B-159 Four Years of Ottawa Hospital Outpatient Chemistry Data Transformed into Seasonally Adjusted Intrapatient Biological, Analytical and Preanalytical Variation

Background The European Federation for Laboratory Medicine has conducted series of short term, biologic variation studies (7 to 10 weekly blood draws). This approach has significant shortcomings including small number of nonrandomly selected subjects, short periods of repeated samplings, rigid exclusion criteria, and the issue of non-intervening seasonal variation. Not only is seasonal variation associated with significant changes of blood and plasma volumes, but also with altered activity levels and food intake. We used a numerical approach (PMID:35137000) to derive the seasonal biologic variation of selected outpatient chemistry analytes. We compare our estimates to those of the EFLM. Methods De-identified Siemens Vista sodium, chloride, bicarbonate (CO2), potassium, creatinine, urea, and phosphate results were obtained from Ottawa Hospital outpatients for November 2009 to January 2014. All measurements were identified with unique patient identifiers and date and time of testing. Results outside their reference interval were excluded from analysis. For each season and test, we tabulated consecutive presumably nonemergent intrapatient paired results that were analyzed between 6am and 6pm on weekdays and separated by up to 2190 hr (3 months). The separation time (hours) was converted into a modulus 24 time yielding hourly intervals of separation from 0 to 1 hr to 23 to 24 hours. For each interval, we determined the standard deviation of duplicates (SDD) between the paired intrapatient results. SDD was graphed against the midpoints of the hourly separation and linear regression was used to determine the y-intercept which constitutes the total of analytical, intra-patient biological and preanalytical variation for each season. The y-intercept was normalized with the grand mean to provide the total seasonal intrapatient CVanalytical+biological+preanalytical. We compared these total patient seasonal variations to the magnitude of the sum of the EFLM intrapatient CV and their usual analytical variation. Results For electrolytes, 95,000 outpatients provided 288,000 electrolyte panels; mean age was 58.5(SD=18.5) years. Between 1000 and 2000 paired observations were used to determine each electrolyte intrapatient total seasonal CVi. The Figure compares the seasonal variation to the EFLM CVi with added analytical variation, based on that of the Roche Cobas. The average standard errors follow: potassium (5.9%), CO2 (8.8%), chloride (4.8%), sodium (1.4%), creatinine (3.1%), urea (8.6%) and phosphate (9.3%). All the outpatient biological variations demonstrate seasonality. The EFLM sodium, chloride and urea variations are close to, but less than the total seasonal CV. The CO2 graph demonstrates higher variation in the winter and spring, coincident with increased respiratory infections and respiratory distress. Conclusion Originally, the EFLM normal subject variation database was used appropriately to determine optimal analytical performance. Despite the bountiful literature on seasonal variation, the database’s purpose has morphed to an all-season tool for determining reference change values of (normal) subjects and recently, to monitoring (normal) subject variation. With these newer applications, the EFLM variation estimates have become less fit for purpose. We must embrace the transformation of real patient data into useful information that will improve patient care.