In an adult with altered mental status, random glucose >350 mg/dL, pH 7.00, pCO₂ (partial pressure of carbon dioxide) 54 mm Hg, HCO₃⁻ (bicarbonate) 12 mmol/L, high anion‑gap metabolic acidosis, negative ketones, and normal brain MRI/CT, what is the most likely diagnosis and what is the appropriate acute management?

Hyperglycemic Hyperosmolar State (HHS)

This patient has hyperglycemic hyperosmolar state (HHS), not diabetic ketoacidosis, and requires aggressive fluid resuscitation with isotonic saline followed by insulin therapy once hemodynamic stability is achieved.

Diagnostic Reasoning

The clinical presentation clearly indicates HHS rather than DKA based on the following criteria:

• Glucose >600 mg/dL (diagnostic threshold for HHS is ≥600 mg/dL) 1
• Severe acidosis with pH 7.00 and bicarbonate 12 mmol/L 1
• Negative ketones – this is the critical distinguishing feature from DKA 1
• High anion gap metabolic acidosis despite absent ketones 1
• Altered mental status consistent with severe hyperosmolarity 1, 2
• Normal brain imaging excludes structural causes 1

The elevated pCO₂ (54 mm Hg) represents inadequate respiratory compensation for the severe metabolic acidosis, suggesting either respiratory muscle fatigue or CNS depression from hyperosmolarity 3. In pure metabolic acidosis, expected pCO₂ should be approximately 24-28 mm Hg (using Winter's formula: expected pCO₂ = 1.5 × HCO₃ + 8 ± 2) 3.

Acute Management Protocol

Immediate Fluid Resuscitation (First Priority)

Administer isotonic saline (0.9% NaCl) at 15-20 mL/kg/h during the first hour to restore intravascular volume and renal perfusion 1, 4. This typically translates to 1-1.5 liters in the first hour for most adults 1.

• Hemodynamic monitoring is essential: improvement in blood pressure, urine output, and mental status indicate adequate resuscitation 1
• Avoid rapid osmolality correction: the induced change in serum osmolality should not exceed 3 mOsm/kg/H₂O per hour to prevent cerebral edema 1
• After initial resuscitation, switch to 0.45% NaCl at 4-14 mL/kg/h once vital signs stabilize, as HHS involves hypertonic dehydration requiring hypotonic fluid replacement 1, 2

Potassium Replacement (Before Insulin)

Check serum potassium immediately and do NOT start insulin if K⁺ <3.3 mEq/L 1, 5.

• If K⁺ <3.3 mEq/L: hold insulin and give potassium replacement until K⁺ >3.3 mEq/L 1
• Once K⁺ >3.3 mEq/L and renal function is confirmed: add 20-30 mEq/L potassium to IV fluids (2/3 KCl and 1/3 KPO₄) 1
• Monitor potassium every 2-4 hours as insulin drives potassium intracellularly, risking life-threatening hypokalemia, respiratory paralysis, and ventricular arrhythmias 5, 1

Insulin Therapy (After Volume Resuscitation)

Once hypokalemia is excluded (K⁺ >3.3 mEq/L), give IV bolus of regular insulin 0.15 units/kg, followed by continuous infusion at 0.1 units/kg/h 1, 4.

• Target glucose decline of 50-75 mg/dL per hour 1
• If glucose does not fall by 50 mg/dL in the first hour, check hydration status and double the insulin infusion rate hourly until steady decline achieved 1
• When glucose reaches 300 mg/dL in HHS, add 5% dextrose to IV fluids and reduce insulin to 0.05-0.1 units/kg/h 1, 2
• Continue insulin infusion until mental status normalizes and acidosis resolves (pH >7.3, bicarbonate ≥18 mEq/L) 1

Bicarbonate Therapy

Bicarbonate is NOT indicated even with pH 7.00 in this scenario 1, 6, 3.

• Bicarbonate therapy is only considered if pH <6.9 in DKA, and this patient has HHS, not DKA 1, 6
• The acidosis will resolve with fluid resuscitation and treatment of the underlying hyperosmolar state 1, 4

Monitoring Parameters

Obtain the following every 2-4 hours until stabilized 1, 3:

• Venous pH and bicarbonate (venous pH runs ~0.03 units lower than arterial, eliminating need for repeated arterial sticks) 3
• Complete metabolic panel (Na⁺, K⁺, Cl⁻, HCO₃⁻, glucose, BUN, creatinine) 1, 3
• Calculate corrected sodium: add 1.6 mEq/L to measured sodium for every 100 mg/dL glucose elevation 1
• Anion gap to track resolution 3, 7
• Urine output and vital signs continuously 1

Resolution Criteria

HHS is considered resolved when 1, 4:

• Glucose <200 mg/dL
• Serum bicarbonate ≥18 mEq/L
• Venous pH >7.3
• Mental status returns to baseline
• Serum osmolality normalizes

Critical Pitfalls to Avoid

Do not start insulin before adequate fluid resuscitation – insulin without fluids worsens intravascular depletion and can precipitate cardiovascular collapse 1, 2.

Do not use normal saline exclusively throughout treatment – after initial resuscitation, switch to hypotonic fluids (0.45% NaCl) as continued isotonic saline can cause hyperchloremic metabolic acidosis and delay osmolality correction 1, 3.

Do not correct osmolality too rapidly – exceeding 3 mOsm/kg/H₂O per hour increases risk of cerebral edema, particularly in elderly patients 1.

Do not overlook precipitating causes – infection, MI, stroke, medication non-compliance, or new diabetes diagnosis must be identified and treated simultaneously 1, 4.

Monitor for complications: thromboembolism (due to hyperviscosity), rhabdomyolysis, and acute kidney injury are common in HHS 4, 2.