Chapters Transcript Video It's High Times for Guidelines: Cannabinoid Hyperemesis Syndrome Clinical Pathway We are going to cover today, the cannabis hyper Emsis syndrome um itself and how we have come about uh a clinical pathway at um the U CS at Benioff children's hospitals. No one involved in the planning of this presentation has any relevant financial relationships. So we'll go through identifying the different anti metic indications and use in cannabis hy parames syndrome, the different mechanism of actions and side effects and introduce uh the pathway. Um that is uh there are two different pathways, one for the emergency room and one for the inpatient service. So I'll start with a uh presentation. Uh So it's Friday at 11 o'clock at children's. Er, you are seeing a 17 year old female that comes in with uh vomiting and abdominal pain for the past two days, multiple prior er visits at different hospitals all over the Bay area has had a lot of extensive work up which has continues to come back. Negative um reports had that uh none of the current anti metics uh have worked. Um on further questioning mom does mention that hot showers do help. These were the initial labs that came back. Uh So a little bit of low of hypochelemia. There were U ketones present in the urine but otherwise, overall, the laboratory data was unremarkable um on physical exam, um maybe Milly tacky ari, very restless, very uncomfortable, kept holding her abdomen and on exam, um reported diffuse tenderness, but there was normally bound and there were active outs. So going through the vomiting differential, it's very long. Um you can go through G I disorders and then non G I or we call extraintestinal from um disorders. Um As we mentioned, this patient has already gone to extensive work up and things have been coming back negative. So our differential, we narrowed it down to these two things, cyclic vomiting syndrome, all versus cannabis hyper emesis syndrome. So what is cannabis? It's one of the most illicit drugs in the use in the world. It's history dates back to 3900 BC. Uh marijuana itself refers to the dried leaves, flower stems and seeds of the uh plant cannabis sativa or cannabis in Dika plant as of 2016, about almost over 41 million in us um were reported to be users. Um most prevalent is actually in young age group of 18 to 25 more than males. And also um people who have associated um anxiety and depression. So common, the compounds have uh these compounds have affinity to the cannabinoid receptors. So, in humans and animals, it's called endo cannabinoids in plants. It's the tetrahydrocannabinol, that's the THC and the canna Bedol, that's the CBD, the synthetic version that is Marinol or uh or uh naval. So heating, this plant changes its composition. So THC A will change into THC CBD A will change into C BT CBD is the non psychoactive. But over the last two decades, there has been an increased cannabis potency um in products. So it has gone up from 4% to 15% percent. It comes in different uh variable of hash oil shatter and bags and the and the amount of of cannabis also is different in these products. And these extracts can deliver very, extremely high large amounts of THC to the body. Sometimes that can be high as almost 80%. So the active component of uh marijuana, it's cc it's half life is long, 20 to 38 30 hours. It accumulates in your fat. It leaches back into the system for a long period of time. It has what they call a biphasic effect. So in low um level doses, it gives you a hyperactive feeling awake, uh awakeness. Um and in high doses causes the sleepiness and we know the different forms that you know uh terms that are used. Um When we hear from patients, you know, I use pot, I use herb, I use grass. Um the receptors are we're gonna focus more on the CB one, there are two types of receptors. CB one and CB two. The CB one is in brain and the G I tract uh in brain, it alters behavior, short impairs your short term memory. It stimulates appetite and analgesia. So a lot of people use it when they um have poor appetite um in the G I tract and inhibits gastric acid secretions. It relaxes lower, lower es su facial sphincter. And that's why you're more likely to vomit or it decreases your gastric emptying at times and more likely to vomit and alters your G I motility. Uh We have seen over the years. Initially, the studies came coming out of Colorado where it uh uh came out first um as uh available uh legally. Um the rise in use in young adults um ca uh from 2011 to to 2013 in Colorado or Denver City. Um it rose dramatically with the legalization. Um And interestingly, the data that came out also back in uh 2019 that use increased significantly um in the age group of 12 to 17 years. So this was a study that we did at our own institution by a uh it was a resident project by Doctor Diaz. Um looking at uh admission rates of 10,000 discharges of cyclic vomiting associated with cannabis. And you can see um from 2016, um the admission rates rose from 15 to 21 to um when it was 2018. Uh the Rome Criteria Room uh Foundation um is um look puts out criterias for functional disorders in G I both in pediatrics and in adults. Um The room four criteria um looking at the functional nausea and vomiting disorders has uh cannabis hyper uh syndrome as part of one of the criterias. Um and cannabis hyper syndrome was first reported back in 2004. So the criteria itself, um the requirement is um that symptoms present for three months or with onset of at least six months, uh stereotypical episodes lasting less than a week, at least three episodes in, in a, in a year. Um No vomiting between episodes. So you're, you're completely fine and beat these episodes. Um And all these criteria should be associated with some history of chronic cannabis use and stops after cessation. So definition of chronic uh use needs to be more elaborated and cessation of cannabis still needs to be more defined. Also, to note that this uh grown criteria um is not for a defined pediatric age group. It's for adults. So the big differences between sick, vomiting and cannabis is cyclic vomiting. Patients will also have personal history or family history of migraine headaches. Um They can be psychiatric or morbidities. The gastric emptying is uh rapid. The cannabis hyper Emy syndrome, there will be chronic cannabis use. Um symptoms improve after cannabis cation and then there is um delayed gastric empty. I'm gonna hand over, I think, I mean, yep. Yep, let's go over ed management. Um This is what our desk looks like in our, uh, in our, er, nice and being