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Inpatient Management of Diabetic Ketoacidosis: Best Practices
Dr Paul Chidester, MD
Chief Medical OfficerOverview of diabetic ketoacidosis
Diabetic ketoacidosis (DKA) is an infrequent but potentially fatal complication of diabetes mellitus. One of two main hyperglycemic crises, and most commonly found in patients with Type 1 Diabetes Mellitus, DKA results from severe hyperglycemia causing an acid-base imbalance, which can lead to organ dysfunction and failure. Within this article, we will provide critical insights for healthcare professionals into the pathophysiology of DKA, its causes and risk factors, how to diagnose it, the initial and later steps in management for diabetic ketoacidosis, what to expect for prognosis and potential complications, and ways to prevent its occurrence.
Understanding the pathophysiology of diabetic ketoacidosis
Absolute insulin deficiency is the hallmark of diabetic ketoacidosis. Insufficient insulin leads to increased glucose production in the liver, higher glucagon secretion from the pancreas, and decreased glucose uptake in peripheral tissues, all of which lead to a rise in blood glucose. The lack of sufficient circulating insulin promotes the oxidation of free fatty acids, causing the accumulation of acetoacetate and beta-hydroxybutyrate, which are called ketone bodies. This state of ketosis (elevated ketone bodies in the blood) precipitates the acid-base imbalance that is a cardinal feature of DKA: metabolic acidosis with an increased anion gap. Anion-gap metabolic acidosis can cause the following pathophysiologic findings:
- Worsening volume depletion
- Critical electrolyte abnormalities
- Organ damage and failure
Causes and risk factors for diabetic ketoacidosis
The underlying causes and additional risk factors for diabetic ketoacidosis can be considered together, with one specific difference: healthcare professionals should look to treat any underlying causes of DKA, whereas it is imperative to modify any known risk factors as part of diabetes care to potentially decrease the risk of complications and of diabetic ketoacidosis episodes in the future.
Causes of DKA
The various causes of DKA lead to either insulin deficiency, volume depletion, or both.
Infections
Infections are the most common causes of diabetic ketoacidosis, with as many as 50% of DKA cases being caused by infections. Bacterial infections are known to potentially lead to metabolic decompensation, especially infections like urinary tract infections, cellulitis, and pneumonia, which are frequently identified along with DKA. Because diabetic ketoacidosis often predisposes to sepsis, this worsens the state of hypovolemia and organ damage.
Inadequate treatment with insulin
Medication non-adherence
Insulin omission is another common cause of DKA. Diabetic ketoacidosis can occur in patients who do not take insulin as it is prescribed, for potential reasons like unaffordability, an inadequate supply, missed insulin doses, or lack of follow-up for diabetes care. Other potential reasons for medication non-adherence may be gastrointestinal illnesses, which limit oral intake. In some cases skipping insulin doses may help prevent hypoglycemia, but in other cases, skipping insulin plus the stress of the illness may be enough to cause diabetic ketoacidosis.
Insulin pump malfunction
Insulin pumps may malfunction, delivering insufficient insulin doses, thus causing severe hyperglycemia. There are many reasons insulin pumps may not work properly, like excessive water exposure, damage from being dropped, clogs or kinks in tubing, dead batteries, technological errors, and others. If insulin pump malfunctions occur, it requires prompt correction to avoid potentially fatal complications.
Risk factors for diabetic ketoacidosis
Understanding the factors that are associated with diabetic ketoacidosis and how to modify them allows healthcare professionals to help reduce patients’ risk of developing diabetic ketoacidosis.
New-onset type 1 diabetes mellitus
Diabetic ketoacidosis can occur with new-onset type 1 diabetes mellitus in patients who are not yet diagnosed. The symptoms of diabetes can be nonspecific: fatigue, frequent urination, anorexia, and weight loss. So in some cases, increasingly severe hyperglycemia that causes DKA may be what prompts patients to seek care, leading to an initial diagnosis of diabetes mellitus. Diabetic ketoacidosis may be the heralding event in newly diagnosed diabetes cases.
Acute illnesses
Acute illnesses cause physiologic stress, which increases the risk of developing diabetic ketoacidosis. Conditions such as myocardial infarction, cerebrovascular accident, acute pancreatitis, major surgery, trauma, starvation ketosis, or eating disorders, can predispose to diabetic ketoacidosis.
Medications
Diabetes medications, other medications that affect blood glucose levels, and medications that affect carbohydrate metabolism can impact the risk of severe hyperglycemia and adult diabetic ketoacidosis. Examples of medications that can predispose to diabetic ketoacidosis include glucocorticoids, antipsychotics, sympathomimetics, diuretics, and sodium-glucose cotransporter-2 (SGLT2) inhibitors.
