Clinical Drug Experience Knowledgebase

Salt Replacement for Metabolic Alkalosis in Acute Exacerbations of Cystic Fibrosis

Background: Hypochloremic hypovolemic metabolic alkalosis contributes to hypercapnia in acute exacerbations of cystic fibrosis. Treatment of the metabolic alkalosis with volume and sodium chloride (NaCl) replacement could reduce hypoventilation and hypercapnia, thereby improving symptoms, sleep patterns and daytime activity level. This would avoid unnecessary treatment with non-invasive ventilation.

Hypothesis: Volume and NaCl replacement corrects hypochloremic hypovolemic metabolic alkalosis and compensatory hypoventilation/ hypercapnia in acute exacerbations of cystic fibrosis and results in symptomatic improvement.

Entry criteria:

Adult cystic fibrosis patient
Admission with acute exacerbation
PaCO2 > 45 mmHg
Primary metabolic alkalosis (acid-base diagram of Stinebaugh and Austin)
Serum chloride (Cl) ≤ 98 mmol/L
Serum albumin (alb) > 25 mmol/L

Intervention:

Normal saline intravenously day(D)1,2,3. (Replace greater of Cl deficiency or acute weight loss, with 2/3 on D1 and remainder D2, D3)
NaCl tablets 3 tds D4 to 10 (calculated to replace 7 mmol NaCl loss in 60 kg subject)

Random allocation to either:

Intervention + standard care (including standard dietary advice) D1-10
Standard care alone (including standard dietary advice) D1-10

Primary outcome measures: (D1, D4, D10)

PaCO2 (performed at same time of day as admission ABG's)
Acid-base status (Stinebaugh and Austin, ABG's)
Serum chloride
Overnight oximetry (% night SpO2<90%) and PtcCO2 (rise in CO2 overnight)

Secondary outcome measures: (D1, D4, D10)

Serum albumin, sodium
Body mass index (BMI)
Spirometry (D1, D10)
Headache scale
Epworth sleepiness scale
Wrist actigraphy (circadian rhythm and daytime activity level)(D1-10)
Urinary chloride, potassium, sodium, pH, osmolality
Baseline ABG's as stable outpatient (within 3 months, pre or post admission)