Welcome everyone. I'm very excited to talk about an item of extreme importance and to introduce everyone to the new era of neuromuscular blockade, monitoring, and reversal. I have packed a lot of content into this webinar. I have been studying this monitoring practice for the last five years. We've included that into our practice five years ago. I've got a lot of information here that we found over those years, and I'm more than happy to describe it to all of you guys. Real quickly, as we get started, conflict of interest. In short, I have no financial relationships with any commercial interests related to the content of this activity in any way, shape, or form. In addition, I will be discussing some uses of Sugamidex later on in the presentation that are not included in the package insert. Learning objectives, we will be able to evaluate the pharmacodynamics and pharmacokinetics of neuromuscular blocking agents to refine monitoring strategies, which enhances patient safety. We'll evaluate neuromuscular blocking agents to refine monitoring strategies that enhance patient safety. Then we'll integrate evidence-based practices of neuromuscular monitoring into patient management strategies. All of this is new and exciting stuff. This webinar began, the idea of this began when I wrote and submitted an article to the AANA Journal in June of 2023, and it was published in this edition. It's titled The Rise of Quantitative Neuromuscular Monitoring, and the link for that article is below where I cover these and other topics. Some of the quick facts here, this is the basis of our discussion today. This is going to highlight all of the ways we were doing this incorrectly for the last 80 years or so. Several things that we have problems with today. Nearly two decades ago, 20 years, experts began recommending the use of quantitative neuromuscular monitoring. However, many anesthesia providers have simply relied on the use of either qualitative or clinical assessment, with the peripheral nerve simulator, we look at them and see ourselves whether we think that they are okay to extubate. We learned this during our training. Unfortunately, everyone is aware that these assessment modalities are inadequate to detect residual neuromuscular block. The potency and duration of action of neuromuscular blocking drugs themselves varies dramatically amongst patients. We all know this. We often joke about the palette of paralytic that had set on the loading dock in July and probably doesn't work very well. Inherent to every patient is going to be a variability that is going to be present with any drug, including neuromuscular blockers. The passage of time is not a reliable predictor of death of paralysis or the patient's ability to be reversed. We often say, at least speaking for myself, oh, it's been 45 minutes after Rucuronium, they are reversible. That is not a way to judge whether they are or not able to be reversed. What we call paralyzed patients is the patient paralyzed and we say, yes, well, those paralyzed patients can still move and breathe at any depth of paralysis, which again flies in the face of what we have always thought. We need to paint a picture of the history of neuromuscular blockade and monitoring just to inform us of how this all came about. Only in 1947 was the discovery of neuromuscular blocking agents. We began to put those into our anesthetic regimens after the synthesis of galamine. Once we started injecting paralytics, that enabled us to provide lower levels of anesthetic gases and narcotics. And we then noticed that we needed to use a peripheral nerve stimulator. It was suggested for the diagnosis of prolonged apnea when the patients weren't breathing postoperatively. They suggested the use of a peripheral nerve stimulator to assess the depth of block. Then in 1965, Churchill Davidson stated that the only satisfactory method of determining the degree of neuromuscular block is to stimulate a motor nerve with an electric current and then observe the contraction of the muscles innervated by that nerve. The peripheral nerve simulator had proven to be effective. Then 1970, Ali et al introduced the TRANA4, which we all know now ranges between one and four. And those contractions are called twitches. So I wanted to go to this slide first, titled what is a twitch anyway? We often say that, oh, they have so many twitches, one twitch, four twitches, three twitches, whatever. Well, what is a twitch anyway? We have to know what we're actually looking at. So I'll play this video. This is a video that I took in the operating room. And it's very clear to see how many twitches this patient has. We'll look at that and then talk about it later. All right, that was a very quick little video there. It is very apparent that the patient's middle finger twitched four times. So often we would say that the patient is four twitches. I believe if we polled the audience, most everyone would agree that that was four twitches. Well, here is the problem with that. A twitch is a full depolarization of a muscle. So how many of those four twitches that we just witnessed was a full depolarization of that muscle group? Well, obviously we have no idea because we cannot see the muscle group with our eyes. So then in 1981, after observing the patients were still moving and breathing even with zero train of four, advancements in neuromuscular monitoring continued with the discovery of the post-titanic count, which ranges typically from one or zero to 15. So patients were still moving and breathing even with zero quote unquote twitches. And so they discovered that if you hit the patient with the tetany 50 Hertz for five seconds and then twitch them again, they would continue to twitch. So they uncovered twitches below train of four. This is an example of that. This is an example of breathing while paralyzed. You see on the quantitative monitor on the top right, it says train of four count is zero. The EMG is the yellow line on the left and it is flat. We will watch this video. So as you can see, the patient was zero twitches and breathing over the