Hyperglycemic crises

Epidemiology

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Etiology

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Pathophysiology

DKA

• Primarily a complication of Type 1 Diabetes Mellitus, but can occur in T2DM.
• Caused by a profound insulin deficiency, often precipitated by the “5 I’s”: Infection (most common), Ischemia (MI, CVA), Infarction, Inadequate insulin, and Initial presentation of diabetes.
• ↓ Insulin → unopposed counter-regulatory hormones (glucagon, cortisol, catecholamines).
• This hormonal imbalance leads to:
  • ↑ Hepatic gluconeogenesis & glycogenolysis → Hyperglycemia.
  • ↑ Unrestrained lipolysis → breakdown of triglycerides into free fatty acids.
  • The liver converts fatty acids into ketone bodies (β-hydroxybutyrate and acetoacetate), leading to ketosis and metabolic acidosis.
• Hyperglycemia causes osmotic diuresis, leading to severe dehydration and electrolyte loss.
• Insulin deficiency → hyperosmolality → K⁺ shift out of cells + lack of insulin to promote K⁺ uptake → intracellular K⁺ depleted → total body K⁺ deficit despite normal or even elevated serum K⁺

Tip

There is a total body potassium deficit in DKA. This becomes important during treatment, when insulin replacement leads to rapid potassium uptake by depleted cells and patients may require potassium replacement.

HHS

• Primarily affects patients with type 2 diabetes
• The pathophysiology of HHS is similar to that of DKA.
• However, in HHS, there are still small amounts of insulin being secreted by the pancreas, and this is sufficient to prevent DKA by suppressing lipolysis and, in turn, ketogenesis.
• HHS is characterized by symptoms of marked dehydration (and loss of electrolytes) due to the predominating hyperglycemia and osmotic diuresis.

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Clinical features

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Diagnostics

Tip

• DKA is the diagnosis in patients with type 1 diabetes who have hyperglycemia, ketonuria, and high anion gap metabolic acidosis with decreased bicarbonate!
• HHS is the diagnosis in patients with type 2 diabetes who have hyperglycemia and hyperosmolality!

• Bedside/Initial Evaluation:
  • Capillary blood glucose (BG) and venous blood gas (VBG) (VBG is preferred; ABG is no longer routinely required to assess acid-base status).
  • Capillary/plasma beta-hydroxybutyrate (BHB): Superior to urine ketones (urine acetoacetate can remain false-positive during recovery).
• Diagnostic Comparison:

Parameter	Diabetic Ketoacidosis (DKA)	Hyperosmolar Hyperglycemic State (HHS)
Blood Glucose	$\ge 200\text{ mg/dL}$ (or prior history of DM irrespective of BG to account for euglycemic DKA)	$>600\text{ mg/dL}$
Venous pH	$<7.30$ (Mild: 7.25–7.30; Mod: 7.00–7.24; Severe: $<7.00$)	$>7.30$
Serum Bicarbonate	$<18\text{ mEq/L}$	$>15\text{ mEq/L}$
Ketones	Elevated plasma BHB ($\ge 3.0\text{ mmol/L}$) or urine ketones	Absent or minimal
Effective Osmolality	Variable	$>320\text{ mOsm/kg}$
Anion Gap	Elevated ($>10\text{–}12\text{ mEq/L}$)	Variable (typically normal)
Mental Status	Alert to stupor/coma (in severe DKA)	Stupor or coma

• Corrected Sodium: Hyperglycemia draws water intracellularly, causing pseudohyponatremia.
  • Correction Formula: Corrected ${\text{Na}}^{+}=\text{Measured }{\text{Na}}^{+}+[1.6\times (\text{BG}-100)/100]$ (use 2.4 if BG $>400\text{ mg/dL}$).
  • If corrected ${\text{Na}}^{+}$ is low, it indicates a severe free water deficit.
• Despite total body depletion, initial serum $K^{+}$ is often normal or elevated because:
  • Acidemia: $H^{+}$ ions enter cells, shifting $K^{+}$ out into the extracellular fluid (ECF).
  • Insulin Deficiency: Without insulin, the $N{a}^{+}/K^{+}$ ATPase pump is underactive, preventing $K^{+}$ from entering cells.
  • Hyperosmolality: Water moves out of cells, dragging $K^{+}$ with it (solvent drag).

