None listed
Conditions
Brief summary
Metabolic acidosis refers to any process that elevates the concentration of hydrogen ions in the body, and is commonly encountered in critical illness. Lactic acidosis, diabetic ketoacidosis, and hyperchloremic acidosis are major examples seen in the intensive care unit (ICU). Metabolic acidosis may impair cardiac function, and sodium bicarbonate can be used to normalise blood pH. Despite being in common clinical usage, the clinical efficacy of sodium bicarbonate is still uncertain. Previous studies exploring the effects of sodium bicarbonate therapy have been limited and of variable quality. The trial aims to assess if the infusion of sodium bicarbonate in vasopressor-dependent patients with moderate metabolic acidosis admitted to the ICU increases the number of vasopressor-free hours at day 7.
Interventions
Sodium bicarbonate 8.4% (1000 mEq/L) will be diluted in a 5% dextrose (D5W) solution (500 milliliters bag). For the preparation, 300 mL of D5W will be removed and 300 mL of sodium bicarbonate 8.4% added to prepare the bicarbonate solution in total volume of 500 mL (final concentration: 600 mEq/L).
Allocated study drug will be continuously infused targeting a pH > 7.30 and a base excess (BE) > 0 mEq/L. The infusion will be maintained until this target is achieved and continued by titration there
Sodium bicarbonate 8.4% (1000 mEq/L) will be diluted in a 5% dextrose (D5W) solution (500 milliliters bag). For the preparation, 300 mL of D5W will be removed and 300 mL of sodium bicarbonate 8.4% added to prepare the bicarbonate solution in total volume of 500 mL (final concentration: 600 mEq/L). Allocated study drug will be continuously infused targeting a pH > 7.30 and a base excess (BE) > 0 mEq/L. The infusion will be maintained until this target is achieved and continued by titration thereafter for a maximum of 5 hours to maintain target pH and base excess levels. The infusion will start at 100 mL/hr and be kept at this rate until both targets (pH and BE) are achieved. Then, once both targets are achieved it will be decreased to 25 mL/hr and kept constant at this infusion rate until 5 hours after the start of the infusion. After 5 hours of the start of the infusion, the infusion will be stopped independently of the results of the arterial blood gas analysis. Arterial blood gases will be obtained in pre-defined moments within the first 5 hours (at 0, 1 [± 0.1 hours], 3 [± 0.5 hours], and 5 [± 1 hour] hours after the start of the infusion), and then at 12 (± 2 hours), 18 (± 2 hours) and 24 (± 2 hours) hours after the start of the drug infusion. The maximum time of infusion is up to 5 hours after the start of the infusion, until RRT start or ICU discharge, whichever comes first. Open-label sodium bicarbonate infusion is allowed if clinically indicated.
Sponsors
Australian and New Zealand Intensive Care Research Centre
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The target population is vasopressor-dependent, adult critically ill patients, with moderate metabolic acidosis. All the diagnostic criteria of moderate metabolic acidosis below have to be fulfilled within the last 2 hours before randomization, and a vasopressor is being infused continuously at the time of randomization. 1. Adult patients (>= 18 years); 2. Patient is within 48 hours of admission to the ICU; 3. Patient is receiving a continuous infusion of a vasopressor drug to maintain mean arterial pressure > 65 mmHg; 4. A dedicated line (central or peripheric) is available (or is about to be made available within 1 hour after randomization); and 5. Patient has at least a moderate metabolic acidosis, defined as: a. pH < 7.30; and b. BE < -4 mEq/L; and c. PaCO2 < 45 mmHg.
Exclusion criteria
1. Proven digestive or urinary tract loss of sodium bicarbonate (e.g., acute diarrhoea, ileostomy, or drainage of pancreatic or biliary duct); or 2. DKA; or 3. Stage IV or V chronic kidney disease; or 4. Using renal replacement therapy (acute or chronic); or 5. Received sodium bicarbonate within 24 hours of screening; or 6. Dysnatraemia (serum Na greater than or equal to 155 mEq/L or < 120 mEq/L); or 7. Hypokalaemia (serum K < 2.5 mEq/L); or 8. Pulmonary oedema with PaO2 / FiO2 < 100; or 9. Hypocalcaemia (iCa < 0.8mmol/L); or 10. Known or suspected poisoning of antidepressant or antipsychotic poisoning agents that may cause high anion gap acidosis (methanol, PEG, aspirin); or 11. Suspected intoxication with unknown aetiology; or 12. Pregnancy or breastfeeding; or 13. Limitation of medical therapy orders (DNR, DNI); or 14. Imminent or inevitable death; or 15. In the opinion of the treating clinical team the patients will almost certainly receive RRT in the next 6 hours; or 16. Traumatic brain injury (or substantial risk for intracranial hypertension); or 17. Clinician believes that being enrolled in intervention or control arm is not in the best interest of the patient; or 18. Previous enrolment in this study ever.
Outcome results
None listed