Diabetic Ketoacidosis

Perioperative Management of T1D

• Patients with T1D are dependent on exogenous insulin administration to maintain metabolic stability and euglycemia. They require insulin administration and close monitoring of blood glucose (BG) throughout the perioperative period.
• The International Society for Pediatric and Adolescent Diabetes (ISPAD) and Society for Pediatric Anesthesia (SPA) have published guidelines for the perioperative management of patients with T1D.^1,2
• These guidelines have been summarized in a separate OA summary (Perioperative Management of Patients with Type 1 Diabetes Mellitus)³ and may be reviewed prior to caring for patients with T1D. Link

Metabolism Overview^1,4

• Insulin promotes glucose uptake, utilization, and storage as glycogen.
• Counterregulatory hormones (e.g., glucagon, catecholamines, cortisol, and growth hormone) impair glucose utilization and promote glycogenolysis, lipolysis, and proteolysis. This results in hyperglycemia, ketosis, and metabolic acidosis.
• Diabetes Mellitus
  • T1D: Patients have a complete lack of endogenous insulin. Insulin administration is required at all times, even while fasting, to maintain metabolic stability, including appropriate glucose utilization and suppression of alternative metabolic pathways.
  • Type 2 Diabetes (T2D): Patients secrete endogenous insulin, but have insulin resistance. They can be managed with oral antihyperglycemic medications that improve insulin function or with exogenous insulin. They develop hyperglycemia but have sufficient basal insulin secretion to prevent the metabolic decompensation observed in T1D. Ketoacidosis is unusual in T2D.

DKA

• DKA is caused by a deficiency in insulin relative to counterregulatory hormones, resulting in the clinical triad of hyperglycemia, ketosis, and metabolic acidosis. Hyperglycemia induces osmotic diuresis, resulting in significant volume depletion and electrolyte loss.
  • Causes of insulin deficiency:
    • New onset or undiagnosed T1D
    • Interruptions in insulin delivery (e.g., missed doses, insulin pump dysfunction, limited access to medical care)
  • Causes of increased counterregulatory hormones:
    • Physiologic stressors (e.g., acute illness, sepsis, trauma)
    • Periods of rapid growth (e.g., puberty)
    • Note: In these situations, DKA may occur despite appropriate insulin administration
• Fluid and electrolyte shifts, hypoperfusion with lactic acidosis, and a generalized inflammatory state contribute to complications of DKA. These include:
  • Cerebral injury, including cerebral edema, altered mental status, and potential permanent neurologic sequelae
  • Renal tubular damage and acute kidney injury
  • Electrolyte derangements due to both osmotic diuresis and transcellular shifts
  • Thromboembolic events, pulmonary edema, acute pancreatitis, and multiple organ dysfunction
• Epidemiology
  • DKA occurs in 6-8% of children with T1D per year and is present in 30-40% of children at the time of T1D diagnosis.
  • DKA and its associated complications are the leading cause of hospitalization, morbidity, and mortality in children with T1D. Cerebral injury is the leading cause of mortality.

Hyperglycemic Hyperosmolar State (HHS)

• HHS is a complication of T2D, characterized by significant hyperglycemia (blood glucose >600mg/dL), volume depletion, electrolyte loss, and hyperosmolarity. However, the presence of basal insulin prevents the development of ketosis and acidosis.
• Complication and mortality rates are higher than those for DKA.
• Treatment considerations are similar, but patients with HHS are likely to need more aggressive volume resuscitation and less insulin than those with DKA.

DKA: Workup and Management^1,4

Clinical Presentation: The signs and symptoms of DKA are nonspecific and may vary by patient. Classic signs and symptoms include:

• Polyuria and polydipsia
• Abdominal pain, anorexia, nausea, or vomiting
• Hyperventilation or deep (Kussmaul) respirations
• Neurologic abnormalities, including confusion, drowsiness, obtundation, and coma
• Volume depletion and electrolyte derangements

Initial Workup

• Any patient with a blood glucose level >250 mg/dL or exhibiting signs/symptoms suggestive of DKA should be evaluated for DKA.
• The following criteria are diagnostic for DKA:
  • Blood glucose >200 mg/dL (note: fasting patients or partially treated patients may have only mildly elevated BG levels, known as euglycemic ketoacidosis)
  • Venous pH <7.3 or serum bicarbonate <18 mmol/L
  • Blood ß-hydroxybuyrate (BOHB) ≥3 mmol/L or moderate or large ketonuria
• Additional labs include serum electrolytes, BUN, and creatinine to evaluate for electrolyte abnormalities and volume depletion.

Emergency Assessment and Triage

• The degree of acidosis is used to categorize the severity of DKA as follows:
  • Mild: venous pH <7.3 or serum bicarbonate <18 mmol/L
  • Moderate: venous pH <7.2 or serum bicarbonate <10 mmol/L
  • Severe: venous pH <7.1 or serum bicarbonate <5 mmol/L
• Clinical assessment should include evaluation of volume status and mental status.
• Level of care
  • Most patients with DKA will require inpatient care with intravenous (IV) insulin and fluids in a setting with clinical practice guidelines and the capacity to monitor symptoms, vital signs, and laboratory results frequently.
    • Patients with mild-to-moderate DKA may be managed on an inpatient unit.
    • Patients with severe DKA or any risk factors for cerebral injury should be managed in a critical care unit.
  • Patients with very mild DKA (ketosis without vomiting or severe dehydration), established diabetes, and experience with sick-day management may be treated in the outpatient setting with subcutaneous insulin and oral hydration. They should be escalated to inpatient care if DKA does not improve.

