Wilderness Medicine Updates
The podcast for medical providers at the edges, bringing you digestible updates at the growing edge of Wilderness Medicine, Wilderness EMS, Search and Rescue, and more.
Wilderness Medicine Updates
Ep. 19 - Methoxyflurane, the Green Whistle, with Dr. Ross Hofmeyr
Exploring Methoxyfluorane for Wilderness Pain Management with Dr. Ross Hofmeyr
In this episode of Wilderness Medicine Updates, host Dr. Patrick Fink discusses the use of methoxyfluorane, an anesthetic gas for pain management in wilderness settings. Joined by guest Dr. Ross Hofmeyr, an anesthesiologist and wilderness medicine expert from South Africa, the episode delves into the history, usage, benefits, and limitations of methoxyfluorane. Highlighting its efficacy, ease of use, and safety, especially for pre-hospital scenarios, Dr. Hofmeyr shares insights into its ideal applications, contraindications, and personal experiences. The episode underscores the significance of methoxyfluorane as a potent analgesic suitable for acute traumatic pain and procedural analgesia in austere environments.
Links
Methoxyflurane at Altitude - Case Report
Methoxyflurane in the Outback - Survivor Clip
WMS Pain Management Guidelines
Chapters:
00:00 Welcome to Wilderness Medicine Updates
00:55 Meet Dr. Ross Hofmeyr
03:14 Dr. Hoffmeier's Background in Wilderness Medicine
04:45 Methoxyfluorine: An Overview
12:20 The Mechanics of Methoxyfluorine Inhaler
20:15 Practical Applications in Pre-Hospital Pain Control
20:53 Analgesic Intervention: Quick and Effective
21:09 Using Methoxyfluorane in Wilderness Settings
22:42 Training Non-Medical Personnel
23:49 Procedural Analgo-Sedation
24:30 Regulatory Considerations and Prescriptions
26:33 Combining Methoxyfluorane with Other Medications
28:10 Monitoring and Safety
29:09 Ambulating Patients with Methoxyfluorane
31:31 Environmental Considerations: Temperature and Altitude
40:10 Cost and Practical Downsides
41:45 Conclusion and Final Thoughts
As always, thanks for listening to Wilderness Medicine Updates, hosted by Patrick Fink MD FAWM.
Connect with us by email at wildernessmedicineupdates@gmail.com.
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And there's this iconic image of this guy coming across the river with this massive green whistle in his mouth. You know, and the paramedics kind of holding him in his hands as he, as he wades through. And all of us in South Africa went, you are my brew. Look at this. They've got lack of, lack of bongs there. Hey. And, and turned out it wasn't marijuana. But it was, it was methoxy, Florin. And that really sort of went bing for many of us in the rest of the world going, well, hang on a moment. Why don't we have this? We, we want this.
Patrick:Hello, and welcome back to Wilderness Medicine Updates, the show for providers at the edges. I'm your host, Dr. Patrick Fink, and I'm happy to be talking today about methoxyfluorine. What is methoxyfluorine, you might ask? And if you ask that question, you probably live in the United States. Methoxyflurane is an anesthetic gas that can be used to treat pain in the wilderness environment. It comes in a nifty little package, and we're going to talk a lot more about that, and I'm super happy today to be joined on the show by Dr. Ross Hoffmeier. Ross is an anesthesiologist who lives and works in an academic setting in South Africa, but he has a much more varied and interesting wilderness practice that goes well beyond the confines of the hospital walls. As you'll discover, Ross is a wealth of information about methoxyfluorane, its prior use in anesthesia, and its use now in the wilderness and pre hospital setting, both its benefits as well as some downsides and some settings where it may or may not be terribly effective. If you want to learn more about Ross, What this medication is, how it's used, how it fits into his pain management plan, ideal settings for its use, contraindications, and most importantly, what made him say that in the cold open, I owe a big thanks to Aaron and Eddie, two listeners who wrote in with questions about methoxyflurane after our last episode on ketamine. I always love getting listener questions and there's more in the inbox, some. Conversations that have been ongoing that are going to bring some interesting episodes to you guys. So please continue to reach out as always wilderness medicine updates at gmail. com and I'll hit you with that again in the outro. Without further ado, here is Dr. Ross Hoffmeier.
Ross Hofmeyr:Mozambique was fantastic. We. flew into the backside of a tropical storm and into a country undergoing civil unrest with people thinking it was going to be going into a civil war. And it was absolutely blissful and peaceful. Sea was a bit heavy some quite big swells, but we got some great diving done and the people were fantastic and we had no problems. So it was really nice.
Patrick:Great. And now you're at the Wilderness Medicine Society Conference in Crested Butte.