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Treatment

Must be managed systematically with parallel focus on fluids, potassium, and insulin.

1. Fluid Resuscitation (First Step)

• Goal: Restore intravascular volume and renal perfusion. Start fluids before insulin.
• Initial Fluid: 0.9% NaCl (normal saline) or balanced crystalloids (e.g., Lactated Ringer’s) at 500–1000 mL/hr for the first 2–4 hours.
  • Note: Use smaller fluid boluses (e.g., 250 mL) in patients with CHF or ESRD to avoid fluid overload.
• Subsequent Fluid: Based on corrected sodium and hydration status:
  • If corrected ${\text{Na}}^{+}$ is high/normal: Switch to 0.45% NaCl (half-normal saline) at 250–500 mL/hr.
  • If corrected ${\text{Na}}^{+}$ is low: Continue 0.9% NaCl at 250–500 mL/hr.
• Adding Dextrose:
  • In DKA: Add 5% to 10% Dextrose (in 0.45% NaCl) once BG falls $<250\text{ mg/dL}$. This allows continued insulin infusion to clear ketones without causing hypoglycemia.
  • In HHS: Add 5% to 10% Dextrose once BG falls $<300\text{ mg/dL}$.

2. Potassium Management (Crucial Safety Step)

Insulin shifts $K^{+}$ intracellularly, causing a rapid drop in serum levels. Always check $K^{+}$ before starting insulin.

• $K^{+}<3.5\text{ mEq/L}$: HOLD insulin. Administer IV potassium chloride (10–20 mEq/hr) until $K^{+}>3.5\text{ mEq/L}$ before initiating insulin.
• $K^{+}$ 3.5–5.3 mEq/L: Give insulin. Add 20–30 mEq $K^{+}$ to each liter of IV fluids to maintain serum $K^{+}$ between 4.0 and 5.0 mEq/L.
• $K^{+}>5.3\text{ mEq/L}$: Give insulin. Do not add potassium to IV fluids. Monitor $K^{+}$ every 2–4 hours.

3. Insulin Therapy

• Route: Continuous IV insulin infusion is preferred for moderate/severe DKA and HHS.
  • Mild/moderate DKA: Can be managed in non-ICU settings with SC rapid-acting insulin analogs (every 1–2 hours).
• Dosing:
  • DKA: Start IV regular insulin at 0.1 units/kg/hr.
  • HHS: Start IV regular insulin at 0.05 units/kg/hr (slower rate to avoid rapid shifts in osmolality, unless mixed features with DKA are present, which requires 0.1 units/kg/hr).
• Target rate of glucose decline: Aim for 50–70 mg/dL/hr (maximum 90–120 mg/dL/hr in HHS to prevent cerebral edema).

4. Bicarbonate Therapy

• Routine Use: Not recommended (can worsen intracellular acidosis, cause hypokalemia, and delay ketosis resolution).
• Indication: Only consider if severe acidemia (pH < 6.9–7.0) with hemodynamic instability or life-threatening hyperkalemia.

DKA Resolution

• Criteria: BG $<200\text{ mg/dL}$ AND at least one of:
  • Venous pH $\ge 7.30$
  • Serum bicarbonate $\ge 18\text{ mEq/L}$
  • Plasma BHB (ketones) $<0.6\text{ mmol/L}$
  • Note: Anion gap is no longer the primary marker of resolution due to hyperchloremic acidosis from large volume saline.
• Transition to Subcutaneous Insulin:
  • Never stop IV insulin abruptly.
  • Administer basal SC insulin 2–4 hours before discontinuing the IV insulin infusion to prevent rebound ketosis.
  • If already taking basal insulin home regimen, it can be continued at the usual dose during IV insulin treatment.

HHS Resolution

• Criteria: Effective osmolality $<300\text{ mOsm/kg}$ AND patient returns to baseline mental status.