Live from the IARS

Welcome back to Depth of Anesthesia. This is a podcast that critically explores our clinical practices. My name is David Hao and I'm a clinical fellow at Brigham and Women's Hospital. Our next two episodes are going to be a special Two part series that we actually recorded live at the International Anesthesia Research Society meeting back in February of this year Dan Saddawi-Konefka and I had the pleasure of hosting a virtual session where we explored a claim that we actually first started thinking about all the way back in May of 2019. Is it necessary to confirm mask ventilation before paralyzing?

Our listeners may recall that this was in fact our very first episode. And so Dann and I took a fresh look at the topic and we actually found a lot more literature to add to the story. So this series will build on some of those discussions that we first started back in that episode from 2019, but I think as a whole Uh the series is a much more complete and nuanced take on this fairly polarizing claim. So thanks to the IARS for allowing us to host this session and for allowing us to publish this audio here. on the Depth of Anesthesia podcast. We're actually hoping to continue similar sessions at future IARS meetings.

So if you are going to be at those meetings in the future, keep a lookout for our sessions. And special thanks to our team member, Michael Fryer, uh, for helping with the audio on this live recording and some of our prior episodes. Michael is the co-founder of Overnight RN and uh he's played a pivotal role. in helping with many of our episodes as an audio engineer. So throughout this two-part series, we'll explore the literature behind some rationales that we've heard around the question of Whether it's necessary to confirm mass ventilation before paralyzing. In this first part, we'll explore some contradictory stances. on whether you can safely immerge a patient after inducing them.

So we'll specifically look at three questions. How long will it take to desaturate to the point of no return? How long will it take for spontaneous respiration to resume? And will neuromuscular blockade administration burn the bridge to spontaneous respiration? Now, as we reviewed the literature for these questions at our live session, we plotted the findings on a graph to help our uh listeners visualize them.

And I'll make this graphic available both on our website and through some of our social media platforms. And I think it'll be helpful to refer to as you listen to the podcast or even after you listen to the podcast. In this second part of this two-part series, we'll then start exploring the rationale that neuromuscular blockade will consistently help mass ventilation or intubation and therefore delaying it is less safe. We'll also touch on some of the larger observational studies we have that provide some additional insights into these claims. So without further ado, here's Dan and I at the IRS starting off with the case presentation.

All right, so today we're going to consider a claim about airway management practices. And our case today is that of a 72-year-old man who's presenting for a laparoscopic umbilical hernia repair. He's 5'10 inches and 120 kilos, so BMI of about 38. And on examination, the patient has a thick neck, malinpotty class 2 airway, and class 2 upper lip bite test Now, for the purposes of our discussion today, we're going to assume that the setting does not have access to Sugammadex. We wanted to make sure that the scope of our literature review was manageable for the time we have today.

So We do have one paper that examines Sugammadex and we'll give that a nod later on. So back to the case. The man is positioned in a 20 degree backup position and fully preoxinated. And induction proceeds with 200 of propofol and 150 of fentanyl. Now after the patient becomes apnec, mass ventilation is confirmed, and then 100 of racuuronium is given.

Dan, what are some of the claims or habits you're seeing here in this case? Yeah, so there are several potential practice practice habits we could talk about. You know, we could look at the choice of propofol and fentanyl for induction agents. There's certainly lots of other choices we could have made. We could look at the doses that were selected.

We could look at the use of backup position. The habits are really everywhere. The one that we picked for this session though is the confirmation of mask ventilation. prior to the use of neuromuscular blockade. And certainly that's something that I was told when I was a trainee several times that the safest approach was to check that you can ventilate before you administer the paralytics so you don't burn any bridges. Alright guys, it's David back here in Present Day.

I'm gonna skip the interactive portion of the live session. won't make a lot of sense in the podcast format because we're using an interactive visual platform. So instead I'm going to ask you the same questions that we ask the audience and give you an opportunity to think about them for yourselves. So first question, what is your level of agreement with the following claim? In situations like the one described, mask ventilation should be confirmed before administration of neuromuscular blockade. The next question is, what is the closest level of evidence that you think exists to support what you believe?

Do you think that there's multiple randomized clinical trials or meta-analysis? Do you think there's a single randomized clinical trial or non-randomized studies? Do you think there's only consensus opinion or case studies? Or maybe you don't know of any evidence, but it's what you believe. And finally, irrespective of whether you're on the check or don't check side.