Ross Hofmeyr:That's right. Yeah, I just wrapped up here in Colorado. If I look a little bit pink in the face, it's because it's been an absolute bluebird, sunshiny day here on the slopes and I've just got in about 20, 000 vertical feet of skiing in for the day.
Patrick:Fantastic. It sounds like a tough lifestyle. I know that your, your job by day is an anesthesiologist. How do you describe the rest of your roles and how that interacts with the world of wilderness medicine? Okay. Okay.
Ross Hofmeyr:as an anesthesiologist or anesthetist, as you say. I'm based at a university hospital in Cape Town in South Africa. and we'll see first heart transplant. My day job there is as a cardiothoracic anesthesiologist. And I do a lot of airway stuff as well. And so that's what pays the bills and brings home the bacon. But wilderness medicine has been my passion for a very long time after. Growing up through search and rescue as a, as a student in training and then as a junior doctor I served as the expedition leader and and doctor for our South African research team in Antarctica winter over there. And I've been involved in wilderness medicine and wilderness rescue ever since. And in the early noughties Mountain Rescue colleague and I started a small company, which has remained small called Wild Medics. We're based in Cape Town in South Africa, and we've been providing wilderness medical support and particularly over the last number of years, wilderness medical training with an African focus and flavor but obviously, you know, trying to incorporate the, the best international practices there as well. So, Wilderness medicine is my my mistress and my passion project. And the anesthesia is my, my day job.
Patrick:I'm glad that you're the person to come on and discuss this topic on the podcast. because after the last podcast on ketamine hospital pain control, I got a number of questions from listeners who wanted to know more about methoxyfluorine. when we were putting together the pain guideline, you were kind of the gas anesthesia guy but methoxyfluorine is not something familiar to me. It's. Not available in the United States outside of some ongoing clinical trials. So I wanted to begin sort of as the I'll play the novice here that I want to know what what is methoxyfluorine? Where where does this fit into the world of pain control and why have I never heard of it? Silence.
Ross Hofmeyr:a volatile anesthetic agent. It's an old drug. The first published clinical trials were in the late fifties, early sixties. It, so it's been around for a very long time. It is fairly unique amongst the inhalational anesthetic agents in that it also provides an analgesic effect. So most of our Inhaled anesthetic agents, particularly fluorinated drugs the ones that everyone's very familiar with would be things like isoflurane, sivoflurane, desflurane, those are the ones that are in modern use. joining us people probably will be familiar with, and we'll definitely talk about this a bit more, of course, is nitrous oxide. And that's commonly been used as an analgesic agent when it's mixed in a 50 50 concentration mix with oxygen, and that's known as oxen that's been used for labor analgesia. It's been used in pre-hospital analgesia. And, and, you know. People are very familiar with that concept of providing an inhalational drug, which gives, it gives pain control. So methoxy and nitrous oxide really are the only anesthetic inhaled agents we have that give that analgesic property. Now, an astute listener is going to say, well, hang on a moment. You can't actually anesthetize somebody with nitrous oxide because the, the, the Mac or the minimum alveolar concentration of the gas, which you need to breathe at sea level to render somebody unconscious is around 104%. and somebody 104 percent of an anoxic show you've got larger problems than anesthetizing them. You're just going to euthanize them. But the concept of giving someone a gas, which has got analgesic properties, I think is familiar to us from, from Entonox. Now, methoxyfluorine is actually right at the other end of the spectrum in terms of potency. So provided only a long time ago. When alveolar concentration, that's really the concentration at sea level of that gas in a breathing mixture, which will render 50 percent of, of patients or 50 percent of subjects non responsive to a surgical stimulus. So you give the person that much gas and half of people won't move or show any sign of a surgical incision. Now we add other agents to try and We work with those values and we monitor depth of anesthesia, et cetera and we're familiar with our everyday volatile agents, something like Desflurane that a lot of people may use the, the MAC value is around 6%. Sevaflurane is a little bit more potent. The MAC value of that is around. Let's say 2 percent for ease of discussion. Isoflurane, even more potent around 1. 2%. And the MAC value of methoxyfluorane So, is 0. 