Sodium bicarbonate administration for metabolic acidosis in the intensive care unit: a target trial emulation
Sebastiaan Paul Blank, Ruth Miriam Blank, Kevin B. Laupland, Alexis Tabah, Denzil Gill, Aashish Kumar, Kyle White, Antony Attokaran, Stephen Luke, Stephen Whebell, Peter Garrett, James McCullough, Philippa McIlroy, Mahesh Ramanan, James McCullough, Kerina J. Denny, Mandy Tallott, Andrea Marshall, David Moore, Sunil Sane, Aashish Kumar, Lynette Morrison, Pam Dipplesman, Ahmad Nasser, David Stewart, Vikram Shah, Kyle White, Adam Suliman, Lachlan Quick, Jason Meyer, Ra’eesa Doola, Rod Hurford, Meg Harward, James Walsham, Adam Visser, Judy Smith, Neeraj Bhadange, Wayne Stevens, Vijo Kuruvilla, Kevin B. Laupland, Felicity Edwards, Tess Evans, Jayesh Dhanani, Pierre Clement, Nermin Karamujic, Kiran Shekar, Dinesh Parmar, George Cornmell, Jayshree Lavana, Denzil Gill, Alexis Tabah, Stuart Baker, Hamish Pollock, Kylie Jacobs, Mahesh Ramanan, Prashanti Marella, Jatinder Grewal, Patrick Young, Julia Affleck, Emma Williams, Peter Garrett, Paula Lister, Vikram Masurkar, Lauren Murray, Jane Brailsford, Janine Garrett, Anamika Ganju, Langa Lutshaba, Cameron Anderson, Antony G. Attokaran, Jaco Poggenpoel, Josephine Reoch, Stephen Luke, Anni Paasilahti, Jennifer Taylor, Christopher Smart, Siva Senthuran, Stephen Whebell, Sananta Dash, Philippa McIlroy, Sebastiaan Blank, Ben Nash, Michelle Gatton, Zephanie Tyack, Sam Keogh
Abstract
PURPOSE: Sodium bicarbonate is commonly administered to treat metabolic acidosis in intensive care units (ICUs). There is limited evidence from randomized trials to support this practice, and observational studies show conflicting results. Our aim was to perform a target trial emulation evaluating the effect of bicarbonate therapy on mortality. METHODS: ≤ 45 mmHg within the first three days. We excluded repeat admissions, toxicology, diabetic ketoacidosis, and pre-existing end-stage renal failure. The treatment intervention was sodium-bicarbonate administration, and the primary outcome was 30-day ICU mortality with ICU discharge as a competing event. We evaluated multiple subgroups, including patients with acute kidney injury, requirement for vasoactive therapy, and pH < 7.2. The primary model utilized a parametric g-computation and rolling entry matching was performed as a sensitivity analysis. RESULTS: We identified 6157 eligible admissions, of which 1764 (29%) received sodium bicarbonate. Bicarbonate therapy was associated with a 1.9% absolute mortality reduction for the primary analysis [risk ratio 0.86, 95% confidence interval (CI) 0.80 to 0.91], and significant benefits were seen across all subgroups evaluated. A similar point estimate of 2.1% was observed in the sensitivity analysis, with a sustained mortality reduction seen at 30 days. CONCLUSION: In this target trial emulation, bicarbonate administration was associated with a small but statistically significant reduction in mortality for patients with metabolic acidosis. Large sample sizes would be required to demonstrate this effect in a randomized trial.