Think about some reasons or rationales that could be given to check mass ventilation prior to giving neuromuscular blockade, again if the goal is to create the safest possible induction and intubation. And what are some reasons or rationales that could be given to not check mass ventilation prior to neuromuscular blockade? Again, if the goal is to create the safest possible induction and intubation. All right, so here's Dan again picking up after the interactive portion of our session. Um to I I think what what you all put in the in the polls are exactly some of the rationales that we've heard uh over time uh shopping this around with different torques.

And I think they they they really do match what you put So the rationale for checking first is really just to not burn that bridge so that we can emerge the patient, but which wouldn't be possible if we've given neuromoscope. That's the claim. Now that actually conflicts with this don't check rationale, which we've heard. And that is that emerging after typical induction, even if you don't get neuromuscular blockade, is not consistently realistic. Right.

So we'll have to put those head to head and see what we can come up with The other rationale for checking first is that it gives more data for future use for this patient. Now because we don't have a lot of evidence to look at that. I think we'd want to look at evidence for is that data useful in the future, what does it look like We don't have a lot to talk about with regard to that, so that's just something to consider as you as you step through your own practice habits. And then the other rationale for not checking is that neuromuscular blockade will consistently help with mask ventilation or intubation and delaying it is therefore less safe.

So uh we'll explore these As we think about informing our practice with evidence, I think it's important to point out that the ideal study to answer this question just doesn't exist yet. And it may never. The outcomes that we care about, things like impossible mass ventilation. Need for emergent surgical airway, need to emerge a patient. They're just very rare.

So to adequately power a study, might need tens of thousands of patients who be randomized to check first or paralyze first. So I think instead what we have to do is use principles and some more upstream measures and then cross-check these conclusions against some larger observational studies to try to piece this all together. Yeah, I agree. And you know, our goal today will not be to definitively answer the question. Uh and one thing we'll ask, if you came in on the partially agree side, I want you to consider maybe the other side is right If you came in on the partially disagree side, consider that maybe the other side is right.

Considering the opposite is a really nice strategy for trying to unbias yourself and come to a more fair and balanced uh weighing of the evidence Alright. So with that, let's start digging into these subclaims. Now the first one we're going to do is this head-to-head, can we actually emerge the patient? They look contradictory. Now here the folks who want to check first might say that, well, if the mask is inadequate, they can wait for patients to spontaneously breathe.

And the folks who say that they don't want to check first, they just want to paralyze, say that waiting for, might say that waiting for patients to breathe spontaneously is just not realistic. So if we were to graph what we're talking about, it might look something like this. At time zero, after pre-oxygenation, patience induced. If mask ventilation is impossible, patients eventually going to desaturate. And we're going to assume that there's just no mask ventilation at all.

If we can mask ventilate, then it sort of becomes moot. We're really talking about the troublesome wounds Now also at some point after induction, assuming the patient remains alive, the induction drugs will wear off enough that they'll start to breathe. So the question is which comes first? Desaturation to the point of no return, or return of spontaneous respiration. To address this as it applies to our paralytic claim, we need to think about three questions.

First, how long will it take? for patients to desaturate to the point of no return. Second, how long will it take for spontaneous respiration to resume? And third, Will additional administration of neuromuscular blockade burn the bridge to spontaneous respiration? So Dan, let's start with the first question that needs to be answered. How long will it take for someone Desaturate to the point of no return.

And we're going to talk about two studies to address this question. I think big picture studies like this, what they do is they induce patients and then see how long it takes them for them to desaturate. Obviously, there's some ethical considerations here, so these patients don't actually desaturate to the point of no return. Instead, they desaturate to about 90%, which is the start of the steep part of the oxyhemoglobin desaturation curve. And so to answer our question beyond that, we have to do a little bit of extrapolation.

So this first study was published by Gensi et al. in uh 1991 and they took 32 ASA 1 to 2 patients presenting for elective surgery under general anesthesia and divided them into three groups that are based on their BMI. The first group was the normal BMI groups, that's within 20% of ideal. Second group was the obese group, so they were more than 20% over ideal, but less than a cap of 45.5 over. And the third group was the morbidly obese group, who were more than 45 and a half over ideal. All these patients were well preoxinated, so n title less than, nitrogen less than 5%, and this was all in the supine position.

Now here's a really important note. All the patients were manually ventilated once after induction. And if there was a concern at this point with how easy the masking was, this patient would be withdrawn from the study. Now everybody else was allowed to then desaturate to 90%. So what they find.

Patients in the normal BI BMI group lasted about seven minutes until they desaturated to 90%. Time to desaturation in the obese group was shorter at about five minutes, and in the morbidly obese group at about three and a half minutes. We should note that these are average desaturation times, which means that some patients desaturate earlier And you can see the standard deviations here on the table. A couple caveats I do want to point out. All patients got a safety breath check after induction, which would likely delay desaturation So in reality the time to desaturation would probably be a little shorter.