16%. So it's actually a very, very potent anesthetic drug The potency just in terms of the MAC value is that ignores how much of the, of the volatile agent is absorbed and, and dissolved into the bloodstream and particularly absorbed into the fat. So that has got a lot of the the, the lipid the has a lot to do with the, the speed of onset of the, of the different agents. the so methoxyfluorine, although it's very, very potent. Has actually, it's actually a little bit of a slow agent to anesthetize patients with. So when it came into clinical practice, and now we're talking, you know, 50s, 60s it was quite popular because Because a lot of the agent is becoming absorbed it then takes a very long time to, to come back out of the system and that gives you a really nice, long analgesic tail. So people would often mix volatile agents and they would use methoxy plus something else to get the patient off to sleep, turn the other agent off, run the patient on methoxyfluorine, and then at the end of the procedure, they may take quite a while to wake up, but they've got this beautiful analgesic tail. So that's really handy. Okay. And that's because it's no longer in clinical use for anesthesia. The problem with using it as an anesthetic agent is that if you use it at high concentrations for long durations, it has got a to take nephrotoxic effect. So it directly causes a in injury. In fact, I'm not quite that simple. it in. chemical byproducts, which cause a, cause a kidney injury. about we now know from the, from the literature, to is that that. and I'm A clinical nephrotoxic effect tends to emerge at around five MAC hours worth of dosage. So if you think of administering one MAC to keep a patient asleep for five hours, that's the kind of dose that you need to cause a clinically evident nephrotoxic event. And biochemical nephrotoxicity is around 2. 5 Okay. problem, of course, is that the moment that people started seeing these renal injuries coming out, there's a greater risk if you've got underlying renal disease and very, very rapidly, the Toxiflurane developed a bad rap and quite quickly it was taken off the market as an anesthetic agent. So that's, that's where it disappeared to. It was, however, even at that time in use as an analgesic agent and it was being used in a very, very simple draw over vaporizer. So effectively, you think about a tube with some wicking material inside, you pour some of the liquid methoxyfluoride inside, the wick helps to spread it around, the gas then vaporizes inside the inhaler, and you suck through it, and you get a, you get an inhaled dose. In fact, there was a, a device which it was called the the analgizer, be careful to pronounce that correctly if you read the packaging and it was being used for for labor analgesia and was also being used for pre hospital analgesia. And in fact, the, the typical labor analgesic dose was up to 15 milliliters or 15 CC of liquid methoxyfluorine into the inhaler and all that number 15 in your head, because Okay. the full duration of the last 50 or 60 years. And there's extensive literature and. You have tens of thousands of documented uses there as a pre hospital analgesic, which makes it very attractive for the kind of work that that you and I do.
Patrick:So the current manifestation is a device which contains some set amount of methoxy fluorine, which can be used in the field, sort of like probably the best analogy to the younger humans listening would be something like a vaporizer type device, right? Like it quite literally has a vaporizable liquid that sits on a wick. And as you breathe through it, it draws off some methoxy fluorine. But you're only achieving the level of the inhalational agent that will deliver analgesia, right? You can't possibly pull on this thing hard enough to make yourself pass out. Am I correct?
Ross Hofmeyr:You're mostly correct. So in fact, the device itself that, that now on the market, and it's sold in different areas of the world under slightly different names. Some, some places call it Penthrox, some call it Penthrop, some call it Penthrane but pretty much the same thing. And it now comes in a, in a big green plastic. Tube that looks a lot like a whistle. So some people talk about the green whistle. Frankly, you know, a big green thing that you suck on, which makes you quite lightheaded and feel a bit high is, as you say, very easily approachable concept to many people the younger people and probably lots of people here in Colorado but uh,
Patrick:Okay.
Ross Hofmeyr:on the device. There were some concerns
Patrick:I,
Ross Hofmeyr:particularly the pre hospital community in Australia that Because methoxyfluorine itself is incredibly aromatic you, you can smell the tiniest concentration of it in the air around you.
Patrick:of
Ross Hofmeyr:about people who were sitting in the back of ambulances with patients who were breathing on these green whistles that they might be getting a, an occupational exposure,
Patrick:much.
