Bill Klaproth (Host): This is an AAOMS On the Go podcast. I'm Bill Klaproth and with me is Dr. Deepak Krishnan. He is a Professor and Division Chief at the University of Cincinnati. Dr. Krishnan joins us to discuss a study recently published in the Journal of Oral and Maxillofacial Surgery titled, “Do Patients with Mental Illness Undergoing Office Based Sedation Require an Increased Propofol Dosage?”

Dr. Krishnan, welcome.

Deepak G. Krishnan, DDS, FACS: Thank you, Bill. It's great to be here.

Host: Yeah, interested to talk to you about this. So what led you and your team to pursue this research topic and what was the development process?

Deepak G. Krishnan, DDS, FACS: Yeah. So this is an interesting group of patients that we've often studied, and this is probably part two of many part series of studies that we are conducting at the University of Cincinnati's Oral and Maxillofacial Surgery Clinic. So one must realize that in our previous studies, we have found that about 30 percent of our patients – young adults, typically aged between 18 and 25 – have a form of a some prevalence of, some form of mental illness, and that can be as low as 20 percent, but in our population we saw from previous studies, it's as high as 30 percent.

And this is our target population for many procedures that we typically do in the oral maxillofacial surgery office under open airway ambulatory surgery kind of anesthesia. And there are some things, some factors about this that are quite relevant. Anecdotally, we have found as clinicians that when somebody has some form of mental illness for which they are either medicated or under therapy – anxiety, schizophrenia, bipolar, whatever it might be – their requirements for anesthesia is through the roof.

However, these claims have not been thoroughly assessed or that anecdote substantiated. So, we set out to investigate that particular aspect of mental illness and sedating patients in our office. But because we use so many drugs to sedate, if we could look at one thing or another, we realized that one of the things, one of the drugs that we were using in the office that required an increased dose, was this particular drug called propofol, which is a general anesthetic that we use routinely in oral maxillofacial surgery offices.

And we were looking particularly as a variable to see if patients with mental illness undergoing office-based sedation, do they require an increased dose of that drug, that particular drug, propofol? And that was what the study was about.

Host: Yeah, that's very interesting. So did your study's conclusion match your original hypothesis?

Deepak G. Krishnan, DDS, FACS: Ah, so that's interesting because the purpose was to kind of measure the association between mental illnesses as either reported by the patient or when you comb their medical history, you get that and whether propofol dose is necessary to achieve what we would consider as a clinician, a satisfactory level of anesthesia, was somewhat related, somewhat, is there an association at all? And in order to do that, we had to carefully design a study, and we couldn't do that in a prospective fashion. We figured the best thing to beat the anecdote was to look at our existing data to figure out if we have enough retrospective cohort consisting of patients that were treated in our center with mental illness to figure out if there was indeed an association. And we got a large number of patients and we had about 410 patients, 409 patients, and when we started looking at them, the results suggest that when you adjusted for multiple variables in the study, mental illness may actually influence the amount of sedative required to achieve satisfactory anesthesia and thus, and that, that amount of sedative was particularly propofol.

So anecdotes may be correct in suggesting that we need more propofol in patients with severe anxiety, severe depression, severe schizophrenia, and other mental illnesses to achieve the same level of anesthesia as somebody who doesn't have that. So yeah, we ended up proving that that is indeed true, but the results were somewhat murky as well.

We had to kind of do multiple statistical analyses to figure out if there was bivariate analysis, which means that you take two variables and very specifically look at that. And when you adjust for multiple covariates, mental illness definitely was statistically associated with propofol dose, but it didn't really make sense when you dug deeper.

Only because of the variability of what we were calling mental illnesses versus so many other covariates that people come in with. So there's so many weaknesses to the study that we intend to address in a future study, but generally speaking, it did prove the point.

Host: So, knowing this, how do you then assess or evaluate what is the proper dosage, specifically speaking of propofol, when treating a patient that does have a mental illness?

Deepak G. Krishnan, DDS, FACS: Yeah, that's interesting too because we haven't really been able to pinpoint a cutoff dose, right? So let's say for instance, somebody said, I need a 10 something of propofol, just hypothetically, if somebody did not have any report of mental illness or were not really taking medications for it. But if somebody did have mental illness, they needed 11 plus. So there was no like cutoff line that we were able to find.

Because we identified that as a potential weakness in the study, now that opens the door for future studies, which we will now figure out what are the other big variables in this that we need to confirm.

Problem with people, young adults with mental illness is that sometimes that's not as simple as a definition. It's very difficult to validate the severity of that mental illness and especially patients adherence to treatment regimens. So on the summer that they are coming in for having surgery done with some elective procedure – say third molars – their anxiety may not be high because they're not in school or they don't have other stressors in life. So they may not be adherent to their medications that they've been prescribed by their primary care. So how do you then adjust for that? Is it the medication that's the issue? Is it the level of anxiety that's the issue?

