SODium BICarbonate for metabolic acidosis in the Intensive Care Unit: A pilot, multicentre, randomized, double-blind clinical trial

INTERVENTION: 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, 3 [± 0.5 hours], and 5 [± 1 hour] hours after the start of the infusion), and then at 12, 18 and 24 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. CONDITION: Emergency medicine ‐ Other emergency care Metabolic acidosis; ; Metabolic acidosis Metabolic and Endocrine ‐ Other metabolic disorders PRIMARY OUTCOME: Number of hours alive and free of vasopressors at day 7 (168 hours) after randomization. This is defined as the time, censored at 7 days, that a patient was both alive and had not received vasopressors for at least 6 hours. If a patient died while receiving vasopressor therapy following the index episode, the patient is assigned zero hours for this outcome. If a patient was weaned from all vasopressors for 6 consecutive hours, then all of the remaining time through day 7 was treated as success, even if the patient died or had vasopressors restarted after weaning within the 7‐day period. The outcome will be assess through patient medical records.[7 days (168 hours) after randomization] SECONDARY OUTCOME: 28 day cumulative vasopressor free hours (through patient medical records)[28 days after randomization] 28 day renal replacement therapy–free days (through patient medical records)[28 days after randomization] 28‐day mortality[28 days after randomization] 90‐day mortality[90 days after randomization] BE in the first 24 hours after the start of the infusion (through blood samples collected and registered in the patient medical records)[24 hours after the start of the infusion] Delta of Sequential Organ Failure Assessment (SOFA) score at 72 hours ‐ defined as the initial total SOFA* score minus the day three (72 hours) SOFA score 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. ; *total SOFA = Sequential Organ Failure Assessment = sum of each organ system point score. The score is based on six different scores, one each for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems. The organ scores are ranging from 0‐4, with the best score being 0 and the worst being 4 points. The maximal (and worst) total SOFA score is 24 points.[72 hours after randomization] Dysnatraemia (Na > 155 mEq/L) (through patient medical records)[72 hours after randomisation] Hospital length of stay (through patient medical records)[90 days after randomization] Hospital mortality[90 days after randomization] Hypocalcaemia needing correction (defined as ionized calcium level < 1.15 mmol/L needing correction, and assessed through patient medical records)[72 hours after randomisation] Hypokalaemia needing correction (defined as potassium level < 3.5 mEq/L needing correction, and assessed through patient medical records)[72 hours after randomisation] ICU length of stay (through patient medical records)[90 days after randomization] ICU mortality[90 days after randomization] Incidence and the maximum stage of acute kidney injury (according to KDIGO criteria) in the first 7 days after randomization (through patient medical records) [7 days after randomization] Mean bicarbonate levels in the first 24 hours of infusion (through blood samples collected and registered in the patient medical records)[24 hours after the start of the infusion] Need of renal replacement therapy in the first 28 days (through patient medical records)[28 days after randomization] PaCO2 in the first 24 hours after the start of the infusion (through blood samples collected and registered in the patient medical records)[24 hours after the start of the infusion] pH in the first 24 hours after the start of the infusion (through blood samples collected and registered in the patient medical records)[24 hours after the start of the infusion] Recurrence of moderate metabolic acidosis (according to the inclusion criteria used in the study) in the first 7 days after randomization (through patient medical records)[7 days after randomization] Strong in difference (SID) in the first 24 hours after the start of the infusion (through patient medical records)[24 hours after the start of the infusion] Strong ion gap (SIG) in the first 24 hours after the start of the infusion (through patient medical records)[24 hours after the start of the infusion] Time to correction of BE (through patient medical records)[6 hours after the start of the infusion] Time to correction of pH (through patient medical records)[6 hours after the start of the infusion]