Patient: 55 y female (ambulatory)
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- Adam Stevenson
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1
2 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
3 Patient: 55 y female (ambulatory) Sodium Potassium Chloride Lab Result (plasma) 133 mmol/l 4.65 mmol/l 94.9 mmol/l Blood Gas Analyzer
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
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!
6 Patient: 78 y male (cancer clinic) Sodium Potassium Chloride Lab Result 136 mmol/l 4.14 mmol/l 96.6 mmol/l Blood Gas Analyzer
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
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!
9 WTF (What s that from?)
10 How can a hospital verify performance of electrolyte methods for hospitalized (critically ill) patients?
11 How can a hospital verify performance of electrolyte methods for hospitalized (critically ill) patients? Are there any tools that we can use?
12 Answer: No
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
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?
15 Blood is a complex mixture of cells, water and dissolved materials Plasma Blood Cells
16 Blood is a complex mixture of cells, water and dissolved materials Plasma Healthy: 93% Water 7% Protein & Lipids Blood Cells Healthy: 43% Hematocrit
17 Blood is a complex mixture of cells, water and dissolved materials Plasma Ill Patients: 93% Water Blood Cells Ill Patients : 43% Hematocrit
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
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
20 TxA-cQ_AUIDigB&biw=1336&bih=841
21 Aren t all electrolyte methods generally the same?
22 Chemistry Analyzer Blood Gas Analyzer
23 Chemistry Analyzer Whole blood (plasma) Specimen Type Blood Gas Analyzer Whole blood (whole blood)
24 Chemistry Analyzer Whole blood (plasma) Specimen Type Blood Gas Analyzer Whole blood (whole blood) Indirect Electrodes Electrolyte Method Direct Electrodes
25 Chemistry Analyzer Whole blood (plasma) Specimen Type Blood Gas Analyzer Whole blood (whole blood) Indirect Electrodes Electrolyte Method Direct Electrodes 90 minutes from collection Turn around time 30 minutes from collection
26 Chemistry Analyzer Whole blood (plasma) Specimen Type Blood Gas Analyzer Whole blood (whole blood) Indirect Electrodes Electrolyte Method Direct Electrodes 90 minutes from collection Turn around time 30 minutes from collection Hemolysis, lipemia, inadequate specimen collection Interferences Hemolysis, inadequate specimen collection
27 Chemistry Analyzer Whole blood (plasma) Specimen Type Blood Gas Analyzer Whole blood (whole blood) Indirect Electrodes Electrolyte Method Direct Electrodes 90 minutes from collection Turn around time 30 minutes from collection Hemolysis, lipemia, inadequate specimen collection Interferences Hemolysis, inadequate specimen collection
28 What effect will lipemia have on the measurement of electrolytes?
29 Why are we concerned about lipemia interference?
30 Why are we concerned about lipemia interference? Interfere with many laboratory tests
31 Why are we concerned about lipemia interference? Interfere with many laboratory tests Capillary electrophoresis abnormal α 2
32 Why are we concerned about lipemia interference? Interfere with many laboratory tests Capillary electrophoresis abnormal α 2 Immunoassays interfere with antigen/antibody
33 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
34 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)
35
36 Indirect Electrode 7% protein + lipid 93% Plasma Water 10uL (9.3 ul)
37 Indirect Electrode -Dilution Effect 7% protein + lipid 93% Plasma Water 10uL (9.3 ul) ul Diluent 9.3ul/199.3uL = 21.4 fold dilution
38 Indirect Electrode -Dilution Effect 7% protein + lipid 10% protein + lipid 93% Plasma Water 10uL (9.3 ul) 90% Plasma Water 10uL (9.0 ul) ul Diluent 9.3ul/199.3uL = 21.4 fold dilution
39 Indirect Electrode -Dilution Effect 7% protein + lipid 10% protein + lipid 93% Plasma Water 10uL (9.3 ul) 90% Plasma Water 10uL (9.0 ul) ul Diluent ul Diluent 9.3ul/199.3uL = 21.4 fold dilution 9.0ul/199.0uL = 22.1 fold dilution (3.2% decrease relative to 93% plasma water due to the dilution effect)
40 - Principle of Potentiometry is used for both electrodes
41 - Principle of Potentiometry is used for both electrodes - InDirect electrodes - DILUTION - Should be affected by plasma changes
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)