Same with schizophrenics and bipolars that were involved in our study. Some of these cohorts were represented by really small groups. So we didn't have a huge number of bipolar patients in our group. So, is that number enough for us to pinpoint and say, hey, you, you know, you got bipolar. We need to throw so much more buckets of propofol at you to get you sedated for this procedure versus not.

So, we could not really like get this to a point of clinical relevance. We just identified that, yeah, you're right, the anecdote that we've always knew, known that, you know, patients with mental illness may need more propofol – or other drugs too – is indeed true. But how much more? We don't know. And how do we get there? We'll have to do future studies.

Host: Well, as you said, this opens the door to further research to understand that. But right now, how can the average OMS apply these findings to their everyday practice?

Deepak G. Krishnan, DDS, FACS: That's the most important part, right? So, how many of us are really looking carefully at patients’ mental illnesses when they are filling out medication lists in our office? There's a certain stigma associated with a teenager coming in that says, “Hey, I've got uh severe anxiety, I take medications for depression.” Or, “I have a family history of schizophrenia. By the way, I also use marijuana for anxiety.” And that becomes now a variable in this whole equation because we know that patients who use cannabinoids will really need more anesthetic. But the clinician needs to be aware of the fact that that's a question to ask. That's a question to ponder a little deeper and also get more investigations through.

So, don't simply check off the box saying, oh yeah, every kid in my neighborhood, my suburb has anxiety, and we should probably add anti-anxiety medications to the public water supply here. No, don't take that lightly because some of the medications that these children or young adults are on have implications in what you can give them in the office. If you add a lot of narcotic pain medication to get them super sedated and they are on a particular class of drugs called SSRIs, that could trigger significant conditions like a serotonin syndrome in the office, which is potentially lethal and so that's something to be aware of and I think studies like what we have done and what we plan to do in the future with this subset of patients and looking at multiple covariables and things like that, will kind of hopefully draw the curtains up and shed some light on a very neglected part of our population that seek our care.

Host: Yeah, and I'm wondering, Dr. Krishnan, what advice you might give to an OMS who may be hesitant in treating patients with complex mental health backgrounds?

Deepak G. Krishnan, DDS, FACS: Yeah, so that severity is what the real difference is. OMSs need to realize that the complexity of an illness sometimes has so many other factors that affect that, including seasons, especially mental illness. You could have seasonal variation in somebody's severity of their mental illness. You could have situational variations. You know, if they're coming in with a relative that is not particularly kind to them, their anxiety level may be higher. If they are being brought in by a mental health institution, there's a different level of management for those patients altogether.

There are some patients that do just fine in our offices with the standard cocktail of medications we do with these kind of medical conditions, but to kind of dig a little deeper is the key. And never shy away from saying, “No, you're not a good candidate for my office anesthetic. As small and simple as the procedure is, you are a candidate for your own safety that I would prefer to do at the outpatient surgery center or in a hospital setting.” And that's the key with these patients is that sometimes they're just not good for you to treat them in your offices and never shy away from saying no to that.

Host: Right. That's good advice. So, knowing that we are paying more attention to mental health as a society, and as you said, more and more people are coming to see an OMS that have a mental health issue, whether it be anxiety or something else. So, knowing this Dr. Krishnan, what implications do you think your findings have then for future research in anesthesia management for patients with mental illness?

Deepak G. Krishnan, DDS, FACS: Yeah, that was the best part that came out of this. We realized when you do a 500-patient study, that there are certain cohorts within that study that require a little bit more, deeper investigation. And that's where we are taking the study next. We, what we found was there were some type of standardizations that we could have done in a prospective manner that would allow us to actually get more meaningful data.

And we fortunately – or unfortunately – practice in a setting that has a lot of cohorts of different types of mental illnesses. And so, we are able to get patients into all of these subgroups and the next level of the study would potentially go into studying each of these subgroups, whether they are patients that are being treated for moderate sedation, which is a lower level of sedation, versus those that require a higher dose of sedatives and what we would call consider general anesthesia.

The types of medications. There are some new medications in the field of outpatient anesthesia that we haven't studied yet. And also kind of looking at those that come in with other layers of complexities. In addition to their mental illness, is there an ability for us to study mental illness with cannabinoids that are being abused by that patient, without the cannabinoids, the marijuana smoking, and then the adjunctive anesthetics that are used by clinicians.

So, the future studies that we are planning out of our center will be prospective in nature. We'll look at multiple medications. We'll look at all the variables that we struggled with in this particular study and standardizing them, and then take it to the next level. So hopefully we'll have some meaningful – more meaningful – data with this cohort of patients.

Host: Well, what you're learning now is certainly the first step in many steps to come. If I could ask you to look into your crystal ball, Dr. Krishnan, I'm just curious, how do you see the evolution of anesthesia practices for patients with mental illness in the next few years? How do you see this unfolding?

