Podcast: The rise of ketamine
Transcript
Dr. Blair Bigham: Welcome to the CMAJ podcast. I'm Dr. Blair Bigham.
Dr Mojola Omole: And I'm Dr. Mojola Omole.
Dr. Blair Bigham: Pain is one of the most common complaints for patients visiting the ER, and pain management has become a quality of care indicator. But we don't always have great options to treat pain. Patients often push back against non-pharmacologic therapies. Tylenol and NSAIDs have often failed prior to their ER presentation. And for many, narcotics bring up concerns for complications and dependence. Sadly, our medications for pain aren't always great. Many people have allergies or contraindications to non-narcotic choices, or are already on chronic opioids. And recently the opioid epidemic has led physicians to avoid narcotics, leaving them to try alternatives that don't have the best scientific evidence for acute pain treatment. Drugs like lidocaine, tricyclics, and gabapentinoids. Ketamine has also entered the scene, and it's making its way center stage in the search for non-opioid pain relief for acute conditions.
Dr Mojola Omole: So for example, when we look at IV lidocaine for pain management in the acute study, systematic reviews have shown that there's inconsistency in the dosing, how long you administer it for, the lack of serum monitoring, and the absolute safety of IV lidocaine for acute pain is still unknown. So until we have large prospective studies on this, we can't routinely be using IV lidocaine for the management of acute pain.
Dr. Blair Bigham: So Jola, I've been trying to use ketamine more and more in my practice, not only for conscious sedations, which I'm a big fan of ketamine for conscious sedations, but also using ketamine for acute pain in much, much lower doses. And we're going to talk a lot more about that today. But it's been a bit of a struggle. A lot of people kind of look at me like I have three heads when I bring up ketamine. Have you tried it where you work?
Dr Mojola Omole: So my situation is I don't get to try it as a surgeon. I have seen some of the anesthesiologists use it to help with pain management post-op. It seems to be two camps: some who believe that it works and others who don't. And so this was a really great topic for this podcast episode.
Dr. Blair Bigham: Absolutely. So this has applications for outpatients in the ER, for inpatients, for postoperative patients. Anesthesiologists, of course, have been using ketamine for a long time, but it does seem like it's really making its way to the forefront for acute pain.
Dr Mojola Omole: Looking at the data, it is probably time for us to start looking at the practices around ketamine, and whether there needs to be an update when we're talking about acute pain and chronic pain and other disorders.
Dr. Blair Bigham: And that makes this episode very timely, especially given the CMAJ article that just came out, Five Things to Know About Ketamine for the Treatment of Acute Pain. The lead author, Dr. William - who I know as Billy - Silverstein, is a General Internal Medicine Fellow at the University of Toronto.
Dr Mojola Omole: Dr. Silverstein, if you had to summarize your paper in one sentence, what's the most important thing you think physicians need to understand?
Dr. William Silverstein: That ketamine at sub-anesthetic doses is effective and safe for treatment of acute pain.
Dr Mojola Omole: So, before writing this paper, what was your experience using ketamine?
Dr. William Silverstein: So truthfully, where I did a lot of my training at Sunnybrook, we have a lot of physician champions of ketamine at Sunnybrook. And David Juurlink, who is one of our co-authors, is a real proponent of using low dose ketamine for treatment of acute pain. And so in that setting, I've seen it used pretty often for when patients have appropriate indications for such. And truthfully, anecdotally, it seems to work pretty well. I recall one of my colleagues was managing a patient that had COVID, had a really severe COVID migraine. They were getting opioids, NSAIDs, and Tylenol, and all these things wasn't really working. And they then have a one time dose of low dose ketamine and kind of poof, their headache went away. So anecdotally I've had very positive experiences with using low dose ketamine for treatment of acute pain.
Dr Mojola Omole: So that's one thing I wanted to chat about that I'm very interested in. When we talk about acute pain, can this be patients who also have like acute on chronic pain? So this is a patient who has migraines, usually well controlled, and then they're just going through a period of just intense migraines that they can't seem to break. Would ketamine be useful in that scenario?