Clinical Presentation of diabetic ketoacidosis
The cardinal features of diabetic ketoacidosis are volume depletion, severe hyperglycemia, anion gap metabolic acidosis, and ketosis. Decreased skin turgor, dry mucosa, tachycardia, hypotension, and acute kidney injury are common, which occur as a result of profound dehydration. Severe hyperglycemia often causes polydipsia, polyuria, anorexia, and fatigue. Mild DKA may present with milder diabetic ketoacidosis symptoms, whereas severe diabetic ketoacidosis usually presents in critically ill patients.
The acid-base imbalance seen as anion-gap metabolic acidosis and the state of blood ketosis cause characteristic findings of nausea, vomiting, abdominal pain, altered mental status, fruity breath odor, and Kussmaul respirations (which are deep compensatory hyperventilation). As a result of the electrolyte abnormalities that are common in diabetic ketoacidosis, patients may present with muscle weakness, cardiac dysrhythmias, and renal dysfunction.
In severe cases of DKA, patients may present with:
- Sepsis
- Altered mental status
- Respiratory failure
- Cardiovascular collapse
- Failure of multiple organs
- Coma
Diagnosis of diabetic ketoacidosis
If a patient’s presentation is concerning for diabetic ketoacidosis on an initial emergency department evaluation, healthcare professionals should first assess hemodynamic status, monitoring for hypotension, tachycardia, tachypnea, hypoxia, and fever.
Next, checking a fingerstick blood sugar level is crucial to screening for possible diabetic ketoacidosis. Additional testing that should be obtained immediately includes the following:
- Complete metabolic panel (for plasma glucose, potassium, sodium, serum creatinine, blood urea nitrogen, anion gap, alanine aminotransferase, aspartate aminotransferase)
- Serum magnesium level
- Complete blood count
- Urinalysis
- Arterial or venous blood gas for blood pH
- Serum beta-hydroxybutyrate level
- Electrocardiogram
To make a diabetic ketoacidosis diagnosis, three findings should be present:
- Hyperglycemia
- Metabolic acidosis with an anion gap
- Ketonemia
More specifically, many findings are common in diabetic ketoacidosis:
- Blood glucose ≥ 250 mg/dL
- Serum bicarbonate < 18 mEq/L
- pH < 7.3
- Anion gap > 12 mEq/L
- Serum and urine ketones (beta hydroxybutyrate is the most common serum ketone tested)
- Blood urea nitrogen elevated
- Serum sodium is usually low as a result of pseudohyponatremia (corrected sodium level is normal)
- Serum potassium may be normal or elevated only initially; usually drops immediately with fluid resuscitation and insulin treatment
Because diabetic ketoacidosis is associated with severe dehydration, patients often have elevated blood urea nitrogen (BUN) and serum creatinine levels, signaling an acute kidney injury. Other signs of severe dehydration, organ dysfunction, and organ damage may include a lactic acidosis, a leukocytosis, an elevated troponin, and others, depending on the underlying etiology. Common electrolyte imbalances include alterations in sodium, potassium, magnesium, and phosphorus levels, which are often low or low-normal.
Initial treatment and management of diabetic ketoacidosis
Initial measures: Insulin and intravenous fluids
Fluid treatment and resuscitation
Key steps for fluid treatment and resuscitation can be summarized as follows:
Step | Description |
---|---|
Initial Step | Aggressive fluid resuscitation. |
Purpose of Rehydration | Resolves volume depletion, restores hemodynamic stability, improves organ perfusion. |
Preferred Fluids | Isotonic normal saline or crystalloid fluids. |
Initial Fluid Volume | Multiple liters over the first two hours, adjusted based on volume depletion and hemodynamic status. |
Fluid Transition | As volume status improves, shift to hypotonic IV fluids (often with glucose and potassium) based on blood glucose, sodium, and potassium levels. |
Glucose Management | When blood glucose improves to ≤ 250 mg/dL, add glucose (dextrose) to IV fluids. |
Electrolyte corrections
Electrolyte imbalances, most notably potassium, must be carefully monitored and promptly corrected to avoid potentially fatal complications during treatment of diabetic ketoacidosis. In DKA, serum potassium concentrations may initially be normal or elevated, as a result of extracellular potassium shifts; however, total body potassium is usually low, which manifests as potassium levels decrease with fluid resuscitation. At the same time, insulin administration can lead to a rapid drop in serum potassium because insulin drives potassium from the extracellular to the intracellular space. As a result, healthcare professionals should focus on repletion (usually with potassium chloride) at the time insulin infusion is begun in patients who have a low serum potassium concentration. Because hypokalemia can cause potentially fatal consequences, it is crucial to carefully monitor potassium levels and to adequately supplement potassium chloride intravenously.