ventilator. So people started looking into this in 1987, a research group demonstrated that painful stimuli, this was actually a tracheal suction catheter placed down in the ventricle. And this was a patient who had no twitches and no twitches at all. So this was a patient who had no twitches and no twitches at all. Tracheal suction catheter placed down the end of tracheal tube to tickle the carina can generate the patient to cough at all levels of skeletal muscle paralysis. So zero PTC, 10 PTC, one train of four, two, three, four twitches. Patients can move and breathe and cough at all depths. Therefore, that's where the quantitative monitor comes into play. The quantitative monitor helps you to determine when you've achieved adequate skeletal muscle paralysis and now other drugs like analgesics or gases are required instead. This is the follow-up to the train of four zero patient who was breathing over the ventilator. I then switched the quantitative monitor to post-tetanic count mode and tested the patient. That patient breathing over the ventilator with a train of four of zero actually had a post-tetanic count of six. This is that study from 1987, stating that when they put the tracheal suction catheter down to 25 patients, one of the 25 patients still coughed when the post-tetanic count was zero. When post-tetanic rose to simply one, 20% of the patients reacted to that stimulation. And then when they reversed all the way up, recovered all the way up to train of four of one, 92% of patients coughed. 25%, 24%, one quarter of those patients were so severe they had to restrain the patient. That's a train of four count of one. So these patients are extremely strong even with deep paralysis. This is that chart from that same study showing that even at post-tetanic count of zero all the way to the bottom left, patients are still coughing and moving. The X-axis is post-tetanic count and you see from zero all the way to 15, patients are still moving and breathing. The link to that article is on the bottom of this slide. This is an example of that. As you see on the quantitative monitor, the top right corner of that monitor says PTC count zero. And as you can see, the patient is breathing very easily over the ventilator. We also note that the sevoflurane in tidal concentration is 1.6%, so adequate. So I made this chart actually to depict these things that I've mentioned so far. So this is a chart showing, the yellow is where the patient appears clinically weak. To us, we look at the patient, we say, oh yeah, they look paralyzed. This is how we used to do it for the last 100 years or so. We look at the patient and determine whether or not they're recoverable or reversible or extubatable. So since it shows that patients move and breathe at every depth, including post-tetanic count of zero, you see TRNO4 on the left, all the way down to PTC zero on the right, still showing muscle function. The purple, that is TRNO4 count of four, and the patient appears normal and extubatable. These are the levels of paralysis like they can extubate. And we've been extubating patients in this range for the entirety of our careers. That typically ranges from 40% TRNO4 ratio all the way up to 100%. It looks exactly clinically the same. And of course, the green is greater than 90% TRNO4 ratio, which is the current standard of care. Every patient should be returned to that level prior to extubation. Then, since we have a surgeon at the University of Mississippi Medical Center named Dr. Patrick Bergen, he's an orthotrauma surgeon, who routinely asks for more paralytics to be given even when the patient is at PTC zero, I came up with a theory that I've titled after him, the Bergen zone, where if the patient is already PTC zero and we administer additional paralytic, what will the subsequent readings be on our monitor? Of course, since PTC zero is the bottom of the monitor with additional paralytic then administered, the patient will still remain PTC zero. But does that mean that the patient stays right at the same place, still with the ability to have muscle function? Or do they go into a sub post-titanic zone of paralysis, which is quote off the chart, which I titled the Bergen zone. And that is a very thought provoking article and the link is on the bottom left. This is a snapshot of the APEX anesthesia board review for our students. And this really highlights a lot of important concepts that we've just discussed. The most common thing that I hear us say, hear clinicians say is, oh, they were pulling great volumes, they're ready to extubate. Well, look, they can pull great volumes, they're extubatable and still be 80% paralyzed. The train of four, there's no fade on the train of four. Oh yeah, they look great. No, actually they're 70% paralyzed. Bottle capacity, we don't really do that very much, but greater than 20 mils per kg. They pass that at 70% paralysis. Sustained tetany, oh, I got a hot battery from the workroom, I licked it and I put it back in the peripheral nerve simulator. There's no fade at all, they're ready. No, actually they're 60% paralyzed. Double burst stimulation, same. Inspiratory force, greater than negative 40 niff, still 50% paralyzed. They lifted their head for five seconds, so they're ready to extubate. No, they're actually still 50% paralyzed. Hand grip, still the same. Oh yeah, they squeeze really, really hard. They're 50% paralyzed still when they pass that. We're putting a tongue blade in their mouth and bite it and I can't pull it out and you're slinging the patient around the OR with the tongue blade, they still pass. Then in February of 2023, Clinical Anesthesiology published an article describing the ASA's new guidelines for the monitoring of neuromuscular paralysis, blockade and monitoring and reversal. This was published shortly after the ASA published their guidance. Now their guidance is located now here on their website. This is the ASA website under Practice, Monitoring and Antagonism of Neuromuscular Blockade published January, 2023. This changed our entire practice. This is available for everyone