Episode 54: Safety and Efficacy of Insulins in Critically Ill Patients Receiving Continuous Enteral Nutrition

Summary

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Podcast Summary: AACE Podcasts

Episode 54: Safety and Efficacy of Insulins in Critically Ill Patients Receiving Continuous Enteral Nutrition

Release Date: December 13, 2024
Host: Dr. Vinh Tang Preacha
Guest: Dr. Cecilia Lo Wang, Professor of Medicine, University of Colorado

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Episode Overview

This episode tackles the nuanced management of insulin therapy in critically ill patients who are receiving continuous enteral (tube) nutrition. Dr. Cecilia Lo Wang joins the podcast to discuss her recent research on the safety and efficacy of various insulin regimens in this challenging inpatient cohort. The conversation focuses on practical challenges, current practices, study results, and actionable takeaways for clinicians managing hyper- and hypoglycemia in this setting.

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Key Discussion Points and Insights

The Challenge of Glycemic Management in Tube-Fed Critically Ill Patients

• High Prevalence of Hyperglycemia: Nearly half of patients—whether or not they have diabetes—develop hyperglycemia with enteral feeds, as tube feeding is a highly non-physiologic, continuous method of nutrient delivery.
  (03:00) Dr. Lo Wang: "Almost half of people with or without diabetes can develop hyperglycemia when they are placed on enteral nutrition, which is a very non physiologic way of eating, especially when it's continuous.")

• Frequent Feed Interruptions: Both planned (procedures, medication administration) and unplanned (tube dislodgement, intolerance) interruptions are common, making stable insulin dosing complex.
  (02:00-03:00)

• Risk of Hypo- and Hyperglycemia: Without tailored insulin regimens, patients are at significant risk for both over- and under-treatment.

Overview of Insulin Strategies in the Hospital

• No Standardized Insulin Approach: Unlike other aspects of inpatient care, there are no universally accepted protocols for insulin regimens in patients on continuous tube feeds.

• Common Hospital Regimens Studied:

  • 70/30 Human Insulin (NPH/Regular) every 8 hours + Correctional Rapid Insulin q4h
  • Basal-Bolus Regimen: Long-acting insulin (glargine or detemir) + Rapid-acting insulin correction q4h
  • Rapid-acting Insulin Only q4h (07:00-08:00)

• Adjustment Practices: Highly variable; adjustments are often up to the provider and may not be made consistently, sometimes falling behind other pressing clinical concerns.
  (10:12, Dr. Lo Wang: "I think that in the long list of different problems that patients are facing ... sometimes glucose falls to the bottom.")

Study Design and Key Findings

• Population: 475 critically ill inpatients on continuous enteral feeds, with or without diabetes, cared for in 2019.
• Endpoints: Glucose time-in-range (70-180mg/dL), hypoglycemia, and hyperglycemia rates.
• Results:
  • Long-acting and intermediate-acting (70/30) regimens were both safe and effective.
    (12:00-13:30, Dr. Lo Wang: "Both long acting and intermediate acting regimens were efficacious and safe ... compared with those on the rapid-acting regimen.")
  • Rapid-acting only regimens underperformed, with more time spent outside target glucose ranges.
  • 70/30 every 8 hours performed at least as well as basal-bolus regimens, possibly with less hypoglycemia.
  • Patients without diabetes fared better overall; average glucose was lower than in those with diabetes.

Clinical Implications and Takeaways

• No International Standard: There’s wide practice variation and no prevailing standard or guideline.
  (17:00, Host: "So are you saying there is no international standard at all?" Dr. Lo Wang: "No.")

• Need for a Basal Component: Regimens lacking basal insulin (i.e., rapid-acting alone) are suboptimal.
  (13:00, Host: "The rapid acting regimen isn't providing any sort of basal at all.")

• Intermediate-acting Regimens (70/30) Are Reasonable Options: This approach may balance efficacy and safety, especially given the unpredictable nature of tube feeding schedules.
  (18:41, Host: "I kind of like the 7030 every eight hours that seems to be not too long of insulin but enough to cover the carb load.")

• Importance of Daily Review: Regular, at least daily, reassessment and adjustment of insulin is critical due to frequent changes in patient status and nutrition delivery.
  (19:47, Dr. Lo Wang: "One of the key points is to assess the regimens, assess the glucose control daily and sometimes even more often than that to keep our patients within the goal ranges.")