And the study also excluded patients with any medical comorbidities, including pulmonary disease. So It's reasonable to assume that in patients who did have pulmonary disease, time to desaturation could also be a little bit shorter. And finally, all these patients were pre-octrinated in the supine position, so a head-up position might have given us a little bit more time. Until desaturation with the increased FRC. So let's start dropping some of these data points on the graph that Dan showed us earlier.

So again, we have oxygen saturation on the y-axis and time from induction on the X And we can plot time to desaturation 90% for each of the groups, but again, the rest is going to be extrapolated. And you'll see that we decided to represent the standard deviations by the width of the curve. So there we go. Our three groups from this article: normal BMI, obese, and morbidly obese. Dan, does this make sense?

I think so. Um what we care about is the point of no return, which is somewhere down here. We don't have that. What we have from the study are just these blue dots and the standard deviations when they're at 90% So what we've done is taken typical desaturation curves and extrapolated some of the data from there. So normal BMI, maybe somewhere in the, I don't know, s uh six to ten minute range, all the way up to morbidly obese, that's maybe around Five minutes.

There were the caveats you gave about the safety check breath. And then there's other practice habits. As Dr. War put in the chat, some people deliver oxygen to the back of the mouth during induction in obese patients. And if that's part of your practice, Abbas, other studies might inform that maybe it goes a little bit longer. Do I have it right?

Yeah, that's exactly right. So Gen C is up on the graph, and let's add some more data points. Uh Dan, I know you have another paper that looks at something very similar, right? Right. So Gen C was all done in the supine position.

And here's a very similar study. It was performed by Dixon and colleagues, published in Anesthesiology in 2005. There are a few important differences between the two studies. First, uh Dixon was performed only in morbidly obese patients. Second, they actually randomized patients to supine or at 25-degree head-up of bed up positions And third, preoxygenation wasn't actually as controlled as Gen C.

So here in this study, they preoxygenated patients for three minutes of normal breathing at 100% FIO2 But there were no rigorous N-tital oxygen concentration endpoints specified, so it may not have been as standardized. Induction was also performed with propofolfentanol and succinylcholine, and it was followed by intubation Intubation was another difference between this study and Gensi's. But similar to Gen C's study, they did perform a safety check breath, in this case to confirm that the endotracheal tube was in the correct position. And then they waited for these patients to desaturate to an SPO2 of 92 %. So there are 21 patients in each group.

And the supine group patients desaturated after about two and a half minutes. Now there was a spread, and it turns out that actually six of these patients desaturated within 90 seconds, within a minute and a half The 21 patients in the 25 degree head of bed up position lasted an average of 3.5 minutes, although there was a spread here as well, with one patient desaturating within a minute and a half. Now some of the caveats that are important for our purposes, there was a safety check breath, meaning that the patients might have actually desaturated a little bit faster had that not been in place. They did exclude patients with certain pulmonary disease. It's conceivable that uh those patients might desaturate faster as well.

On the other hand Because they didn't track entitled oxygen concentrations, uh, it's possible that pre-oxygenation could have improved uh or allowed for slightly longer times before desaturation, and other strategies weren't employed, things like oxygen in the back of the mouth Hyploinasal cannula, all of those might have increased the the time before desaturation. Now with those caveats This paper actually aligns pretty well with Gen C's. So here's what Gensi's paper looked like, and we're going to compare it mostly to the morbidly obese arm because these patients were all morbidly obese. And when we overlay the two Here's the supine position and here's the head of bed up position. Altogether, we have a spread of times for patients to desaturate.

And that spread is pretty wide, even in patients of similar BMI. We haven't considered in this analysis supplemental oxygen during induction. And there may be other things that you do that would make you think that your data might look a little bit different. And if you have those, I'd encourage uh just more digging into the literature to see how it might apply. Okay, so the next question we have is if we want to wake them up, how long will it take for someone to have a return of spontaneous respiration?

And to make this a consistently safe approach, we'll want to make sure that the distributions between the desaturation curves and the spontaneous respiration curves do not overlap. So we're going to touch on three studies to try to answer this question. Now, big picture of the way these studies are done is they induce patients with a specified induction regimen after fairly robust preoxination, and then they wait until they start to breathe again. So the first study we'll take a look at was published by Stefan Nudo in 2012. Now what they did was they induced patients and recorded the time to return a spontaneous respiration.