uh, Aggie's uh China cup is there with her Earl Gray tea. Um, so next slide. So what do you do with a teenager like this? These kids oftentimes look really, really sick, they're very impressive, very uncomfortable, frequent retching, um, very, very severe abdominal pain. Um, and so for the residents in the program, you know, when you see a kid like this who looks really uncomfortable, you want to be thinking about um um managing working this kid up and managing it and sort of in parallel, you wanna be taking your history but not taking a, you know, an in depth history kind of getting the the key data and starting your work up. Um And if you ever have a kid like this and you're like, this kid looks terrible. Um by all means come and grab one of the uh pen fellows or attendings. Um So we can come in and evaluate with you. This could, could have uh an ovarian to or a type of pregnancy. Um So, um and uh we want to get started in our work up uh quickly. Um her belly is very soft um which is typical of these kids with cannabis hyper. So they look terrible but their bellies they really don't have guarding. Um And uh uh can you click again, Sabina? Yeah. So one thing in, in very quickly you want to get a heads assessment on this kid. And so you ask the mom to step out of the room, you ensure confidentiality, tell the kid, I'm not gonna tell your mom anything that you don't want me to unless you're gonna hurt yourself, hurt somebody else. Uh And you want to ask sexual activity. And uh do you, do you ever use marijuana? And next Sabina? Uh yeah, so she's, she's been smoking marijuana frequently for, for two years. So you really feel like this is probably cannabis hyper next slide. Um So traditional management of dehydration and um for campus hyper is to use your typical anti medics like Zofran Compazine. Um and to give IV fluids. Next slide, the problem is that typical anti metics don't work. Um We've seen that in our own institution. Uh It's, it's um you know, there's a growing body of literature uh that supports that, you know, ODCI really is kind of terrible for cannabis hyper. We, we, we reviewed um 20 patients who received ha for uh a few years ago um in our er and it was stunning how many anti medics they got, you know, Zofran followed by Compazine, followed by, by everything and nothing really worked for them and all these drugs can cause prolonged QTC. And so um so we need to find a better way and there's a small study but there's again, a growing body of literature to suggest that Capas and Haloperidol um are much more effective than our traditional anti medics next slide. So this is our Ed pathway. Um I've, I've clipped it down um on, on the sides of uh on each side. There's a lot of information in, in including differential diagnosis labs to get and things like that, um which you can look at in the, in the pathway. Um, when you, if you have a high suspicion for CHS, you want to start IV fluids and we always get an EKG or, or ECG, we're, we're looking for signs of prolonged QT. Um um Top cap, topical capsacin is in our pathway. You can give it very early on. Uh some attending, some of our providers have had success just giving capsacin. We'll talk about that in a minute. Um But you can use it either by itself or you can use it with parad. Um So, uh and then the next step is uh is QTC, prolonged use capsacin and alternative therapies. Can you go to the next slide, please? And if you look here, it says, administer 2.5 mg of hal haloperidol in here, it says al alternate with diphenhydrAMINE 25 to 50 mg. IV. I usually give both at the same time uh with the idea um that be that uh anticolonergics can prevent dystonic reactions and also um for the sedative effect. So I give Haloperidol and Benadryl together. Uh Here it has a um the box says if initial QTC is uh uh less than 44 60 milliseconds, you can give parol uh if it's greater than 4 60. Um you know, you may not want to use Haloperidol. This is also fuzzy as Sabina said, this is an iterative process. We're learning, we're discussing these patients with cardiology. Um And so we'll, we'll talk a little bit more about that in a couple of slides. You, you give your first dose of hell haloperidol. Is it effective? Yes, you can send them home if it's not, you can repeat the dose of haloperidol uh and, or capsacin and then you and then you move on. So, next slide. So uh it, so uh let's talk about caps for a minute. Uh Can you click? Yeah. So capas, uh it's one thing that is very clear is that the optimal concentration is unclear. All the studies tend to use different formulations. 0.025 5% cream up to 0.1% cream. We've sort of landed on 0.075% cream is what we're gonna be using. Uh here at children's uh it's cheap. Um The problem is it's not on formulary yet. Uh We are, we are working to get it put on our formulary. Uh If you have a patient and you want to use capsacin, the pharmacy oftentimes has it as a nonformulary drug. Um So you can call and enquire about it. Um And so next slide, Capsacin, it's the active ingredient in chili peppers. Um it binds to this receptor. Tr PV, don't ask me what that stands for. Uh It uh but what this receptor does, it's present in the G I track and I believe the CNS as well. Um It tr PV decreases substance P release and substance P is a paramedic agent. When it, when it hits the brain, what happens in a chronic cannabis use is a TRPP receptor is down regulate. Um And so that leads to more substance p and more vomiting. Uh When you give topical capsacin or you take a hot shower that activates Tr PV and decreases your substance P release. Uh And so it can help decrease volume. That this is the main theory. It's not for sure that this is what's happening, but this is what most people feel is, is why capsacin and hot showers work. It's like uh the biggest study out there was a retrospective study done in 2021. Um uh It was retrospective, 201 patients was suspected or confirmed in cans hy premises. 