Disclosures Speaking Honoraria Radiometer (Canada) Nova - PowerPoint PPT Presentation

Disclosures • Speaking Honoraria – Radiometer (Canada) – Nova Biomedical, – Draeger – Roche Diagnostics (Canada) • Research Support (Reagents, Instrumentation, Travel) – Nova Biomedical – Abbott Laboratories (Canada) – Roche Diagnostics (Canada) – Radiometer (Canada) – Instrumentation Laboratories (Canada) • ALOL Biomedical Inc. – Clinical laboratory consulting company 2

Patient: 55 y female (ambulatory) Lab Result (plasma) Blood Gas Analyzer Sodium 133 mmol/L Potassium 4.65 mmol/L Chloride 94.9 mmol/L

Patient: 55 y female (ambulatory) Lab Result (plasma) Blood Gas Analyzer Sodium 133 mmol/L 157 mmol/L Potassium 4.65 mmol/L 5.4 mmol/L Chloride 94.9 mmol/L 117 mmol/L

Patient: 55 y female (ambulatory) Lab Result (plasma) Blood Gas Analyzer Sodium 133 mmol/L 157 mmol/L Potassium 4.65 mmol/L 5.4 mmol/L Chloride 94.9 mmol/L 117 mmol/L Huge Difference!

Patient: 78 y male (cancer clinic) Lab Result Blood Gas Analyzer Sodium 136 mmol/L Potassium 4.14 mmol/L Chloride 96.6 mmol/L

Patient: 78 y male (cancer clinic) Plasma Lab Result Blood Gas Analyzer Sodium 136 mmol/L 157 mmol/L Potassium 4.14 mmol/L 4.8 mmol/L Chloride 96.6 mmol/L 118 mmol/L

Patient: 78 y male (cancer clinic) Plasma Lab Result Blood Gas Analyzer Sodium 136 mmol/L 157 mmol/L Potassium 4.14 mmol/L 4.8 mmol/L Chloride 96.6 mmol/L 118 mmol/L Enormous Difference!

WTF (What’s that from?)

How can a hospital verify performance of electrolyte methods for hospitalized (critically ill) patients?

How can a hospital verify performance of electrolyte methods for hospitalized (critically ill) patients? Are there any tools that we can use?

Answer: No

Answer: No We need to establish verification materials & a verification system or tool to address the UNIQUE challenges provided with hospitalized & critically ill patient populations

Answer: No We need to establish verification materials & a verification system or tool to address the UNIQUE challenges provided with hospitalized & critically ill patient populations What are the specific challenges?

Blood is a complex mixture of cells, water and dissolved materials Plasma Blood Cells

Blood is a complex mixture of cells, water and dissolved materials Plasma Healthy: 93% Water 7% Protein & Lipids Blood Cells Healthy: 43% Hematocrit

Blood is a complex mixture of cells, water and dissolved materials Plasma Ill Patients: ≠ 93% Water Blood Cells Ill Patients : ≠ 43% Hematocrit

In the clinical laboratory, we currently assume the cells, water and dissolved materials DO NOT VARY and have NO BIAS OR INFLUENCE ON TEST RESULTS

In the clinical laboratory, we currently assume the cells, water and dissolved materials DO NOT VARY and have NO BIAS OR INFLUENCE ON TEST RESULTS

https://www.google.ca/search?q=hold+that+thought&source=lnms&tbm=isch&sa=X&ved=0ahUKEwjM2unG7tPdAhVi7IMKHR TxA-cQ_AUIDigB&biw=1336&bih=841

Aren’t all electrolyte methods generally the same?

Chemistry Analyzer Blood Gas Analyzer

Chemistry Analyzer Blood Gas Analyzer Whole blood (plasma) Specimen Type Whole blood (whole blood)

Chemistry Analyzer Blood Gas Analyzer Whole blood (plasma) Whole blood (whole blood) Specimen Type Indirect Electrodes Electrolyte Method Direct Electrodes

Chemistry Analyzer Blood Gas Analyzer Whole blood (plasma) Specimen Type Whole blood (whole blood) Indirect Electrodes Direct Electrodes Electrolyte Method Turn around time 30 minutes from collection 90 minutes from collection

Chemistry Analyzer Blood Gas Analyzer Whole blood (plasma) Specimen Type Whole blood (whole blood) Indirect Electrodes Electrolyte Method Direct Electrodes 90 minutes from collection Turn around time 30 minutes from collection Hemolysis, lipemia, inadequate Hemolysis, inadequate Interferences specimen collection specimen collection

Chemistry Analyzer Blood Gas Analyzer Whole blood (plasma) Specimen Type Whole blood (whole blood) Indirect Electrodes Electrolyte Method Direct Electrodes 90 minutes from collection Turn around time 30 minutes from collection Hemolysis, lipemia , inadequate Hemolysis, inadequate Interferences specimen collection specimen collection

What effect will lipemia have on the measurement of electrolytes?