Ross Hofmeyr:to methoxyfluorine. And so the, the modern device is actually packaged with an, a little activated charcoal absorber. That clips into the exhalation valve. So it's got a one way valve. So when you, when you suck on it, it sucks through the device. And when you blow on it, it blows out through an exhalation valve. And you can put this little absorber onto it. And, and that then is supposed to capture a lot of the methoxyphore in it, but go out into the environment. And it's It's worth that I mentioned the absorber device because you can actually vary the dose that the patient is receiving by getting them to, to close the the air entrainment hole that's on the absorber. And if you take the absorber off completely, which for us in a wilderness environment where we're out in the fresh air would be entirely safe. Then they actually get a much lower dose of the methoxy because it. It entrains some air through the absorber hole on, and we actually documented this and quantified this in some work that I did a few years ago at Duke University in their altitude chamber. Unfortunately, I can't send you to the publication of that work. It's been presented at the WMS. It was supported by a grant from the Wilderness Medical Society, but we showed that actually you can vary the dose quite significantly by either occluding the hole, adding the absorber or, or leaving it open. So you asked whether. you can give somebody too much with with methoxyphorin inhaler? And the short answer is that for an adult patient breathing normal adult tidal volumes the answer is no. If you use the standard dose that comes in the vial, it's a three mil vial. Remember we said earlier. That for labor analgesia, they were giving 15 milliliters. So it's literally a fifth of the dose that was being used there. That gives you around 0. 3 years, 0. 26 to 0. 29 Mac hours worth of dose exposure, and that's, that's enough to make you feel a little bit dizzy, maybe a bit lightheaded, sometimes people complain of a bit of nausea or a bit of headache but it's certainly. And the best, the best expression that someone said to me is it makes me feel goofed. You just feel a little bit dizzy and out of it. But obviously it takes away a lot of your, a lot of your pain. For a normal size adult breathing on the device, they're not going to be able to get an anesthetic dose. So that's really quite safe. There is some concern and there've been a number of papers published where they've used this for pediatric analgo sedation and pediatric procedural sedation. And in fact, If somebody is unable to breathe through their mouth to breathe with the device, in fact, the outer diameter of the inhaler itself fits perfectly into the inner diameter of a normal medical face mask, so your anesthetic face mask, and so in some of those studies, they have They put it into a face mask and held that for for children. And there with a much smaller tidal volume, actually, there is a risk of approaching an anesthetic dose. One of the effects of methoxyfluorine, of course, the side effects is it causes drowsiness. Well, it's an anesthetic, so we're not really surprised. It's also quite a potent respiratory depressant. And so our. Our common practice and our common guidance is that it should, in a non monitored or out of hospital setting, it should be self administered by a patient. So if they start to get a little bit drowsy or their respiratory rate starts to decrease, they're naturally going to take it out, drop it, or they're going to inhale less of it. Rather than than holding it with with a face mask. So that's the, that's the caveat. It is not going to put you to sleep if you're using it as an analgesic in an adult patient. It's in most countries where it is currently available. It's off label for pediatrics in any case. But the proviso is don't attach it and breathe it through a mask.
Patrick:Much like nitrous oxide, we give the patient the control over the mask here, you're having them hold the whistle. And so if they're dosing themselves too heavily and becoming goofed, as you said, they will no longer be able to hold it to their mouth. Yes.
Ross Hofmeyr:Absolutely.
Patrick:so just want to confirm my understanding. You can modulate the dose by essentially controlling how much air is co inspired with the anesthetic agent. So if you were to the. air intake, then all of the gas which is being inspired is coming across the methoxyfluorine wick and get your highest level of, your highest dose. Allow the, allow that to be open to air, you get sort of a moderate dose, and then if you take the whole off, you're going to entrain further more air and result in a further lower dose, is that correct? This transcript
Ross Hofmeyr:That's that's 100 percent correct. So the highest doses, if you include the entrainment hole,
Patrick:Dakota is
Ross Hofmeyr:if you leave the entrainment hole open with the scrubber on, you get a slightly lower dose. And if you take the scrubber off, you get the lowest dose. And
Patrick:award
Ross Hofmeyr:it's so aromatic
Patrick:Doctor of
Ross Hofmeyr:who's practiced a little bit of anesthesia will probably have experienced
Patrick:Human
Ross Hofmeyr:a gas induction for a child using something like Sivaflurane. If you put a mask on and you crank that right up to a high concentration and the first breath or two is really concentrated volatile, people will often find that quite irritant. They'll have a bit of a cough. They might balk at that. And it's quite similar for me with Mesoxiflurane. I often tell people. To take their first one or two small breaths, keep the entrainment hole open, get a feel for the taste and the smell of the methoxyfluorine, see if it's having an effect on their pain. And the onset of analgesia is actually quite rapid. It's within you know,
Patrick:Yeah.
Ross Hofmeyr:getting used to that, if they're finding that they want more analgesic effect to then close that hole and to take nice, deep slow breaths through the inhaler.
Patrick:Okay, so now I think that's a pretty good overview of the nuts and bolts of the anesthetic background of methoxyfluorine, as well as the actual mechanics of the inhaler. And I'll put a link in the show notes to pictures of both the older green whistle and the newer device that has come out. Where does. Methoxyfluorine fall into your practice for pre hospital pain control? Where does it fit in with oral analgesics, IV, or, or stronger, you know, narcotic type medications? In what settings are you choosing to use it?