25 patients were less than 21. And one thing uh just to emphasize is that there's a paucity of data in adolescent patients. Um in the literature, topical capsacin was given to 100 and 49 patients in the, in the other pa in the other patients. Um 50 patients they, they were patients who did not receive capsacin as part of their part of their care for cannabis hyper syndrome. Um And they served as the control, the primary outcome was need for less than or equal to one rescue anti medic after initial agent click again. Sabina. So in the, in the caps group, 55% of the patients required either zero or one rescue anti medic. So more than half you didn't have to do multiple, multiple ants in the control group, it was only 21%. So the control group required, you know, greater than one rescue anti medic. Um And this was sta statistically significant. Next slide, these are just um some of the numerous case reports um on use of capsacin. And if you notice uh very few adolescents were involved in any of these that slide, I'm not gonna go through this. It's in the guideline, but this is how to give um caps, how to apply, you apply it to the stomach, um how to stop capa and burn. There are kids who really cannot tolerate capsacin. Um It, it can be very uncomfortable. Uh You wanna tell patients that it's gonna burn a little bit to begin with. But if it's really burning and a kid can't take it, you can uh pour some, pour some milk on it and um that can help relieve their symptoms. Um Next time, haloperidol is uh an uh P thiazine. It's a dopamine antagonist and a very effective anti metic. It does have side effects, extra parameter symptoms, such as uh um dystonic reactions, uh acas things like that and it also has cardiac uh side effects of a very bad one actually uh click again. Um So this is torsades um which is um a form of V that um when you have a prolonged QTC that can uh devolve into torsades. And this is very bad. And um and how paradols been associated with development of this, this is why we are very cautious with Hala Para and why we get EKG S on one next slide. The, the um havoc study uh was a perspective, joint perspective study out there on how do how para versus a dance for uh can premises. Uh They had a small 13 patients received Haldol, uh 17 patients received dance big dose, 8 mg. And what they measured was outcomes. Uh The outcome measured was reduction on a 10 point nausea, pain scale and Hal Para was significantly better at reducing nausea and pain uh versus a dance. Next slide safety and quickly go through this. Uh This study looked at um lodo for kids who are having post nausea and vomiting. Uh They monitored their EKG S and and cardiac rhythms and they found a low incidence of QT prolongation in in this group of, of Children that uh click. There's another study out there that found that in patients without risk factors, if you give paradols, 2 mg or less, you can do, you can do so without ongoing EKG monitoring. We're using a little bit bigger dose. Um But uh yeah, so in this patient, in your patient that we're seeing as a kid that I actually saw a few months ago, um you get your EKG and you know, the highlighted portion as a cardiologist would tell you never look at that. But of course, we always do because we're not cardiologists. So when you see that it's on the prolonged side, then you want to start measuring on your own. And when you, when we measured it ourselves, um the QTC was 0.459. So in this case, you're now you're at a, a fork in the road. Do you not give it because it's very close to 4 60. Um Do you give it because it's under 4 60 or do you call cardiology? I believe in this case, I felt comfortable. I I felt comfortable with my man measurement um to give her uh to give her para. So we gave it to her, excited. Um and she had received Zof friend before I even saw her. She also got Benadryl patient felt much better and was discharged. And what we want these kids to go home on are next a capsacin cream for the next time this happens with instructions on how to uh apply it. And we want to encourage these kids to um to stop uh marijuana just to, to stop marijuana use completely. Um Next slide risk factors. I'm not gonna go through these, but they're a bunch of medications and there are other risk factors. These are on the pathway. So you don't have to memorize this next slide. Um So one other case, 19 year old male past medical history of cannabis, hy premises vomiting 20 times a day for like the last two or three days he has on, on it in his, in his chart, it says his prolonged QTC. So um he looked terrible. Um And so we got an EKG on him next. So in this kid, when we measured it, it was actually next 4, 78. So like a legit long QTC. And so again, you're faced with, well, maybe we should just not use hal haloperidol um for this child. Um My feeling is haloperidol really seems to help these kids versus everything else. Um And so I called the cardiologist who was on, it was I think it was the elect electrophysiologist and electro physiologist is like it's OK to, to give him a dose of haloperidol. So we did next slide uh and he got initially felt better and, but required admission um because of return of symptoms. So the, the take home point is, you know, uh it's not clear what a hard stop is for prolonged QT in these kids. And so depending on your attending, um you know, you may call cardiology or you may just decide not to use haloperidol. And that's and that's ok. So, uh and this is a work in progress. So I will turn it over to the next speaker. Hi, everyone. I'm I'm Bella Doci. I'm with pediatric hospital medicine. So as we transition to inpatient care, I just want you to know that this is a bird's eye view of our inpatient guideline, which I hope you've been able to access and save for your reference. There's a lot of information on this guideline. But in the next slides, we'll take a, a closer look at the steps of the inpatient pathway. Our goal ultimately is to have these pathways located in some central online location for easy access. But uh for the moment that location is to be determined, we're trying to figure out where the best place will be for this next slide, please. So, one clarification is that for both ed and inpatient um inpatient, these pathways are meant for adolescents who are greater than or equal to 40 kg in weight, they're excluded if they're less than 40 kg, if they're pregnant or if they have congenital, prolonged uh QT. Uh and the key measures in these pathways include getting an EKG prior to um initiation of haloperidol. Um So that we know where as Jim mentioned, we need to be very aware of their existing QTC. We want to document reevaluation after every intervention and we want to make sure we're um raiding their pain and nausea. Uh Next slide, please So again, cutting out like the top of the slide, um whether the patients admitted from the ed or as a direct admission or a word to word transfer, the inpatient team should repeat the history, rethink the differential, consider what screening labs were sent and if any and, and then think about what needs to be done. And I'm gonna Sabina, if you could just go to the next slide just really briefly and