How should Hyperosmolar Hyperglycemic State (HHS) be managed in patients with Chronic Kidney Disease (CKD)?

Management of Hyperosmolar Hyperglycemic State (HHS) in Patients with Chronic Kidney Disease

In patients with chronic kidney disease (CKD), management of Hyperosmolar Hyperglycemic State (HHS) requires careful fluid resuscitation with isotonic saline at a reduced rate of 10-15 mL/kg/hr initially, followed by close monitoring of renal function, electrolytes, and mental status while adjusting insulin therapy to achieve gradual glucose reduction. 1, 2

Initial Assessment and Diagnosis

• Diagnose HHS based on blood glucose ≥600 mg/dL, arterial pH >7.3, serum bicarbonate >15 mEq/L, effective serum osmolality ≥320 mOsm/kg H₂O, minimal ketonuria/ketonemia, and altered mental status or severe dehydration 2
• Calculate effective serum osmolality: 2[measured Na⁺ (mEq/L)] + glucose (mg/dL)/18 2
• Correct serum sodium for hyperglycemia by adding 1.6 mEq to sodium value for each 100 mg/dL glucose >100 mg/dL 1, 3
• In CKD patients, HbA1c may be unreliable for monitoring glycemic control, especially with eGFR <30 mL/min/1.73 m², and continuous glucose monitoring or self-monitoring of blood glucose should be used instead 4

Fluid Therapy Modifications for CKD

• Begin with isotonic saline (0.9% NaCl) at a reduced rate of 10-15 mL/kg/h (rather than 15-20 mL/kg/h used in patients with normal renal function) to restore circulatory volume while avoiding fluid overload 1, 2, 5
• Target a more gradual correction of estimated fluid deficits over 24-36 hours in CKD patients, with careful monitoring for signs of volume overload 2, 5
• Adjust fluid therapy based on frequent assessment of volume status, urine output, and hemodynamic parameters 1, 5
• Consider balanced electrolyte solutions rather than 0.9% saline to reduce the risk of hyperchloremic acidosis in patients with CKD 5

Insulin Therapy

• After excluding hypokalemia, administer an IV bolus of regular insulin at a reduced dose of 0.1 U/kg body weight (rather than 0.15 U/kg) followed by continuous infusion at 0.05-0.1 U/kg/h 1, 2
• Adjust insulin infusion rate based on plasma glucose levels, aiming for a more gradual glucose decline of 50-70 mg/dL/h to prevent rapid shifts in osmolality 1, 2
• When plasma glucose reaches 250-300 mg/dL, add dextrose to hydrating solutions while continuing insulin infusion at a reduced rate to prevent hypoglycemia 1
• Continue insulin infusion until mental status improves and hyperosmolarity resolves 1

Electrolyte Management in CKD

• Monitor potassium levels closely, as CKD patients may have baseline hyperkalemia but can rapidly develop hypokalemia during treatment 1, 6
• Once renal function is assessed and serum potassium is known, add potassium at a reduced dose of 10-20 mEq/L (rather than 20-40 mEq/L) when serum levels fall below 4.5 mEq/L 1, 2
• Monitor phosphate levels and consider replacement only in patients with cardiac dysfunction, anemia, respiratory depression, or serum phosphate <1.0 mg/dL 1
• Avoid bicarbonate administration as it does not improve outcomes and may worsen intracellular acidosis 1

Monitoring During Treatment

• Check blood glucose every 1-2 hours until stable 2
• Monitor serum electrolytes, blood urea nitrogen, creatinine, and calculated osmolality every 2-4 hours 1, 2
• Assess fluid input/output, vital signs, and mental status frequently 2
• Monitor for signs of cerebral edema (lethargy, behavioral changes, seizures, incontinence, pupillary changes, bradycardia, respiratory arrest) 1
• Target a slower rate of change in serum osmolality, not exceeding 3 mOsm/kg/h, to prevent neurological complications 1, 2

Transition from IV to Subcutaneous Insulin

• Administer basal insulin 2-4 hours before stopping IV insulin to prevent rebound hyperglycemia 1, 2
• For long-term management in CKD patients, individualize HbA1c targets ranging from <6.5% to <8.0% based on risk for hypoglycemia 4
• Consider SGLT2 inhibitors for patients with eGFR ≥20 mL/min/1.73 m² and GLP-1 receptor agonists for ongoing glycemic management after resolution of HHS 4

Special Considerations for CKD Patients

• Be vigilant for acute kidney injury (AKI) as a complication of HHS, which occurs more frequently in patients with pre-existing CKD 7, 6
• Consider early nephrology consultation for patients with advanced CKD (stages 4-5) or those requiring dialysis 4
• Implement a team-based, integrated approach for ongoing management of diabetes in CKD patients after resolution of HHS 4
• Maintain protein intake of 0.8 g/kg/day and sodium intake <2 g/day for long-term management after resolution of HHS 4

Identification and Treatment of Precipitating Causes

• Obtain bacterial cultures of urine, blood, and other sites as needed 1
• Administer appropriate antibiotics if infection is suspected 1
• Identify and treat other precipitating factors such as medication non-adherence, stroke, or myocardial infarction 2