Ketoacidosis related to Diabetes (DKA)  remains a life-threatening emergency for patients with diabetes, and having a well-structured DKA order set is paramount to ensure timely and effective care. See the importance of having a DKA order set at your institution, the key elements of a high-quality DKA order set, and the essential components of DKA management based on the latest American Diabetes Association (ADA) guidelines.


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Hannah Day: 

Hello, I'm Hannah Day. I'm a nurse practitioner specializing in diabetes management for 9 years, board certified in advanced diabetes management, and a certified diabetes care and education specialist for 14 years. Today I'll be presenting on treatment of ketoacidosis related to diabetes and leveraging guidelines and protocols to avoid pitfalls.

Please feel free to put questions in the chat during the presentation and a member of the Glytec staff will answer. Prior to working at Glytec, I was a co-leader for my hospital system diabetes improvement initiative. One objective was improving IV insulin infusion safety, which included updating the DKA protocol.

Our team of physicians, pharmacists, and critical care nurses developed a nurse-driven DKA protocol that was initiated in the emergency department and continued into the ICU setting. Eventually, we incorporated Glucommander IV into the protocol to simplify the insulin infusion part and to leverage the alerts and reminders.

As you all know, there's more to DKA treatment than insulin alone. So today, I'll review the treatment essentials of managing ketoacidosis related to diabetes. Then why implementing and hardwiring a DKA protocol is important. I'll also review how Glucommander IV can be an essential part of treatment.

Then finally avoiding pitfalls in DKA management.

This is the American Diabetes Association algorithm for treatment of DKA, which provides a high level overview of the main treatment components, including four pathways for managing IV fluids, potassium, insulin, and assessing the need for bicarbonate. Many of you are likely familiar with this treatment algorithm, last updated in 2009, and have likely referenced this in creating DKA treatment protocols at your institutions.

In the upcoming slides, we will take a closer look at the components and break them down using a stepwise approach. The necessary treatment of ketoacidosis related to diabetes includes three main components aimed at treating the three main problems, hyperglycemia, which may be mild when it comes to euglycemic DKA, metabolic acidosis, and ketosis.

Ketoacidosis can be defined as mild, moderate, or severe. Treatment is similar regardless of severity, however, the type of insulin therapy may differ. Mild DKA can be treated with SubQ insulin, but moderate to severe DKA requires IV insulin therapy. Diagnosis is based on blood glucose greater than 250 mg/dL, again, a lower glucose is present with euglycemic DKA, pH less than 7.3, positive ketones, anion gap greater than 12, or 16 if potassium is used in the calculation, and serum bicarbonate of less than 18. Diagnosis is made based on lab results, symptoms, and history of present illness. Early signs of ketoacidosis are nausea, vomiting, abdominal pain, hyperventilation, and as hyperglycemia worsens.

Neurologic symptoms can appear and can progress as we know common causes are infection, inappropriate adjustment, or cessation of insulin therapy, new onset diabetes and myocardial infarction. Management is focused on fluid resuscitation, electrolyte replacement, and insulin therapy. We'll take a deeper dive into the guidelines related to these treatments.

As I mentioned, ketoacidosis related to diabetes can be classified as mild, moderate, or severe. As severity increases, we see higher levels of ketones or beta-hydroxybutyrate, and the anion gap increases. The more severe the DKA, the lower the pH and bicarbonate. Also, note the hyperglycemia hyperosmolar syndrome, or HHS, laboratory characteristics.

Sometimes it's not clear if the diagnosis is DKA or HHS. A study in 2020 showed that 1 in 4 patients presenting with hyperglycemic crisis actually had combined DKA and HHS. These patients have twice the mortality rate compared to those with DKA or HHS alone. The researchers also observed that the development of hypoglycemia and hypokalemia, two common complications related to insulin therapy, is associated with increased mortality independently of hyperglycemic crisis category.

Therefore, treatment methods should be aimed to resolve hyperglycemia, acidosis, and ketosis with special attention to avoid the complications of hypoglycemia and hypokalemia.

As we were developing a treatment protocol, because of the many moving parts of DKA treatment, we decided to take a stepwise approach. The purpose of this approach was to simplify as much as possible and allow for a mostly nurse driven protocol. Four main steps were outlined as you see here, aligning with the ADA treatment algorithm.

