Post Hypercapnia Respiratory Alkalosis (PHRA)

Post-hypercapnia respiratory alkalosis is an important ICU acid-base phenomenon that occurs when chronic hypercapnia is corrected rapidly, leading to alkalemia due to persistently low serum bicarbonate despite normalization of PaCO₂. It is especially relevant in COPD exacerbations, neuromuscular respiratory failure, obesity hypoventilation syndrome, and prolonged mechanical ventilation weaning.

🔷 Definition

Post-hypercapnia respiratory alkalosis (PHRA) refers to:

Development of metabolic alkalosis and alkalemia after rapid correction of chronic respiratory acidosis (hypercapnia).

🔷 Pathophysiology (Stepwise Mechanism)

 Step 1 – Chronic Hypercapnia State

Occurs in diseases causing long-standing hypoventilation:

• Severe COPD
• Obesity hypoventilation syndrome
• Neuromuscular weakness
• Chronic chest wall disorders

Compensation Mechanism

Kidneys attempt to normalize pH by:

✔ Increasing bicarbonate reabsorption
✔ Increasing hydrogen ion excretion
✔ Generating new bicarbonate

👉 Result:

• High PaCO₂
• High serum HCO₃⁻
• Near-normal pH

This compensation takes 3–5 days to reach maximal effect.

✅ Step 2 – Rapid Correction of Hypercapnia

Occurs when:

• Mechanical ventilation initiated
• NIV started aggressively
• Airway obstruction relieved
• Sedation/paralysis reversed

What Happens?

PaCO₂ falls rapidly → CO₂ is eliminated quickly.

However:

• Renal compensation persists
• Kidneys cannot excrete bicarbonate immediately
• Excess bicarbonate remains

 Step 3 – Development of Metabolic Alkalosis

Now the patient has:

• Normal/low PaCO₂
• Persistently elevated bicarbonate
• Result → alkalemia

🔷 Acid-Base Pattern

Typical ABG Evolution

Before Correction (Chronic Hypercapnia)

After Rapid Ventilation Correction

👉 This is PHRA

🔷 Why Kidneys Cannot Correct Quickly?

Renal bicarbonate excretion requires:

• Reduced proximal reabsorption
• Increased distal secretion
• Volume and chloride availability

These changes take several days.

🔷 Clinical Importance in ICU

1️⃣ Respiratory Drive Suppression

Alkalemia decreases respiratory drive → ventilator weaning difficulty.

2️⃣ Neurological Effects

• Confusion
• Seizures (rare)
• Reduced cerebral blood flow

3️⃣ Cardiovascular Effects

• Arrhythmias
• Reduced coronary perfusion

4️⃣ Electrolyte Disturbances

Often associated with:

• Hypokalemia
• Hypocalcemia
• Hypophosphatemia

5️⃣ Oxygen-Hemoglobin Dissociation

Alkalosis shifts curve leftward → impaired oxygen delivery.

Recommended Approach

• Allow permissive hypercapnia
• Gradual PaCO₂ normalization

Target:

• Maintain near baseline PaCO₂ initially
• Avoid sudden normalization

2️⃣ Correct Volume and Chloride Deficiency

Metabolic alkalosis often chloride-responsive.

Treatment:
✔ Isotonic saline
✔ Potassium chloride

3️⃣ Correct Electrolytes

Particularly:

• Potassium
• Magnesium
• Phosphate

4️⃣ Consider Acetazolamide

Mechanism:

• Carbonic anhydrase inhibitor
• Promotes bicarbonate excretion

Used in:

• Difficult ventilator weaning
• Persistent metabolic alkalosis

5️⃣ Avoid Excess Diuretics

They worsen:

• Chloride depletion
• Volume contraction
• Alkalosis severity