Inpatient DKA Management

• The primary goals of DKA treatment are to restore fluid balance, correct acidosis and reverse ketosis, and restore euglycemia. Resolution of ketoacidosis is defined by normalization of the anion gap or serum BOHB ≤1 mmol/L and venous pH ≥7.3.
• Fluid Management
  • Patients with DKA can have significant volume depletion due to osmotic diuresis. Extracellular fluid volume deficits can range from 5% to 10%, depending on the severity of DKA.
  • For hemodynamically stable patients: Replace the estimated volume deficit over 24-48 hours with nondextrose-containing crystalloid fluids.
  • For patients with signs of shock: Restore circulating blood volume with normal saline boluses (20mL/kg). Reassess circulatory status after every bolus and repeat until circulation is restored. PALS guidelines should be followed for ongoing resuscitation.
• Glucose Management
  • Insulin Therapy
    • Volume repletion alone can markedly decrease BG levels. However, insulin administration is still necessary to restore normal cellular metabolism. Insulin administration should begin one hour after initiation of IV fluid resuscitation.
    • Insulin should initially be administered as a continuous IV infusion (starting range 0.05-0.1 units/kg/hr) and can be changed to SC insulin boluses as DKA resolves.
    • Criteria for changing from IV to SC insulin:
  • Normal anion gap or serum BOHB ≤1 mmol/L
  • Venous pH ≥7.3
  • Blood glucose <200 mg/dL
  • Patient is tolerating oral intake
  • To prevent hypoglycemia, 5% dextrose should be added to IV fluids when the patient’s blood glucose level decreases to 250-300 mg/dL. Dextrose should be started sooner if BG is dropping precipitously.
• Electrolyte Management
  • Potassium
    • Patients with DKA have a total-body potassium deficit due to diuresis. However, serum potassium levels may initially increase due to transcellular shifts induced by acidosis. Insulin administration shifts potassium into the intracellular space, resulting in hypokalemia.
    • Clinical implications: Hypo- and hyperkalemia can both affect cardiac function with significant EKG changes. Hypokalemia causes PR prolongation, T wave flattening/inversion, ST depression, and prominent U waves. Hyperkalemia causes tall, peaked T waves and a short QT interval.
  • Timing of potassium replacement:
    • For hypokalemic patients: Begin potassium replacement prior to insulin therapy.
    • For other patients: Begin potassium replacement when the patient is normokalemic and has documented urine output.
  • Phosphate
    • As with potassium levels, patients with DKA have a total-body phosphate deficit and a shift from the intracellular to the extracellular space. Extracellular phosphate levels will decrease following volume resuscitation and insulin administration.
    • Clinical implications: Severe hypophosphatemia leads to decreased ATP with impaired cellular function and decreased 2,3-DPG with changes in hemoglobin-O₂ affinity and oxygen delivery to tissues. Manifestations include metabolic encephalopathy, impaired myocardial contractility and arrhythmias, respiratory failure, and muscle dysfunction with rhabdomyolysis.
    • Phosphate should be replaced along with potassium. Phosphate replacement can cause hypocalcemia and hypomagnesemia, which should be monitored.
• Cerebral Injury Management^1,4
  • Clinically significant cerebral injury is most likely to occur within the first 12 hours of DKA treatment. Risk factors for cerebral injury include:
    • Decreased level of consciousness
    • Very young age (<5 years)
    • Severe acidosis (venous pH <7.1 or serum bicarbonate <5 mmol/L)
    • pCO₂ ≤20 mmHg
    • Serum urea nitrogen concentration >20 mg/dL
    • Significant electrolyte disturbances, including hyper- or hypokalemia
  • Administer IV mannitol (0.5-1g/kg) or hypertonic saline (2.5-5mL/kg) for cerebral edema management.
  • Escalate to a critical care unit if the patient is not already in the ICU.

DKA in the Perioperative Setting^1,2,5

• During the perioperative period, multiple factors, including fasting, physiologic stress, pain, nausea, and immobility, affect metabolic homeostasis and insulin requirements. This puts patients with T1D at risk for both hypoglycemia and hyperglycemia/DKA.
• Anesthetic medications may mask the clinical signs of both hypo- and hyperglycemia and impair the patient’s ability to self-report their symptoms. Therefore, it is important to check BG at least hourly in the perioperative period. Patients with BG >250mg/dL at any point in the perioperative period should be evaluated for DKA.
• DKA diagnosis in the perioperative period
  • If DKA is diagnosed preoperatively and the procedure is not emergent, the procedure should be cancelled, and the patient should be admitted for DKA management. The procedure can be rescheduled once DKA has resolved.
  • If the procedure is emergent or DKA is diagnosed intraoperatively, DKA must be managed in the operating room with postoperative admission for ongoing management.
    • Frequent laboratory analysis for glucose levels, electrolytes, and acid-base status is necessary to appropriately manage insulin, fluid, and electrolyte administration
    • When possible, consult an endocrinology service for guidance regarding optimal management