?

Dr. Nadia Maccabee-Ryaboy: Interestingly, as you heard with the Rome criteria, a positive urine drug screen is not one of the criteria. That there are patients who might come to our clinics or emergency department and have a positive drug screen for THC, but be vomiting for a completely other reason.

There are also patients who can come in with cannabinoid hyperemesis syndrome and have a negative urine drug screen. Synthetic cannabis as well as cannabidiol, there are some products that won’t come up positive, at least at our facilities quick drug screen, and those patients still might have cannabinoid hyperemesis syndrome.

So, the first step for these patients is just to get that good history, and if a patient tells you that they’re having chronic cannabis use and the clinical picture fits, one doesn’t need to get the urine drug screen. But if a clinician can’t get a really good history, then they might discuss ordering that urine drug screen, as one piece of data as considering this diagnosis.

And the one other piece of workup that I forgot to mention that is emphasized in this guideline is, in addition to the labs and imaging that one would consider, would be an EKG. Because many of the agents that we’re going to recommend as anti-emetic therapy can prolong QTC. So, starting off the bat with getting an EKG and seeing, well, what management options will be available based on that QTC.

Dr. Courtney Herring: I feel like you already know what’s coming. I think the next step is you have a patient coming in, we’ll say an emergency department being the most common environment here of that hyperemetic phase, intractable vomiting. How are you going to help that patient?

Dr. Nadia Maccabee-Ryaboy: So, the key treatment for cannabinoid hyperemesis syndrome when they come initially to the emergency department would be supportive care. So, IV fluids, resuscitate them, and then treating their symptoms. So, as I had mentioned, as we had talked about earlier, Zofran and Compazine often don’t help. So, our guideline recommends some other agents that literature suggests may actually be more effective in CHS, and that includes droperidol, olanzapine, aprepitant, also called Emend, Benadryl and Ativan can be considered, and also topical capsaicin.

Dr. Courtney Herring: And out of those, I know aprepitant’s really made a forefront med as a second tier maybe still, but really moving forward of not even just for the emergency or acute care, but also even in the outpatient world is my understanding. What’s your take on aprepitant and how to use it, depending on where you are?

Dr. Nadia Maccabee-Ryaboy: Interestingly, it’s not a new med, it’s just new for us. It’s been used for patients who have nausea and vomiting due to chemotherapy in the oncological world for quite some time, but there have been some studies that show that it’s also really beneficial in cannabinoid hyperemesis syndrome. It’s an oral medication, often done in a three-dose series. Because it’s oral it can be tried in clinic, and if it’s kept down and the patient can also keep down fluids, they might not need emergency department care.

Also, if we start that three-dose series in the hospital, we sometimes send patients home with future doses, or even with a future pack to try at the first onset of the hyperemetic phase, if it were to occur again in the future.

Dr. Courtney Herring: And that even sounds like there’s an opportunity to translate that to the outpatient world, or even urgent cares per se, in regards to having that three-day pack of aprepitant. In the adult world they have used it more, and as you call out oncology, droperidol is another one that in the adult world they’ve used for a myriad of reasons. And so, I think some of these are common use drugs, or known drugs, by other specialties outside of pediatrics, it’s just saying what indications can you use them for? And really hopefully elevating, we need to elevate this. I think this is an underappreciated diagnosis in our adolescent population.

I like that we talked about aprepitant. You talk about resuscitation, but also ongoing potential just supportive care with IV fluids. Tell me more about the IV fluids. I think there’s some particulars that I was really interested when I read the guidelines that I wouldn’t have thought of offhand, including dextrose.

Dr. Nadia Maccabee-Ryaboy: Yeah, so definitely in the emergency department, the initial resuscitation, you just give the patient isotonic fluids, either normal saline or LR. However, once a patient is admitted, this guideline really emphasizes the importance of adding dextrose to the fluids, which we don’t usually do for teens who are on some IV fluids in the hospital. The reason being that THC is stored in adipocytes. So if a patient has been fasting for days, because they aren’t able to tolerate food and drink, then they’re probably starting to break down their fat cells and potentially releasing more THC, which can prolong that hyperemetic phase.

So, if we nip that in the bud and give them more sugar, then we can theoretically reduce the lipolysis and the ongoing release of THC. And so, if a patient has actually been fasting for several days, we’d even consider doing D10, which we don’t often do in pediatrics rather than just D5. Again, really trying to stop that catabolism.

Dr. Courtney Herring: It’s just a great call out of, again, very specific pathophysiology associated with cannabinoid hyperemesis, and not that bucket of cyclical vomiting. Just a great idea of how you continue to manage that.

So with that, we’re coming into more of the social context of this. In regards as we’re dealing with adolescents, as we do, young adults obviously a little different as they’re not minors, what are tips around discussing this with the teenager themself, and or parents?

Dr. Nadia Maccabee-Ryaboy: Yeah, so I think that really hits home with a key part of this guideline is that, yes, we can use IV fluids and anti-emetics and put a band-aid on the symptoms, but the mainstay I think of treating this syndrome holistically is trying to use our resources, whether it be social work, psychology, adolescent medicine specialists, to help our patients be able to cease any future cannabis use.