First being fluid resuscitation and attention to potassium. Second, insulin infusion. Third, maintenance fluids and electrolyte replacement. And four, resolution and transition to SubQ insulin. I'll review each of these steps in more detail. So step one, initial or loading fluids typically includes two liters of normal saline infused over two to three hours.

Lactated ringers is sometimes preferred to avoid potential non Anion gap, hyperchloremic acidosis that can develop during DKA treatment with normal saline. Attention to potassium is key in step one before insulin is administered. If the initial potassium is less than 3.3, the insulin infusion initiation should be delayed until potassium is replaced, rechecked, and above 3.3. If insulin administration needs to be delayed to replace potassium, keep in mind, volume repletion alone through initial fluid resuscitation can initially reduce glucose by 35 to 70 mg/dL per hour. This is an example protocol of step one. You'll notice guidance related to use with end stage renal disease.

First is loading fluids of two liters. This section includes nursing guidance when blood glucose is less than 250, and guidance for patients who may be at risk for volume overload. The next part of this step is assessment of the potassium with treatment if it's less than 3.3, directions for when to recheck, and when to notify the physician or the advanced practice provider.

So step two is insulin. Insulin therapy not only lowers serum glucose concentration, but also diminishes ketone production by inhibiting lipolysis. According to the ADA algorithm, insulin may be initiated with or without a bolus of IV insulin. The goal is to decrease glucose 50 to 70 milligrams per deciliter per hour.

And if glucose is not decreasing, always check the infusion site. If no site issues, then increase the infusion rate. According to the ADA algorithm, once glucose is less than 200 milligrams per deciliter, the insulin infusion should be reduced to two to five units per kilogram per hour and titrated to maintain glucose between one 50 to 200 milligrams per deciliter.

Insulin protocols and algorithms may be used to guide titration, but as we know, this can be complex and difficult to adhere to in a busy ICU environment. Not just the insulin rate calculations, but staying on time with glucose checks in order to ensure those timely rate adjustments. Initially, glucose must be checked hourly to ensure IV insulin rates are adjusted appropriately.

As I mentioned, we implemented Glucommander IV to calculate the insulin infusion rate adjustments, as well as provide timely prompts for glucose checks, safety guardrails, and alerts. Step 3, step 3 is maintenance fluids and electrolyte replacement. Serum electrolytes, BUN, and creatinine should be measured every 2 to 4 hours depending on the disease severity and the clinical response of the patient.

These lab results are necessary to guide the IV fluid type and rate during DKA treatment. Specifically, sodium, potassium, and glucose to guide the type and creatinine to help guide the rate. The choice of normal saline or half normal saline is driven by the corrected sodium levels and the potassium balance.

Because potassium is as osmotically active as sodium, potassium replacement via IV fluids may be another indication to use half normal saline. To calculate corrected sodium, you add 2 milliequivalents per liter to the sodium value for each 100 milligrams per deciliter of glucose above 100. The rate of IV fluids initially is 250 to 500 milliliters per hour, depending on the patient's volume status.

For patients with renal disease or heart failure, use caution, but keep in mind fluid resuscitation is still needed. Potassium chloride should be added to IV fluids when potassium is less than 5.3. We'll talk more in detail about this on the next slide. And then dextrose containing fluids are needed when glucose falls below 200 to 250 milligrams per deciliter at a rate of 150 to 250 mls per hour and continued until DKA resolution.

Potassium replacement is a key component of DKA treatment. Despite total body potassium depletion, mild to moderate hyperkalemia is common in patients with hyperglycemic crisis. Insulin deficiency and acidosis cause potassium to shift out of cells, so patients may present with elevated serum potassium.

But, insulin therapy, correction of acidosis, and volume expansion then decrease serum potassium concentration, driving the potassium back into the cells and further reducing the serum potassium. So, potassium replacement should begin if serum potassium is less than 5.3. If it's greater than 5.3, it's important to closely monitor potassium every two hours. Begin replacement once it drops below 5.3. The goal is to keep it between 4 and 5 milliequivalents per liter. So generally, 20 of potassium in each liter of fluid is sufficient to maintain a serum potassium concentration within that normal range. Potassium replacement protocols are very important to prevent severe hypokalemia and to prevent subsequent interruptions in insulin due to this.

Rarely DKA patients may present with significant hypokalemia about 5% of cases in such cases, as we discussed in step number one, potassium replacement should begin along with fluid therapy and insulin treatment should be delayed until potassium concentration is restored to 3.3 or higher to avoid any, um, arrhythmias and respiratory muscle weakness.