Dr. William Silverstein: Yeah, definitely. So for low dose ketamine, it's when anybody has an exacerbation of their acute pain. For example, there are studies in the sickle cell disease population, when patients have a flare of their sickle cell disease, there's been studies to show that use of ketamine in that context works quite well. So definitely it's not only for when somebody has a novel acute pain, like if they're post-op or they just had surgery, but also in scenarios where patients have flares of diseases that give them pain chronically, there's definitely data to support its use there.
Dr Mojola Omole: What got you interested in looking at ketamine for acute pain?
Dr. William Silverstein: Yeah, so we have a lot of patients admitted to us who have pain from various issues, back pain, stomach pain, chest pain. And a lot of our patients are elderly, they have comorbidities that don't let us use NSAIDs. Tylenol works, but I think it only works so well. And then obviously we're aware of the negative side effects that opioids can have for management of acute pain.
Dr. William Silverstein: And so, in exploring alternative treatment plans for this, ketamine is a very interesting option because there really are not that many side effects that we're limited in using it for, whereas for NSAIDs and opioids, you're a bit more cautious in using it. And I think we're all keenly aware of the negative effects that opioids have had, and I think most inpatient internists are looking for ways to avoid opioid therapy if you can. And so this just seemed like a really nice way to advance the quality of care of patients.
Dr. William Silverstein: And yeah, so I think that was my own personal anecdotal clinical experiences looking for a pain medicine that can help, just given the barriers that we have to accessing other modalities of pain management.
Dr Mojola Omole: So I guess just a little bit more of a nitty gritty that might be of interest to some of our listeners is, so you have a patient, let's say they come in like the migraine situation. Is it a one time dose that they're getting of this ketamine, or is it something that they continually get?
Dr. William Silverstein: The way ketamine is dosed, it sort of depends, but basically, for intravenous ketamine, it can either be given as an intermittent infusion or it can be given as a continual infusion. I think if it's somebody's first time on ketamine it probably makes sense to start with an intermittent infusion, and then see how somebody responds to that. And then depending on the quality of their pain, the nature of the pain, it could make sense to up-titrate the dose. You could consider giving a continual infusion, or just use intermittent dosing. So with intermittent dosing it's usually given every four hours, and then a continual infusion obviously is run continually.
Dr. William Silverstein: I think a lot of this also depends on hospital policy, what's available on the ward, nursing requirements, et cetera. But that's how you could start it, either with intermittent infusions or continual infusions, depending on the pain syndrome that the patient is presenting with.
Dr. Blair Bigham: Billy, walk me through this in real life. How do you write the prescription for ketamine for acute pain?
Dr. William Silverstein: Yeah. So for example, at Sunnybrook there's a really nice order set that we use to guide this, but it's weight based dosing. And so I think the first thing is obviously weighing the patient, making sure they have an appropriate indication for such, and going from that. And then I think depending on how you want to dose it, as we spoke about, you could either use continual infusion or intermittent infusion. And so basically what you would write is ketamine IV 0.1 milligrams per kilogram. And then if you're planning to run it as an infusion, 0.1 milligrams per kilogram per hour. If you're planning to run it as a one time infusion, 0.1 milligrams per kilogram IV over 10 to 15 minutes.
Dr. William Silverstein: We then ask that, for monitoring purposes, that nursing monitor pain scores and mental state, things like agitation and confusion at baseline, and every four hours until ketamine is discontinued. And then I think from a safety perspective, including that if the patient is receiving ketamine and is experiencing hallucinations, irrational behaviors, agitations, those sorts of thing, stop the infusion, notify the MD and then institute the institution's behavioral policies, if necessary.
Dr. Blair Bigham: And how did you get this to work out in practice at your institution? The other week I tried to do this in my emergency department. I ordered 10 milligrams of ketamine over 10 minutes for someone with horrible pain. And I was told I needed an RT and a resuscitation room, and it just became so complicated that I gave up. How do you guys do this where you work?