And so, often patients will have cannabis use disorder or co-existent mental health disorders that need to be addressed, whether it be on the outpatient or inpatient setting, both therapeutically and sometimes pharmacologically as well. And if we ignore the fact that they’re chronically using cannabis for a reason, that they’ve been starting that, and just send them home and say, “Stop using.” Then they might just bounce back and come back to our hospital, and we’re going to start all over again.

So, we have to treat this holistically, non-judgmentally, often using motivational interviewing and asking what are their intrinsic motivations? Why do they maybe feel a need to stop cannabis use? And try to empower them to identify their own reasons for stopping cannabis use, instead of giving them our talk from on high and telling them, “You need to stop.” And talking down to them.

Dr. Courtney Herring: I love that [inaudible 00:13:12] motivational interviewing, you have not had practice in it. I did a whole course through the AP on motivational interviewing, and felt was really beneficial actually of how to not only introduce but open conversation, and be the active listener. It was great. So, I love that call out, especially in this population of patients, no matter if it’s CHS or beyond in adolescent medicine.

I heard a couple of things. One is I would call it actually if you have in your community addiction medicine as well, in that psychiatry bucket, they are becoming, it sounds like more and more involved, given the prevalence of cannabis use across ages, starting in of course adolescents, and markedly increased through adult life, especially in the twenties and early thirties. And so, I would call that out as that’s a part of your catchment of assistance.

And then, two, is I heard of course cessation. There is a cure for this. It’s not an easy cure for a lot of people, but how do you get to that discussion of cessation and resources allotted? So, I think that was a great call out, and probably leading into if you had five takeaways, what would be your five takeaways for [inaudible 00:14:19] for this guideline or CHS management at large?

Dr. Nadia Maccabee-Ryaboy: I think the first one is that CHS is a diagnosis of exclusion, that requires a in-depth, confidential history with our patients, and then a thorough exam and targeted lab approach to exclude alternative diagnoses. Secondly, that any thorough treatment of cannabinoid hyperemesis syndrome provides both supportive care, with these great antiemetics that we’ve identified in [inaudible 00:14:49] containing IV fluids, but also utilizing consultants and motivational interviewing to help patients cease all cannabis use for the long term.

And then I think thirdly is just keeping in mind that treatment, we’re still studying this, we’re still learning, and so this is an ongoing opportunity for research. So, we think medications like aprepitant are really on the cutting edge in helping our patients, but a lot of the research has been done with adults. And so, this is a great opportunity for us to help our teenage patients, and also study and look to what do they say helps them the most.

So, there isn’t a one size fits all. A lot of it is there’s a menu of potential antiemetics that might work, and we’re going to have to listen to our patients and as a case by case basis, figure out what helps them.

Dr. Courtney Herring: Yeah, and I’ll tag in four and five. I think four is understanding your community. As the CDC published this year, their survey from 2022 already describes over 6% of 12th graders are using daily cannabis, so this is real. And the idea that prevalence is going to only go up. And my fifth one is more of a personal, but I think as you hear, hopefully you’ll agree, it’s utilization of resources. These young people, and then obviously anyone who comes in with CHS, are taking up a fair amount of emergency and hospital resources.

And so, when you’re looking at long scale of, one, how are we covering that? How are we helping those patients get the resources, not only acutely but beyond acutely? And we talk about cessation programs. You’re really not helping just them individually, you’re helping public health as well as utilization of healthcare. So, I just caution us that everything comes at a literal cost, as well as obviously individual. So, that’s it from me today.

Dr. Nadia Maccabee-Ryaboy: Yeah, thank you so much for having me in. This is such an important topic. I think that some people, often patients, will say, “I’ve never heard of this before.” And that’s why we have to talk about it because I think it removes some of the stigma when we talk about this and we say, “This is a medical issue, and non-judgmentally we know we need to help you through this.”

So, I love that we’re talking about it because I think the more that we do, the more knowledge that’s out there, the more we can help these patients, and hopefully they’ll be more aware that this is a potential risk of their use.

Dr. Courtney Herring: Yeah, I love this topic partly because it’s an ever-growing interest, and it’s a backwards interest. It’s now with the legalization coming through and really downstream effects, and we’re really seeing unplanned opportunities for optimization-

Dr. Nadia Maccabee-Ryaboy: Absolutely.

Dr. Courtney Herring: … and a lot in health care. And we’re not even hitting the high points of how it’s being studied around early cannabis use being detrimental to mental health and including psychosis. And so, there’s so much to unpackage here, and the evidence is getting stronger and stronger about we need to take this extremely seriously for our young people. So, I love always having you, Nadia, you are an amazing guest and I always love sharing space, but also being able to share your voice to not just me, so again, thank you for being here.

Dr. Nadia Maccabee-Ryaboy: Thanks Courtney.

Dr. Courtney Herring: All right, to all our listeners, on behalf of Evidence-based Charm, care of Talking Pediatrics, thank you for your attention. Until next time, I’m Courtney Herring signing off.

Dr. Kade Goepferd: Thank you for listening to Talking Pediatrics. Come back next time for a new episode with our caregivers and experts in pediatric health. Our showrunner is Cora Nelson. Episodes are produced, engineered and edited by Jake Beaver and Patrick Bixler. Our marketing representatives are Amie Juba and Krithika Devanathan. For information and additional episodes, check us out on your favorite podcast platform or go to childrensmn.org/talkingpediatrics.