Why are we concerned about lipemia interference?

Why are we concerned about lipemia interference? • Interfere with many laboratory tests

Why are we concerned about lipemia interference? • Interfere with many laboratory tests • Capillary electrophoresis – abnormal α 2

Why are we concerned about lipemia interference? • Interfere with many laboratory tests • Capillary electrophoresis – abnormal α 2 • Immunoassays – interfere with antigen/antibody

Why are we concerned about lipemia interference? • Interfere with measured analytes • Capillary electrophoresis – abnormal α 2 • Immunoassays – interfere with antigen/antibody • Spectrophotometric assays – Lipoprotein particles absorb light – AST, ALT, glucose

Why are we concerned about lipemia interference? • Interfere with measured analytes • Capillary electrophoresis – abnormal α 2 • Immunoassays – interfere with antigen/antibody • Spectrophotometric assays – Lipoprotein particles absorb light – AST, ALT, glucose • Indirect Electrodes (Na, K, Cl)

Indirect Electrode 7% protein + lipid 93% Plasma 10uL (9.3 uL) Water

Indirect Electrode -Dilution Effect 7% protein + lipid 93% Plasma 10uL (9.3 uL) Water + 190 uL Diluent 9.3ul/199.3uL = 21.4 fold dilution

Indirect Electrode -Dilution Effect 7% protein 10% protein + lipid + lipid 93% 90% Plasma Plasma 10uL (9.0 uL) 10uL (9.3 uL) Water Water + 190 uL Diluent 9.3ul/199.3uL = 21.4 fold dilution

Indirect Electrode -Dilution Effect 7% protein 10% protein + lipid + lipid 93% 90% Plasma Plasma 10uL (9.0 uL) 10uL (9.3 uL) Water Water + 190 uL Diluent + 190 uL Diluent 9.3ul/199.3uL = 9.0ul/199.0uL = 22.1 fold dilution 21.4 fold dilution (3.2% decrease relative to 93% plasma water due to the dilution effect)

- Principle of Potentiometry is used for both electrodes

- Principle of Potentiometry is used for both electrodes - InDirect electrodes - DILUTION - Should be affected by plasma changes

- Principle of Potentiometry is used for both electrodes - InDirect electrodes - DILUTION - Should be affected by plasma changes - Direct electrodes - NO DILUTION - Should be unaffected by plasma changes - (Blood Gas Analyzers)

What is the distribution of plasma water content amongst different patient populations?

Waugh Equation (1969) Plasma Water Content = 99.1 – (total protein *.73) – (triglycerides *1.03) = .93 normal total protein reference intervals (adults) (6.4-8.6 g/dL) normal triglycerides reference intervals (adults) (32-134 mg/dl)

Community Testing Children Plasma Water Content 50 120.00% 45 100.00% 40 35 80.00% 30 Frequency 25 60.00% Frequency 20 Cumulative % 40.00% 15 10 20.00% 5 0 0.00% Bin

Hospitalized Children Plasma Water Content 18 1.2 16 1 14 12 0.8 Frequency 10 0.6 8 Frequency Cumulative % 6 0.4 4 0.2 2 0 0 Bin

0.99 0.98 0.97 Plasma Water Concentration 0.96 0.95 0.94 0.93 22 24 26 28 30 32 34 36 38 40 42 Gestational Age (weeks)

How could plasma water changes theoretically influence electrolyte measurement?

7% protein + lipid 93% water Indirect 130.2 mmol/L Direct 140 mmol/L Normal plasma

7% protein + lipid 10% protein + lipid 93% water 90% water Indirect Indirect 130.2 127.4 mmol/L mmol/L Direct Direct 140 140 mmol/L mmol/L Hyperlipid Normal Hyperprotein plasma plasma

7% protein 1% + lipid 10% 99% protein + water lipid 93% water 90% water Indirect Indirect Indirect 130.2 127.4 138.6 mmol/L mmol/L mmol/L Direct Direct Direct 140 140 140 mmol/L mmol/L mmol/L Hyperlipid Normal ICU patient Hyperprotein plasma plasma plasma

What do we do in the lab to assess the potential effect of lipid (plasma water) on the measurement of electrolytes? https://www.google.ca/search?q=questions+cartoon&source=lnms&tbm=isch&sa=X&ved=0ahUKEwjJ1dGdmIHeAhVJ7YMKHSIzAAEQ_AUIDigB&biw=1440&bih=850

Intralipid is used as a lipoprotein substitute to test interference • Emulsion used for IV administration as a source of calories and essential fatty acids • Intralipid particles range from 200 – 600 nm (mean 345 nm) • Are smaller than large chylomicrons but bigger than medium and large VLDLs • Effect is NOT identical with pathologically induced lipemia