Why prioritize insulin administration over fluid replacement in a patient with severe hyperglycemia, such as diabetic ketoacidosis (DKA) or hyperglycemic hyperosmolar nonketotic syndrome (HHNS), and a history of diabetes, possibly with comorbid conditions like hypertension, cardiovascular disease, or impaired renal function?

Why Fluid Replacement Takes Priority Over Insulin in HHNS

In hyperglycemic hyperosmolar nonketotic syndrome (HHNS), fluid replacement must be prioritized over insulin administration because the primary pathophysiology is severe dehydration with total body water deficits of 9-10 liters (100-200 ml/kg), and aggressive fluid resuscitation is the cornerstone of therapy that directly addresses mortality risk. 1, 2

Critical Pathophysiologic Distinction Between DKA and HHNS

The fundamental difference lies in what kills the patient:

• In DKA: Insulin deficiency and ketoacidosis are the prominent features, making insulin therapy the cornerstone of treatment 3
• In HHNS: Hyperglycemia, osmotic diuresis, and profound dehydration dominate the clinical picture, making fluid replacement the cornerstone of therapy 3
• The mortality in HHNS is primarily driven by severe hyperosmolarity, circulatory collapse, and thrombotic complications—all directly related to volume depletion rather than insulin deficiency 2, 4

The Fluid-First Protocol for HHNS

Initial Resuscitation Phase

Begin with isotonic saline (0.9% NaCl) at 15-20 ml/kg/hour during the first hour to restore circulatory volume and tissue perfusion. 1, 5 This aggressive initial fluid therapy:

• Restores intravascular volume and prevents vascular thrombosis 2
• Improves renal perfusion, allowing the kidneys to excrete excess glucose 2
• Begins correction of hyperosmolarity (target: not exceeding 3 mOsm/kg/H₂O per hour) 5, 1
• Stabilizes hemodynamics before insulin-induced intracellular fluid shifts 3

Why Insulin Must Wait

Insulin administration should be delayed until adequate fluid resuscitation is achieved because:

• Insulin drives glucose (and water) intracellularly, which can precipitate vascular collapse in a severely volume-depleted patient 3
• Fluid replacement alone will lower glucose by 50-100 mg/dL through improved renal perfusion and osmotic diuresis 2
• Starting insulin before volume restoration increases risk of hypotension and thrombotic complications 4

The Insulin Initiation Threshold

Once hypokalemia is excluded (K+ ≥3.3 mEq/L) and initial fluid resuscitation has begun, administer IV regular insulin at 0.15 U/kg bolus followed by 0.1 U/kg/hour infusion. 1, 5 However, the insulin infusion rate in HHNS is typically lower than in DKA because:

• These patients retain some endogenous insulin secretion 2
• They are exquisitely sensitive to exogenous insulin 2
• The goal is gradual glucose reduction (50-75 mg/dL per hour) to avoid rapid osmotic shifts 1

Critical Monitoring During Treatment

Monitor the following every 2-4 hours: 1

• Serum electrolytes, glucose, BUN, creatinine, and osmolality
• Hemodynamic parameters (blood pressure, heart rate, urine output)
• Mental status changes (which may indicate cerebral edema from overly rapid correction)

Common Pitfalls to Avoid

Never start insulin before confirming potassium ≥3.3 mEq/L, as insulin will drive potassium intracellularly and can precipitate fatal cardiac arrhythmias. 6, 7 This is an absolute contraindication.

Avoid overly rapid correction of hyperosmolarity, particularly in elderly patients who comprise the majority of HHNS cases. 4 The induced change in serum osmolality should not exceed 3 mOsm/kg/H₂O per hour to prevent cerebral edema. 5, 1

Do not use hypotonic saline initially in patients with hemodynamic instability—isotonic saline (0.9% NaCl) should be used first until vital signs stabilize, then switch to 0.45% NaCl for ongoing correction of free water deficit. 2, 5

The Elderly Patient Consideration

Age is the single best prognostic indicator in HHNS, and elderly patients face unique challenges: 4

• Reduced glomerular filtration rate limits glucose excretion
• Impaired thirst mechanism prevents adequate oral rehydration
• Coexisting conditions (heart failure, renal insufficiency) complicate aggressive fluid therapy
• Higher mortality from precipitating illnesses (stroke, MI, infection)

In elderly patients with heart failure or renal impairment, fluid administration must be carefully titrated with hemodynamic monitoring, but fluid replacement still takes priority—just with more cautious rates and closer monitoring. 4

Resolution Criteria

Continue insulin infusion until mental status improves and hyperosmolarity resolves, not just until glucose normalizes. 1 HHNS resolution requires:

• Improved mental status
• Effective serum osmolality <320 mOsm/kg
• Hemodynamic stability
• Adequate urine output

Transition to Subcutaneous Insulin

Administer basal subcutaneous insulin 2-4 hours before discontinuing IV insulin to prevent rebound hyperglycemia. 1, 6 Many HHNS patients will not require long-term insulin therapy and can be managed with oral agents after recovery. 2