Ross Hofmeyr:Okay. That's a great question. So the first thing to recognize is that we're limited in the dose that we can administer. So we're giving about a three mil initial dose and depending on how rapidly somebody is breathing and, and you know, whether they're occluding the holes in the So the breath they're taking, that gives you about 20 to 30 minutes worth of analgesia. And then we can repeat that dose once if we're following the the package insert. So you're really looking at an analgesic intervention, which is it's immediately available. It's very quick to prepare that, you know, the device can be active within 20, 30 seconds, if you, if you're familiar with using it and it's giving you, let's say 32. To 60 minutes of analgesia the two main areas that I like to use it in my practice are number one Patients who particularly in the wilderness setting have had a traumatic injury and they need potent analgesia. So it is a potent analgesic. I wouldn't use it for you know, someone who's got a small laceration that just needs a bit of care. It's a potent analgesic. It's immediately available to be administered. It doesn't require me to get out IV access. It doesn't require me to open any vials. I don't have to draw up any drugs. I don't have to check any concentrations. It's very much. Open the packaging, pour in the methoxy, give the patient a brief instruction, and allow them to start breathing. And that then frees me up to continue with my other interventions. So it's a very good bridge to providing IV analgesia, or perhaps intramuscular analgesia if you're dealing with less severe pain, but as you well know, lots of considerations around giving giving IM drugs. It's excellent in giving you that first 20 minutes while you are completing your primary and maybe secondary survey, establishing IV access, and then starting to titrate in you know, rapid acting or a more longer acting analgesic, whether that's going to be something like acetaminophen or it's going to be stronger in opiate or ketamine or other things. So that's the first really useful space is an analgesic bridge. You do need a conscious, cooperative patient, and they do need to have moderate to severe pain but it gives you that first 20 to 30 minutes.
Patrick:Okay.
Ross Hofmeyr:I'll say this with caution because obviously it depends on the regulatory environment where you're working but we have trained a lot of our wilderness first responders our SAR personnel, and then we've trained some of our non
Patrick:Okay.
Ross Hofmeyr:medically trained tour guides and wilderness guides and expedition leaders who have got wilderness first aid training, wilderness first responder training and are working fairly independently in remote areas, we've trained many of them to administer methoxyfluorane as an analgesic agent. We've got a very quick little checklist. And so if I've got a team who are doing a guided investigation, Motorcycling trip through Cambodia somebody comes off with a shoulder dislocation or a tibfib fracture and they're in severe pain, then that team can immediately administer methoxyphorin while they're stabilizing the patient, splinting, et cetera, et cetera. And often that gets you through that first really painful period of of immobilization and so forth.
Patrick:much.
Ross Hofmeyr:More seldom, but it does definitely have some efficacy and that is for procedural analgoacidation. If you're doing a painful procedure in a remote environment and you've got very, very limited monitoring. And Matt Wilkes has got a lovely case report of using methoxy for placement of a suprapubic catheter at four and a half thousand meters altitude, where it was, it was used for exactly that that purpose. So and again, there's plenty of publications in adults and kids of using methoxy for procedural sedation. So I think that's a reasonable indication, although I will say again, the caveat depends on your regulatory environment. In South Africa, for instance, it's not actually licensed for procedural sedation. It's only licensed for acute traumatic pain.
Patrick:In places where it is available, let's stick with South Africa because you're most comfortable with that. Does it require a prescription to obtain it? And how does one go about getting a hold of methoxyfluorine?
Ross Hofmeyr:Yeah. So in South Africa, it's a, it's a prescription drug. It's it's a schedule five out of seven level scheduling. So it's actually quite a high schedule drug. That's because they didn't change the scheduling when it came back from its, you know, anesthetic use. That does require a prescription. And so it's supposed to be used on a named indication, named patient basis. The way that we get around that for our wilderness usage is that we have a very defined protocol, and a non
Patrick:by
Ross Hofmeyr:this is a situation. The patient's past the checklist. Can I go ahead and give them the Foxy? And, and we then prescribe it as part of a, of an expedition kit. Much the same way that we do a lot of our other prescription medications that go into those kits.
Patrick:And in that kit or in your personal med kit that you might either carry with you recreationally or as a responder, are you carrying just the two vials of methoxyfluoride or do you carry more?
Ross Hofmeyr:Yeah, I carry an inhaler and well, the delivery device and two vials because the, the likelihood of needing more than one. inhaler for one patient in my normal practice is quite low. I do obviously have access to other agents, so if I did have another patient where I didn't have IV access and I had acute severe pain, I'd have options to do things like intranasal ketamine or intranasal fentanyl other things like that. And those, those still remain really, really good options. I'm not advocating that, you know, methoxy is better than other drugs. There's some, there's some good literature out there. But certainly in terms of The ease of deliverability by less trained personnel and the ease of freeing up your hands so you can do other tasks,
Patrick:CastingWords
Ross Hofmeyr:there.
Patrick:How do you feel about administering methoxyfluorine to a patient who has already received other centrally acting medications? you've, you've provided intramuscular fentanyl or intranasal ketamine, and now you're approaching a painful transition or splinting or what have you, you want to consider using methoxyfluorine for breakthrough of that next level of analogous sedation. How do you feel about the combination of those and how do they play together?