to read and I will go over their eight primary recommendations. The link to this paper is at the bottom. Number one, when neuromuscular blocking drugs are administered, we recommend against clinical assessment because it's insensitive to the recovery of the patient. Number two, we recommend quantitative monitoring, not qualitative. If your goal is to avoid residual blockade, then when you use the quantitative monitor, please confirm a train of four ratio greater than 90% before you extubate. Number four, they recommend using the adductor pollicis for monitoring. Number five, they do not recommend the eye muscles for monitoring. All of these things fly in the face of what we've always done. Number six, use Sugamidex over Neostigmine at deep, moderate and shallow depths of neuromuscular blockade. Number seven, suggest Neostigmine would be a reasonable alternative to Sugamidex if you're at minimal blockade, which is greater than 40% train of four ratio only. Number eight, of course, if you're using Atrocurium or Cis, you can only use Neostigmine, of course, but you should wait at least 10 minutes and then make sure that they're 90% train of four ratio before extubating. All of this combined to force the AANA to have a round table discussion about these guidelines to fully discuss all of the ASA's recommendations and how important it is to follow their guidance. There was a great round table discussion at annual Congress 2023 conducted by Mr. Flowers. This is up to date. It is a clinical continuing education resource for us and it updates the current guidance as things come available. And look at these really interesting findings when we look on up to date under monitoring of neuromuscular blockade. Evaluations of train of four made subjectively just by looking at the patient with a peripheral nerve stimulator cannot assure recovery. This is just amazing. Facial nerve. If you use the facial nerve, it's less accurate than the ulnar, but the only way that you would justify using the face is if you could not access the hands or feet. When you use the face, 52% of patients go to the recovery room paralyzed. That is the best that we've always done. And the main reason is because 10 on the temple is not a technique. You cannot put a hot battery, lick it with your tongue, stick it in there, put it up on 10, stick it on the face and stand on the button. You're stimulating muscles, not nerves. We're supposed to be stimulating nerves and watching the specific muscle group, not the group of muscles. We tend to overestimate when we do this, especially at moderate levels of neuromuscular blockade. And when we use this method, 96% of the time, we have overestimated the patient's recovery. So when you use the peripheral nerve simulator in its proper technique, which we very rarely do, what this gives you, the best that we can possibly do is that you can now perform a TRNF-4 analysis in which your patients who are fully reversed and the ones that are 75% paralyzed look identical to you. And you'll overestimate the patient's recovery by at least two twitches. That will probably cause you to administer the wrong reversal agent in the wrong amount. And you'll send 52% of your patients to pack you paralyzed. That's the best we've always done. We can certainly do much better. Okay? We'll go back to this just real quick. When you're using the peripheral nerve simulator in that way, 52% of your patients go to recovery room paralyzed, and you likely administered reversal agents to many of those patients when they didn't actually need reversal because they were already 90% TRNF-4 ratio. So now we'll go back to this. What is a twitch anyway? We all agreed earlier that it was four twitches, correct? It must be four twitches because the patient's finger moved four times. However, like I mentioned, we actually are trying to measure the full depolarization of the muscle. And since our eyes can't see the full depolarization of the muscle, only the monitor can. So let's look and see how many twitches this patient actually has. As you can see, this patient has exactly one twitch, okay? All of this was so mind-blowing to me that I just started writing. I started writing to everyone that I possibly could. I wound up publishing these eight articles on this topic itself, including the AANA journal article that I mentioned earlier. Let's go into some of the science behind this. Electromyography. During voluntary contraction, the action potential is sent from the brain to the motor unit, leading to the contraction of the muscle fibers. EMG therefore allows us to measure the electrical response of the muscle or its action potential. That's what we were looking for when we saw the patient's hand moving. EMG is the one that most closely equates to mechanomography, which is the gold standard. This is the innervation of the hand. We monitor the ulnar nerve and then the adductor pollicis is innervated by that nerve. Okay, this is a neosignine reversal guide that we used to use in the past, back when I came through my program. If the patient was deeply paralyzed with no twitches or one twitch, we simply had to wait. I mean, can you even imagine these days waiting? No, we cannot, but that is what we had to do. Once the patient recovered back up to two to three twitches, we could give a full dose of neostigmine. Then four twitches, you could titrate it down if you wanted to, but typically everybody just gave the max. You're really just kind of going willy-nilly. We don't know exactly what we're doing when we're just looking at the patient. Interestingly, at the bottom of that chart on the top half of the screen, 24 ratio greater than 0.9% or 90% requires no neostigmine. Do not reverse these patients if they are already recovered. So this is an updated version showing, and I've edited this to show the ASA's current guidelines. If you are a PTC of zero, neostigmine is not indicated as you see on the far right. Sugamidex is indicated because it is a one-to-one molecular encapsulation of the rocuronium or vecuronium that you've administered. And so it can reverse