Authors' reply to Comment on "A 29-year analysis of acute peak salicylate concentrations in fatalities reported to United States poison centers".

Background/Objectives: The threshold salicylate concentration commonly recommended to initiate extracorporeal elimination, in the absence of significant end-organ toxicity, is 100 mg/dL. Unfortunately, the grade of evidence to support this decision is low. Our primary aim is to describe highest reported salicylate concentrations in patients who died from acute salicylate ingestions. Our secondary aim is to determine if age or coingestants varied with highest reported salicylate concentration. Methods: We analyzed acute salicylate fatalities reported to the National Poison Data System (NPDS) between 1 January 1986 and 31 December 2014. Included were patients who died during the index hospitalization and for which acute salicylate toxicity was the primary cause of death. We used descriptive statistics with standard deviations (SD) or 95% confidence intervals (CI) where appropriate. We created a general linear model that evaluated the association of age and coingestions with salicylate concentrations. We divided the patients into age quartiles to assess a possible interaction between age and salicylate concentration. Results: We identified 602 acute salicylate fatalities that fit inclusion criteria. The mean peak reported fatal salicylate concentration across all age groups was 99.19 mg/dL (+/- 50.2 mg/dL). The median peak fatal salicylate concentration was 97.0 mg/dL. The oldest quartile had a lower mean concentration (age> 57 years; 90.4 mg/dL) than the youngest quartile (age< 30 years; 111.6 mg/dL, mean difference 21.2 mg/dL, 95% CI 6.1-36.3). Fatalities with a coingestant had a lower mean concentration of 91.5 mg/dL compared to 104.8 mg/dL among those ingesting salicylates alone (mean difference 13.4 mg/dL, 95% CI 21.4-5.3). Increasing age and the presence of any coingestions were negatively associated with fatal concentrations (estimates; 95% CI 0.41; 0.61-0.021 and similar to 14.43; 22.45-6.42, respectively). When opioids were a coingestant, mean concentration was 72.8 (mean difference 32.1 95% CI 23.1-41.1). Conclusions: Using the current recommended hemodialysis threshold of 100 mg/dL, more than half of the patients would be deprived of this critical life-saving therapy. Additionally, increasing age and ingestion of other substances, especially opioids, are associated with lower peak fatal salicylate concentrations. A prospective, randomized controlled trial considering salicylate concentrations and other clinical factors may provide further guidance for hemodialysis.