then we'll come back to this. I want to make a point. Um So there these tables are also located on our, on our pathways. They're a reminder to consider your, you know, to reconsider your differential. Um And one point that we wanted to make is um if, especially if the patient hasn't had a thorough history and hasn't been evaluated in the ED, is that a die one in the differential for recurrent vomiting is cyclic vomiting. Sabina already mentioned it. But it's, and, and, and think about how it's distinguished from cannabis hyper. And then remember with regard to screening labs, remember that screening labs can change if the vomiting is a first episode versus a recurrence. Um And or if based on the specific clinical or historical red flags that uh the patient presents with these labs are merely a suggestion, but they're not necessarily comprehensive for every situation. And then with regard to consultations, we suggest appropriate consultations as well. And I'd like to highlight here the utility of getting integrative medicine involved very early. So now I'd like you to go back to the previous slide, Savina, please. Ok. So um at this point, you know, you have a high suspicion for CHS in the inpatient setting. Um based on that information that we've gathered and the key then is to initiate appropriate timely treatment. Um And this lower box will outline the key in interventions IV fluids, topical capsacin, as Jim mentioned, acid suppression uh with an H two blocker or A PP I and then for vomiting, haloperidol. Ok. Um Next slide and then the one after that, please. Ok. So we're, now we're gonna focus on that lower half of the guideline. Um and which specifically goes over a haloperidol use. Um And I'm actually gonna go to the next slide to make it easier to read. And it's all just so basically as in the Ed and you want to investigate those risk factors for prolonged QT. And as Jim said, all of this is a work in progress, progress. If somebody has a risk factor and if you go later, when you go back and look at the risk factors, the use of Zofran is one of those that doesn't necessarily mean that you can't use haloperidol. It just means that you have to be very careful about checking QTC and just being very thoughtful about this. Um So similar to in the emergency room and if it wasn't already done, you're gonna get your um EKG prior to or just after that first dose of haloperidol. And as Jim mentioned, if it's less, if the QTC is less than 4 60 great, go down the pathway. If it's greater than 4 60 you know what we said in the pathway is that the patient may be, it may not be a good candidate. But we also mentioned that this is a work in progress. And you know, our initial guidelines were developed with cardiology input, but clearly things are changing and we're getting to a point where we may tolerate a slightly higher QTC um for initiation of haloperidol use. Um And then the other point is that even after that first EKG, we're gonna follow the QTC. So, ideally at 24 hours, we're gonna repeat it. And if um the patient is in the hospital for longer than 24 hours, we definitely want to document the QTC prior to discharge. And then another important point is let's say you're on that pathway and at 24 hours, you repeat the QTC and it's risen and it's either greater than, or equal to a four or 80 or if it has risen greater than or equal to 30% above the baseline, that's a, a good reason to just stop this and go back to our traditional antia metics which are gonna take are gonna be less effective but, and, and may take longer to work, but we shouldn't be using halo care at all. Um Next slide, please. OK. So we're at that point where we're clear we're using haloperidol. If it was given in the emergency room, then start with the dose. The last dose that was given in the Ed if um you, if it's, if it was a direct admission, for example, and we're just starting from scratch. Um We start at a slightly lower dose than they do in the Ed. We're just gonna be, you know, a little bit slower. Um In the Ed, the goal is to try to uh treat the patient, see if we can avoid admission. So they'll start a little bit higher. So on the inpatient setting, you know, we'll start with one or 1.5 mg is and, and um ideally, although this slide says, well, consider scheduled dosing, the ideal is that you do Q six hour dosing and you alternate with uh IV diphenhydrAMINE. So if that initial low dose, the one or the 1.5 mg is insufficient, then with your next dose, six hours later, you're gonna increase by 0.5 mg and you're gonna keep doing that until you get to a dose that works for that patient. The max is 5 mg. IV although hopefully we won't get to, you know, that high a dose. Um And then one other point I want to make is when you just either in the Ed or in the inpatient setting is when you discuss the use of haloperidol with the family. Please be clear that the, the doses that we're using for the antiae effect are much lower than the dosing required for anti, for the antipsychotic effect because I think people know have heard of this as an antipsychotic and they have are, are less likely to have heard of it for as an antiae. Um, next slide please. Um, ok, so we're at that point where we're trying um whatever the dose was, we're going up, we're increasing by every six hours if we have to, if there is no improvement uh with progressively increasing doses of haloperidol and you're up to 5 mg q six hours at that point, you probably should discontinue, reevaluate and start thinking about your differential. Um If, if you're like following the left hand side of the pathway, if your symptoms start to, you know, provide a resolved, you have relief from the medicines, then probably what we would do is start getting the patient to take um oral fluids and, and start eating a little bit. Probably we would give them one additional dose at whatever that dose was that worked for them. Um Before we stop the haloperidol. Um And then we start making plans for discharge. Um ideally, you're gonna um you know, have integrative medicine, you're gonna have a social worker, you're gonna make, be making referrals for kind of kind of a cessation programs. Um And then you're gonna make sure you document the QTC uh prior to discharge. Um And I think that's where I'm gonna pass it off to Doctor Matthews for her expertise in integrated medicine. Thank you so much Bella. So just wanted to, um, I think echo the, the thoughts that have been shared thus far about, you know, thinking about as someone comes in from the ed and all the way to the and if they