I have no disclosures, and I'm too short, so let me move this. What I'm going to try to do in this talk, since most of us know how to treat DKA and HHS, is kind of talk about the myths and talk about where there's controversy. So the first thing we're going to talk about is, should we, in that first resuscitation when we're giving fluids, should we be giving normal saline or should we be using balanced crystalloids? Well, the people who did the SALTED trial and the SMART trial, again at Vanderbilt, went back and pulled from their 21,000 patients, 94 patients who received balanced fluids, 78 who received saline, that also were admitted for DKA. And when they evaluated those patients, they saw that the resolution of DKA, which they used the ADA definition of a glucose less than 200, bicarb greater than or equal to 15, and a pH greater than 7.3, and a closure as an anion gap, was shorter in the patients who received the balanced fluids, typo, I always have one that I miss, for 13 hours versus 16.9, with a p-value of 0.002. So and the discontinuation of insulin actually was shorter in the group that was resuscitated initially with balanced fluids. So you have to take this with a grain of salt because it's a single center study and it's a sub hoc analysis, but it's kind of intriguing where we should maybe have another study that looks at this in a more scientific rigor. But balanced crystalloids may be preferred fluid for fluid boluses when the patients present with DKA or HHS. Then your second question that is kind of controversial is how much fluid should we resuscitate with? Cerebral edema being more common in children, it's something that most of these studies or a lot of these studies come from the pediatric population, but there are some adult studies that look at how much volume as well. In the interest of time and only 15 minutes, there's probably about 20 studies that I found and they compared either 10 per kilo or greater than 10 per kilo. Some used 15 and some used 20. Not consistency within the study, so the heterogeneity of the data makes some of the decisions a little different, but we do have a theme. There was about 1,500 patients included in all of these studies and the hospital length of stay was actually longer in all the trials that used less fluid as the fluid bolus up front and the patients were in the hospital about a half a day longer. Bicarb normalization was a little bit quicker in the more aggressive resuscitation, but not statistically significant. We know that about 20.3% of patients in all these studies had presented with acute kidney injury with that elevated serum creatinine and there was a 6.2% faster resolution of acute kidney injury in the patients who were resuscitated with larger amounts of fluids, but no difference in cerebral edema, which was the current concern of these studies that if we were more aggressive with fluid up front, we might actually cause more cerebral edema and that was not shown to be true in any of these 20 trials. So then patients' studies have taken this one step further and said, well, what if I look at fluid resuscitation versus the makeup of that fluid? And probably if I asked 20 of you in the room, what fluids do you use for DKA, we might get a slightly different answer, right? Some people have the, we have to have acetate, some people want chloride, others want phosphate. So the makeup everybody uses is different. So this one study that was published in the New England Journal of Medicine looked at comparing patients who got normal saline versus half normal saline and that 10 mL per kilo versus 20 mL per kilo bolus. And then they compared replacing fluids with 5% of their body weight versus 10% of the body weight. And they were randomized in a 2.2, 2 times 2 factorial design. It was a multi-center trial and they had about 13 centers in this study and actually had quite a number of episodes and over 12,000 children. The one thing, the only thing they showed different in these studies is the Glasgow Coma Scale dropping to below 14 was about 3.5% and clinically apparent brain injury was about 0.9%. So again, they were looking to see, just like the previous studies, if I was more aggressive up front with my fluid bolus and then gave more fluid to the patient, would I cause more cerebral edema? And the answer was no. So neither the rate of administration nor the sodium content of the IV fluids significantly influenced neurologic outcome in these children. So it doesn't matter how much sodium I give them or how much volume, neither of those are associated with the development of cerebral edema. This study was in the Journal of Emergency Medicine and looked at, again, comparing different bolus rates plus maintenance rates. So the other study, a lot of people don't calculate percent, 5% of the total weight versus 10. This was probably more similar to what we might do as we calculate 1 1⁄4, 1 1⁄2. Some people use twice maintenance fluids for DKA. This was a small study done in an emergency department and they only had 25 in each arm. But again, time to metabolic normalization was significantly faster in the faster fluid group with an odds ratio of 2, p-value of 0.05 compared to that slower fluid group when adjusting for the presenting, even when they statistically adjusted for the presenting bicarb in those patients. And there was no difference in length of stay or length of treatment. So again, showing us that that more aggressive fluid resuscitation and fluid maintenance rate does cause the patients to resolve their DKA faster. This was a retrospective study done at Texas Children's Hospitals where they used to use their baseline resuscitation fluids or maintenance fluids was half normal saline-based and they switched to using an LR-based fluid. So they did an ad hoc analysis of looking six years prior and then six years after the implementation or the change in their protocol. And they also used to give 3,500 per meter squared. And when they changed their fluid, they dropped that resuscitation fluid to 2,500 per meter squared. So similar to the other studies we've been looking at is people are saying, which fluid is the best fluid