PURPOSE: To determine whether there is an interaction between baseline serum chloride concentration and pH and treatment effects in Intensive Care Unit (ICU) patients receiving intravenous fluid therapy with balanced solution versus 0.9% sodium chloride (saline). METHODS: A secondary analysis of a randomized controlled trial in which patients were divided into cohorts according to quartiles of baseline serum chloride concentration and pH. The primary outcome was day-90 mortality. RESULTS: From 4846 patients with outcome data available, 4823 with relevant baseline data were included in this analysis, with 1347, 1333, 993 and 1150 patients in the chloride quartiles of <
102, 102-106, 107-109 and >
109 mmol/L, respectively. Data were also analysed in pH quartiles of ≤ 7.27, 7.27-7.34, 7.34-7.39 and >
7.39. The risk-adjusted odds ratio (95% confidence interval [CI]) for day-90 mortality for patients assigned balanced solution compared to saline was 1.23 (0.95-1.58), 0.95 (0.73-1.25), 0.88 (0.64-1.21), and 0.76 (0.57-1.01) for lowest to highest chloride subgroups, respectively (P value for interaction = 0.10), and 0.89 (95% CI 0.69-1.15), 0.94 (0.70-1.27), 0.96 (0.67-1.38) and 1.15 (0.82-1.60) for pH quartiles from lowest to highest, respectively (P value for interaction = 0.63). CONCLUSIONS: There were no significant differences in the treatment effect of balanced solutions compared to saline according to baseline serum chloride concentration or pH.