Ross Hofmeyr:So I think From, if you ask how I feel, I feel quite comfortable, but then I'm giving patients, you know, multimodal analgesia and anesthesia on a day to day basis. I think anybody who's approaching, you know, using multiple drugs for a patient must recognize the drug interactions and, and you must, you must work to mitigate those interactions. Fentanyl and all the other opiates, potent respiratory depressants. As is methoxyfluorine. So if I were going to have a painful transition, as you suggest, and I wanted to add something, and I knew the patient had opiates on board, opiates and volatiles are very synergistic I would be that much more conscious and careful to monitor the, the patient's respiration. It certainly wouldn't stop me using it and, and let's say we had a patient who we'd had to do a rapid extrication, they'd already had some fentanyl or morphine on board. We then recognize, let's say they've got a fracture dislocation and the limb has got vascular compromise. We need to do a better reduction. Would I consider using methoxy for that on top of other agents? Absolutely. And, and, you know, getting the patient engaged and you know, empowering them to help. deal with their pain has got a significant amount of value in the field.
Patrick:You implied that we're in a situation that has less or no monitoring available. Is there ever a situation in which you would consider it necessary to have monitoring available before giving methoxyfluorine? Or is this fine on its own? You're No problems. I'm handing it out
Ross Hofmeyr:I think
Patrick:a conscious participatory patient.
Ross Hofmeyr:yeah, yeah. So in a, in an adult patient who's got acute traumatic pain and is conscious and communicative I, I think that normal clinical monitoring, talking to the patient, observing the patient Would would be enough for me to be comfortable. I don't feel that we would need to have any kind of you know, monitoring on the patient. I would be cautious about embarking on doing a, you know, Pediatric sedation using methoxy without some kind of some kind of monitoring. But I think in the normal context of our wilderness medicine and rescue, it's a, it's a very safe drug.
Patrick:Okay. Can you safely ambulate the patient while they are using methoxyfluorine? I recall an image from perhaps a lecture you gave which I think there was perhaps a gentleman crossing a river while methoxyfluorine. Tell me about that.
Patrick here with a quick side note, I found this clip from Survivor and clipped it for you, and a link to that YouTube clip is in the show notes. Back to Ross.
Ross Hofmeyr:Yeah. So that actually was a signature event that, that work a lot of us in the rest of the world up to the concept of Methoxy Fluor. And I might be showing my gray hair a little bit here, but it was an episode from the. First series, I believe of survivor. And they had they were doing survivor down in Australia where, as we said earlier, the Foxy Fluray has been in use for a long time. And one of the quite serious contenders to, to win the show. Was was cooking in an open fire. And, and he fell into the fire with, I think he lost his balance. And he sort of fell into the fire with his, with both hands. And obviously, you know, the medical team was called in and they had to evacuate this guy and the quickest way to get him. Art was was to cross the shallow river to a helicopter. And there's this iconic image of this guy coming across the river with this massive green whistle in his mouth. You know, and the paramedics kind of holding him in his hands as he, as he wades through. And all of us in South Africa went, you are my brew. Look at this. They've got lack of, lack of bongs there. Hey. And, and turned out it wasn't marijuana. But it was, it was methoxy, Florin. And that really sort of went bing for many of us in the rest of the world going, well, hang on a moment. Why don't we have this? We, we want this. So would I ambulate a patient? Yes, I would. With the proviso again, it does make people often feel quite lightheaded, feel a little bit dizzy. I'm not going to imply that any of the listeners of your very august podcast would ever have, you know, tried something like nitrous oxide in a, in a nonclinical setting. But if anyone ever has had an inhalational anesthetic, ever had nitrous oxide it does give you this very sort of swirly lightheaded feeling, quite pleasantly like being a little bit tipsy. And so I would quite happily ambulate a patient, but with assistance, probably just, you know, walking next to them, making sure that they didn't trip over something.
Patrick:I'm glad that you described that because I personally certainly have no. Sort of a similar experience. When you're using methoxyfluorine, are there environmental considerations such as temperature or altitude which either limit or potentially augment its use? Okay. Okay.
