Diabetic medications- Do you know all the new diabetic medications?

Diabetic Medications

There are a myriad of diabetic drugs out there, all with strange and difficult to pronounce names. So how do we keep this straight? It’s not important that you know the specific names. Rather recognize the class. You can look the names up and quickly learn which class it belongs to. Once you know the class you should know what to do and what to worry about. 

There are 6 main classes of diabetic medications:

  • Metformin
  • Insulin
  • Sulfonylureas
  • GLP-1 agonists
  • DPP-4 inhibitors
  • SGLT2 inhibitors

 

Separate these into your hypoglycemics and non-hypoglycemics. 

Hypoglycemic agents 

  • Insulin

    • Replaces the body’s endogenous insulin
    • Insulin comes in a variety of forms classified by there duration and onset of action
      • Short acting- such as novolog (Aspart) and humalog (Lispro)
      • Moderate acting- such as regular insulin or NPH
      • Long acting- such as glargine (Lantus) and detemir (Levimir)
    • Again, it’s not important to recognize and memorize these. Instead recognize that insulin comes in 3 different formulations, all with a different time to peak onset and duration of action. If you recognize that, you can look up which category the insulin your patient took fits into and in turn what time you can expect to see it’s peak effect and how long you can expect it to last. 

 

  • Sulfonylureas– such as glimiperide, glipizide, glyburide
    • These directly stimulate insulin release from pancreatic beta-cells
    • These can be scary overdoses and are long acting too 
      • They can experience rebound hypoglycemia and often require a D10 drip and admission to the hospital for monitoring
      • Recognize one pill can cause serious harm and risk in a young pediatric patient
      • Treated with D10. Might also get octreotide in the hospital

 

  • GLP-1 agonists? – such as liraglutide (Victoza), dulaglutide (Trulicity), semaglutide (Ozempic)
    • Stimulates insulin release from the pancreas on a glucose dependant basis
    • Generally thought not to cause hypoglycemia but rare reports of these leading to hypoglycemia do exist in the literature
    • These are subcutaneous injections
      • Pen SQ injection which may resemble an insulin pen
      • Some are once weekly injections (Dulaglutid [Trulicity], semaglutide [Ozempic])

 

Non-hypoglycemic agents

  • Metformin

    • Guideline recommended first line agent for diabetes mellitus type 2
    • #5 most prescribed drug in the U.S. 
    • Lots of off-label uses (indications other than diabetes)
      • Weight loss
      • Slows cardiovascular progression
      • Slows colon and prostate tumor progression
      • Pre-diabetes
      • Improve fertility
    • Rare complication of severe and life threatening lactic acidosis
      • Occurs in an overdose 
      • Or in renal failure as metformin is cleared by the kidneys
      • Classic presentation is an OD or elderly patient who developed a renal insult
      • Will look like any other acidotic patient
        • Sick appearing, possibly altered
        • Deep rapid respirations in an attempt to compensate for the acidosis
      • Carries a 30-50% mortality rate 
  • DPP-4 inhibitors– such as inagliptin (Tradjenta), sitagliptin (Januvia)
    • These prevent the inactivation of the glucagon like peptide -1 (GLP-1) which is responsible for insulin release from the pancreas on a glucose dependant basis
    • Do not commonly cause complications that we need to be concerned about in the pre-hospital setting
  • SGLT2 inhibitors
    • These inhibit the ability for the sodium-glucose transport protein-2 from re-uptaking glucose in the kidney, thereby letting glucose “spill” into the urine
    • Can also act as an osmotic diuretic and as such have gained FDA approval for the treatment of heart failure even in the non-diabetic patient
    • Rare complication of euglycemic ketoacidosis
      • Occurs in the previously uncontrolled diabetic
      • They continue to have a suppression of insulin so despite spilingl glucose into the urine and effectively lowering blood glucose the patient still cannot get glucose into the cells where it is needed, thus, lipolysis must be performed in order to compensate
        • This breakdown of fatty acids leads to the production of ketone bodies
        • This is the same process that leads to classic DKA 
        • Difference here is the patient is spilling there extra blood glucose into the urine so when we obtain a finger stick glucose it is in the high normal range (150-200)
      • These patients present and look just like a DKA patient (and they are in DKA!) but will have a glucose in the 150-200 range

 

Take Home

Know the classes. Know which ones cause hypoglycemia. Know which ones have rare complications. Look up the rest. 

 

Mac 3 vs Mac 4 – Is there one blade to rule them all?

Episode Transcript:

 Ross:

Welcome to EMS Cast, where we provide high level education for you, the providers on the streets. I’m your host Ross Orpet 

 

Matt:

and I’m Matt Mendes. 

 

Ross:

And today we’re going to be talking about one of my favorite topics. It’s called, Ross was right and Matt was wrong. Today we’re going to be talking about a study that looked at intubation blades and specifically which Macintosh intubation blade may be better than the other.