Dr. William Silverstein: Yeah, so I think the real key is really having institutional support and endorsement of this. And so at Sunnybrook, for example, there's actually an order set for low dose ketamine for pain management on the medicine floors that's been approved by pharmacy and therapeutics and what not. And so having the institution believe in this as a therapy, I think is really key, because as you've stated, there's a lot of concern in giving ketamine at these low doses on the floor. I think it's fair enough, ketamine is an anesthetic. Usually if you're giving an anesthetic at a milligrams per kilogram to intubate someone, that's a totally different story. But I think a 10th of the dose, the data's pretty compelling that those anesthetic effects really do not occur. And so I think a real push on this and a real area to move forward is really starting to garner that institutional support.
Dr. Blair Bigham: One of the things I always have a hesitancy over is using opioids when I have elderly, very sick inpatients, and I'm so worried about precipitating delirium. Any connection between ketamine and delirium? Maybe it reduces delirium, or any concerns there?
Dr. William Silverstein: Yeah. So I don't know of any data to show that ketamine helps with delirium. That being said, we know that at the doses that are used to treat pain, those adverse effects of high dose ketamine that are seen with anesthesia, the hallucinations, the dissociations, we know that it doesn't occur anymore than placebo at low doses. And so I think obviously if someone is frankly psychotic, that's a pretty strong contraindication to using ketamine. But I think otherwise there's pretty compelling data that the adverse effects of ketamine don't occur any more frequently at low doses as compared to placebo. And so I think it's fairly reassuring that it's probably safe to use at those low doses.
Dr Mojola Omole: So we've talked about what's exciting. What are some of the biggest concerns or challenges with giving ketamine in the hospital?
Dr. William Silverstein: So I think, before giving it, obviously contraindications need to be considered. So ketamine is not recommended in patients that have psychosis, those with severe cardiovascular disease, patients with liver dysfunction. And then the data in pregnancy is mixed. And so consulting with an expert in that setting is recommended. I think, truthfully, there's probably a lot of stigma as well with respect to ketamine. I think a lot of people view ketamine as an anesthetic agent, which it is, but the doses that are used for pain are a 10th of what's used for anesthetic doses. So, whereas in the operating room a dose of one to four and a half milligrams per kilogram is being used, on the floor, for low dose ketamine, it's really a dose of 0.1 milligrams per kilogram. And so I think a big barrier that has to be overcome is that those adverse effects that are seen with high dose ketamine, things like hallucinations, dissociation, they really do not occur more than placebo at doses used to treat pain.
Dr. William Silverstein: And so I think there really needs to be a big cultural shift to really accept that low dose ketamine is safe, it's effective. And there are institutes that are administering it on the ward now, but obviously that requires quite a lot of institutional buy-in. It requires buy-in from our allied health colleagues, pharmacy and therapeutics, that sort of thing. So I think the data's pretty reassuring. So I think something that we're hopeful for is that by showing what the data is, showing how safe it is, that some other institutions will be excited about this and try to uptake it.
Dr Mojola Omole: So Dr. William Silverstein, AKA Billy, is the lead author of Five Things to Know About Ketamine for the Treatment of Acute Pain. He's a General Internal Medicine Fellow at the University of Toronto. Thank you so much for joining us. This has been really informative, and hopefully our listeners have found nuggets to be able to implement in their own practice.
Dr. William Silverstein: Thank you so much, it's been a pleasure. And thanks for having me.
Dr. Blair Bigham: So the CMAJ article really focused on acute pain, but we know that people are using ketamine with an even wider lens, using it for chronic pain and even depression.
Dr Mojola Omole: So one physician who's doing just that is Dr. Marshall Ross. He's an emergency physician out in Calgary, and he's the Chief Scientific Officer at the Newly Institute.
Dr. Blair Bigham: Thanks for joining us.
Dr. Marshal Ross: Yeah, thanks for having me. It's a pleasure to be here.
Dr. Blair Bigham: Marshall, were you surprised to see Dr. Silverstein's review in CMAJ?
Dr. Marshal Ross: To be honest, I wasn't. I have been a proponent of ketamine for some time. I was familiar with most of the literature that was quoted, and I was quite happy to see this message being disseminated to my colleagues across the country.
Dr. Blair Bigham: When did ketamine become a regular tool in your toolbox for acute pain?