Insulin Therapy
Intravenous insulin infusion
Insulin therapy is another mainstay in the management of diabetic ketoacidosis because an absolute insulin deficiency is one of the underlying factors. Once fluid resuscitation has begun and potassium supplementation has been given, treatment with insulin analogs should be initiated to treat diabetic ketoacidosis. According to the American Diabetes Association guidelines, among others, intravenous insulin infusion is preferred over subcutaneous injections to manage acute diabetic ketoacidosis. Regular insulin is preferred because of its rapid onset and short duration of action.
- An initial bolus insulin dose is recommended first, dosed at 0.1 units/kg of body weight.
- This is followed by a maintenance insulin infusion, with the rate starting at 0.1 units/kg of body weight/hour
- Titration of the maintenance insulin infusion is done to facilitate a gradual reduction in blood sugar levels in order to achieve plasma insulin sufficiency.
- The goal of blood glucose reduction is usually 50-75 mg/dL/hour. Too rapid correction of blood sugar can precipitate cerebral edema.
Transitioning to subcutaneous insulin therapy
During the treatment of diabetic ketoacidosis, DKA is considered to have resolved once ketone levels, bicarbonate, and the anion gap have normalized. When the blood sugar level reaches about 250 mg/dL, intravenous insulin is usually transitioned to subcutaneous insulin therapy, and intravenous fluids are switched to hypotonic saline or crystalloid with dextrose added to prevent hypoglycemia. At this point, patients may be able to tolerate oral intake and insulin dosing should be adjusted to account for that.
Glucose monitoring
Intensive glucose monitoring, usually either by blood sugar checks each hour or, in critically ill or high-risk patients, via continuous glucose monitoring.
Use of Computerized Dosing Algorithms
Computerized insulin dosing algorithms are available to aid in the treatment of diabetic ketoacidosis (DKA). One such tool, EndoTool, offers personalized insulin dosing recommendations based on each patient’s unique characteristics and physiology. It also prompts nursing staff on when to initiate supplemental dextrose therapy and when to check the next blood glucose level. Additionally, EndoTool guides caregivers on when patients are stable enough to transition to subcutaneous insulin. Utilizing EndoTool in DKA treatment has been associated with faster resolution of the condition, fewer blood glucose checks, reduced hypoglycemia, and shorter duration of insulin infusion.
Special considerations
Euglycemic diabetic ketoacidosis
Euglycemic diabetic ketoacidosis represents the situation of ketoacidosis, yet with a blood glucose concentration in the normal or near-normal ranges. Euglycemic diabetic ketoacidosis can occur when patients with diabetic ketoacidosis receive insulin treatment prior to when blood glucose is checked or in patients treated with certain medications, like sodium-glucose cotransporter-2 (SGLT2) inhibitors. The treatment of euglycemic diabetic ketoacidosis usually requires using both insulin and glucose to resolve the acidosis while preventing dangerous hypoglycemia.
Other Considerations
Pseudohyponatremia management
Low serum sodium concentrations usually occur in patients with DKA, as a result of fluid and electrolyte shifts between the extracellular and intracellular spaces, depending upon the degree of hyperglycemia. Glucose drives water into the intravascular and intracellular spaces, causing a decrease in extracellular sodium. As a result, sodium levels should be corrected for the degree of blood sugar elevation, as the correction of volume depletion and the restoration of cellular fluid balance will help equilibrate sodium.
Severe metabolic acidosis treatment
Sodium bicarbonate treatment is not used universally for the metabolic acidosis in the treatment of diabetic ketoacidosis. However, in patients who have a severe acidosis (pH < 6.9) or critical hyperkalemia, sodium bicarbonate therapy can be given to help resolve the acidosis.
Hypomagnesemia management
While magnesium levels may initially be high in cases of diabetic ketoacidosis, insulin deficiency may result in magnesium losses from the urine in the midst of fluid resuscitation, causing hypomagnesemia. If hypomagnesemia is present, adequate correction of serum potassium levels requires concurrent correction of hypomagnesemia.
Hypophosphatemia management
In general, routine phosphate supplementation is not recommended in diabetic ketoacidosis. However, phosphorus levels should be monitored and therapy should be given in cases of severe hypophosphatemia to prevent cardiac or respiratory complications.
