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

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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


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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

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SLIDE 3

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
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SLIDE 4

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
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SLIDE 5

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!

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SLIDE 6

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
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SLIDE 7

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
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SLIDE 8

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!

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SLIDE 9

WTF

(What’s that from?)
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SLIDE 10

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

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SLIDE 11

Are there any tools that we can use?

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

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SLIDE 12

Answer: No

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SLIDE 13

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

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SLIDE 14

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?

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SLIDE 15

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

Blood Cells Plasma
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SLIDE 16

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

Blood Cells Plasma Healthy: 93% Water 7% Protein & Lipids Healthy: 43% Hematocrit
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SLIDE 17

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

Blood Cells Plasma Ill Patients: ≠ 93% Water Ill Patients : ≠ 43% Hematocrit
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SLIDE 18

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

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SLIDE 19

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

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SLIDE 20 https://www.google.ca/search?q=hold+that+thought&source=lnms&tbm=isch&sa=X&ved=0ahUKEwjM2unG7tPdAhVi7IMKHR TxA-cQ_AUIDigB&biw=1336&bih=841
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SLIDE 21

Aren’t all electrolyte methods generally the same?

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SLIDE 22 Chemistry Analyzer Blood Gas Analyzer
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SLIDE 23 Specimen Type Chemistry Analyzer Blood Gas Analyzer Whole blood (plasma) Whole blood (whole blood)
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SLIDE 24 Specimen Type Chemistry Analyzer Blood Gas Analyzer Whole blood (plasma) Whole blood (whole blood) Electrolyte Method Indirect Electrodes Direct Electrodes
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SLIDE 25 Specimen Type Chemistry Analyzer Blood Gas Analyzer Whole blood (plasma) Whole blood (whole blood) Electrolyte Method Indirect Electrodes Direct Electrodes Turn around time 30 minutes from collection 90 minutes from collection
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SLIDE 26 Specimen Type Chemistry Analyzer Blood Gas Analyzer Whole blood (plasma) Whole blood (whole blood) Electrolyte Method Indirect Electrodes Direct Electrodes Turn around time 30 minutes from collection 90 minutes from collection Interferences Hemolysis, inadequate specimen collection Hemolysis, lipemia, inadequate specimen collection
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SLIDE 27 Specimen Type Chemistry Analyzer Blood Gas Analyzer Whole blood (plasma) Whole blood (whole blood) Electrolyte Method Indirect Electrodes Direct Electrodes Turn around time 30 minutes from collection 90 minutes from collection Interferences Hemolysis, inadequate specimen collection Hemolysis, lipemia, inadequate specimen collection
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SLIDE 28

What effect will lipemia have on the measurement of electrolytes?

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Why are we concerned about lipemia interference?

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Why are we concerned about lipemia interference?

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

  • Interfere with many laboratory tests
  • Capillary electrophoresis

– abnormal α2

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SLIDE 32

Why are we concerned about lipemia interference?

  • Interfere with many laboratory tests
  • Capillary electrophoresis

– abnormal α2

  • Immunoassays

– interfere with antigen/antibody

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SLIDE 33

Why are we concerned about lipemia interference?

  • Interfere with measured analytes
  • Capillary electrophoresis

– abnormal α2

  • Immunoassays

– interfere with antigen/antibody

  • Spectrophotometric assays

– Lipoprotein particles absorb light – AST, ALT, glucose

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SLIDE 34

Why are we concerned about lipemia interference?