Dr. Marshal Ross: Well, I'm an emergency physician. I worked for years as a transport physician. So ketamine has always been one of the most important tools in my toolbox. I started using ketamine for acute pain fairly early on after I finished residency. So I've been a staff physician for about six years, I'd say I've been using ketamine for five and a half.
Dr. Blair Bigham: Marshall, tell me about why you became so interested, not only in acute pain, but also in chronic pain and opioid use.
Dr. Marshal Ross: I would say when I was deciding what specialty I wanted to enter, I was considering mental health, I was considering addiction medicine, I was considering emergency medicine. The reason I ended up going into emergency medicine was because there were effective tools to fix things. Setting a fracture is very satisfying. Stitching a cut is very satisfying. Whereas I felt in the world of mental health, there weren't that many tools that were highly effective. It seems like someone comes in with a heart attack or a gunshot wound, and I have millions and millions of dollars of resources at my disposal. But someone comes in with a life threatening disease, say opiate use disorder, and I basically give them a pamphlet and hope that they follow up as an outpatient. And I felt like we were really under-serving a large group of patients who were in need.
Dr. Marshal Ross: And so when I read about buprenorphine and naloxone as a treatment that could be provided in the emergency department, and some of the outcomes that Gail D'Onofrio was having down in Yale, I became very enthusiastic about bringing this presentation to the emergency department where I work. And that was a transition for me away from critical care and towards improving the treatment of addiction and mental health through the emergency department.
Dr Mojola Omole: So can you touch a little bit about how patients with opioid addictions, how you use ketamine in the emergency department?
Dr. Marshal Ross: In my mind, for patients with opiate use disorder, opiates are not a great pain medicine. Often most of their painreceptors are flooded. There's really minimal incremental effect, and you quickly approach the threshold for respiratory depression. So instead I like to use other modalities, obviously acetaminophen, anti-inflammatories, regional anesthesia, and ketamine bolus. And so really, I think that this is an ideal patient population to use an alternative analgesic modality such as ketamine.
Dr. Blair Bigham: Are there any other emerging medications that you're using, or that you see other people using for acute pain? Lidocaine or amitriptyline, or any of the gabapentinoids?
Dr. Marshal Ross: I haven't seen too much. I think where we in the emergency department can make a bigger difference is in improving our regional anesthesia skills. I think you can solve most pain with a bit of lidocaine injected in just the right place. So that's where I see the future of pain management in the emergency department. And I think that's also a probably under-served area of pain control in the emergency department.
Dr. Blair Bigham: Awesome. The future is bright.
Dr. Marshal Ross: I hope so.
Dr. Blair Bigham: Getting people off opioids would be a huge win.
Dr. Marshal Ross: Yeah, it sure would.
Dr. Blair Bigham: And then you've been expanding beyond acute pain in your use of ketamine. You've used it for chronic pain and depression. Tell us a little bit about that.
Dr. Marshal Ross: Yeah. So I do a lot of work in the mental health sphere. We run a clinic where we use ketamine and ketamine-assisted psychotherapy to treat depression. One of the powerful indications for ketamine is in treatment-resistant depression. So if you take people who are depressed, they're on multiple antidepressants, they don't work. They've had adjunctive therapy, it doesn't work. They're still depressed. About 70-80% of these patients will respond to ketamine. And that's pretty amazing. Those results are similar to ECT or electro shock therapy.
Dr. Blair Bigham: And what route are you using for those patients? Are they going home on oral ketamine? Is this a one time IV dose?
Dr. Marshal Ross: The best evidence for ketamine in depression is definitely with IV ketamine. What we're doing at the Newly Institute is we're providing sublingual ketamine in a dosage that is essentially equivalent to what you'd get through the IV protocols. We're monitoring patients in the clinic and providing them with psychological support throughout their experience. And so it's a slightly different model than 'get the IV ketamine and leave'. It's really more about exploring your unconscious psyche and removing barriers to exploring past traumas.
Dr. Blair Bigham: Can you just draw the ketamine right out of the bottle, like the IV formula, and put it under the tongue? Or is there like a wafer that you order? I'm not familiar with other ways to give ketamine other than IV.