And this is maybe a long held debate, at least between Matt and myself. Is the number three blade better or is the number four blade better? 

 

Matt:

Yeah, I think that you’re right. The number three is probably better for most people. 

 

Ross:

Give the listeners a little background about what our argument has always been.

 

Matt:

Well, what I was taught and what I believed dogmatically until this study came out was that the MAC four was big enough for everyone and would never be too big. And that the extra length gave you a better lever arm to lift with. And so the Mac four, if you just use that on everyone, you never had to think about it and you were always gonna be successful.

 

Ross:

We’ve never really had data. Nobody’s ever really looked at this question before, so I think you’re right. I think there’s been two fields of thought on this, and one of them is, well, if you use the four, it’s always going to be long enough. You’re never going to have to switch blades because you have too short of a blade.

And if it’s too long, you just go in a little less, then you normally would.

 

Matt:

And long enough, because the whole point is that the tip of that blade is supposed to hit, really the hyoid bone, but the hyo-epiglottic ligament, which then lifts the epiglottis outta your way and gives you that goal post view of the cords, and really makes your view easier.

The length is super important. If you don’t have a long enough blade, you will be in really bad shape. I think people were over afraid of that length problem. 

 

Ross:

And just as a reference, that ligament is essentially what makes up our vallecula. 

But the other school of thought was the Mac four blade is pretty big. And some people experienced, myself included when I would use a Mac four, it just seemed to have a lot more volume and I felt like I had less opening or less view to pass that tube. So that was the other field of thought was, well, the MAC four is a little big, and so if you can use a Mac three, that would be preferable. You’ll get a better view. And the MAC three should be big enough for most people, especially if you think about it beforehand. Is this person appropriate for a Mac three or is this somebody larger who I may need a Mac four.

 

Matt: 

The trick with direct laryngoscopy is to line up the opening of the mouth, the mouth hole, with the opening of the airway, the airway hole, also called the glottic opening, and get those two circles to align into one straight view. And so if you have a big blade in the way of that, you will have a reduced view.

What I think came to play here is that, that extra space between the three and the four matters. 

 

Ross:

And there’s a lot more that goes into getting that view. It’s not just blade size, you know. It’s going to be positioning the patient at the appropriate level. Making sure that their ear to the sternal notch angle is appropriate. Making sure that your distance from their mouth is appropriate to line those angles up.

But this study is specifically looking at the Mac blades. So start us off with where this study went and what it looked at. 

 

Matt: Well, the title is The Impact of Macintosh Blade Size on Endotracheal Intubation, success in Intensive Care Units. And this is a retrospective multi observational study and the name of the trials called the MacSize-ICU Study, which is pretty cool.

This was all adult patients, so 18 and up. Mac three versus Mac four. They did this in French ICUs, so it was only in France and it was in a number of ICUs there. And the background was essentially what we just talked about. There’s a lot of dogma about why you should always use a Mac four. And then there was a lot of good hypothesis about why you should always use a Mac three.

And I think that they attempted to be the first true study to answer this. There’s two previous studies where they did this with a mannequin and then in like 30 patients with no teeth. And both of those showed preference for the Mac three. But this was the first one where they were doing this in a more organized approach on real people.

 

Ross:

And you found one other study from Canada that you found pretty interesting, right? 

 

Matt:

Yeah. They also cited this study where in Canada, in the nineties, these anesthesiologists were kind of annoyed with how there wasn’t that great of evidence for different blades, and they came up with all these mathematical equations and angles and measurements to describe the amount of mouth to glottic opening you get and how much the blade dips down into your view when looking at that. And they compared all these different blades, including Miller Blades and some other brands, and basically they found that the MAC blades gave you the best view when you took into account, far space view. Which is what you can see at the glottic opening. The Mac three for most people gave you the most amount of advantage with the view. It was only when people were taller and needed that longer blade to get into the vallecula that the Mac four kind of took over and surpassed it. But it is true that if they are taller, you’ll get a way better view of the Mac 4. 

 

Ross:

Sounds like a lot of math and angles and not very pragmatic, but still, you know, pretty interesting.

 

Matt: No, but one of the coolest parts of the paper was that they were talking about the guy who made the McIntosh Blade ,McIntosh, and I guess, way back in the day, that middle part of the curve, they would flatten that out. Because, McIntosh said, “you can’t see through the crest of the hill”.

And I think that explains the whole, the whole basis for these studies is that, that curve can dip down and worsen your view. 

 

Ross: 

So then why isn’t it a Miller Blade better? 

 

Matt:

Well, the Miller Blade is way more of a skill and way harder to control the epiglottis and the airway. I think the length of the Miller blade, like if you move just a little bit off or incorrectly in an ambulance or on scene or in a chaotic environment, you kind of lose that clutch on the epiglottis and that perfect view.