Ross Hofmeyr:based in Bulawayo as an anesthetist early in his career and, and there was this observation that Entonox or nitrous oxide analgesia did not work well at high altitudes. You speak to the average anesthetist from Denver or Johannesburg or Mexico City, they'll tell you nitrous oxide is a useless analgesic. You speak to me in Cape Town or Durban or anywhere else on the coast will say it's, it's a very useful drug and it has got a potent analgesic effect. We can talk about the greenhouse gases and other things in a, in a, in a different discussion. So what Mike James did was he did a nice study, he looked at different altitudes and he showed that yes, the effect of nitrous oxide was diminished with altitude because as most of us are familiar with, it's not so much the concentration of a gas that has a biological effect, but the partial pressure thereof. So the classic example is At sea level, we breathe normal air with 21 percent oxygen, and we don't get hypoxic. You go up to the summit of Everest, you are breathing normal air with 21 percent oxygen, but you get severely hypoxic. And the reason is that, obviously, the ambient pressure on the summit of Everest is around 28 kilopascals, so, you know, it's less than a third of sea level pressure. So there's less than a third of the number of molecules that are around for us to breathe. Now, Nitrous oxide is delivered as a gas, and so as the ambient pressure decreases, if you give the same concentration, the partial pressure will decrease and the effect will therefore decrease. And quite some time ago some, some erudite wilderness medics and, and writers in the field had proposed that methoxy might be a useful agent for prehospital analgesia, but at high altitude, it would suffer the same degrading effect. And so We, we set out to look at this. Now, the volatile agents, when you are breathing through an, a, a vaporizer, a vaporizer actually works by generating saturated vapor inside the device. So our standard anesthetic vaporizers for things like subsevaflurane and isoflurane. They've got a vaporization chamber and they got a bypass channel and we vary the amount of of gas that we give by changing the amount that flows through the vaporization chamber or the bypass channel. And we're very familiar with talking about this in, in percentage. But actually what we should be talking about is we should be talking about the partial pressure that we're developing. So delivering rather. So, I mean, about 10 years ago, actually, Mike James and Mike Grocott of Everest fame. And myself wrote a paper on this in the British Journal saying, well, we should be talking about the map, the minimum alveolar partial pressure rather than the minimum alveolar concentration of a volatile agents, because then regardless of what device we use and what altitude we delivered it at, we would be giving the same dose of agent. Now, the, there's a useful effect with the vaporizers in that as the density of the gas changes. Because you got this bypass going through a saturation chamber, you end up giving a different concentration, but actually pretty much the same partial pressure. So your vaporizers just work pretty much regardless of the altitude that you use them at. Now, because methoxyfluorane is a draw over vaporizer, we should be delivering Again, the sat in the same saturated vapor on this. No one had ever tested. There's the one case report of Wilkes who'd used it a high altitude and it actually seemed to work very well on. So what we actually then did with a grant from the WMS is we put methoxy fluorine inhalers into an altitude chamber at Duke University at varying altitudes on. We measured the amount of gas we're getting out. We actually measured that very, very accurately using a mass spectrometer on. We showed that At, across a wide range of altitudes, we delivered exactly the same partial pressure. So the device is delivering the same amount regardless of altitude, which is very useful. And that means it fits in with our understanding of saturated vapor, etc. The caveat to all of that is that if you know your science well, you will know that the saturated vapor pressure of, of any substance, any liquid or gas, is fixed. at a specific temperature. So the only thing that changes SVP is the change in temperature. And that does, I believe, have relevance for us in the wilderness setting, because if you are giving the device to somebody Outdoors here, perhaps in Crested Butte now where it's a few degrees below zero Celsius versus somebody who's just had a hyena gnaw on their ankle in the felt in Africa where it might be 30 degrees Celsius, then you are going to be delivering a different Dosage to the patient. We've got no actual experimental data to show how much the dose varies We don't know what the effect of holding the device and in a hand to keep it warm is And that's really an area where we could definitely have some some further work. So altitude no difference. It will work Temperature you must anticipate decreasing efficacy with decreasing temperature
Patrick:I seem to recall, and I looked this up in response to a listener comment, but I think that the freezing temperature of the actual methoxyfluorine liquid is quite low, and perhaps not clinically relevant here, but it did occur to me that that problem with the vapor pressure, right, regardless of altitude, at a colder temperature, you're going to produce less vapor from that wick. And the same question came to me, which was, okay, if you hold it and warm it, could you achieve a reasonable dose yet? The error that's being drawn across it remains your environmental air temperature. So I don't know if it would be at all meaningful to to sort of cuddle it with your hands and protect it from the environment or if that's just a pointless exercise. It sounds like there's a budding. Research project here for any wilderness medicine fellows out there who
Ross Hofmeyr:Absolutely.
Patrick:to write a grant and get some funding.
Ross Hofmeyr:Absolutely. As as my as my mentor, Mike James would say this is an area of opinion as yet unsullied by evidence
Patrick:um, do you have any personal experience using it in the cold
Ross Hofmeyr:on myself, on patients.
Patrick:either?
Ross Hofmeyr:So yes, we have used it in cold environments. and I've used it in I'm going to have to estimate that what the ambient temperature would have been probably would have been between about minus two and minus five Celsius. I apologize. The American listeners that I'm not fluent in Fahrenheit. In the snow on a mountainside. And the patient did describe a Good analgesic effect. They did describe the side effects of the, of, of the dizziness well lightheadedness rather let's call it. So it was clear that the, that the drug was working whether it would work in minus 10, minus 20, I don't know, but we've used it outdoors we've used it in cold environments and it has worked.