those patients, neostigmine cannot. If your PTC is between one and 15, let's say, still no neostigmine is indicated. You can titrate the sugamidex down and likely be somewhere between four and eight milligrams per kilo. Moving on up, trinofluor count one to three, that's moderate block. Sugamidex is still the only indicated reversal agent. Again, no neostigmine. Then moving on up, four twitches with a trinofluor ratio between 10% and 40%, that is shallow block. Look to the right, still no neostigmine is indicated, only sugamidex. Then you keep moving up to minimal blockade, four twitches with a trinofluor ratio between 40% and 90%. Still, sugamidex is an option, or you could choose to try neostigmine. when the patient is in minimal block, it doesn't really take all that much. Sometimes it does, sometimes it doesn't. You could titrate it to affect, just like all of our other drugs, typically somewhere between 15 and 40 mics per kilogram. And again, we'll repeat that if the patient is greater than 90% TRNA4 ratio, that is acceptable recovery. They've achieved their goal and no psigemidex is indicated, no niastigmine is indicated. And so bio is the time of the CYA dose of reversal because you literally don't need it because you've documented that the patient is already recovered. This is an example of that. This is a case that I relieved on for lunch one day. It was a thoracotomy and the patient was at one twitch. By the time the cardiovascular anesthesia fellow came back in from lunch, there were one twitch and they had started to sew. So I gave report, I left, and then approximately 30 minutes later, I came back and saw the patient in the hallway being rolled to the recovery room, extubated with face mask O2. I looked at the chart to see, since it was TRNA4 of one and niastigmine is not indicated for TRNA4 of one, I looked to see what the fellow gave the patient for reversal. They gave the patient a full dose of niastigmine. So since the ASA said that niastigmine is not indicated for that and is incapable of reversing that patient fully, I took a quantitative monitor to the recovery room. The patient was still adequately sedated, very comfortable and did not mind getting the ulnar nerve monitor. So I twitched the patient and they were 42% recovered. You see there's a massive amount of fade. The fourth twitch is 42% the height of the first. To the left, the EMG, the first twitch is in white. You see that it is the strongest and every twitch after that fades. I then gathered the patient's nurse, the recovery room head nurse and our OR pharmacist and I grabbed a vial of Sugamidex. I injected 50 milligrams of Sugamidex to this patient and waited 30 seconds. And then after that is the next slide. The patient then recovered to 96%. You see on the left, the EMG waveforms are, all four of them are almost identical. The fourth switch is 96% the height of the first twitch and the patient is now considered fully recovered. This was a thoracotomy case as well. These are the patients that we can now avoid missing. The next is a video of a Sugamidex injection. This is 200 milligrams of Sugamidex injected into a patient starting with the Trenofor ratio of 26%. We'll watch the recovery before our eyes. Thank you. Monitoring this will be 10 seconds. Afternoon, a little anesthesiologist comes in. 67, 61. You don't have any specimens, do you? No, I don't have specimens. Okay. No, they don't. So we're about at a minute and a half now, to 89, 92, all right. There's a great example of just watching the patient's recovery before our eyes. I had recruited a medical student who was observing that day to hold the video camera while I took care of the patient, and that is how we can successfully recover patients prior to extubation. All of this led us down a little bit of a rabbit hole. We decided to conduct a research study at our institution. From left to right, this is Austin Kahn, CRNA, myself, our OR pharmacist, Yasmeen Elua, and Zach Kahn, CRNA. The four of us studied 105 patients, and what we did was titrate Sugamidex to a train-of-four ratio of 90 percent, regardless of the depth of the patient, regardless of their weight, and regardless to FDA recommendations. We gave the patients 20 milligrams of Sugamidex every three minutes until they reached 90 percent train-of-four ratio, and then we stopped and recorded how much it actually took. The results of that, AANA reached out for Austin and I to fly to San Diego for annual conference last fall, and we unveiled the findings of our research study. The findings are fascinating. We came away with three statistically significant findings, and all of those are the subject of a one-hour presentation just on the findings of this study. I have gone subsequently across the country delivering these results in this presentation to different groups, and I'm going several places across the country this year to do that. This is an example of one of our patients, the eighth patient that I had. Once again, if the patient was suitable for Sugamidex, which is less than 40 percent train-of-four ratio, we instituted the protocol, which was 20 milligrams every three minutes. I just take one 200 milligram vial, dilute it down to 10 cc's, and give one cc every three minutes. This patient appears that they started at a train-of-four ratio of approximately 25 percent. After the first injection of 20 milligrams, the patient was 98 percent. Then I subsequently threw the other 180 milligrams in the trash, because it is not needed, and extubated the patient. This is another example. This is not a study patient, but just a great example of the titrated Sugamidex methodology. 