They also recorded whether anybody needed rescue interventions because of desaturation. So the study had 24 healthy adult volunteers who were well pre-oxygenated, minimum of three minutes or until the end expired oxygen is greater than 90. They were then induced with probe two mics per keg and either Remy two mics per or one and a half per. Now similar to Gen C and Dixon, a single small positive pressure breath was given a minute after induction But then after that, the airway was left completely unsupported. Only if the SATS dropped below 80% did the practitioners then intervene with jaw thrust, positive pressure ventilation, things like that.

So let's talk about the findings. So for the REMI 2 mics per group, the time from induction to spontaneous respiration was about six minutes. And for the REMI group, for the REMI 1.5 per group, the time was a bit shorter at 4.7 minutes. Now, across the entire study, the SATS dropped below 80% in a total of five volunteers, four of whom were in the REMI2 mics per group, and only one of those actually required positive pressure ventilation. I just want to point out that this is an incredibly important outcome because here we have young and healthy patients who are desadding into the 80s with this induction regimen.

This is after fairly robust preoxination. We'll say there are a couple of caveats like we've seen in the other articles. Again, we have a safety check breath. The population was young healthy, so you might expect that older or sicker patients might be a bit more sensitive to the meds. Take a little bit more time to start breathing.

And these patients were also supine, and anybody with a BMI greater than 30 was excluded. So let's head to the graph. We have the results from the prior two studies, Gen C and Dixon, and uh let's go ahead and add the results from Stefanudo So you can see our two groups here, uh the two mics per group at uh about six minutes, uh, and the 1.5 mic group at about 4.7 minutes for return to spontaneous uh respiration. Dan, what do you think? Yeah, I'm thinking about something you said earlier, and that is that if we want emerging the patient to be a safe approach, we really need these curves to not overlap.

Now in this case, Stefanudo, these are young healthy folks we'd be comparing most appropriately to Gen C's normal BMI group over here. And if you look, the spread of this two mics per in the Remy group has pretty significant overlap So to me it's not that surprising that even though there were only 12 patients in this arm, one patient actually desaturated below a level of 80% and needed rescue positive pressure ventilation. So it strikes me that we either need to push these curves out further this way or move these curves in further this way to find a saf safe uh regimen. I want to talk about another study that also used Probe 2 Remy 1.5 per.

It's a pretty well-done study. And it also will give us a little bit of a check. Is there anything special about Stephen Udo? uh maybe it shouldn't apply more broadly. So this study was done by Zhao and colleagues uh and uh it was thoughtful in its design. It was a prospective randomized trial Patients were randomized to two different induction regimens.

Now one of those included succinyl choline and one of those did not. And we'll talk about the one that did not now and we'll add the succinylcholine in just a little bit. So this non-paralyzed group were induced with propofol tuper and REMI 1.5 fur. That's exactly the same as the Stephanudo paper These were similar patients as well. They were ASA 1 to 2.

They were all women presenting for laparoscopic gynecologic cases. Now uh 60 seconds after induction, the patients were actually intubated. So induction meds, then intubation. And then they waited. And they tapped the patients on the shoulders every 10 seconds and called their names.

And as soon as the patients either started breathing or opened their eyes, uh the time was documented and the patients were reinduced. Good study. Yeah So in the group that received 2 per of propofol and 1.5 per of remifentanil, apnea time, so the time until they started breathing again from induction was right around four minutes with about a one-minute standard deviation. Now the same caveats exist with Stefan as with Stephanudo's study, in that all of these are young and healthy patients. And it may be that other patients who are more sensitive to the apnea-inducing effects of these induction agents Would have longer apnea times.

So let's put it on the graph and we'll see that it aligns really well with the Stefanudo paper. Here's the Stefanudo paper of 2 per with Remy 1.5 per. And if we add on top the gel paper, they do overlap. And that makes a lot of sense given that the methods were fairly similar and the patient populations were similar as well. Alright, so our last study trying to answer the question of how long it'll take to breathe, again, is here is a little bit different because this study was designed as a dose finding study rather than an apnea time study This study was looking for the optimal induction regimen for smooth insertion of a cuffed oropharyngeal airway versus LMAs.

What this means for us is that the induction doses of propofol were variable because they were trying to find the optimal dose So because of that, looking at standard deviations for apnea time won't be as meaningful, but looking at the mean induction doses and mean apnea times could still be helpful for our purposes. So the population was 75 ASA 1 to 2 patients presenting for elective surgery, and they all got varying doses of propofol and additionally randomized to either fentanyl at 1 mic per or saline. Now the group that received just propofol got an average dose of about 2.5 to 3 MGS per keg. Their average apnea time was just around 3 minutes. And the group that received fentanyl as well had an average propofol dose of about 1.5 So average apnea time was 2.6.