Patrick:I think that in freedom units, that would be around, like, 20 to 25 degrees Fahrenheit. When you are carrying it, do you keep it close to your body if you are in a colder environment? Or do you attempt to keep it isolated from the elements? Or is it just in your pack with your other Okay,
Ross Hofmeyr:that goes inside my jacket to prevent it from freezing. As, as you said, the freezing point of methoxyfurane is well below zero Celsius, so actual freezing of the agent is is not really an issue. And I think The con the, the issue really is how cold does it get in that vaporization chamber and you know, will, will it vaporize efficiently for analgesic effect? And I don't know the answer to that question when we're talking, you know, deep Sub-Zero temperatures.
Patrick:it really sounds like it's a, it's quite an ideal medication for that the pre hospital environment because it requires such Little access, it's so easy to use, it's titrated by the patient. Are there downsides that you see to it?
Ross Hofmeyr:So the first one that comes to mind particularly, you know, coming from an African setting is, is cost. In. In my South African rands, a methoxyfluorine combo kit with the inhaler and two vials is probably around a thousand times more expensive than a, than an ampoule of morphine which, you know, in our, in our government hospital practice costs next to nothing. So, you know, the cost, the cost is definitely higher. There's a theoretical downside in terms of environmental contamination, and I mean, you know, the greater global environment although the amount of methoxy that we use in the environmental dwell time of methoxy makes it a fraction of the risk of you know, other greenhouse gases like nitrous oxide. Another small downside is although the, the delivery device itself is very light, it is somewhat bulky to carry. So you could carry a couple of syringes and multiple ampules of you know, opiates and other things for the bulk that you need to, to carry in Methoxy combo kit on the plus side, they are, they're very, very robust. You know, they can get kicked around and thrown around in a pack. The, the little ampule itself is very, very tough. So it doesn't get, I mean, I've never. Broken one accidentally even when, you know, dropping packs out of vehicles, other things like that other downsides, not, not a whole lot. I mean, it becomes another thing that you have to carry another thing that you have to dispose of. I tend to throw mine in the plastic recycling, and that's the end of that.
Patrick:Okay. Very good. Well, I appreciate you taking the time to discuss this with me. And for us, it's been fun watching the. Sunset behind you in Colorado as I'm here in Hawaii where the sun is definitely still up thanks for for making the time to join us on for For future episodes. You're a wealth of knowledge
Ross Hofmeyr:Well, thanks very much, Patrick. And yeah, if I can encourage the listeners that if they haven't gone and had a look at the WMS acute pain practice guidelines for which Patrick is the the lead author and really lit the fire under all of us to get that done, then that, that those guidelines are a really, really great resource. And yeah. If you're going to read one thing after listening to this conversation, then open up the WMS CPG. They're free. They're online. And if anyone does want to look me up and reach out for more information, I've got quite a lot of stuff that you know, I can send out to people. My email is easy. It's Ross at wild medics with an X. com. Podcast description.
Patrick:Yeah, we'll put links to everything I can find about you down there, Ross, so that you can be bothered to no end by our listeners.
Ross Hofmeyr:Fantastic. Thank you.
Patrick:And that's a wrap on my conversation with Dr. Hoffmeier. Thanks again, Ross, for joining us on the show. I really appreciate the time and the expertise, and I hope that everyone listening out there learned something. At times Ross gets deep. I hope that everyone out there found something that they can take away or found some inspiration. It's always great to learn more, expand our boundaries, expand the toolkits that we have available to us for managing pain in austere environments. As I mentioned with Ross, all of the links can be found down in the show notes, including pictures of the green whistle and links so that you can connect with Ross and his company, Wild Medics, if you're interested to do so. As I mentioned in the introduction, thanks so much to Eddie and Aaron for the questions that created this episode. And I would encourage all of you to continue to reach out. It's wildernessmedicineupdates at gmail. com, even if you just want to say, Hey, give a shout out, or if you have specific questions, things that we can dive into more, because if you have a question, other people have a question and there's no such thing as stupid questions here. We can always take it to that next deeper level. I'm still not on any social media because I just can't handle that, but I do appreciate it. If you give the show a ranking or a review on iTunes or Spotify, that helps this show get out to reach more listeners. As I've mentioned before, this is a passion project. I'm not making money on it. I am losing money on it, but I enjoy bringing this content to you guys and hearing back that it is delivering value. To you. So thank you for listening. And as always, another way you can support the show is to share this episode with someone you think might appreciate it, or maybe they want to hear about avalanche physiology or how to make tourniquets out of space blankets that episode you think they might appreciate. Share it with your fellow nurse, doctor, paramedic, medical student, nursing student, SAR member, or fellow recreationalist who just wants to learn more and be prepared for those situations in the outdoors. Until next time, stay fit, stay focused and have fun.