Dr. Marshal Ross: Yeah. We work with local compounding pharmacies to make rapid dissolving tablets that go under the tongue. It's like a chalky tablet that creates a paste under your tongue and absorbs through your mucus membranes.
Dr. Blair Bigham: Very cool. What sort of responses do you get from other physicians when they hear about how much you're using ketamine? Do you get any pushback?
Dr. Marshal Ross: In the world of emergency medicine, ketamine is a bit of a darling. So we like ketamine for multiple indications, for chronic pain, for acute pain, for resuscitation. So generally ketamine is a well accepted medication in the world of emergency medicine. I would say particularly in more recent graduates, the use of ketamine for a variety of indications is very well accepted.
Dr. Blair Bigham: Can you think of a story that sticks out in your mind about a time that ketamine worked especially well for one of your patients?
Dr. Marshal Ross: I think what stands out the most to me are mental health patients that I've worked with. We had a patient recently come through our protocol at the Newly Institute, came in consistently looking at her feet, would not make eye contact, really would not engage in therapy, was really closed-down. And I worked with her and watched her over the last four weeks completely transform. She became a completely new person. I was actually just on a call with her before I got on the line with you guys, and she was bright, she was interacting with her kids, she was talking about her plans for the weekend. She was thanking me for my care, saying she felt like a new person, felt like this fog of depression had been lifted. And she said a large part of the reason was being able to explore past trauma that she was never able to work through, and that was in her unconscious psyche keeping her back. After years of therapy, unable to process this trauma, she was able to work her way through it. And ketamine was a big part of that.
Dr. Marshal Ross: And seeing the transformation of this person is, I think, the most powerful patient interaction that I've had.
Dr. Blair Bigham: Sounds pretty amazing. You're really on the cutting edge of the future of ketamine. What do you think is required to bring ketamine more into the mainstream?
Dr. Marshal Ross: That's a great question. I think it depends on what setting we're talking about. In the emergency department, I think it just takes some knowledge translation and some additional comfort with low dose ketamine treatment. In the mental health world it's a little bit more complicated, because it's not as easy as simply writing a prescription and sending someone home to take their ketamine dose. You need infrastructure, you need to have staff, you need to be able to monitor people safely, screen them properly. And so I think there's a number of barriers to rolling this out on a wider scale.
Dr. Marshal Ross: But I do think that certainly the work we're doing at the Newly Institute, we're building multiple clinics across the country to broaden access to this treatment. And there's other organizations doing similar work. And I think this is really what it's going to take to broaden access to the wider population.
Dr Mojola Omole: When I reached out to my department's anesthesiologist and I was like, "Hey, doing this episode on ketamine, is anybody in the department doing it?" She's like, "ou know, some people swear by it," but she thought that there wasn't robust evidence for it for acute pain from the anesthetic point of view. Because I think when you see people in the PACU, in the K hole, so that's what they see. And so I found that interesting that anesthesia actually was not as keen for it, versus mainly the people who deal with like the chronic pain. And so I thought that that was interesting.
Dr. Marshal Ross: Yeah. I mean, remember the only Health Canada indication is for intubation in the ICU. It's for general anesthesia. And so that's how most anesthetists view ketamine, as a general anesthetic agent. There's been less exploration of the uses of the various dosing protocols. I think that that's more readily embraced by emergency physicians.
Dr. Blair Bigham: Marshall, thanks so much for joining us. This has been really helpful.
Dr. Marshal Ross: Well, thanks so much for having me. It was a pleasure.
Dr. Blair Bigham: Okay, Jola, let's see if we can come up with some takeaways from what we've heard.
Dr Mojola Omole: Number one for me is that ketamine is safe and effective in the treatment of acute pain using low doses. And that we do not need any special monitoring for this. And that we need administrative buy-in to be able to start implementing this. And it is one more tool, so we can avoid opioid dependencies in our patient populations.
Dr. Blair Bigham: Absolutely. And I really took away how low that dose has to be: a fraction of what I would use for a conscious sedation or for an intubation. I remember, in residency, trying out ketamine on a patient with acute pain in the ER. I think we had used something like 30 or 40 milligrams, and we didn't run it over 20 or 30 minutes. We sort of just pushed it, and the patient did become a little bit uncomfortable with some hallucinations. So I think this idea of 10 milligrams, 20 milligrams over 10 or 20 minutes is the key to making ketamine work safely.
