2025 PACUPrep BCCCP Preparatory Course Hyperglycemic Crisis (DKA & HHS) Diagnostic Evaluation and Severity Stratification of DKA and HHS
Diagnostic Evaluation and Severity Stratification of DKA and HHS

Diagnostic Evaluation and Severity Stratification of DKA and HHS

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Objective

Rapid and accurate diagnosis of DKA and HHS determines the urgency and intensity of treatment.

1. Clinical Manifestations and Physical Examination

Early recognition of key signs—dehydration, respiratory compensation, and mental status changes—guides severity assessment and initial level-of-care decisions.

  • Volume Depletion: Polyuria (from osmotic diuresis) and polydipsia are classic symptoms. Intravascular volume loss is often severe, estimated at 6–10 liters. This manifests as tachycardia, orthostatic hypotension, dry mucous membranes, and delayed capillary refill.
  • Neurologic Status: The patient’s mental state can range from fully alert to profound coma. This spectrum correlates strongly with the degree of metabolic acidosis in DKA and the effective serum hyperosmolality in HHS.
  • Respiratory Compensation: Kussmaul respirations—a pattern of deep, labored breathing—represent the body’s attempt to expel CO₂ to compensate for severe metabolic acidosis.
Pearl Icon A shield with an exclamation mark, indicating a clinical pearl. Clinical Pearls: Physical Exam Nuances
  • Skin turgor assessment may be blunted and unreliable in elderly patients despite severe dehydration due to age-related loss of skin elasticity.
  • The depth of Kussmaul breathing reflects the severity of acidosis; however, coexisting COPD or respiratory muscle fatigue can mask this critical sign.

2. Laboratory Evaluation

A focused lab panel—including glucose, electrolytes, acid-base status, ketones, and osmolality—is essential to confirm the diagnosis and inform classification.

Essential Tests and Formulas

  • Plasma Glucose: A threshold of >250 mg/dL (13.9 mmol/L) is typical for DKA, while >600 mg/dL (33.3 mmol/L) is characteristic of HHS.
  • Serum Ketones: Direct measurement of β-hydroxybutyrate (BHOB) is the preferred method. A level >3 mmol/L confirms significant ketonemia. Older nitroprusside urine tests are less reliable as they only detect acetoacetate and can underestimate the degree of ketosis.
  • Acid-Base Status: A venous blood gas (VBG) is an acceptable proxy for an arterial blood gas (ABG) for assessing pH. A venous pH <7.3 or serum bicarbonate <18 mEq/L confirms metabolic acidosis.

Key calculations are required for accurate assessment:

Corrected Sodium (Nacorr) = Nameas + 1.6 × ((Glucose – 100) / 100)
Anion Gap (AG) = Na+ – (Cl– + HCO3–)
Calculated Osmolality = (2 × Na+) + (Glucose / 18) + (BUN / 2.8)
Pearl Icon A shield with an exclamation mark, indicating a clinical pearl. Clinical Pearl: Tracking Resolution

Use the quantitative β-hydroxybutyrate (BHOB) assay not only for diagnosis but also for monitoring the response to therapy. Serial measurements of BHOB, along with the anion gap, are the most accurate indicators of ketoacidosis resolution.

3. Diagnostic Criteria for DKA

The diagnosis of Diabetic Ketoacidosis (DKA) requires the classic triad of hyperglycemia, ketonemia, and metabolic acidosis. It’s also crucial to recognize the presentation of euglycemic DKA, particularly in patients using SGLT2 inhibitors.

  1. Hyperglycemia: Plasma glucose >250 mg/dL (13.9 mmol/L) or a known history of diabetes.
  2. Ketosis: Serum β-hydroxybutyrate (BHOB) ≥3 mmol/L and/or a significantly elevated anion gap (>12 mEq/L).
  3. Acidosis: Venous pH <7.3 and/or serum bicarbonate <18 mEq/L.
  4. Euglycemic DKA (eDKA): A critical subtype where glucose is <250 mg/dL (often <200 mg/dL) but the criteria for ketosis and acidosis are met. This should be highly suspected in patients on SGLT2 inhibitors presenting with nausea, vomiting, or malaise.

4. Diagnostic Criteria for HHS

Hyperosmolar Hyperglycemic State (HHS) is characterized by extreme hyperglycemia and hyperosmolality, with minimal to no ketosis and a near-normal acid-base status.