20 milligrams was given to this patient at a train-of-four ratio of just under 10 percent. Then 10 minutes was waited until the conclusion of that recovery to determine if the patient needed more. After the first 20 milligram dose, it got them from 10 percent to 65 percent. Then the second dose of 20 milligrams got them from 65 to 85, and then a third dose got them from 85 to 92. In this method, we can now titrate Sugamidex just as we would neosinephrine. The clinical endpoint for neosinephrine is what you determine to be adequate, let's say systolic of 110. If the patient is less than 110, what will you do? Do you give the entire syringe of neosinephrine? No, of course not. You simply give a small amount of it until the patient reaches your clinical endpoint, reaches their goal. Our goal is 90 percent. That's been established for almost 20 years. All we have to do is just titrate the medication up to 90 percent, and then we simply stop. This is another example of that. This patient started at train-of-four in which neostigmine, of course, is not indicated. Sugamidex was given in a 20 milligram dose, and it got them from train-of-four of two all the way up to about 85 percent. Then just like neosinephrine, we would titrate it down. We don't have to go very much farther with it, so let's go even smaller. Let's just do 10 milligrams. Then the patient got to 96 percent, and we stopped. This method results in cost savings that are extraordinary. This is an example of a failed neostigmine reversal. This patient was reasonable. Now, not per ASA guidelines, but reasonable at approximately 20 percent train-of-four ratio. We have certainly given neostigmine at deeper depths of paralysis than this over the last 80 years, I assure you, myself included. Train-of-four for 20 percent, full dose of neostigmine was administered and failed. It only got the patient to 76, 78 percent. Then, of course, neostigmine has been maxed out. It has a ceiling effect. No additional neostigmine will improve the patient any further. Sugamidex is the only drug that would be indicated at this point, so a rescue dose of sugamidex was given, just like the thoracotomy case that I described earlier. This patient recovered to 94 percent and was then adequate to excavate. This is a chart. This is one of my charts, one of my patient records showing the appropriate use of neostigmine. The purple below, if you refer back to the Bergen zone chart, the purple indicates levels of paralysis that look clinically recovered to us. The patients look like they're ready to excavate. They'll run around the room. They'll pass all of our tests. However, the monitor shows us that the patient is not adequately reversed. But since I knew that the patient was very close to 90 percent at the time of reversal, you look below, indicated here. The patient was 81 percent. Then, neostigmine was administered a titrated amount, just one milligram because I only had to get nine percent more. Then, the patient recovered to 94 and then subsequently 97 percent. The patient was successfully extubated. This is appropriate use of neostigmine. This is another chart. This is actually a patient in complete renal failure. They are receiving a renal transplant in this surgery. You see at the top, I administered approximately 300 mics of fentanyl on induction or peri-induction. Then, the patient received 30 milligrams of rocuronium. You see now that the patient started out normal, 100 percent by the time this captured, it said 90 percent trinafour ratio. Then, the patient starts decreasing their muscle function. They got all the way down to approximately 13 percent, which is still trinafour of four and 13 percent. They never lost a single twitch after the 30 milligrams of rocuronium. High patient variability. Some patients go all the way to zero post-satanic. Some wind up trinafour of one. This patient just happened to be four twitches and 13 percent. Then, as you see, I did not give any additional rocuronium for the entire case. The patient then starts metabolizing themselves slowly upwards. This patient, despite their renal failure, is a fast metabolizer of rocuronium. At the time of renal reperfusion, the connection of the new kidney to the blood supply, the patient had recovered themselves already to 87 percent. Then, by the conclusion of the surgery, the patient had recovered themselves to 94 percent and no reversal agents were indicated. No reversal agents were given. The patient was successfully extubated and was able to avoid unnecessary medications. The takeaways at this point, there are four ways that we can reverse patients. Some of them spontaneously recover. Just like the kidney transplant patient, no reversal agents are indicated. Of course, you can use neostigmine and glycopyrrolate. Neostigmine, glycopyrrolate, and then if they fail, you can use cigamidex or you can just go straight to cigamidex only. Again, patients that spontaneously recover to trinafour ratio 90 percent do not require any reversal because they are already reversed. No more CYA doses. Neostigmine is only indicated to reverse minimal paralysis, trinafour ratio greater than 40, and only cigamidex can reliably reverse paralysis deeper than 40 percent trinafour ratio. We should return every patient to their pre-paralytic state. If they're in the pre-op holding room, they are 100 percent recovered. We're supposed to be returning them to the exact pre-paralytic state that they came with. That's how recovered I would like to be. I would like to not be any percentage paralyzed when I wake up from anesthesia. You can do this by whatever means necessary. When using a peripheral nerve simulator with the proper technique, patients who have four twitches, no fade, sustained tetany, breathing, good tidal volumes, head lift, and following commands are still somewhere upwards of 50 percent paralyzed even after you have administered a reversal drug. This is because our eyes cannot detect the extent of neuromuscular paralysis in the same exact way that our eyes cannot detect the percent of oxygen bound to hemoglobin. Therefore, just like oxygen saturation, neuromuscular blockade can only accurately be measured by a monitor. 