Outpatient vs. Inpatient Considerations

• Hospital management allows for frequent (even overnight) insulin dosing, which is impractical in the outpatient setting (e.g., cystic fibrosis with nocturnal feeds).
• Bolus feeding is more physiological but not always tolerated in critically ill patients. (04:37-06:33)

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Notable Quotes and Memorable Moments

• On the challenge of insulin timing:
  Dr. Lo Wang (01:57):

  "The difficulty is that we really don't have a standard way of delivering insulin...one of the ways that we could manage this is with basal bolus regimens. And the problem is that if the basal insulin is adjusted for continuous tube feeds...then when there's planned and unplanned interruptions, patients can become quite hypoglycemic."

• On lack of guidelines:
  Dr. Lo Wang (17:03):

  "If you read the consensus statements and...the clinical practice guidelines by the professional societies on inpatient management of hyperglycemia, there's really no strong recommendation either way."

• On study findings and clinical practice:
  Dr. Lo Wang (18:53):

  "What this study kind of reassured us, although of course there are many limitations...is that 7030 is no worse and maybe better than basal bolus."

• On the need for daily adjustments:
  Dr. Lo Wang (19:47):

  "A key point is to assess the regimens, assess the glucose control daily and sometimes even more often than that to keep our patients within the goal ranges."

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Timestamps for Important Segments

• 01:05: Dr. Lo Wang introduces herself and her clinical role
• 01:57 – 04:13: Discussion of challenges with insulin management and tube feeding interruptions
• 04:37 – 06:33: Different tube feeding regimens (continuous vs. bolus vs. cyclic; inpatient vs. outpatient)
• 07:06 – 09:40: Study methodology and hospital insulin regimens explained
• 11:54 – 13:45: Key findings: comparison of regimens; patient demographics
• 15:16 – 18:53: Discussion of previous related studies; nuanced analysis of 70/30 vs. basal bolus
• 17:00 – 17:45: Current state of international and national guidelines
• 19:47 – 20:30: Dr. Lo Wang's clinical takeaways for listeners

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Key Takeaways for Clinicians

• Critically ill patients on continuous tube feeds are at major risk for both hypo- and hyperglycemia; lack of standardized insulin regimens remains a challenge.
• Both intermediate-acting (70/30) every 8 hours and long-acting basal bolus regimens are effective and relatively safe; rapid-acting-only approaches are less effective.
• Insulin regimens must be re-evaluated daily, and even more often if glycemic control is not within target.
• Large, prospective studies are needed to further clarify optimal insulin strategy in this population.

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Transcript

[A]

Foreign.

[B]

Welcome to ACE Podcasts. Thanks for tuning in as we elevate clinical endocrinology by taking deep dives into trends and topics that can help us improve our patient care and global health. Find the Latest episodes on aace.com podcasts and now let's meet the endocrine experts who will be talking with us today. Hello and welcome to this edition of the ACE Podcasts. My name is Vinh Tang Preacha. I'm the host of today's podcast. I also serve as the editor in chief of Endocrine Practice, the Official Journal of Ace. Today we're lucky to have our guest speaker, Dr. Cecilia Lo Wang, who will be talking about her article entitled Safety and Efficacy of Insulins in Critically Ill Patients Receiving Continuous enteral nutrition. Thanks Dr. Luang, for joining us today. Could you introduce yourself to the audience and tell us what you do?

[A]

Sure. Thank you so much, Vin. My name is Cecilia Lo Wang and I'm very happy to be here. I'm professor of medicine at the University of Colorado in Aurora, Colorado and I am the medical director for the glucose management team for our hospital, which is the University of Colorado Hospital Metro.

[B]

Great. Excellent. Well, thanks for joining today's podcast. Your paper covers a very important topic, especially in inpatient diabetes care. Before we jump into your paper, can we talk a little bit about how to manage insulin, especially in people on tube feeds? I feel like that is very challenging for all of us, especially with timing of the insulin and trying to correct the hyperglycemia without causing hypoglycemia. Could you give us some quick pointers on what are the key treatment points and what are the pitfalls?