  • Interfere with measured analytes
  • Capillary electrophoresis

– abnormal α2

  • Immunoassays

– interfere with antigen/antibody

  • Spectrophotometric assays

– Lipoprotein particles absorb light – AST, ALT, glucose

  • Indirect Electrodes (Na, K, Cl)
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SLIDE 35
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SLIDE 36

Indirect Electrode

93% Plasma Water 10uL (9.3 uL) 7% protein + lipid
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SLIDE 37

Indirect Electrode

  • Dilution Effect
93% Plasma Water 10uL (9.3 uL) + 190 uL Diluent 9.3ul/199.3uL = 21.4 fold dilution 7% protein + lipid
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SLIDE 38

Indirect Electrode

  • Dilution Effect
93% Plasma Water 90% Plasma Water 10uL (9.3 uL) + 190 uL Diluent 9.3ul/199.3uL = 21.4 fold dilution 10uL (9.0 uL) 7% protein + lipid 10% protein + lipid
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SLIDE 39

Indirect Electrode

  • Dilution Effect
93% Plasma Water 90% Plasma Water 10uL (9.3 uL) + 190 uL Diluent 9.3ul/199.3uL = 21.4 fold dilution 10uL (9.0 uL) + 190 uL Diluent 9.0ul/199.0uL = 22.1 fold dilution (3.2% decrease relative to 93% plasma water due to the dilution effect) 7% protein + lipid 10% protein + lipid
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SLIDE 40
  • Principle of Potentiometry

is used for both electrodes

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SLIDE 41
  • Principle of Potentiometry

is used for both electrodes

  • InDirect electrodes
  • DILUTION
  • Should be affected by

plasma changes

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SLIDE 42
  • 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)
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SLIDE 43

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

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SLIDE 44

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)

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SLIDE 45
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SLIDE 46 0.00% 20.00% 40.00% 60.00% 80.00% 100.00% 120.00% 5 10 15 20 25 30 35 40 45 50 Frequency Bin Community Testing Children Plasma Water Content Frequency Cumulative %
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SLIDE 47 0.2 0.4 0.6 0.8 1 1.2 2 4 6 8 10 12 14 16 18 Frequency Bin Hospitalized Children Plasma Water Content Frequency Cumulative %
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SLIDE 48 0.93 0.94 0.95 0.96 0.97 0.98 0.99 22 24 26 28 30 32 34 36 38 40 42 Plasma Water Concentration Gestational Age (weeks)
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SLIDE 49

How could plasma water changes theoretically influence electrolyte measurement?

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SLIDE 50 Normal plasma 7% protein + lipid 93% water Indirect 130.2 mmol/L Direct 140 mmol/L
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SLIDE 51 Normal plasma Hyperlipid Hyperprotein plasma 7% protein + lipid 93% water 10% protein + lipid 90% water Indirect 130.2 mmol/L Direct 140 mmol/L Direct 140 mmol/L Indirect 127.4 mmol/L
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SLIDE 52 Normal plasma Hyperlipid Hyperprotein plasma ICU patient plasma 7% protein + lipid 93% water 10% protein + lipid 90% water 1% 99% water Indirect 130.2 mmol/L Direct 140 mmol/L Direct 140 mmol/L Indirect 127.4 mmol/L Direct 140 mmol/L Indirect 138.6 mmol/L
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SLIDE 53

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
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SLIDE 54

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

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SLIDE 55 ISE Indirect Na,K, Cl (Manufacturer Package Insert) Lipemia: “Intralipid does not interfere in the tested concentration range up to 2000 mg/dL (corresponding to approximate L index of 2000). There is poor correlation between the L index (corresponds to turbidity) and the triglycerides concentration. Pseudohyponatremia may be seen with lipemic specimens as a result of fluid displacement”

Chemistry Lab Analyzer

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Blood Gas Analyzer (Direct Electrode)

  • Lipemia should have NO effect
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SLIDE 58

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!

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SLIDE 59

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!

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SLIDE 60 Plasma Indirect Electrode Direct Electrode Sodium 133 mmol/L 157 mmol/L Potassium 4.65 mmol/L 5.4 mmol/L Chloride 94.9 mmol/L 117 mmol/L Triglyceride 3.21 mmol/L H Index 15 I Index L Index 162

Patient: 55 y female (ambulatory)

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SLIDE 61 Plasma Indirect Electrode Direct Electrode Sodium 136 mmol/L 157 mmol/L Potassium 4.14 mmol/L 4.8 mmol/L Chloride 96.6 mmol/L 118 mmol/L Triglyceride 2.79 mmol/L H Index I Index L Index 202

Patient: 78 y male (cancer clinic)

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SLIDE 62

What happens to the electrolyte results (lab result) after we try to remove the lipemia?