get admitted all the way to the floor, really starting to think about an integrated approach and thinking about um not only, you know, stopping the vomiting, but thinking about often kind of the complex psychosocial issues that might be going on for a patient. As Jim said, these kids often look miserable. So there often can be a lot of anxiety and stress and insomnia, um or hypersomnia given the medications. So thinking about not only the kid who's vomiting and, and helping stop the vomiting, but again, taking an integrative holistic approach to think about how to support the patient. Um Specifically, I just wanted to talk about the efficacy around getting an integrative medicine team involved around using acu thera or acupuncture acupressure for patients can be extremely effective for acute vomiting. Um And so I know many of you are familiar with uh C bands and nausea bands, they're much more readily available on the floors now. Um And so we use those quite a bit, we use them quite a bit for patients that are receiving chemotherapy. But I also love to use these for kids that are admitted either for cyclic vomiting or for Cannavo cannabinoid hyper MS S. And just quickly the mechanism of action that's happening here is that the point, the acupuncture point is called pericardium six. And it's what it's doing is stimulating a part of the brain. So the acupuncture point is kind of pushed on, on the wrist. It's three fingers from the wrist, crease straight in the median part of the wrist. Um and it's activating a part of the brain that helps control nausea, retching and vomiting. And there's quite a bit of literature around the efficacy of this for relieving nausea and vomiting that next slide. So not only do we use pericardium six and nausea bands or, you know, for kiddos, outpatient that might have chronic nausea, vomiting issues. I will often recommend relief bands, which is a little bit of an East has an E stem component, but just wanted to give a quick illustration that there's actually quite a few points on the body that target the digestive system. One of the tenets of Chinese medicine is really like the baseline is where you enter as kind of treating and thinking about the digestive system. So for example, looking at the points that are listed here on the left, the second one down, stomach 36 we know that there's evidence that when you stimulate stomach 36 you're actually activating the parasympathetic nervous system and can stimulate things like gastroparesis and kind of helping with digestion. We also have started offering and implementing aromatherapy which has been really well received by patients. Um And there's literature as well that shows essential oils and aromatherapy can be really helpful as adjunctive therapy to help reduce nausea symptoms. I think next slide and I'm passing the baton. Thank you. Um So, um now that we've made the patient feel better, um we have a good idea for what's going on. Um I think it's the, the discharge planning and the next steps. I think um the primary um recommendation, first recommendation is always to encourage um stopping uh cannabis or THC use. Um You know, I think when, when I've seen kids in the Ed and they represent um after having been diagnosed with cannabis, um hyper, you know, they'll say I stopped it, doctor, I stopped it and then I'll ask when the lesson they actually used it and they actually said it's been a while and I'll say what it's a while and they'll say like a week I used it last week. So I, I try to be very granular and say it's gotta be at least two or three months um to actually um improve on symptoms and not have um a recurrence of these symptoms in between. But um you know, as, as Sabina mentioned, um this timeline is still a little fuzzy. So um what we do try to emphasize is that you need to stop at least for a few months. Um, it, we've talked about, um, Capsacin, I, I've given Capsacin and, um, for home before if, especially if patients have responded well to it in the ed. Um, currently there are studies that have, um, that are looking at oral haloperidol but, um, there are no, um, published, um, guidelines yet. Um, and if Zofran has worked in the past, then, certainly, I think it's something that we should try and can discharge patients home with. Um As we've all talked about um this multimodal approach to um helping patients um feel better and do better at home. It's to approach things also from um providing mental health resources and um other support services. So super excited to say that um as of this past month, we actually have um substance use and mental health navigators in the ed now. Um So if there are resources that you've identified for your patients who are candidates for discharge, um or even ones who get admitted, but you feel like they may benefit from um these services certainly refer to our substance use navigators to help with um facilitating connections to those resources as well. Next slide, please. Um I won't go through all of these but um there aren't a ton of resources um for um outpatient settings, but I do want to highlight that um U CS F has an adolescent medicine program um with substance use consultation. It prior to this, it was um referred to as Yup, which was the youth outpatient substance use program, which is no longer um but you can still refer to um the adolescent medicine program um and the addiction services there and then also Highland Bridge um clinic um patients can actually drop in there and they've been a wonderful resource for us um in terms of um providing patients with next steps and then there's a list of um other resources as well. Next slide, please. Um Here are a list of provider or a list of resources for the provider as well as um certain um other mental health resources. Next slide, please. Um in terms of future directions, um droperidol um which is um related to haloperidol is I think uh more commonly accepted and used um in the adult population. But as of now, there aren't very many um accepted um guidelines for pediatrics. Um It does have a shorter half life. Um So haloperidol may be um better just because it lasts a little bit longer and may address um the symptoms for a little bit longer. But um here are a couple of studies that have looked at Dr in um CHS next slide, please. Um So um gaps in knowledge, I think um as we've gone through the slides, we've identified some of them, but just to be a little bit more um concrete. Um Right. Now we rely on the room criteria. However, as Savina mentioned, there are no pediatric diagnostic criteria that have