  1. Severe Hyperglycemia: Plasma glucose >600 mg/dL (33.3 mmol/L).
  2. High Serum Osmolality: Calculated effective osmolality >320 mOsm/kg.
  3. Minimal Ketosis: Serum BHOB <3 mmol/L; urine nitroprusside test is typically negative or trace.
  4. Absence of Significant Acidosis: Arterial pH >7.3 and serum bicarbonate >18 mEq/L.
Quick-Reference Table: DKA vs HHS Diagnostic Thresholds
Parameter Diabetic Ketoacidosis (DKA) Hyperosmolar Hyperglycemic State (HHS)
Plasma Glucose >250 mg/dL (>13.9 mmol/L) >600 mg/dL (>33.3 mmol/L)
Arterial pH <7.30 >7.30
Serum Bicarbonate <18 mEq/L >18 mEq/L
β-Hydroxybutyrate (BHOB) ≥3 mmol/L <3 mmol/L
Anion Gap >12 mEq/L Variable / Minimal Elevation
Serum Osmolality Variable (285–320 mOsm/kg) >320 mOsm/kg
Mental Status Alert to Coma Confusion to Coma

5. Severity Stratification

DKA is classified as mild, moderate, or severe based on the degree of acidosis and the patient’s mental status. HHS severity is primarily stratified by the level of hyperosmolality and its corresponding neurologic impairment.

DKA Severity Stratification Flowchart A flowchart showing the classification of DKA into Mild, Moderate, and Severe categories based on arterial pH, serum bicarbonate, and anion gap levels. MILD DKA pH: 7.25 – 7.30 HCO₃: 15 – 18 Alert MODERATE DKA pH: 7.00 – 7.24 HCO₃: 10 – <15 Drowsy SEVERE DKA pH: <7.00 HCO₃: <10 Stupor/Coma
Figure 1: DKA Severity Categories. Classification is primarily based on the degree of acidosis (pH and bicarbonate) and its impact on mental status. All categories have an anion gap >12 mEq/L.

HHS Severity Categories

  • Moderate Impairment: Serum osmolality 320–349 mOsm/kg, typically associated with confusion or significant lethargy.
  • Severe Impairment: Serum osmolality ≥350 mOsm/kg, often leading to stupor, coma, or seizures.
Pearl Icon A shield with an exclamation mark, indicating a clinical pearl. Key Point: The Persistent Anion Gap

If the anion gap remains elevated (>12 mEq/L) after the serum pH has normalized (>7.30), it signals ongoing ketoacid production or the presence of a mixed acid-base disorder. Do not stop insulin infusion based on pH alone; anion gap closure is a key therapeutic endpoint.

6. Level-of-Care and Monitoring Frequency

The initial severity assessment directly guides the appropriate level of care (ICU vs. medical floor/step-down unit) and the intensity of monitoring required for safe and effective management.

Admission Criteria

  • ICU Admission: Generally required for severe DKA (pH <7.0, bicarbonate <10 mEq/L, or stupor/coma) and HHS with severe neurologic impairment (e.g., GCS <12) or profound hyperosmolality (≥350 mOsm/kg).
  • Step-down or Medical Floor: Appropriate for patients with mild to moderate DKA who are alert and hemodynamically stable.

Monitoring Intervals

  • Glucose: Hourly point-of-care testing until stable and <200 mg/dL.
  • Electrolytes, BUN, Creatinine, Osmolality: Every 2–4 hours during initial resuscitation to guide fluid and electrolyte replacement.
  • Acid-Base Status (VBG/BHOB): Every 4 hours or as needed based on the clinical trajectory to monitor for resolution of acidosis and ketosis.
Pearl Icon A shield with an exclamation mark, indicating a clinical pearl. Clinical Pearl: Focus on Trends

Effective management relies on interpreting trends, not single values. The rate of change in glucose, the anion gap, and BHOB provides more valuable information than any isolated measurement. These trends should guide all therapy adjustments, including fluid rates and insulin titration, and inform the decision to safely de-escalate care.

References

  • Fayfman M, Pasquel FJ, Umpierrez GE. Management of hyperglycemic crises. Med Clin North Am. 2017;101(3):587–606.
  • Self WH, Evans CS, Jenkins CA et al. Balanced crystalloids vs saline in adults with DKA. JAMA Netw Open. 2020;3(11):e2024596.
  • Ramanan M, Attokaran A, Murray L et al. Plasmalyte vs saline in severe DKA (Scope-DKA). Intensive Care Med. 2021;47(11):1248–1257.
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