So I think it’s just more finicky and way more of a skill. But theoretically the whole reason they would use a Miller Blade was the straight blade, while harder to use,  didn’t have that dip down. So that was kind of the backup for anterior airways where getting rid of that dip would be an advantage.

But again, it’s just a way harder skill. 

 

Ross:

Yeah. Getting rid of that  crest of the hill. But I agree. I used to think when I was a paramedic that a Miller was a brute force instrument where you would just shove it in, back up until you found the epiglottis, and everything would drop right in. 

Right? You’re supposed to lift the entire epiglottis with it. You’re supposed to lift everything with it. It sounded like a brute force skill. But when I started going into the OR and practicing these intubation skills a lot more, I found that it’s actually way more of a finesse skill than a Mac blade is because you have to really know where you are. And then you really have to kind of dip down and grab that epiglottis to get it outta your way. So I agree. It’s a tough skill and it’s a very finesse skill. 

 

Matt: 

I hate the Miller .

 

Ross:

I’m not a huge fan of it either.

Matt:

But back to the methods and materials. So this was what they call a retrospective observational study, which is just a, a fancy way of saying this wasn’t the classic, double blinded, randomized control trial, where you know the first patient gets an envelope that tells you what to do and then the next patient gets a different envelope, that tells you a different way to do it. They just let people intubate how they would normally intubate with the plan of seeing how that would all pan out in the data.

If Ross was working one day, then all those patients that were getting intubated in these French ICUs would get intubated with a Mac three. However, Ross likes to do it. He was allowed to use whatever meds he wanted. They didn’t control any of that stuff.

And then if I were working, everyone would get intubated with a Mac four. Again not controlling for anything. And then they just looked at all the data after the fact. Or retrospectively, retrospective means they looked back on it. And then observational means they were just kind of seeing what happened. They didn’t control for a lot of stuff. 

 

Ross: 

They mentioned this as a limitation in their limitation section as well. That allowing choice of blade may have overestimated the success rates of physicians because they were just more likely to choose what they were most comfortable with.

 

But I agree with you. I see this as a strength. I think that it’s more pragmatic and I really want to know what happens when the physician or the provider takes their best shot at it, with what they’re most comfortable with, that they’ve trained the most with. 

 

Matt:

Yeah, if I’ve been using a Mac four since 2007. And you’ve been using a Mac three since 2007, and you are better on the first try than me, then that’s way more interesting to me than if you force me to use a three and force you to use a four. 

 

Ross: 

You will inevitably get some baseline characteristic differences with this approach, which is feared to potentially favor one blade over the other.

For example, maybe physicians were more likely to choose a Mac four if they perceived the airway to be more difficult or if it was a bigger patient. Or maybe they even chose a different drug for that reason. And that’s why we do something that’s called propensity score matching, which is essentially attempts to match patients with one another across groups to more even out those characteristics.

So in the paper they give us patient characteristics for the MAC three group and the MAC four group kind of pre-match and post matching. And although, you know, this propensity matching is very well accepted within the scientific community as a good way to do a trial. It’s not perfect and you can’t always account for every variable, and so it is subject to some bias. But one thing that I found interesting in looking, even at the pre propensity matching, was that they were fairly even groups. The main differences they saw was that there tended to be more males in the MAC four group and they were slightly taller by a centimeter on average.

 

But when you look at the, the MAC four group, they actually had lower mallampati  scores before they started the intubation. The mallampati  score kind of favored the Mac four group. If you look at the pre-match. 

 

Matt: 

Just a reminder,  mallampati  scoring is like open your mouth and how much of the back of the mouth you can see is graded one through four and grade one being the easiest, grade four being the hardest, and that’s thought to be a predictor of difficult intubation views.

So if you open your mouth and you have a grade one view, it should be an easy intubation. If you open your mouth and you have a grade four view, it should be a hard intubation.

 

Ross: Yeah. So pre-match, the MAC four group actually had more grade one and two patients than the MAC three group did before they did their propensity matching.

 

But I will say that the mallampati  data was missing in the vast majority of cases. Something like only 500 of the 2000 cases actually documented this data. So there was a lot of missing data there. 

 

Matt:

No one checks it anymore cuz it’s worthless. 

 

Ross:

Right. It doesn’t actually tell you a whole lot.

So how did they define attempts?

 

Matt:

So any entry and exit of any intubation device into the patient’s mouth. So blade in and out counts. And that was one attempt. 

 

Ross:

There was a whole bunch of stats that went into helping to do this matching of patients, which was honestly, pretty dizzying for either of us to understand. So we’re gonna breeze over that and go to the results section now.

So what did this show?