[A]

Yeah, I think you hit the nail on the head. It can be challenging. We know that almost half of people with or without diabetes can develop hyperglycemia when they are placed on enteral nutrition, which is a very non physiologic way of eating, especially when it's continuous. And there are a number of things that can cause interruptions in the tube feeding. So some of these are planned. So for example, when tube feeding is stopped in order to prepare for procedures the next day or to administer medications or sometimes placement needs to be rechecked, et cetera, but then there are lots of unplanned interruptions. So for example, when people develop symptoms with their tube feeding or it's the tube is dislodged, there are different reasons for unplanned interruptions for tube feeding. And I think the difficulty is that we really don't have a standard way of delivering insulin. So we don't have standard insulin regimens for patients receiving continuous tube feeds. So one of the ways that we could manage this is with basal bolus regimens. And the problem is that if the basal insulin is adjusted for continuous tube feeds to cover the calories being received while people are receiving the tube feeds, then when there's planned and unplanned interruptions, patients can become quite hypoglycemic. So that's one issue. The other is that patients can become very hyperglycemic. And then also many patients receiving continuous tube feeds are in the icu, so they're critically ill. They may be receiving high dose glucocorticoids, they may be receiving pressors, et cetera. So other reasons for becoming very hyperglycemic. And so being able to kind of balance those two issues can be an issue. And then I think the other problem is that in order to manage potential hypoglycemia because of longer acting insulins being received, when patients are in continuous tube feeds, there's often an as needed dextrose infusion order. But because those are as needed, it may or may not be noticed when tube feeds are interrupted. So may or may not be started at the right time.

[B]

I know we're talking about continuous enteral nutrition, but when I'm on the endocrine service, I hate the 24 hour tube feed for use in patients. Is there any role for bolus feeding or overnight feeding? Because I always try to convince the nutrition service to consider that because that's way much more manageable than 24 hour tube feeding.

[A]

That's interesting that you say that, because the. I think in some sense continuous tube feeding may be easier to manage if patients aren't also taking PO or trying to eat in addition to the tube feed. Because the tube feeding is being received continuously, we can try to manage the insulin in a fairly stable way. It's when there's a combination of tube feeding plus taking PO intake that it can be more difficult. But I would say that bolus tube feeding is probably one of the more physiologic ways of delivering tube feeding. And we can use carb ratios or fixed doses of insulin to manage bolus tube eating. Cyclic is one of the most difficult, I think, because patients are being fed usually overnight so that they can try to eat during the day. And of course that isn't physiologic. We don't normally eat overnight and it can cause very, very severe hyperglycemia. And trying to manage types of insulin oftentimes we might be using intermediate acting at the start of cyclic tube feeding, and oftentimes we have to give a second dose. And then how do you divide doses up and then give the right proportions to manage? Sometimes late night or early morning hyperglycemia can be a challenge. So they all have different challenges.

[B]

I guess I'm thinking more of the outpatient person because I follow people with cystic fibrosis related diabetes and sometimes they're recommended to have overnight tube feeds. And so I'm increasing the intermediate insulin overnight so they can eat during the day.

[A]

Absolutely. And I'm sorry to interrupt. I think that's such a different situation because trying to translate what we do in the hospital to what's done in the outpatient setting, it's very different. We can give insulin every four hours, even overnight in the hospital, and that's really not something that we would want someone to be doing outside the hospital. It's very disruptive.

[B]

But it sounds like bolus tube feeding, as long as there's not large residual volumes from the tube feed, might be a good strategy. More physiologic, maybe?

[A]

Yes, I think that that's more physiologic. And I think that what you said, though, is the balance is that some patients just can't tolerate larger volumes in that short amount of time. So that's the difficulty.

[B]

Okay, great. Well, let's jump into your paper because I think it's very interesting. It studies three different ways of giving insulin in patients who are on continuous tube feeds in hospital. Maybe you can help us, walk us through the study. Who was in the study and what were the interventions that you studied?

[A]

Yeah, so what we were interested in doing was to study how we manage our patients on continuous tube feeding in the hospital. And we tried to focus the question to patients who were critically ill receiving continuous tube feeds with or without diabetes. And we looked at both the efficacy, what we called efficacy, which was really the point of care. Glucoses in the target range of 140-180mg perdb, balanced with hypoglycemia or severe hyperglycemia. And our standard practice in our hospital is to use one of three regimens and either 70, 30 insulin Q8 hours with correctional rapid acting insulin every four, or what we call long acting insulin, which was really more of a basal bolus regimen. So long acting insulin with either glargine or Dedimir vid in addition to rapid acting insulin, correctionally delivered every four hours. And then the third Regimen was just rapid acting insulin only every four hours. And the key difference here is that at that time, in this period of time that we were looking at, we hadn't started using nutritional doses of the rapid acting insulin. This is something we started doing more frequently in the past year, but this particular calendar year that we studied, we hadn't started that practice yet.

[B]

Okay, so before we move on, the 70:30 insulin, does that apply to all 7030s or is that a particular brand of 70:30, or does it matter?