10 on the temple is not a technique. We simply made it up. It does not exist in any medical literature. Peripheral nerve stimulation intends to stimulate nerves because peripheral muscle stimulation is not a technique. Quantitative monitoring changes the way we deliver anesthesia, including your gases, narcotics, paralytics, reversals, everything. These changes can be the most challenging for the most experienced providers because we can now accurately measure the depth of paralysis for the first time. It looks very different from what we have been doing for our whole career. I had the pleasure of going on a surgical mission trip to Rwanda in Central Africa. On February 12th of 2023, I carried one of the quantitative monitors down there. We did the first quantitative monitored surgical case in the country of Rwanda. These anesthetists, their eyes were huge. Their jaws were on the floor. They could not understand what they're seeing. They were so shocked that the patients could be so very paralyzed. And still ready to extubate, seemingly ready to extubate. Just like this 20-year CRNA, who had the patient on the quantitative monitor, extubated the patient and left the operating room. And the last recorded recovery level of that patient was 37%. They look ready to extubate guys. But they're not. We can now eliminate residual paralysis and it is very exciting. These are my references and I'm happy to answer any questions. Okay, so I see a couple of questions coming in to us today. Thank you for those. Blake, first question. Let's see here. Did you cover the max dose of neostigmine being lowered? Yes, traditionally that has been a maximum dose of 70 mics per kilo, which on a 70 kilo patient would be 4.9 milligrams, and so traditionally we've rounded up to 5 milligrams. The ASA guidance lowered that to 50 as a maximum dose, and then since it's only indicated for minimum paralysis, which is greater than 40 percent trinofluoride ratio, much less neostigmine can be used in a titrated fashion. So anywhere between 15 and 40 mics per kilo of neostigmine is now the indication to be given at trinofluoride ratios between 40 percent and 90 percent. Okay, I think there are a couple of similar questions like that. I think you covered it. Next question. When a patient is in the Bergen zone, do you continue to administer paralysis at the surgeon's request? That is a very good question, and now that we have the monitor and Sugamidex, I would say yes. However, I did take the Bergen zone presentation. I put all of that information into a PowerPoint slide, and I delivered that to the orthotrauma department in their grand rounds, and we worked back and forth just communicating what this information was, and Dr. Bergen had a very good point that these large muscle groups, the gluteus maximus in particular, it's very, very difficult to paralyze, and so when he's boving through that muscle or retracting the muscle, it feels still tight, and so he's asking for more paralytics even when we're at PTC0. Now that we have Sugamidex, which can reverse all levels of paralysis, then we're now able to achieve deeper levels of paralysis and still recover the patient, whereas in the past we could not. So in the past, I would have given maybe a small dose of rocuronium or whatever the paralytic is, but now we can give larger doses in hopes of paralyzing those larger muscle groups. Okay. Has quantitative monitoring become standard of care at your hospital? That is also a very good question. So standard of care, after looking at this for now five years, standard of care is 90% train-of-four ratio. So that standard of care has been established for almost 20 years. So every patient should be recovered to 90% train-of-four ratio. That is the standard. The question for all of these hospital systems is how are we going to achieve the standard of care without a monitor? Our eyes cannot see the neuromuscular junction, only the monitor can. So a monitor is essential to achieve the standard of care. If in a lawsuit the standard of care was not proven to be achieved, now you are liable. So since the only way to achieve standard of care is with the monitor, that becomes a very easy decision to invest in the monitors. Other institutions have studied the cost of them, the cost of instituting the monitor versus the cost that they were spending on respiratory complications. And the cost of the monitors is much less than the respiratory complications that they were already experiencing. So it's actually a money saver, not an expense. Okay, great. What are the companies that make this equipment? There are several. Our institution uses the TwitchView monitor. There's also Tetragraph, TofWatch. There are several out there now. GE has one as well. Okay, great. I believe there's a question on access to the slides. Can we make them available? I believe they actually are available, but Blake, would you have any opposed to getting them to some folks who request them? Absolutely. No problem whatsoever. I did just notice a question that popped up that I would like to cover. It said, so are you saying that we're covered legally if we deliver less than the FDA recommended two milligrams per kilo? That is the subject of my titration of Sugamidex lecture, and I do go over that in depth. Keep in mind that the standard of care is not two milligrams per kilo. The standard of care is not four milligrams per kilo. The standard of care is 90% Trina-4 ratio. Okay there's questions are still coming in. Let's see here seeing which ones we have not covered yet. Yes, why recommend neostigmine and a lower depth rather than low-dose Sugamidext? So I believe that just as the ASA guidance suggested if you look at that sentence very closely it said neostigmine may be considered as a reasonable alternative to Sugamidext. So they're really you know kind of covertly saying Sugamidext is the better drug. One in the package insert states that one in 25 million bound complexes may disassociate. So we've looked into that as well during our research study and there's some interesting information regarding that. But Sugamidext has less side effects than neostigmine. It is more expensive however as everyone knows. But at some point it's going to be generic and at some point the price will come down. Then I believe at some point there will likely not be neostigmine in the drawer and Atrocurium, Cis-Atrocurium that in the future I do believe