All right, so back to the graph. You'll see that we've plotted the two groups studied in this paper without standard deviations. The fentanyl and propofol group at 2.6 minutes and the saline propofol group at 2.9. That makes a lot of sense because it wasn't uh a standard dose of propofol, but rather different ranges. uh including the standard deviations would probably overestimate the the variance in this population. Now we haven't in this uh in this graph uh shown other induction regimens But I think it's worthwhile thinking about.

There are some uh drugs that have less uh apnea induction. Um you might extrapolate out of that. You might find that there's other studies that help answer that question You might find that there's not, and then do some studies to add to this literature. Let's talk about the uh third part of this, which is that neuromuscular blockade additionally might burn the bridge, might make it so that we can't come back to spontaneous respiration. So to kick that off, we'll go back to the JOW paper.

This is the one where patients were induced, intubated, and then tapped on the shoulder until they started breathing. I mentioned that there was a second arm to this paper. And that's where instead of Remy 1.5 per, they gave Remy 1 per with sucks 0.6 per. Otherwise exactly the same. Now in this case, times to spontaneous breathing were no different.

And if you look at the graph, the curve, so here's Jou, the original. We had the sex arm, it almost completely overlays that. They lie right on top of each other I think David we have one more study with paralytic and time to spontaneous respiration. Is that right? Yeah, so this study is unique because it actually measures the time from induction to recovery of T1 to 10% and 90% of baseline.

So What they did was they took 115 ASA 1 and 2 patients presenting for elective surgery and induced them with a non-standardized regimen, so opioids, propofol, other agents. Then the patients either got rock and sugamidex or sucks at a mig per. The sugamidex was given specifically three minutes after the rock, and then train of four was measured every 15 seconds to time the return of T1. So for the rock and sugammadex group, return to T1 of uh 10% was four point four minutes and to ninety percent was six point two. And in the sucks group, the return to T1 of 10% was 7.1 minutes and 90% was 10.9, so a bit longer.

I do think it's important to observe that there's a fairly large standard deviation on the T1 at 90% in the SUX group. It's probably the largest standard deviation we've had so far. The other aspect of this is, Dan, I think in this study, using something like return of spontaneous respiration might not make a whole lot of sense because of the lack of standardization with the induction regimen. Uh and I'm wondering if you have anything that might help us better understand or contextualize how T1 relates to what we're looking for. Sure, sure.

So the the idea here is that uh paralysis When it gets in the way of ner of spontaneous respiration, it's because the patient is still paralyzed. So we can't really look at time to apnea since they got a whole bunch of different propofol regimens, but we could look at how long it took for their their strength to come back Now what does T1 at uh 10% mean versus 90? So uh that's the they take the baseline first twitch height and then how long does it take to get back to 10% of those? And what does it mean as it relates to to our pri our purposes Well, there was a study published in 2004 in ANA by L.

Orbany. We're not showing that here. But uh long story short, they did look at return to spontaneous respiration after succinylcholine and looked at uh T1 heights, uh varying percentages. And it turns out that at least in intubated patients that they looked at, return of breathing was most correlate most closely correlated with a T1 height of 10%. So this one right here.

Now that was in intubated patients. In non-intubated patients, 10% may not be sufficient to keep the pharynx patent. So we've included the 90% here as well because that's certainly more than adequate. So in non-intubated patients, the truth probably lies somewhere between these. Great.

So let's wrap up this graph with our final four data points. So first up are the sucks groups for return of T1 to 10% and 90%. And then we'll throw in the rock and sugamate X groups for return of T1 again to 10% and 90%. And Dan, I think that completes our graph. What do you think?

Yeah, so as I look at it, first thing I notice there's a ton of overlap between the desaturation curves and these induction regimens So to safely emerge patients, we either need to find strategies for longer times before desaturation or shorter times before return of spontaneous respiration. The other thing I'll mention is at least for adding succinocholine , that does seem to prolong uh the time at doses of one meg per keg, maybe not at the 0.6 per keg. So lots of stuff to think about there It's David again back in present day. So that wraps up the literature that we found around the question of if there's an impossible airway, can we emerge the patient safely with or without neuromuscular blockade?

We've plotted two studies that address the question of how long it will take for someone to desaturate to the point of no return. We then added three studies to answer the question of how long it will take for someone to have return of spontaneous respiration. And then we finish the graph with four final data points that describe the impact of neuromuscular blockade on emergence. For part two of this two-part series, we'll look at the claim that neuromuscular blockade improves mask ventilation And we'll also examine some larger observational studies to see how things actually stack up in practice. So thanks for joining me on this special show today.

Stay hungry and keep asking questions, and we'll see you for part two.