been established for um our patient population. Um Additionally, we don't know why some user users are affected more than others. Um And then as I've alluded to, I think, um you know, dose and duration of cannabis, it's kind of hard to know how much and for how long and why um certain patients have these symptoms and why some have um profound symptoms with smaller doses, et cetera, et cetera. Um And then can I think uh other things around dosing are whether or not in frequent users develop symptoms? And then what is, what exactly is chronic heavy use? Um Treatment is still evolving. Um We're looking at what um are the best medications to use for symptoms. And then I think um as always, I think resources for outpatient follow up are um ever evolving and um hopefully will become more available as time goes on next slide, please. Um Next steps are to get this vetted through um UC of Mission Bay um with the sub specialists and then also to get reviewed with PNT next slide, please. And finally, um I would say that um 7 a.m. meetings are tough, but this group has made it amazing. Um And, and super fun to um get up for and rally for. Um as a result of our collaboration, there's been a couple of uh forums that we've presented at, um, those listed here and then our, here's a nice picture of our, um, Doctor James Sue who presented at the conference in 2022. Thank you very much. I think I have time for more questions. Right. Sarah. Yes, of course. Thank you all. That was really wonderful. Um, you guys have done a really lovely job of answering some of the questions in the chat. Um, a couple of questions that have come up for me. I've been, um, somebody asked a little bit about what labs you would do in the, er, to work up a patient that you suspect might have um, cannabis hyper and specifically, I'm wondering about the use of a U A to confirm or refute uh, cannabis use. Yeah, I think uh I'll take a stab at that. Um, I think getting a urine is totally, totally reasonable, totally appropriate. Um, uh, I think these kids tend to look pretty stereotypical, very uncomfortable once you see when you're like, oh my gosh, they all, a lot of them look, look the same, very uncomfortable. I think the most important thing is getting a good belly exam. Um, and uh, you know, determining that it's, it's, their bellies are nice and soft but they are very uncomfortable and so in the urine is important labs, if they haven't had labs before or even if they have, it's totally reasonable to get a chemistry, a light pace CBC, you know, I don't think you have to go crazy with it. You get your liver enzymes um and then um and get a heads assessment. I think that's really important. Don't, don't get your history, go out and talk to the attending, you know, and not get the heads assessment because most of these kids will, most of these kids will, will tell you. Um I had a kid a couple of years ago, uh who is 12 and he looked terrible and I walked in and I was like, this kid has cannabis hyper, but he was 12 and no one had done a heads assessment. So I kicked mama of the room and he had been smoking marijuana since he was nine almost daily. And so, you know, they're not gonna, I don't, I've not found kids being hiding, hiding from it. And if they, if they really say they're not smoking marijuana, then maybe something else is going on. Would you guys be able to go back to that slide with the differential diagnosis labs and consults again? Somebody's hoping to see that and then, ok, no, I was just gonna say the dovetail off of that gym. I mean, I, I couldn't agree more, but I've also had teens minimize how much they use. Um And I think, um in the past, I've thought I kind of put it in my head that it had to be chronic and heavy and, you know, I was thinking that there had to be a ton that they were using and they're like, you know, uh, they actually say that they don't use it that frequently and they can't really quantify how much and stuff like that. So it can be a little confusing, especially because they present so, um, in, in extreme discomfort and, um, are so symptomatic that you do a belly work up because you're not sure what's going on. Especially for first time presentations. I've also had that experience where it's a little bit unclear if the kid is or isn't using marijuana. And I'm wondering if you guys can comment on sort of the differences or similarities between cyclic vomiting and cannabis hyper emesis and how you kind of try to tease out what might be happening if you don't get a great history from the child. So sir, I can answer that. So I think in those scenarios, you know, you can always do a drug screen, right? If you are like, hm, am I not getting the history complete or is there something that's going on? Uh But as Jim said, as you know, a lot of times they usually tell us, right? I think it's making sure they are being told this is all confidential. Um, the um, the sickly vomiting and cannabis hy premises, the uh symptoms are very similar and that's the biggest always, the confusion is how do you differentiate they all are fine in between these episodes, right? Um not always, you will get the migraine story, right? That that is family history of migraine or, and sometimes it's actually both happening, you know, it's can be both happening um to one patient. So yeah, and I just to add to that uh to what Nisa was saying. Um if a kid is saying, you know, I, and I, I've read into this multiple times where like I use it once a month for the last two months, you know, you wonder about it. Um But I, I don't think there's any reason why you can't use Halo para as your first line in those kids as well. Um And uh um yeah, I lost my thought. Sorry. Sounds good. Um Similarly, we're getting a, well, I have a question for you, which is why, why is it that it seems like Zofran is less effective? Is their thoughts about why the mechanism there? No. Who knows? I don't, Sabina. Do you know what? Um I think it's the pathways, right? I mean, if you just showed the chili pepper pathway and the haloperidol pathways, it's um I think it's just we are targeting a different pathway. Um But, and you know, some patients do respond to too, right? So I think it's still a lot more to learn of why some things are working and some things don't work. Sabina quickly. The next slide has the differential in the labs. Oh Yeah, there we go. That's perfect. We have another question about whether you guys are seeing this clinically with kratom use or synthetic marijuana products. So there is um there is actually a case report of um you know, the