Identifying and treating underlying causes
Identifying and treating underlying causes of diabetic ketoacidosis is crucial to manage it effectively. If bacterial infection is present, prompt antibiotic treatment is imperative to improve outcomes. If acute illness is present, hemodynamic stabilization and disease-specific treatment to avoid further organ damage is crucial. If insufficient medication treatment is the etiology of the severe hyperglycemia, identifying and mitigating the cause can prevent recurrent episodes.
The role of infections
Urinary tract infections, pneumonia, and cellulitis are common infectious etiologies that can precipitate diabetic ketoacidosis, confirmed by this randomized controlled trial. The identification of the underlying infection requires appropriate testing, including urinalysis, urine cultures, blood cultures, chest radiographs, and other imaging as necessary. If critically ill patients present with sepsis, fluid resuscitation for sepsis occurs concurrently with fluid replacement for diabetic ketoacidosis. Furthermore, administration of the appropriate antibiotic therapy within 1-2 hours of presentation is critical for improved patient outcomes.
Complications and prognosis of diabetic ketoacidosis
DKA is an emergency, necessitating prompt, appropriate treatment. Measures to avoid severe acute complications of DKA should be integrated into the initial management because the potential immediate complications of DKA can significantly increase mortality.
- Organ failure often occurs as a result of hypoperfusion and circulatory dysfunction from severe DKA. Patients with signs of ongoing volume depletion and hypoperfusion may require additional fluid resuscitation.
- Severe hypokalemia increases the risk of fatal cardiac dysrhythmias, and severe hypoglycemia can cause irreversible cognitive damage or coma. Monitoring of serum potassium concentration, aggressive potassium supplementation, and continuous glucose monitoring may be required in some patients.
- Rebound hyperglycemia is possible when insulin infusions are discontinued prematurely, allowing the acidosis to worsen, the anion gap to reopen, and hyperglycemia to increase. Transitioning from intravenous insulin infusions to subcutaneous insulin administration should be done based on clinical judgment.
- Aggressive fluid resuscitation may cause flash pulmonary edema, leading to respiratory failure and adult respiratory distress syndrome. In patients with heart failure, kidney failure, or other conditions that may lead to fluid overload, fluid resuscitation should be supplied judiciously under professional discretion.
- Cerebral edema is a rare complication of rapid correction of blood glucose, less common in adult patients and more common in pediatric patients, but its occurrence is associated with a poorer prognosis. Continuous glucose monitoring may be indicated to avoid rapid overcorrection of blood sugar.
Mortality and prognosis
The prognosis for diabetic ketoacidosis depends upon the case severity (mild diabetic ketoacidosis or severe diabetic ketoacidosis); the underlying cause; the promptness, appropriateness, and effectiveness of treatment, and the presence of other comorbidities. While the mortality rate for DKA has decreased in recent years, severe diabetic ketoacidosis may have a mortality rate as high as 5% during the immediate treatment period. Furthermore, appropriately managing diabetes mellitus after diabetic ketoacidosis has resolved, in order to prevent recurrence, is imperative to improving prognosis.
Some particular findings could denote a poorer prognosis in cases of diabetic ketoacidosis:
- Lactic acidosis
- Bacteremia
- Severely low serum bicarbonate concentration
- Severely decreased blood pH (acidosis)
- Prolonged ketosis
- Profound serum potassium abnormalities
- Acute kidney failure
- Pulmonary edema
- Circulatory collapse
Long-term management and prevention of diabetic ketoacidosis
Long-term management
Patients who have developed DKA previously are more likely to develop recurrent DKA. After resolution of the acute diabetic ketoacidosis event, it is imperative to adjust the maintenance insulin regimen to achieve better glycemic control. Following discharge from the hospital, additional titrations of insulin dosage and other antidiabetic medications are necessary to optimize diabetes treatment. Close fingerstick or continuous glucose monitoring, in combination with quarterly glycosylated hemoglobin (HbA1c) assessments, is essential to ensure optimal glycemic control and to help titrate medications.
Prevention of diabetic ketoacidosis
By identifying factors associated with elevated blood sugar and diabetic ketoacidosis, some cases of DKA can potentially be avoided. Adjusting insulin levels appropriately during times of physical illness, physiologic stress, or medication changes is an important strategy to maintaining glucose control.
Cases of physical illness
Physical illness may lead to increases or decreases in blood glucose levels. Infections and inflammatory conditions commonly raise blood sugar, potentially requiring higher levels of insulin or other antidiabetic medications to keep blood sugar levels under control. In contrast, gastrointestinal illnesses or other conditions associated with less oral intake may increase the risk of low blood sugar, necessitating decreases in insulin and medication dosages to prevent hypoglycemia.
