Abstract
BACKGROUND: Salicylate toxicity remains a significant cause of morbidity and mortality. At therapeutic levels, most salicylic acid (SA) is albumin-bound, but in overdose, the free fraction rises, driving toxicity. Albumin supplementation has been hypothesized as a strategy to reduce free SA, yet quantitative data are limited. METHODS: An in vitro model was developed to assess albumin's binding capacity for salicylic acid across overdose-relevant concentrations. Solutions of SA (SA30 ≈30 mg/dL, SA50 ≈50 mg/dL, SA100 ≈100 mg/dL, SA120 ≈120 mg/dL) were combined with albumin ranging from 1-8 g/dL, representing subphysiologic to supraphysiologic concentrations. One solution (SA120-A) was prepared at pH 7.0 to evaluate binding in acidic environments. Free SA was quantified in each sample. RESULTS: Increasing albumin reduced free salicylate under all conditions. From 1-8 g/dL, free SA decreased by 38.56 mg/dL (95% CI [37.62, 39.49] at SA50, 38.49 mg/dL (95% CI [37.77, 39.20] at SA100, 38.83 mg/dL (95% CI [37.85, 39.81] at SA120 (pH 7.4), and 52.77 mg/dL (95% CI [51.54, 54.01] at SA120 (pH 7.0). Correction of hypoalbuminemia (1-4 g/dL) reduced free SA by 11.33 mg/dL (95% CI [11.14, 11.53] at SA30, 21.07 mg/dL (95% CI [20.19, 21.94] at SA50, 18.40 mg/dL (95% CI [18.12, 18.68] at SA100, 18.27 mg/dL (95% CI [16.93, 19.61] at SA120 (pH 7.4), and 21.40 mg/dL (95% CI [21.00, 21.80] at SA120-A (pH 7.0). Increasing albumin further to 8 g/dL reduced free SA by an additional 17.49 mg/dL (95% CI [17.42, 17.56] at SA50, 20.09 mg/dL (95% CI [19.62, 20.55] at SA100, 20.57 mg/dL (95% CI [20.18, 20.95] at SA120 (pH 7.4), and 31.37 mg/dL (95% CI [30.12, 32.62] at pH 7.0. SA30 fell below quantification beyond 5 g/dL. CONCLUSION: Albumin addition reduced free salicylate, supporting its potential as a "protein sink" in salicylate toxicity. Further research is needed to determine the clinical relevance and safety of this theoretical intervention.