Sodium bicarbonate for severe metabolic acidaemia.

Jaber and colleagues¹ report the results of a thoughtfully designed trial examining sodium bicarbonate administration to critically ill adults with acidaemia. We congratulate the authors on this accomplishment and pose two questions.

First, the composite primary outcome chosen by the authors—28-day mortality or an organ failure at day 7— has important limitations. Components of the outcome are assessed at differing timepoints, dysfunction in organ systems mechanistically unrelated to the intervention are included in the composite (eg, haematological dysfunction), and the outcome’s relevance to patients is unclear. For phase 3 clinical trials involving acute kidney injury, a National Institute of Diabetes and Digestive and Kidney Diseases work group has recommended as a patient-centred outcome the use of major adverse kidney events— the composite of death, new receipt of renal-replacement therapy, or persistent renal dysfunction (defined by plasma creatinine values or glomerular filtration rate).^2,3 Can the authors report what proportion of patients in each study group experienced a major adverse kidney event by 28 days (understanding that the data might be censored at hospital discharge)?

Second, one contributor to acidaemia among critically ill adults is receipt of 0·9% sodium chloride. What volume of intravenous fluid did patients receive before enrolment, and what proportion of that fluid was 0·9% sodium chloride? If bicarbonate administration in the trial was, in part, correcting saline-induced hyperchloremic metabolic acidosis, preferential use of balanced crystalloids for initial resuscitation might diminish the need for, and effect of, subsequent bicarbonate therapy.⁴