TY - JOUR
T1 - Sodium Bicarbonate for Metabolic Acidosis in the ICU
T2 - Results of a Pilot Randomized Double-Blind Clinical Trial
AU - Serpa Neto, Ary
AU - Fujii, Tomoko
AU - McNamara, Mairead
AU - Moore, James
AU - Young, Paul J.
AU - Peake, Sandra
AU - Bailey, Michael
AU - Hodgson, Carol
AU - Higgins, Alisa M.
AU - See, Emily J.
AU - Secombe, Paul
AU - Campbell, Lewis
AU - Young, Meredith
AU - Maeda, Mikihiro
AU - Pilcher, David
AU - Nichol, Alistair
AU - Deane, Adam
AU - Licari, Elisa
AU - White, Kyle
AU - French, Craig
AU - Shehabi, Yahya
AU - Cross, Anthony
AU - Maiden, Matthew
AU - Kadam, Umesh
AU - El Khawas, Khaled
AU - Cooper, Jamie
AU - Bellomo, Rinaldo
AU - Udy, Andrew
N1 - Funding Information:
Dr. Higgins’ institution received funding from the National Health and Medical Research Council (NHMRC) investigator grant. Dr. Young disclosed government work. Dr. Maeda disclosed work for hire. Dr. French disclosed the off-label product use of Sodium bicarbonate in critical illness. Dr. Cooper’s institution received funding from the NHMRC of Australia and Eustralis Pharmaceuticals Pty Ltd (Pressura Neuro). Dr. Udy disclosed that he received trial consumables from Integra Lifesciences. The remaining authors have disclosed that they do not have any potential conflicts of interest.
Publisher Copyright:
© 2023 Lippincott Williams and Wilkins. All rights reserved.
PY - 2023/11
Y1 - 2023/11
N2 - OBJECTIVES: To identify the best population, design of the intervention, and to assess between-group biochemical separation, in preparation for a future phase III trial. DESIGN: Investigator-initiated, parallel-group, pilot randomized double-blind trial. SETTING: Eight ICUs in Australia, New Zealand, and Japan, with participants recruited from April 2021 to August 2022. PATIENTS: Thirty patients greater than or equal to 18 years, within 48 hours of admission to the ICU, receiving a vasopressor, and with metabolic acidosis (pH < 7.30, base excess [BE] <-4 mEq/L, and Paco2 45 mm Hg). INTERVENTIONS: Sodium bicarbonate or placebo (5% dextrose). MEASUREMENTS AND MAIN RESULT: The primary feasibility aim was to assess eligibility, recruitment rate, protocol compliance, and acid-base group separation. The primary clinical outcome was the number of hours alive and free of vasopressors on day 7. The recruitment rate and the enrollment-To-screening ratio were 1.9 patients per month and 0.13 patients, respectively. Time until BE correction (median difference,-45.86 [95% CI,-63.11 to-28.61] hr; p < 0.001) and pH correction (median difference,-10.69 [95% CI,-19.16 to-2.22] hr; p = 0.020) were shorter in the sodium bicarbonate group, and mean bicarbonate levels in the first 24 hours were higher (median difference, 6.50 [95% CI, 4.18 to 8.82] mmol/L; p < 0.001). Seven days after randomization, patients in the sodium bicarbonate and placebo group had a median of 132.2 (85.6-139.1) and 97.1 (69.3-132.4) hours alive and free of vasopressor, respectively (median difference, 35.07 [95% CI,-9.14 to 79.28]; p = 0.131). Recurrence of metabolic acidosis in the first 7 days of follow-up was lower in the sodium bicarbonate group (3 [20.0%] vs. 15 [100.0%]; p < 0.001). No adverse events were reported. CONCLUSIONS: The findings confirm the feasibility of a larger phase III sodium bicarbonate trial; eligibility criteria may require modification to facilitate recruitment.
AB - OBJECTIVES: To identify the best population, design of the intervention, and to assess between-group biochemical separation, in preparation for a future phase III trial. DESIGN: Investigator-initiated, parallel-group, pilot randomized double-blind trial. SETTING: Eight ICUs in Australia, New Zealand, and Japan, with participants recruited from April 2021 to August 2022. PATIENTS: Thirty patients greater than or equal to 18 years, within 48 hours of admission to the ICU, receiving a vasopressor, and with metabolic acidosis (pH < 7.30, base excess [BE] <-4 mEq/L, and Paco2 45 mm Hg). INTERVENTIONS: Sodium bicarbonate or placebo (5% dextrose). MEASUREMENTS AND MAIN RESULT: The primary feasibility aim was to assess eligibility, recruitment rate, protocol compliance, and acid-base group separation. The primary clinical outcome was the number of hours alive and free of vasopressors on day 7. The recruitment rate and the enrollment-To-screening ratio were 1.9 patients per month and 0.13 patients, respectively. Time until BE correction (median difference,-45.86 [95% CI,-63.11 to-28.61] hr; p < 0.001) and pH correction (median difference,-10.69 [95% CI,-19.16 to-2.22] hr; p = 0.020) were shorter in the sodium bicarbonate group, and mean bicarbonate levels in the first 24 hours were higher (median difference, 6.50 [95% CI, 4.18 to 8.82] mmol/L; p < 0.001). Seven days after randomization, patients in the sodium bicarbonate and placebo group had a median of 132.2 (85.6-139.1) and 97.1 (69.3-132.4) hours alive and free of vasopressor, respectively (median difference, 35.07 [95% CI,-9.14 to 79.28]; p = 0.131). Recurrence of metabolic acidosis in the first 7 days of follow-up was lower in the sodium bicarbonate group (3 [20.0%] vs. 15 [100.0%]; p < 0.001). No adverse events were reported. CONCLUSIONS: The findings confirm the feasibility of a larger phase III sodium bicarbonate trial; eligibility criteria may require modification to facilitate recruitment.
KW - clinical trial
KW - metabolic acidosis
KW - shock
KW - sodium bicarbonate
KW - vasopressor
UR - http://www.scopus.com/inward/record.url?scp=85169512113&partnerID=8YFLogxK
U2 - 10.1097/CCM.0000000000005955
DO - 10.1097/CCM.0000000000005955
M3 - Article
C2 - 37294139
AN - SCOPUS:85169512113
SN - 0090-3493
VL - 51
SP - e221-e233
JO - Critical Care Medicine
JF - Critical Care Medicine
IS - 11
ER -