Situations of physiologic stress
Physiologically stressful events, such as a major surgery, critical illness, or severe organ dysfunction or failure, may cause an increase or decrease in blood sugar, necessitating adjustments to insulin therapy regimens and the dosing of other antidiabetic medications.
Changes in medications
Some medications are commonly associated with increased blood sugar levels:
- Corticosteroids
- HIV antiretroviral medications
- Immunosuppressants
- Antipsychotics
For patients taking these medications, whether short-term or long-term, close monitoring of blood sugar levels, adjusting insulin doses accordingly, and even using low-dose insulin therapy in insulin-naive patients (if indicated) can help prevent diabetic ketoacidosis.
Appropriate follow-up
For patients with diabetes, especially insulin-dependent diabetes mellitus, routine follow-up for diabetes care with their primary care physician or endocrinologist is crucial to monitor blood sugar levels over time, ensure adequate glycemic control, and help prevent severe hyperglycemia complications, such as diabetic ketoacidosis.
Conclusion
While diabetic ketoacidosis occurs infrequently amongst patients with insulin-dependent diabetes mellitus, it causes severe and potentially fatal complications, which makes it imperative to provide prompt, effective treatment. By understanding the pathophysiology of diabetic ketoacidosis, its causes, and risk factors, how to make the diagnosis, the initial and ongoing steps in the treatment of diabetic ketoacidosis, the potential complications, and how to prevent recurrence, healthcare professionals are better poised to apply sound clinical judgment in cases of diabetic ketoacidosis and to improve patient outcomes.
About EndoTool
Made by Monarch Medical Technologies, EndoTool is the only patient-specific insulin dosing system which simplifies the complex task of glycemic management in hospital environments. The recommended dosing is different for each patient based on multiple clinical characteristics. The FDA-cleared platform is utilized in hundreds of hospitals across the United States and is fully integrated with all major electronic medical records. To see how EndoTool can support your health system, get in touch today.
About the author
References
Ahmad R, Narwaria M, Singh A, Kumar S, Haque M. Detecting Diabetic Ketoacidosis with Infection: Combating a Life-Threatening Emergency with Practical Diagnostic Tools. Diagnostics (Basel). 2023;13(14):2441.
Aldhaeefi M, Aldardeer NF, Alkhani N, Alqarni SM, Alhammad AM, Alshaya AI. Updates in the Management of Hyperglycemic Crisis. Front Clin Diabetes Healthc. 2022;2:820728.
Brandstaetter E, Bartal C, Sagy I, Jotkowitz A, Barski L. Recurrent diabetic ketoacidosis. Arch Endocrinol Metab. 2019;63(5):531-535.
Elendu C, David JA, Udoyen AO, et al. Comprehensive review of diabetic ketoacidosis: an update. Ann Med Surg (Lond). 2023;85(6):2802-2807.
Guenego, Agathe et al. “Insulin Pump Failures: Has There Been an Improvement? Update of a Prospective Observational Study.” Diabetes technology & therapeutics vol. 18,12 (2016): 820-824.
Misra S, Oliver NS. Diabetic ketoacidosis in adults [published correction appears in BMJ. 2015 Nov 02;351:h5866. doi: 10.1136/bmj.h5866]. BMJ. 2015;351:h5660.
Modi A, Agrawal A, Morgan F. Euglycemic Diabetic Ketoacidosis: A Review. Curr Diabetes Rev. 2017;13(3):315-321.
Nunes RTL, Mota CFMGP, Lins PRG, et al. Incidence, characteristics and long-term outcomes of patients with diabetic ketoacidosis: a prospective prognosis cohort study in an emergency department. Sao Paulo Med J. 2021;139(1):10-17.
Sharma PV, Jobanputra YB, Lewin K, Bagatell S, Lichtstein DM. Diabetic Ketoacidosis in Patients with Type 2 Diabetes on Sodium-Glucose Cotransporter-2 Inhibitors – A Case Series. Rev Recent Clin Trials. 2018;13(2):156-160.
Umpierrez GE, Davis GM, ElSayed NA, et al. Hyperglycemic Crises in Adults With Diabetes: A Consensus Report. Diabetes Care. 2024;47(8):1257-1275.
Wu XY, She DM, Wang F, et al. Clinical profiles, outcomes and risk factors among type 2 diabetic inpatients with diabetic ketoacidosis and hyperglycemic hyperosmolar state: a hospital-based analysis over a 6-year period. BMC Endocr Disord. 2020;20(1):182.
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