 

Matt:

There were 629 intubations with the Mac three. 1,510 intubations with the Mac four. The Mac four was chosen initially more than the Mac three, like we said, in men and taller people. But they match this on the back end.

 

Ross:

What were the results?  

 

Matt:

MAC three was 79.5% successful on the first attempt and a Mac four was 73.3%, about a 6% difference, and this was considered statistically significant. So before we talk more about the stats, one thing you always want to ask yourself is, they use the word significant a lot, and statistically significant is one thing, and then clinically significant is another thing. Something may be statistically significant but not clinically significant. In other words, it’s not that useful to you, even though mathematically there was a notable difference.

Here I think a 6% difference, if I were that 6%, I would want you to use Mac three. The other mathematical value they’ll use to try and answer the clinically significant thing, is this number needed to treat score. They got a number needed to treat score of 14.6, which is pretty good. 

 

Ross:

The number needed to treat truly is how many patients would you have to intubate with a Mac three to see one patient outcome affected by that choice in a positive manner.

 

Matt:

If you Google what’s a good number needed to treat score, you can’t really get a straight answer. Lower is better. Scores of like 1, 2, 3, 4, 5 are very rare. And then obviously, in the hundreds and thousands it probably doesn’t matter. So 14 is a good score. It means, it probably is worth it to us to know, and probably is clinically significant.

The one thing that was super interesting was that glottic view (how well you could see the opening of the airway or the cords, as we say) simply was not different between the two groups. Which was fascinating to me. 

 

Ross:

That was interesting. Why do you think that was? 

 

Matt: This probably represents that the extra space makes a difference. That as soon as you start to introduce a tube, the blade plus the tube takes up a lot of your eye space. And often times when we miss a tube, it’s because that last second where we’re about to put the tube into the cords, we completely lose our view. And then something happens and we goose it.

The other aspect of this that was interesting is they looked at all these other things that also increased first pass success rate and the use of something called burp or backwards upwards rightwards pressure, which is where you put your, hand on the trachea and push backwards upwards and rightwards, all with respect to the patient. This increased first pass access rate. And what Burp does is it’s a type of laryngeal manipulation. Essentially moves the glottic opening into a better view and makes it easier to see everything. So I think that all this means is that, you can get a really good glottic view with either blade, but millimeters matter once you start putting other stuff in the mouth. And when you intubate somebody, you have to put other stuff in the mouth. So I think that’s, obviously a theory, but that’s my best guess at why you saw similar views with both, but more success with the three. 

 

Ross:

BURP was a technique that was taught initially to theoretically avoid vomiting or aspiration during your intubation attempt. We’ve had multiple studies now that have shown that that doesn’t actually help prevent those rates of aspiration. But laryngeal manipulation is a good technique when you are intubating somebody and maybe they’re a little anterior or you’re having difficulty getting that view. You can actually take your non laryngeal blade hand, reach around and push down. So your right hand, reach around and actually push down the larynx and manipulate those cords until you get them to drop into view for you. And then you can have somebody hold that there for you. 

 

Matt:

A lot of times once you get it there, if you’re lifting up hard, you don’t have to have someone hold it. It’ll just stay there because of the way the rigid anatomy and the ligaments work. Yeah you can have someone hold it for you. But if you’re alone in the back of an ambulance, I wouldn’t be disheartened to not try this. Cuz it’ll hang out there in the vast majority of cases without you needing to have someone hold it for you.

The other thing I was wondering is, if they did this study with a bougie, which obviously takes up way less of your eyesight space than a styletted tube, would then the Mac three and Mac four have had similar outcomes? Is that 6% all related to loss of view when you put the tube in?

 

Ross:

Some limitations to this study. It was, like we talked about, retrospective and observational. So they didn’t control for a lot of things and they kind of just let providers do what they did and they looked at the data afterwards, which can always be a risk for bias at the end of the day.

Another big limitation was the failure to enroll enough patients to reach their power calculation. When you set out to do these trials and to find a statistically significant difference. You do what’s called a power calculation, which essentially tells you, you need this many patients in order to find a difference if there actually is a difference or be confident that that difference you found is real. And they actually fell short of that power calculation.

And so they talk about this as really more of a hypothesis generating study, meaning we looked at this, we found this difference. We think it might mean something, but truly we need a bigger, and maybe even a randomized trial to let us know if this difference actually does exist. 

 

Matt:

And hopefully we do get a trial. I don’t know if we will, but I think it’s an important question. I think the other important question is how do you know when you need a four? Because like I said, if you can’t get that tip of the blade in the vallecula, you’re just not in a good situation. So I think those are the two questions I’d like to see answered going forward.

But I think there was already enough theory and pragmatism to the MAC three over the Mac four before this trial that, I think it is changing my practice and I will go to a Mac three on most adults who are of, you know, relatively normal size when you’re standing at the foot of the bed. 

 

Ross:

Welcome to the dark side.