So this is an order set example of Step 3, the Ongoing Fluids and Potassium Replacement. This is a nurse driven protocol to adjust IV fluids based on the corrected sodium, the potassium, and the glucose values. Eight IV fluid options are listed in the EMR as PRN with administration instructions guiding which fluid type to use based on the lab results.

And step four is resolution of DKA and transition off of IV insulin therapy to subcutaneous insulin. Resolution of DKA can be determined once the patient meets several criteria. The blood glucose should be less than 200 or within the target range, and the patient should be able to tolerate oral intake.

The correction of ketoacidosis can be determined by the pH, beta-hydroxybutyrate, electrolytes, and bicarbonate concentrations. The anion gap, which is calculated by subtracting the major anions, chloride and bicarbonate, from the major cations, sodium and or potassium, will return to normal when keto acid anions like beta-hydroxybutyrate have disappeared from the serum.

So the anion gap should be less than 12, or less than 16 if potassium is used in that calculation, bicarbonate greater than or equal to 18, and pH greater than 7.3. Subcutaneous basal insulin should be administered at least 2 hours prior to stopping IV insulin infusion to assure that appropriate bridge to SubQ therapy once the IV insulin infusion is stopped.

In order to estimate the transition basal dose and the ongoing subcutaneous insulin doses, one must first estimate the total daily dose of SubQ insulin the patient will need. The total daily dose can be calculated a few different ways. Glucommander will calculate a total daily dose based on current insulin needs.

Approximately half of the total daily dose can be used as the basal dose. The remaining 50%, the total meal boluses. further divided into three meals. Additional methods to calculate a TDD from the literature include using the home regimen if it's known and if it was working well for the patient. You may consider an adjustment to the home total daily dose based on the patient's current clinical status though.

You may calculate the average insulin infusion rate during a time when the rate is stable. Using the overnight rate can give you a good idea of what the basal insulin needs may be. And then finally, a weight based dosing approach can be utilized. 0.3 to 0.7 units per kilogram per day can be used to calculate a total daily dose, which can then be distributed 50/50 for basal and bolus insulin.

Of course, ongoing monitoring of glucose and SubQ insulin dose adjustments are necessary as the patient's clinical condition continues to evolve and insulin needs change. Transition from IV to SubQ insulin is complex and requires careful assessment of the patient's clinical status and insulin needs in order to prevent severe glycemic excursions or recurrent DKA.

For transitioning patients from IV to SubQ insulin, it's recommended to follow a standard process. According to the ADA guidelines, having and following a transition protocol is associated with less morbidity and lower costs of care. Basal insulin should be administered 2-4 hours prior to stopping the insulin infusion, and the dose of basal insulin can be calculated based on the insulin infusion rate during the last 6 hours when stable glycemic goals were achieved. 

The Joint British Diabetes Society for Inpatient Care Guidelines support continuing the home basal insulin during the insulin infusion therapy if it's known and appropriate. If following this practice, ensure the basal dose is taken into account when you're determining the total SubQ insulin dose needs following cessation of the IV insulin therapy. Also, caution should be taken with this approach as home basal doses may not always be reflective of inpatient insulin needs.

DKA treatment protocols must also address euglycemic DKA as we're seeing an increase in incidence with the use of SGLT2 inhibitors. Euglycemic DKA is diagnosed when a patient presents with ketoacidosis, an elevated anion gap, low bicarbonate and low pH, but glucose is only mildly elevated or near normal, less than 200 to 250.

How common is euglycemic DKA? Some literature points to 2.5 percent to 5 percent of DKA cases being euglycemic DKA. Some higher, such as 10%. As I mentioned, with the increased use of SGLT2 inhibitors, the incidence is decreasing as these are known to increase the risk of euglycemic DKA.

Other causes include prolonged fasting, pregnancy, or having taken insulin recently or right prior to arrival. Treatment of euglycemic DKA follows the same principles of DKA treatment. Fluids, electrolyte replacement, and IV insulin infusion therapy. Insulin is still needed despite the near normal. glucose levels in order to reverse the ketosis.

This means that dextrose containing fluids are needed when IV insulin is started to prevent hypoglycemia and allow for the continuation of insulin until that acidosis is resolved. The concentration and rate of dextrose containing fluids may need to be adjusted with treatment of euglycemic DKA. If the anion gap is remaining elevated and the insulin infusion rate is low, consider increasing the dextrose concentration or the rate at which dextrose is infusing to allow for an insulin rate high enough to reverse the ketosis.