synthetic use of uh CBD in a and you know, as a seizure for seizure patient um that they developed vomiting this little child um because it was being used as an anti seizure which is used um at this point. Um So yes, there can be, but I think it's the, I think as we talked about earlier in the slides is where is the product being made? What's in the product? How clean is the product? What is the amount in there? Right? I mean, I think there is so much difference in what is being sold out there, you know where you are buying it from? Uh what compounds are in there. So, ok, thank you. Someone else is wondering about if you guys have any numbers for prevalence in the past few years since the pandemic. And also whether um your sense is that the prevalence is higher in the United States where cannabis is legal? Well, cannabis has been legal in Amsterdam for a long time but I wonder if he with the er s over there. So, um, but you mean, I, I don't know, I don't know, Jim, if you have looked at, oh, I think, I think in states where cannabis is legal, I, I, I'm pretty sure. Although I, I, now that I'm thinking about it, maybe I'm, maybe I'm just assuming, um, uh, and the prevalence has increased a lot. I don't have precise numbers. Um, but they anticipate with, with more states um, having legalized cannabis that the prevalence is going to continue to increase. I think the only study that we saw was the one from Colorado where they, there was one study that showed a market increase in number of ed visits after legalization. I, I assume that they're gonna be a lot more studies from different states as, as you know, the years pass. Oh, yeah. And I think our, our study at children's was that study, right? 2016, 2018. That's when California, um, marijuana legalization, uh laws were changing. So we saw a jump. Um, doctor is ok, I'm sorry, just to go back one second. Um, we are seeing it, it's not rare in our, er, um, and I would say that's one way to, to differentiate sick with vomiting from cannabis hy premises is when they come in and they're a teenager I would ask about marijuana. Um, it could certainly be sick with vomiting, but I'll ask the other uh, other presenters we don't see sick with vomiting that often without, without cannabis hy premises. Sabina may see it frequently but we don't in the, er, the cannabis hyper, it's, it's coming, it's here. Um, and um, the, there was one other question, uh that someone had actually one question is, does anyone know if caps is covered by Medic? So I, yeah, I don't know the answer to that one. And um, and then someone asked about uh whether um what you do if you've ensured confidentiality and the um and the kids smoking marijuana, what do you tell the parents? My experience has been most of the kids I've had are like, oh my parents know about my cannabis use and so they're fine with you um with you, with you talking to the parents and I usually have the parent come in and we have a discussion together, but I have not run into, I don't think I've had a patient who said, please don't tell my mom if they did, it would kind of be api D situation where I'm not gonna tell your parents that you're having sex, but I'm gonna tell you you got an infection down there, you know. So it's, it can be tricky, but I have not run into that. But I think Jim, it will be interesting how, what do you do in these scenarios in your documentation when now with the chart being able to be accessed and if you are documenting them as cannabis hyper syndrome as a bill that going out and the parents are seeing those I have, I have an answer for that Sabina and that is that all, all adolescents, if you're asking any sensitive information, we, we are supposed to make them sensitive visits. So none of that should be seen by, by parents. I don't know if the urine drug screen can be seen on my chart but like, uh, can, um, chlamydia gonorrhea testing is, does not show up on, on charts. And as far as yes, uh, in terms of the bill they get, well, I don't know what to do about that and I have an answer to the prevalence question. So I, I'm looking at this one study, um, that was from 2021 that looked at uh 458 patients who kept, uh coming back to an, er, for nausea and vomiting. And then out of those 458 they, 321 of those had cannabis use and out of those 3, 2321 uh I think it was 12, 12 to 16, the numbers vary but between two different studies, uh 12 to 16% prevalence uh in those who use cannabis. But I think another study showed a much higher prevalence up to um, like 30%. So I think it really is variable and I think that it's, I think it's one of those things that it's, it's hard to diagnose. And so, um, I, as this becomes much more common, I think people will know to ask, um, and we might see the, uh the numbers actually change. Thank you. Thank you. That's great. I was also wondering, you know, I know you guys are sort of representing the inpatient side of the work up and management of cannabis hy parames, is it? And, and doctor Nara, you described this case scenario of a teenager just looking absolutely terrible in the, er, is it your sense that these kids when they're outpatient are having similar but milder episodes or is it thought that it's really just these really high spiking symptoms that bring them into the hospital? I think there are kids that you see, who aren't that sick. Um, and I have sent kids home without even putting an ID in after discussions with them but who I think clearly had canvas hy premises and I think their siblings were starting to wane on their own. Um, so I think those kids are good candidates for, for, uh, think about caps, um, and telling them, you know, how to apply it and, and use it and try that. Um, and that's something that the, you know, primary care physicians in their offices can, can do. Um, and, um, and certainly go to the, er, if they're getting really sick, some of these kids come in and they've been, they've been vomiting for days. I don't know how they tolerate it. But, um, um, but yeah, so there is, there is a spectrum. I have a question. Have you in the, er, seen or heard about, you know, passive exposure? Like somebody in the room a younger child with parents, we see kids, we see kids coming in, infants coming in stone from, from getting to the gummies. But I have not seen a kid that I thought might have cannabis hyper premises because their parents, you know, and we do smell a lot of marijuana in rooms with parents. So I just wanna mention another question that doctor Doshi kindly answered in the chat, but I think it's an important