Dr. Blair Bigham: Billy also talked about how important it was to have buy-in from the institution. Sounds like every institution is going to need to look at some policies and do a bit of work with allied health and pharmacy, and maybe do a bit of education around the differences between ketamine doses for anesthetic or sedation purposes, versus when we're just using it in a very low dose for acute pain. A lot of acute pain like migraines and low back pain, we see these in rapid assessment zones, in emergency rooms or urgent care centers. We don't necessarily see these in places that have suction on the wall and a bag valve mask readily available. And so I think it's really important that institutions embrace this in low acuity areas, and that we not have to try to move people into a high acuity zone just to be able to treat their pain and get them on their way.
Dr Mojola Omole: It's a perfect topic for inservices, for both allied health, nurses, physicians, just to learn more about ketamine for pain management. Listening to Dr. Silverstein, it never occurred to me that we can give that to a patient on the ward when we can't manage their pain with just opioids. I've had patients who are like that, and using ketamine could have made a difference in terms of their pain.
Dr. Blair Bigham: Absolutely. And giving you that avenue for people who are on chronic opioids, or maybe on Suboxone or methadone and you're going, "Jeez, I really want to be able to get this patient's pain under control!" You just feel like you have so few options. But here ketamine comes to the rescue.
Dr. Blair Bigham: Jola, do you have any other go-to's in your back pocket for people who are in really bad pain on the wards? Let's say they're allergic or have a contraindication to an NSAID, and you've tried a bit of morphine. Anything else in your back pocket, or?
Dr Mojola Omole: I call anesthesia for acute pain management. Because for me, nothing cures faster than cold, hard steel. So if it can't be cured by steel, I don't know. But in all seriousness, it is actually important because oftentimes you do feel tied. Because we go through, you feel like you've maxed out in terms of how much Dilaudid you can give the patient, you've added long-acting, you've added Gabapentin, Lyrica, all of those things. And sometimes we have patients who have Crohn's who are acute-on-chronic. So being able to use something like ketamine would be very useful for that population. So for me, postoperatively, I use small doses of Dilaudid. I only give out 10 tabs of one milligram. And then I ask the patient if they can tolerate NSAIDs to be on it, Q6, and then Tylenol Q4 also. And only using the Dilaudid as needed.
Dr Mojola Omole: And in addition to that, I, in general, love regional anesthetic for patients, and try to make sure that all my patients if possible can have blocks, because I do find that that really cuts down on the amount of opioids that's needed. And it's not just me. Studies have been done, one out of North York General that showed that you can decrease opioid use by using regional anesthetic.
Dr. Blair Bigham: I have a pretty similar approach when I'm discharging patients from the ER: maximize their Tylenol, maximize their NSAID, a touch of narcotic if I can't get away from it. And then also I think it shows a bit of our desperation to avoid opioids. Sometimes I'll dabble with a bit of a gabapentinoid, send someone home on Lyrica, amitriptyline. And I get criticized. There's not a lot of good evidence for that. But there's just so much evidence for harm when I send people home on high doses of narcotics. And in the ICU we've had adverse events where people are just very sensitive to a small squirt of Dilaudid, and all of a sudden you're chasing your tail. So I really think that we're just so desperate for more evidence and more options for treating acute pain that ketamine, I think, is certainly in its prime right now.
Dr. Blair Bigham: And that's it for this episode of the CMAJ podcast. Let us know what you think. Are you a ketamine convert, or are you skeptical? Leave us a rating or review in Apple Podcast, Spotify or wherever you get your podcast.
Dr Mojola Omole: Also, please share this episode. Rating, reviewing and sharing episodes is the best way to make this podcast easier for others to discover. We really appreciate it.
Dr. Blair Bigham: This episode was produced by PodCraft Productions. I'm Blair Bigham.
Dr Mojola Omole: I'm Mojola Omole. We'll be back in exactly two weeks. Be well, and thanks for listening.