As we've reviewed, there are many moving parts to safe and effective treatment of DKA, including frequent monitoring of labs, changing fluids, timely electrolyte replacement, and the frequent titration of the IV insulin infusion. A standard protocol is recommended for many reasons, but most importantly to provide timely treatment and to avoid the complications of hypoglycemia and hypokalemia.

Without a standard protocol, you may see high variability among orders. This leads to confusion, particularly as the patient transfers from the emergency department to the inpatient setting and care is handed off between clinicians. This was a main driver for my institution in developing a DKA protocol. 

Having a standard protocol can avoid variability in orders, which simplifies the process for prescribers and for nurses, and allows for a standard treatment process that's applicable to most patients. A protocol can allow for nurse driven directives, which ensure treatment timeliness and efficiency. And it can also ensure treatment begins as soon as possible, such as in the emergency department and continues through transfer to the inpatient setting.

Transitions of care and handoffs are times of increased risk for patients. Referring to a protocol to discuss what treatments have been completed, what is in process, what are the next steps, is key to avoiding treatment interruptions and potential errors. Also, having a standard protocol allows for quality improvement.

Deviations in care or gaps in processes can be more readily identified and corrected when the preferred process is documented. Our ultimate goal as clinicians is to provide high quality care to patients, treating their illness while avoiding harm. We've reviewed how a standard approach is important to manage the many moving parts to DKA treatment.

Let's now review how Glucommander IV is leveraged in the safe and effective treatment of DKA. The Glucommander software helps to simplify the insulin infusion management for the prescriber and the nurse while providing safety guardrails and alerts to align with best practices. The prescriber selects the initial IV multiplier and target range, then the algorithm calculates the infusion rates for the nurse, aiming for the target range while avoiding steep drops in blood glucose.

As mentioned, the goal is to decrease the blood glucose no more than 50 to 100 milligrams per deciliter per hour. The meter max feature comes into play with patients presenting with severe hyperglycemia above the glucose meter's readable limit. It allows the nurse to proceed with a glucose point of care value, not having to wait on a serum glucose value that's already old once it's resulted.

The Meter Max feature is also a safety guardrail that adjusts the algorithm to proactively avoid steep drops in blood glucose. Glucose velocity warnings will detect larger declines in blood glucose and prompt for sooner blood glucose checks and insulin rate adjustments to avoid hypoglycemia.

Glucommander IV supports and aligns with DKA management guidelines by prompting for hourly blood glucose checks and reminders to ensure dextrose containing fluids are added once blood glucose drops below 250. The IV meal bolus feature also allows for additional insulin coverage when the patient starts eating to avoid glucose excursions.

It includes alerts and warnings to prevent premature discontinuation of IV insulin therapy before the anion gap closes. And finally, to support a safe transition to SubQ insulin therapy once DKA has resolved, the Glucommander calculated total daily dose can be used to determine initial SubQ doses of basal and prandial insulin.

In a 2018 study comparing the use of Glucommander IV versus a standard paper based insulin infusion protocol in patients with DKA, Glucommander treated patients experienced less hypoglycemia reached target and resolution sooner and had shorter length of stay. Among those treated with Glucommander IV, best outcomes were seen with an initial multiplier of 0.01 and a target range between 120 to 180 milligrams per deciliter. The group of patients treated with a 0.01 multiplier and a target range of 120 to 160 milligrams per deciliter had the highest percentage of patients achieving DKA resolution without significant hypoglycemia. 

Thus, Glytec's recommendation for initial multiplier and target range for DKA patients is 0.01 and 120 to 160 milligrams per deciliter. This same study also compared outcomes across categories of mild, moderate, and severe DKA. Regardless of whether patients were treated using Glucommander IV or a paper protocol, time to resolution was longer for severe DKA versus mild to moderate DKA. In this study, time to resolution for those treated with Glucommander IV was about 28 hours for severe DKA versus 16 to 20 for mild or moderate DKA.

In comparison, for those treated with the paper protocol, time to resolution was 31 hours for severe DKA and 26 to 30 for mild to moderate DKA. The bottom line here is that the more severe the DKA, The lower the bicarbonate, or the higher the anion gap, the longer time to resolution. This highlights the importance of ensuring DKA has resolved before transitioning to SubQ insulin therapy in order to, uh, avoid recurrent DKA.