[A]

No, it doesn't matter. So we were using human insulin, NPH 7030, so it wasn't the analog premixes.

[B]

And how does a provider, your hospital decide among these three? Is it a provider preference or is there, are there different factors that go into, like which one of these that people go on?

[A]

So we do have a tube feeding order set. We had one that at the time of the study. And so the tube feeding order set includes various options. So one is the rapid acting insulin, only one is 70, 30q8 hours, and one is the basal bolus. And so preferentially, if providers were to use the order set, they would have that option of 70, 30q8 hours. But in reality, the main service that would use 70, 30 q 8 hours was the specialized glucose management team.

[B]

So the basal bolus, the only difference between the rapid every four hours versus the basal bolus is basically the basal. Right? It's the same basically.

[A]

Exactly. Yeah. So with the basal bolus, what we call long acting, in the paper, people would have the addition of basal insulin. Okay.

[B]

And how are adjustments made? I mean, so let's say someone's glucose is in the 2002. So is there an adjustment to the regimen or is this the same thing as continuous throughout?

[A]

This was up to provider practice. And so I think that just is, as in many, many hospital settings across the country, as I understand it, this can vary quite a bit. And so when patients become hypoglycemic, I think there are changes made to reduce the overall amount of insulin that's delivered, or sometimes insulin is held. And then when there's hyperglycemia, it may or may not be addressed for a few days. And so when patients are being managed by the glucose management team, we would often make changes, sometimes up to two times a day or more often when, you know, based on how blood sugars are doing. But we would make changes at least once a day.

[B]

Okay. I mean, it would make sense that a change would have to happen every day based on what happened in the past 24 hours. Right.

[A]

I think that it would make sense and we strongly encourage our clinical teams and our trainees to review glucoses daily and make these changes daily. But I think that in the long list of different problems that patients are facing and that clinical teams are trying to manage, sometimes glucose falls to the bottom. So it may not be something that's done every day unless a glucose is extremely severely low or high. So sometimes it's just missed.

[B]

Okay, so let's get back to your study. So it sounds like the patients were divided into three groups, mostly by provider preference. Tell us what you found.

[A]

Yeah. So we did the analysis in a number of different ways. So again, this was the calendar year, 2019. It identified 475 patients that met our criteria of receiving continuous tube feeding and subcutaneous insulin. So we excluded patients who were receiving IV insulin or were not receiving continuous tube feeds. And we ended up with about two thirds of the patients with diabetes and about a third without diabetes. And so that ended up being about 491 admissions with continuous tube feeds and a total of almost 2,400 days of tube feeding. And about 41% of those patients were on medical services. About 59% were in on surgical services. And about a third of patients were receiving glucocorticoids. And most of the patients had type 2 diabetes. There are very few with type 1 or other diabetes. And what we found is that both long acting and intermediate acting regimens were efficacious and safe. So in other words, higher time and range. So glucose is between 70 and 180 and less time in hypoglycemia or hyperglycemia compared with those on the rapid acting regimen.

[B]

I guess that's not so surprising because the rapid acting regimen isn't providing any sort of basal at all.

[A]

Absolutely. And I think that this is a reminder to people that because we see this surprisingly often when patients are starting started on tube feeding and they don't receive kind of proactively insulin to cover their nutritional needs. And so we're still seeing this fairly often. So I think it's a reminder that we do need to be thinking about nutritional needs when we're taking care of our patients on enteral nutrition.

[B]

Were these people on enteral nutrition also eating po?

[A]

So that wasn't defined. So that wasn't something that we were able to identify in our search.

[B]

Okay. I was just wondering, maybe a certain number of them were eating and they were having breakthrough hyperglycemia just because the Q4 hour regular is definitely not going to be able to handle any additional calories.

[A]

Absolutely. And you bring up an interesting point. So many of the people who were eating as well as receiving continuous tube feeding, generally they weren't eating very much because they were, you know, this was during kind of that calorie count period, trying to figure out whether or not it's appropriate to stop the continuous tube feeding because they're taking enough po. But many patients on continuous tube feeding are not eating. So they're NPO and receiving the tube feeding for a reason. It's because they either have issues with swallowing or they're intubated, et cetera. So I would say it's probably a low percentage of patients who are also eating while they're on the continuous tube feeding or they're taking in very little po.