Deepak G. Krishnan, DDS, FACS: Yeah, I hope that safety remains first in our dealings with this new societal awareness. And I also feel that patients do get labeled with sometimes diagnoses that never leave them. So the astute oral maxillofacial surgeon providing anesthesia for these patients in their offices will understand the implications and the little undulations in what mental health truly means to a patient.

Somebody is anxious about a procedure does not necessarily mean they need to be medicated for anxiety on a chronic basis. Somebody who has true conditions like schizophrenia, bipolar, other severe mental illnesses, do need to potentially be treated in a hospital-based setting and not good candidates for office-based setting.

But in the crystal ball, I also see oral and maxillofacial surgeons dabbling with newer medications that have better safety margins, that are easier to manage these patients without the complications expected from some of the current medications that we have.

We also probably at some point will have the societal pressures to continue our practices in outpatient surgery centers as well as hospitals as opposed to being cowboys that do everything in the office and resist going to the hospital under any circumstance. So, if I have a wishing list, you know that would be that fewer of our colleagues move away from this trend of, “I want to do everything and anything in my office and I hate going to the hospital,” versus, “You know what, these are, there's a subset of my patients that I need to truly treat in the hospital and my presence there is much more valuable than before and I need to reserve time at least once a month, once every couple of weeks, to go to the hospital.” Even if the procedures are small and not necessarily intense or serious or anything too big or complex, the very fact that I can do it much more safely with another provider in a, in another setting, different from my office is valued and that's where I hope that we will truly take this.

Host: Yeah, that is important as well. Even for somebody that might have anxiety about the procedure to help comfort them and put them at ease, more so in a hospital setting, that seems to make sense.

Deepak G. Krishnan, DDS, FACS: Yeah. The economics play a big role in this, you know, the cost of and the efficiency of providing care in an outpatient surgery center versus an OMS office versus a hospital. It's significantly different, and certain insurances, third party payers, don't necessarily accept the idea that a tooth extraction has to be done in a hospital setting, even if they're not good candidates.

It's counterintuitive if you think about it. It's not the procedure that you're trying to do, it's managing the patient in a different setting that you're trying to do, and so those pressures are real in the real world, and hopefully the third parties will also adhere to these ideals of safety.

Host: Yeah, that does add another layer on it. Absolutely. Well, Dr. Krishnan, this has really been informative. Before we wrap up, is there anything else you want to add about your study?

Deepak G. Krishnan, DDS, FACS: Yeah, so this, what I've learned from – thank you for that question, because what I've learned from trying to put this together is the fact that can you imagine every third person that comes to us brings a burden of mental illness to our offices? We as a society have ignored that, have kind of hidden behind the concept of grit resilience and take it you know, like you mean it attitude.

And that's sometimes okay. But it's not always the best way to take care of our patients. When people have different coping mechanisms and if you are not familiar with their coping mechanisms, don't poo-poo the idea that they are struggling with their anxiety or mental illness. And be aware of the fact that different people cope with it differently, and what you deem as resilience may be a significant coping mechanism that is failing for somebody and their built-up anxiety will come under attack under anesthesia in your office and may trigger a catastrophic event. And you don't want to be at the receiving end of that.

And so, be aware that different people bring different levels of mental illnesses and coping mechanisms to your practices. And that number is higher now than ever. Primarily because of our understanding of mental illnesses and also our awareness of that.

And that not only applies to our patients, but it applies to people around us, our office staff, our families, our friends, and ourselves. So pay attention to mental illnesses, mental health in particular, not necessarily illness. And don't take that lightly.

Host: Very well said. Yeah, the old, you know, suck it up and deal with it. And yeah, don't be a baby. That’s uh, that doesn't quite, uh, work, uh, always right? And that could be the worst thing you could do for people. Is that right?

Deepak G. Krishnan, DDS, FACS: That's absolutely right. I don't think that has ever worked and what you leave behind is a trail of traumatized patients that you have made worse for the next person that's trying to help them. So that's not necessarily a good methodology of practice. Be kind, be empathetic and do the right thing and if that means going to the hospital, that's okay. There's a reason why you do things in the hospital.

Host: Absolutely. And you don't want that leading to medical complications as you referred to.

Deepak G. Krishnan, DDS, FACS: Indeed.

Host: For sure. Dr. Krishnan, this has really been interesting. Would love to have you back when you do the second and third parts of your research as well. Thank you so much for your time. I really appreciate it.

Deepak G. Krishnan, DDS, FACS: Absolutely. Thank you very much and I appreciate AAOMS giving me this opportunity to share my work.

Host: You bet. We are happy to do that. And once again, that is Dr. Deepak Krishnan. And for more information on the study, visit AAOMS.org/JOMS. That's J-O-M-S. And if you found this podcast helpful, please share it on your social media and make sure you subscribe so you don't miss an episode. Thanks for listening.