and which fluid amount is the best amount? Again, no difference in cerebral edema or time to recovery was slightly longer. And that once they dropped their fluid resuscitation amount, they had patients staying in the hospital longer, showing us that we don't need to be that conservative when we're trying to resuscitate these patients. So in summary of these, when we look at these meta-analysis, there's about 1,500 patients in all of these studies, showing us no difference in the development of cerebral edema, time to recovery of DKA is longer in those conservative regimens, time to discharge was no different. So perhaps the only question I think I've come up with so far is, should our initial fluid boluses be LR versus normal saline? That I think, in my opinion, requires another study. The only thing that came out in one of the trials that they did see a higher incidence of cerebral edema in patients transferred from outside centers, telling us that we need a partner with our referring centers to make sure that we're all doing the same thing, to make sure patients are not arriving in a state that makes them have worse neurologic outcomes. The next question I found was, should we be using pH or bicarbonate to transition our patients onto sub-q insulin? There's only two of these that I found, one pediatric and one adult. The pediatric trial looked at the duration of insulin infusion and showed that it was about three hours shorter when you just looked at correction of their CO2 versus a pH or a closure of their anion gap. The length of stay was 3.2 hours shorter in the patients who were transitioned using that CO2, and there was no difference in adverse events. And I know at my center, we actually use the CO2 as our marker of when we transition patients over. But the study was designed slightly differently, and they looked to see it with when the anion gap normalized, because I know my adult colleagues use anion gap. But the CO2 was still below 16, did that make a difference? And what they found, that there was an odds ratio of almost 5 for having transition failure if you only use the anion gap and the patient had not corrected their CO2, telling us that our CO2 is probably the best marker to make us comfortable in transitioning over to sub-q insulin. Alright, am I going fast enough? So then we look at low dose versus standard dose insulin, two trials looking at lower dose of insulin, 0.05 per kilo versus 0.1 per kilo, which was standard. Only about 100 patients in these two trials, and you can see no statistical difference in time to reach a glucose less than 250, time to resolution of acidosis, and no difference in hypokalemia or hypoglycemia. So again, no difference. And then the last thing I found that was quite intriguing is people were using sub-q insulin. So if we look at our mild to moderate patients with DKA, could we not put them in the ICU and put them on the floor and use sub-q insulin? And they used the standard definition in most of these trials. This is an adult trial that used 0.3 units per kilo of Lyspro, and they repeated another 0.2 an hour later if they were still greater than 250, and then they gave 0.2 units per kilo every two hours until the glucose was less than 250, and then dropped that corrective dose and probably added some dextrose into the fluids. The pediatric trial was similar, looking at 0.15, so kind of a little bit lower dose. And what we saw was no difference in the time to DKA resolution. Length of stay was no difference in the patients that were randomized to the double bag method or using a standard ICU protocol. And then the IV, this was actually, there was more hypoglycemia in the patients in both these trials that were randomized to an ICU trial with continuous infusion insulin. And it was about $500 less expensive. I think where these studies show us, and I think are important, is if we get to another pandemic or we're in a season where we don't have a lot of ICU beds, maybe these DKA patients who have mild to moderate DKA, we could be managing on the floor with a different regimen. We just need to be prepared and make sure that we've educated everyone on how to do this because it would be a total change in the paradigm for our patients. There was one trial that looked at regular insulin with a calculation. I think this is a little bit more complex, but they had the same result. This is giving somebody a Q4 hour dose of insulin versus our shorter acting, which might be kind of nice in a pediatric patient who doesn't want to get stuck that many times. But again, resolution of DKA was 10 hours shorter and no adverse effects. There are two trials that are looking at giving a dose of Glargine at the time you start that insulin infusion in the ICU. And what that did is it actually had a three-hour shorter resolution of the DKA. So starting the insulin infusion like you standardly would, but also giving that first dose of Glargine. This was a pediatric single center in moderate to severe patients, but they showed a shorter infusion time of about 14 hours in the insulin-only group versus six hours in the Glargine group, a half a day shorter length of stay, and no extra hypoglycemia. And a singular study showed with adults using that Glargine dose, and it doesn't, given within that three hours of presentation for DKA, three hours shorter time to resolution and no hypoglycemia. So in conclusion, sorry, I'm talking really fast. We might consider LR maybe better than normal saline, but we really need a more regular study to show a difference. Positive bolus and IV fluid administration is associated with a longer time to resolution, so we shouldn't try to be conservative on our patients. Mild to moderate DKA may be treated outside of the ICU with sub-Q regimens, and this could help preserve our ICU beds. The addition of sub-Q Glargine too early in the course of DKA may shorten the ICU length of stay, and multi-center randomized trials are needed to actually answer all these questions because they're all single center trials. Thank you.

diabetic ketoacidosis

hyperglycemic hyperosmolar syndrome

fluid management

subcutaneous insulin

multi-center research