just kind of seeing the writing on the wall that it'll all be Rocuronium and Sugamidext. What is the break-even time in months and or years of paying off the monitoring and using less Sugamidext? That is a very good question and again part of my Sugamidext titration presentation. Rutgers had a study where they looked at it over a five-year period and if I remember the numbers correctly they were spending around five million dollars over that period in respiratory complications and once they instituted the quantitative monitor and Sugamidext that cost went down to six hundred thousand. And so they wound up saving a considerable amount of money. I would have to look for that study and I can send that specifically out. It breaks down all of the cost details. Can Sugamidext be used on dialysis patients? That is a very good question as well. We looked into that. Right now the package insert states that Sugamidext is quote not recommended in renal failure patients. Our Sugamidext rep is very close to us and visits us often and we talk in depth and about all of these issues. He sends me all of the latest research on all these subjects and so what we've come up with and we do a lot of renal failure patients at University Medical Center in Mississippi. The reason it's not recommended is because they were not able to do studies on renal failure patients with Sugamidext. So since there is no data on that and it was not included in the FDA package insert they cannot specifically recommend it. However we use it, I use it, speak for myself on this, now for every renal failure patient that I've had in the last three years because at the end of the day you don't know how variable the patient will react to the paralytic. Whether it's cis-atrocurium, atrocurium, rocuronium, they're all going to vary. Some are going to be fast metabolized or some slower and you cannot predict the depth of paralysis achieved by the drug that you chose. You cannot predict the rate of metabolism of the patient to that drug and you therefore cannot predict the depth of paralysis at the conclusion of the surgery because you cannot also predict the conclusion of the surgery. So you're just left without a get out of jail free card if you're using any other drug besides rocuronium. So with the quantitative monitor the thought right now the theory is that we can just simply titrate it up to 90% trinofluoride ratio and now you can avoid overdosing Sugamidext. If you overdose Sugamidext that means you've given more molecules than rocuronium molecules and those molecules of free Sugamidext just circulate in the patient's body. They do not leave. The package insert states that they found Sugamidext up to seven days in renal failure patients. That unbound Sugamidext just spins around running in circles looking for one thing, rocuronium and decuronium. So when those patients come back to the operating room sometimes emergently you give rocuronium and nothing happens because those free Sugamidext molecules now just found their rocuronium and they bound it. So you have to bind all the Sugamidext molecules before you can then give additional rocuronium and it will work as it is supposed to. Renal failure going to dialysis. We ran into this as well where one of our patients their kidney did not start producing urine. They had to go to dialysis. They used a high flux filter which is in the package insert but we've always heard is what is needed to remove Sugamidext. Well they came back Monday morning for surgery for evacuation of hematoma around the kidney and to look at the at the graft site. Induced with rocuronium, absolutely nothing happened. The patient stayed 100 percent train to four ratio. After additional rocuronium was given the patient then responded appropriately. That was after a high flux filter. So I went back in the package insert and it states that yes it can only be removed by a high flux filter because a high flux filter removes more Sugamidext than other filters. Nothing is 100%. In fact it says it's approximately 70% of Sugamidext in the patient's body can be eliminated with the high flux filter. So nothing will remove at all. So a correct dose, an accurate dose, a specific dose, titrated, customized dose of Sugamidext in molecules to reverse the rocuronium molecules that are present. The paralytic molecules that are present would be indicated in these patients as well. Okay multiple questions phrased a little differently but for clinicians here who work in institutions where they do not have quantitative monitoring, how would they go about establishing that there? It does take a lot of information. It takes a lot of detail. It takes a lot of conversations. It is an additional expense. However like Dr. Burrell put in the chat just now that it only takes five cases of post-operative pulmonary complications to pay for these monitors. That's not even considering the ventilators. If you have a case of post-op ventilation and ICU admission on ventilator, I asked our intensive care team and they said that that cost is $13,000 versus potentially a $115 vial of Sugamidext. So the cost savings are astronomical. That is one in. Another in for your administration is to ask them you know why do we have to continue putting 50% of patients in PACU paralyzed that reduces the time spent from moving them from the OR to the PACU. They spend longer time in the PACU. That means longer time into the ASU and getting home. So all of these minutes add up and it's very very expensive. So a $20 sticker for the patient's hand and a $2,000 monitor that we have are now five years old. You amortize that out across days, months, weeks, and years and the cost is extraordinarily small in comparison to your facility continuing to have pulmonary complications that are now preventable. Let there be one lawsuit where an expert witness gets up and says yeah all they had to do is have the quantitative monitor and this Mrs. Smith wouldn't have had that complication and they write that malpractice check and then everybody in your state will have that monitor. Can you use Sugamidext to