We discussed the increasing incidence of euglycemic DKA, so can Glucommander be used in the treatment of euglycemic DKA? In partnership with Emory University School of Medicine, Glytec analyzed data from 2017 to 2021 of patients treated on Glucommander IV with lab results indicative of euglycemic DKA.

The analyzers concluded that euglycemic DKA can be safely and effectively treated with a computerized insulin dosing algorithm such as Glucommander. Median time to bicarb greater than 18 after Glucommander was started was about 14 hours. But remember, the treatment between euglycemic DKA and DKA is similar, but dextrose containing fluids are needed sooner from the initiation of the insulin infusion.

Finally, let's talk about avoiding pitfalls. A DKA protocol is important to standardize the care of the patient presenting with DKA, but should also be optimized to avoid common pitfalls with DKA management. A quality improvement approach should be taken to monitor for these pitfalls and update processes to avoid them.

Two complications of DKA to be avoided are hypokalemia and hypoglycemia. To prevent hypokalemia, remember that close monitoring of potassium along with proactive replacement is important. Be sure to include potassium in the maintenance fluids when warranted and consider a nurse driven protocol to ensure this step occurs.

To prevent hypoglycemia. A key step is ensuring dextrose containing fluids are infusing. Once blood glucose falls below 200 to 250 milligrams per deciliter. This was a pitfall we identified at my institution as we traced hypoglycemia back to this missed step. The alert and Glucommander can be leveraged to prompt the addition of dextrose to fluids, but orders must also be in place for this to occur in a timely.

Another pitfall is prolonged time to resolution. This can be avoided by ensuring timely treatment that is free of interruptions. Also, be sure to set appropriate expectations. Remember, the more severe DKA, the longer time to resolution. With euglycemic DKA, a low infusion rate may prolong time to resolution, so include steps to address this in your protocol, such as increasing the dextrose concentration, or the rate if it's clinically appropriate.

Finally, we must avoid recurrent DKA. A standard transition protocol must be in place that includes directions to calculate a total daily dose, orders for a SubQ insulin regimen that includes basal insulin, bolus or Prandial Insulin when eating, and Correction Insulin, and giving that Basal Insulin at least 2 hours before stopping the insulin infusion.

Consider including specific DKA resolution criteria in your protocol. visible to the care team so all are on the same page when it comes to DKA resolution and transition.

When designing or updating your DKA protocol, start with a high level list of treatment guidelines and be sure your protocol addresses these. Then assess if your protocol addresses the pitfalls we discussed. Be sure to obtain prescriber and nursing feedback regarding if there are ways to clarify or simplify.

The prescribers and nurses who order and treat DKA who use the protocol are your best resources when it comes to optimizing the protocol and optimizing care of the patient with ketoacidosis related to diabetes. I'll leave you with three takeaways from this presentation. First, design or update a DKA protocol based on guidelines and continue to update as new updated guidelines become available.

Consider a nurse driven process or some nurse driven components. Second, think continuous quality improvement. Perform audits, find where your pitfalls are, and make updates. And finally, simplify where you can. Consider a stepwise approach, a job aid, and leverage Glucommander IV's algorithm, safety guardrails, and alerts to follow best practice guidelines.

So, speaking of updating as new guidelines become available, we are looking forward to the updated consensus statement on hyperglycemic crisis in adult patients with diabetes based on the vast amount of new evidence that has emerged since these were last updated in 2009. Here's a quick look at some of the updates to diagnostic and resolution criteria based on Dr. Umpierrez's recent presentation at the European Association for the Study of Diabetes 2023 conference. In recognition of the wide range of glucose levels at presentation, particularly in euglycemic DKA, the hyperglycemia threshold is lowering to greater than 200 milligrams per deciliter from 250 or having a prior history of diabetes irrespective of glucose levels.

Anion gap is no longer included in the main definition of DKA, but may be utilized when ketone testing is not available, and is considered less reliable for DKA resolution. Instead, there will be quantitative cutoffs for ketone measurement for diagnosis and resolution, with strong recommendation for beta-hydroxybutyrate versus urine ketone measurement, as beta-hydroxybutyrate is the predominant ketone during acidosis and bicarb less than 18 for diagnosis and greater than or equal to 18 for resolution. Some previous sources cited 15. Once published, I know we will all review closely and work to update our institution's protocols to align with these updates.

Thank you so much for your time today. 

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