43 What is the distribution of plasma water content amongst different patient populations?
44 Waugh Equation (1969) Plasma Water Content = 99.1 (total protein *.73) (triglycerides *1.03) =.93 normal total protein reference intervals (adults) ( g/dl) normal triglycerides reference intervals (adults) ( mg/dl)
45
46 Frequency 50 Community Testing Children Plasma Water Content % % 80.00% % 40.00% Frequency Cumulative % % % Bin
47 Frequency 18 Hospitalized Children Plasma Water Content Frequency Cumulative % Bin
48 Plasma Water Concentration Gestational Age (weeks)
49 How could plasma water changes theoretically influence electrolyte measurement?
50 7% protein + lipid 93% water Indirect mmol/l Direct 140 mmol/l Normal plasma
51 7% protein + lipid 93% water Indirect mmol/l 10% protein + lipid 90% water Indirect mmol/l Direct 140 mmol/l Direct 140 mmol/l Normal plasma Hyperlipid Hyperprotein plasma
52 7% protein + lipid 93% water Indirect mmol/l 10% protein + lipid 90% water Indirect mmol/l 1% 99% water Indirect mmol/l Direct 140 mmol/l Direct 140 mmol/l Direct 140 mmol/l Normal plasma Hyperlipid Hyperprotein plasma ICU patient plasma
53 What do we do in the lab to assess the potential effect of lipid (plasma water) on the measurement of electrolytes?
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 nm (mean 345 nm) Are smaller than large chylomicrons but bigger than medium and large VLDLs Effect is NOT identical with pathologically induced lipemia
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
56 Blood Gas Analyzer (Direct Electrode) Lipemia should have NO effect
57
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!
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!
60 Patient: 55 y female (ambulatory) 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 0 L Index 162
61 Patient: 78 y male (cancer clinic) 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 0 I Index 0 L Index 202
62 What happens to the electrolyte results (lab result) after we try to remove the lipemia?
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 mmol/l Triglyceride 3.21 mmol/l 2.52 mmol/l H Index 15 Indicator of hemolysis 36 I Index 0 Indicator of icterus 1 L Index 162 Indicator of lipemia 16
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 0 Indicator of hemolysis 13 I Index 0 Indicator of icterus 0 L Index 202 Indicator of lipemia 30
65
66
67 Sodium: 16 mmol/l Chloride: 52 mmol/l Potassium: 100 mmol/l Sodium: 140 mmol/l Chloride: 104 mmol/l Potassium: 4.4 mmol/l LDH: 58,000 U/L AST: 500 U/L ALT: 150 U/L LDH: 360 U/L AST: 25 U/L ALT: 30 U/L Am J. Clin. Path. 37: 445, 1962
68 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, 3 rd Edition Hemolysis
69 How do we currently detect hemolysis? Hemolysis Index (Automated Clinical Chemistry Systems) Spectrophotometric assessment Blanked bichromatic measurements 405 nm and 700nm
70
71
72 Edward R. Burns, Noriko Yoshikawa Department of Pathology, Albert Einstein College of Medicine and Montefiore Medical Center, New York, NY.
73 Frequency Distribution of H Index (NICU, Well Baby Nursery) N= H Index
74 Frequency 500 Distribution of H Index (NICU, Well Baby Nursery) % of all specimens are visually hemolyzed N= H Index
75 What are Hemolysis Rates at RUH? 4.7% (overall hemolysis rate-venipuncture)
76
77
78 Clinical Laboratory Parameters Hematocrit? Plasma Water Concentration? Protein Concentration Triglyceride Concentration Patient Characteristics Ambulatory? Intensive Care? Burn Patient? Renal Disease? Medications/Treatments TPN? Chemotherapeutic Agents? The Patient
79 EDITORIAL COMMENT NOT
80 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 plasmacentral lab indirect and whole blood-direct methods.
81
82 Thank you for your time and attention!
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