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SLIDE 63

Patient: 55 y female (ambulatory)

Plasma Lab Blood Gas Lab (after air fuge) Sodium 133 mmol/L 157 mmol/L 155 mmol/L Potassium 4.65 mmol/L 5.4 mmol/L 5.38 mmol/L Chloride 94.9 mmol/L 117 mmol/L 111.2 mmol/L Triglyceride 3.21 mmol/L 2.52 mmol/L H Index 15 36 I Index 1 L Index 162 16 Indicator of hemolysis Indicator of icterus Indicator of lipemia
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SLIDE 64

Patient: 78 y male (cancer clinic)

Plasma Lab Blood Gas Lab (after air fuge) Sodium 136 mmol/L 157 mmol/L 155 mmol/L Potassium 4.14 mmol/L 4.8 mmol/L 4.74 mmol/L Chloride 96.6 mmol/L 118 mmol/L 112 mmol/L Triglyceride 2.79 mmol/L 1.92 mmol/L H Index 13 I Index L Index 202 30 Indicator of hemolysis Indicator of icterus Indicator of lipemia
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SLIDE 67 Sodium: 16 mmol/L Potassium: 100 mmol/L Chloride: 52 mmol/L LDH: 58,000 U/L AST: 500 U/L ALT: 150 U/L Sodium: 140 mmol/L Chloride: 104 mmol/L Potassium: 4.4 mmol/L LDH: 360 U/L AST: 25 U/L ALT: 30 U/L Am J. Clin. Path. 37: 445, 1962
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Hemolysis

“release of K+ from as few as 0.5% of erythocytes can increase K + values by 0.5 mmol/L” – Tietz Textbook of Clinical Chemistry, 3rd Edition

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How do we currently detect hemolysis?

  • Hemolysis Index (Automated Clinical

Chemistry Systems)

  • Spectrophotometric assessment

▫ Blanked bichromatic measurements

 405 nm and 700nm

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SLIDE 71
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SLIDE 72 Edward R. Burns, Noriko Yoshikawa Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, New York, NY.
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SLIDE 73 50 100 150 200 250 300 350 400 450 500 100 200 300 400 500 600 700 800 900 1000 1100 1200 1300 Frequency H Index Distribution of H Index (NICU, Well Baby Nursery) N= 852
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SLIDE 74 50 100 150 200 250 300 350 400 450 500 100 200 300 400 500 600 700 800 900 1000 1100 1200 1300 Frequency H Index Distribution of H Index (NICU, Well Baby Nursery) N= 852

75-80% of all specimens are visually hemolyzed

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What are Hemolysis Rates at RUH?

  • 4.7% (overall hemolysis rate-venipuncture)
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SLIDE 78 The Patient Medications/Treatments Clinical Laboratory Parameters Hematocrit? Plasma Water Concentration? Protein Concentration Triglyceride Concentration TPN? Chemotherapeutic Agents? Patient Characteristics Ambulatory? Intensive Care? Burn Patient? Renal Disease?
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SLIDE 79

EDITORIAL COMMENT

NOT

https://www.google.ca/search?q=eeyore&source=lnms&tbm=isch&sa=X&ved=0ahUKEwiH8L2px4HeAhWpz4MKHexJAAEQ_AUIDigB&biw=1440&bih=850
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Overall conclusions

  • Errors in electrolyte measurement related to

patient plasma water (and hematocrit) are currently NOT detected by QC or external proficiency testing programs

  • These factors are a component of the

technical limitation to achieving concordance of results between plasma- central lab indirect and whole blood-direct methods.

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Thank you for your time and attention!