reverse an allergic reaction of rocuronium? Another great question and I don't have a great answer for that. That has been postulated. That has been suggested and it makes perfect sense because you are encapsulating that rocuronium. Interestingly, paralytics are the highest potential group for producing allergic reactions. We usually think that it would be other things like antibiotics and things like that but it's actually paralytics such as rocuronium. It's certainly worth a try. Now you have to have your patient's condition in consideration. If the you know patient's belly is open let's say and the surgeon is working you couldn't just reverse the rocuronium probably right then so it would really depend on the actual scenario that you're looking at but Benadryl epinephrine would probably be first line with the consideration of Sugamidext as well. Is there a need to calibrate or check baselines with these monitors prior or during induction? Excellent question. The short answer is no. However, comma, the baseline does establish your entire basis of monitoring this patient and comparing your data against itself throughout the entirety of the surgery. So let's say you push the propofol or induction agent check your baseline you see on the monitor you see the patient's hand moving you see on the monitor that it says for twitches 100% that gives you the confidence that that monitor is placed in the right location it is recording accurately. Now you administer the paralytic agent you see the patient respond to it and now at the end of the case you just simply have to get them back to your baseline back to 100%. That makes life so much easier for you because this scenario happens quite often. You forget to put the sticker on you forget to turn the monitor on you administer the paralytic and then 20 minutes later you say oh shoot I forgot to turn it on you turn it on at that moment. Well what is it going to say at that moment? It's going to say trina 4 0 possibly even PTC 0 which could possibly be true. That's probably where they are. However what if you accidentally put the monitor on the wrong nerve or it's on the knuckle and not the adductor pollicis or the stickers bad or there's some other sort of technical difficulty and it stays PTC 0 the entire case. Now you're confused well I never saw a baseline so I don't know if that's really PTC 0 or if it's just a technical problem. So it makes you more confused there are going to be you 1% or maybe 2% technical difficulties using the monitor but 98 99% of the time if you can get a baseline that is the best way to go about managing your case. What do you think about a strategy of just administering larger doses of Sugamidex and foregoing neuromuscular monitoring? Sure well therefore you know you must consider that you would be advocating for the administration of drugs into a patient that they don't need. So if the patient does not need a medication and then we give them a medication all we're doing is putting them at risk for complications that they did not ask for. Okay medications are only indicated if there's a clinical need for those medications. Additionally Sugamidex is very expensive now it will become at some point less expensive but right now you would be advocating for instead of $115 per vial giving $230 in reversal or 500 or 800 or a thousand dollars of reversal agents when they're actually not even needed. So just like titrating neosynephrine we're not just going to inject the whole vial we'll titrate it up for the patient's need. Kind of a good rule of thumb is give the patient anything they need nothing more and nothing less. Can you talk about Sugamidex and oral contraceptives? We do have a handout that flags when a patient is on oral contraceptives and Sugamidex is given. If Sugamidex is given during that procedure an additional paper is printed out and given to the patient post operatively it will bind those oral contraceptives and it's recommended to have a backup contraceptive for the next seven to ten days. What exactly is the we cut off for the use of Sugamidex during pregnancy? I've seen no indication to cut it off in pregnancy whatsoever. Now one of those caveats is going to be that there's no studies there for that because you'll not ever get any statistically significant studies in pregnant females really for any drug. So there's no just like propofol propofol is not indicated in pregnancy only because there's never been a study that proved its efficacy or lack of harm to the fetus. So we'll just continue to gather evidence much like propofol in pregnant females. Okay and let's see we'll go last question does local anesthesia also have a Bergen zone? Oh see that's very very good I'm glad you brought that up because one of the questions that I posed to the ortho trauma group during their presentation at Grand Rounds was when we do total hips or knees and we do them under spinal are you still having the same problems with retraction of the muscles the muscles being tight and there were a lot of blank faces but one of the residents said no I've noticed that during spinal anesthesia the muscles are completely relaxed. So that brought about the suggestion which is in that Bergen zone paper as well about the possible combination of local anesthetics which of course blocks sodium channels. I'm not sure at this moment it would have to be studied if we could even block all muscle function with rocuronium or manipulation of the neuromuscular junction. I'm unsure at this point just because of that Bergen zone theory but we do know that paralysis can occur with other drugs not neuromuscular blocking drugs like local anesthetics. So possibly injecting a local into that muscle group help in the relaxation of that muscle absolutely. Thank you Blake that's all we have time for today. Thank you so much for attending today's webinar. Thank you very much.

neuromuscular blockade

neuromuscular monitoring

quantitative monitoring

TwitchView technology

Sugamidex

patient management

neuromuscular blockers

reversal agents

clinical applications

patient outcomes