[B]

Okay. It is somewhat surprising, or maybe not the 70, 30 every eight hours where it's the same as basal bolus. And I guess I'm just trying to understand. I mean, I guess in the 70, 30 you're sort of having the rapid acting insulin in there and you're getting a Basil as well. So I guess maybe it's not so surprising that they were relatively equal. What do you think?

[A]

That was surprising to me. So we had published this very small retrospective study a few years ago looking at 70, 30 given two or three times a day compared to basal bolus. And in that very small group of 22 patients, we found that there was less hypoglycemia with 70, 30q8 hours compared to q12 hours versus the basal bolus and also improvement in less hyperglycemia as well. So that's kind of why our practice changed over to 70, 30 Q8. And so the idea was that patients were having some degree of glycemic control because of that regular insulin acting sooner and then the NPH in that 70, 30 giving the basal coverage. But because it was being delivered Q8 hours, that total dose for each dose was lower than kind of the long acting dose. And so the risk for hypoglycemia was thought to be lower.

[B]

Well, I wonder if in the basal bolus, instead of every four hours, if you did the regular every six or eight hours, you might have better results.

[A]

Well, so the basal bolus was a combination of either largine or De Mer twice a day plus rapid acting Lispro insulin Q4. And so of course, other strategies that are used by different clinical teams across the country include NPH Q8, NPH Q6. There's actually a publication of NPH used Q4 and then some teams use regular insulin Q6. I mean, there's so many different regimens out there. And then of course Lispro Q4 to cover both nutritional and correctional needs.

[B]

So are you saying there is no international standard at all?

[A]

No. And if you read the consensus statements and kind of the clinical practice guidelines by the professional societies on inpatient management of hyperglycemia, there's really no strong recommendation either way. So they mention use of basal bolus or intermediate acting regimens and there's no way of determining initial doses, et cetera.

[B]

Makes me feel a little bit better. But it sounds like you need some sort of basal however you want to, you know, do that, either very long acting or intermediate acting throughout the day plus a more rapid acting. But there isn't a standard how to do that. Right.

[A]

Well, you know, one other point I wanted to make is that we saw big differences between patients with and without diabetes. And so of course this is not surprising that patients without diabetes developing stress hyperglycemia from the tube feeding may look very different from Those with type 2 diabetes receiving tube feeding. And so the average glucose of those without diabetes was, you know, much better than those with type 2 diabetes. And we didn't see differences in hypoglycemia, but the average glycemia over these two feeding days was much improved in those without diabetes. And so I think that in terms of whether or not a patient needs to have basal insulin, I would argue that the patients without diabetes may not need basal insulin and that might be a reason that intermediate acting or the shorter acting regimens might work better. And one thing we didn't test, and we couldn't test this because it wasn't practice at the time was rapid acting only covering both nutritional and correctional needs.

[B]

That makes sense. I mean, I, I kind of like the 730 every eight hours that seems to be not too long of insulin but enough to cover the carb load. I don't know.

[A]

Yeah, that's kind of how we feel about it. So the reason that we decided to do this study was that all we had to justify that 70, 30 q 8 hour regimen was that small retrospective study. So we wanted to take a more global look to see how patients were doing on that. And I think what this study kind of reassured us, although of course there are many limitations to the study, is that 7030 is no worse and maybe better than basal bolus. And so I think there's still a lot more work to do, but it was reassuring.

[B]

Are you aware of any large head to head studies looking at this in detail?

[A]

I am not aware of any and I think that this would be a really good area for future study for a randomized trial.

[B]

Yep, I agree. Can you give us some key two or three takeaways from your studies before you leave us?

[A]

Yeah, I think that one is that there are a number of different options to adequately treat hyperglycemia associated with continuous enteral nutrition and some of the different strategies are quite effective. So using intermediate acting insulin regimens e.g. 70, 30q 8 hours with correction every four, or using long acting in addition to correctional insulin every four, both are effective. And I think one of the key points is to assess the regimens, assess the glucose control daily and sometimes even more often than that to keep our patients within the goal ranges.

[B]

I think these are very important points and it shows that I guess we need to learn more about this and I think the key is to look at the glucoses every day and try to make our best adjustments. And so really thank you for joining us today and for people who want to read more, this is in the April 2024 endocrine practice. It's online and really appreciate you doing this research and I hope you can continue to give us more information about this.

[A]

Thank you so much Vin. I really enjoyed this conversation.

[B]

Thanks so much for joining. Thanks for listening to another great ACE podcast. Join us for another [e-mail] podcasts and help us in our mission to elevate clinical endocrinology. Together we are ACE.