one, which is, um, do you guys see this, the hyper emesis episodes happen during acute use of marijuana or does it sort of happen as kids are tapering off, use in a kind of a withdrawal phase or does it vary? No, it's, it's, they're, they're using. And, um, and I don't, I think one of the questions is, how long do you have to stay off of marijuana for the symptoms to go away? I don't know that that's, I don't think that's well, um, documented or, or understood. Um, and so we'll see kids coming in with cannabis type premises who they say they haven't used marijuana in like two or three weeks and they're vomiting or they were abstinent for, for weeks or months. And they said I've smoked a couple of times in the last week and now they're having symptoms again. And so, but, um, yeah, it's, uh, so I, yeah, I don't, I don't know if Sabina or Bella have experience with, you know, kids saying no, I haven't used it in two or three weeks and they're still having symptoms. Usually, most of them will say they're still smoking. So it's very similar. Sarah, that when you read about cyclic vomiting, there are the three phases. You know, it's the paranormal phase when it's, you're just using it, but you're going about your normal eating and everything and then you go into that hyper phase. Um, that's when that's where the, all the symptoms are vomiting, hot showers, abdominal pain, and then you go into that recovery phase, right? So it's the same kind of spike that happens that you also see in cyclic vomiting, that's why it gets confusing and then you're completely fine and it's not that these patients may have stopped using cannabis, they may be still chronically using and go home and find for a while and then they have another spike. So there may be something more that we still don't understand, right? So about what kicks off in a cute episode, even in a child that's had one episode prior. And one other point that excuse me for a long time was um it's called cannabis hyper. Um but they have a lot of abdominal, they have really, they're really uncomfortable. And so um for a while, it was like, well this kid in a lot of pain. So it was a canna premises and that's, it's documented literature. Lots of these kids have really severe pain in addition to how are you addressing that pain in the, er, and Motrin or? Yeah, I, well, I, well, actually, no, we, I get mo, uh, morphine occasionally if you know, I mean, some of these kids really are uncomfortable. Um, and, and I think the main thing is getting Haldol and Benadryl getting sedated, giving them IB fluids, I think. Um, I think that's the way I, I approach most of these because their bellies again are usually pretty benign. I don't know if or a, do a, they do do something different. No, I think they get so much better after the halal and kept and that the pain seems to resolve. So, Sarah, I mean, I, yeah, I, I don't think I have given a separate pain medication. Uh, agreed. I, I think I, I end up call it pulling on capsacin, um, quicker and then try it. So, um, especially if I'm worried about CHS. So, and that usually helps symptoms. But would you guys almost say that the response to the caps in the halal, if present is somewhat diagnostic? It sounds like these kids are really responding quite robustly. Well, I would temper that a little bit in that. Um, you know, someone asked in the, in the chat how many of these kids are getting admitted? And it's a lot like, you know, um, we give Parol and sometimes there's a good effect, not always or they have an effect but they need, you know, they need repeated doses and Bell and uh, Sabina can talk more about that. Um, but uh and I don't, I honestly, I don't have any experience with caps and I've not used it yet. So I, I that's, that's on my agenda. I have one comment which is I just came off of inpatient service and we had a, a teenager with diagnosed cyclic vomiting who was on a regimen of haloperidol at home and when oral haloperidol and normally it does work for her. And at the point that, and, and she comes in whenever it doesn't work. And so this is a kid with cyclic vomiting who's on Haloperidol. So I think that it can work in cyclic. So I think it, it's not the use of halo. The response to haloperidol is not diagnostic for um, ch si agree. I agree that's helpful. We have one other question in the chat which is, have you guys seen any patients get dyco dystonic or reactions or anesthesia from the doll in your experience? So I think you're muted. I, I haven't yet. I mean, in, in this context and in this dose, I have not seen that reaction. I don't know if the other providers have. So I have with Compazine, I have seen a couple kids over the years who got really, I thought I, I thought it was a and when I was preparing for this talk, um I looked at an ACAS usually doesn't develop immediately after, at least that's my understanding. Um, but these kids will get, they feel really restless, they'll feel like they're coming out of their skin. They, you know, um, that's with Compos. I've not seen it with Haloperidol but they're, they're both Penia. Um, and that's another reason why I give Benadryl, um, to these kids. Uh, and I tell them when I give them, uh, Compazine or help her at all, I tell them you might feel a little bit weird or anxious after we give it just, it's a side effect. It's not anything dangerous. Just try to take some deep breaths because usually with the composing like the nurse who will come and say, hey, your kid's freaking out, we just gave compass by the time I get to the room, the kids asleep. And so, um so I don't think it lasts very long. I and I've not seen a dystonic reaction at cos like I'm usually, I'm, I'm always giving Benadryl with it. Yeah, I haven't either. And, but I'm gonna refer to one of the only randomized studies about haloperidol um use that looked at safety. And again, a lot of the these studies are very small and this study looked at 13 patients and the only um there were only three events and they were only with high dose haloperidol. And in this study, high dose was 0.1 per kilo so much higher than we're even advocating using. And this safety outcomes for that study that there were three events all with high dose. One patient had moderate anesthesia and the other one, the other two had acute dystonic reactions which resolved with Benadryl. Well, that's pretty reassuring and I think with that we're also out of time. So thank you all so much for coming and talking with us. We really appreciate hearing all the things that you guys have been working on. Created by
