The AVL OMNI™ Analyzer is intended to be used for the measurement of pH , pCO2, pCO2 , sodium, potassium, ionized calcium, chloride, hematocrit and total hemoglobin and the hemoglobin derivatives: OzHb, COHb, MetHb, HHb, SulfHb and metabolites; glucose, lactate and urea nitrogen in samples of whole blood, serum, plasma, aqueous solutions as appropriate, in a clinical laboratory setting by personnel minimally qualified to perform and to report these results.

Device Description

The AVL OMNI™ Analyzer is a fully-automatic, microprocessor-controlled system that can perform up to 17 tests per sample.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the AVL OMNI™ Modular Analyzer, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state quantitative "acceptance criteria" in a typical pass/fail format with specific thresholds. Instead, it implicitly defines acceptance through the concept of "substantial equivalence" to predicate devices and the demonstration of "no significant difference in mean values" and "correlation" during clinical trials. The "reported device performance" is largely described qualitatively.

Parameter/Test	Acceptance Criteria (Implicit)	Reported Device Performance (Qualitative)
Substantial Equivalence	The device should be substantially equivalent in function, safety, and efficacy to specific legally marketed predicate devices.	Stated as substantially equivalent to "Combi Analyzers" and specifically for Urea Nitrogen to NOVA Biomedical ULTRA H [K960120] and i-STAT 200 Portable Clinical Analyzer (K940918).
Precision	Demonstrated acceptable "Within-Run (S_wr), Between-Day (S_dd) and Total (S_T) precision." (No numerical thresholds provided).	"Typical Within-Run (S_wr), Between-Day (S_dd) and Total (S_T) precision were evaluated" for all assays. The conclusion statement implies the precision was found acceptable.
Linearity in Aqueous Solutions	Demonstrated linearity across a known range of values. (No numerical thresholds provided).	Aqueous standard solutions measured on three AVL OMNI™ units demonstrated linearity. The conclusion statement implies the linearity was found acceptable.
Linearity in Serum	Demonstrated linearity by diluting patient-sample pools. (No numerical thresholds provided).	Patient-sample pools diluted and measured on two AVL OMNI™ instruments demonstrated linearity. The conclusion statement implies the linearity was found acceptable.
Interferences	No significant effects on measurement from various analytes or drugs. (No numerical thresholds provided).	"No significant effects on measurement were demonstrated at the concentrations evaluated" for urea nitrogen.
Clinical Correlation	No significant difference in mean values (P<0.05) when compared to legally marketed predicate devices in a clinical setting.	"In all evaluations, there was no significant difference in mean values (P<0.05) obtained on measurement by the AVL OMNI™." Additionally, for Urea Nitrogen, a direct comparison showed equivalence to a photometric method on the Boehringer Mannheim/Hitachi 917 Analyzer (K953239).
Safety and Effectiveness	Device should be safe and effective. (General regulatory requirement and implicit goal of all testing).	Demonstrated safe and effective, and equivalent to predicate devices based on clinical and non-clinical trials.

2. Sample Sizes Used for the Test Set and Data Provenance

Sample Size (Clinical Tests): Specimens were "remnant from patient specimens of both whole blood and serum or plasma collected for routine analysis on existing instrumentation." Patient populations included "extreme ranges of clinical values." The total number of patient specimens or individual data points is not specified.
Sample Size (Non-Clinical Tests):
- Precision: "samples of each of the specimen types suitable for measurement on the AVL OMNI™." The number of runs or samples is not specified.
- Linearity in Aqueous Solutions: "Each of three AVL OMNI™ units" were used, with serially diluted solutions. The number of measurements or dilution series is not specified.
- Linearity in Serum: "two AVL OMNI™ instruments" were used, with patient-sample pools mixed in varying ratios. The number of samples or ratios is not specified.
Data Provenance: The data is retrospective, as it used "remnant from patient specimens... collected for routine analysis on existing instrumentation." The country of origin is not specified, but given the submitter's address in Roswell, GA, USA, it's likely primarily US-based, though this is an assumption.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

The document states that "personnel trained to perform and report these analyses" operated the devices in the clinical setting. It does not mention a specific number of experts used for ground truth establishment or their qualifications (e.g., radiologist with X years of experience). The ground truth for the clinical correlation studies appears to be the results obtained from the legally marketed predicate devices.

4. Adjudication Method for the Test Set

No explicit adjudication method (e.g., 2+1, 3+1) is mentioned. The comparison was directly between the AVL OMNI™ and the predicate devices, with statistical analysis ("no significant difference in mean values (P<0.05)").

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

This section is not applicable. The device described is an automated analyzer, not an AI-assisted diagnostic tool that would typically involve human readers interpreting images or data with and without AI assistance. Therefore, an MRMC study related to AI assistance for human readers was not performed.

6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was done

This section is applicable. The AVL OMNI™ Modular Analyzer is described as a "fully-automatic, microprocessor-controlled system" that performs measurements. The clinical and non-clinical tests described are evaluations of this standalone algorithm/device performance against predicate devices and established testing methodologies (precision, linearity, interferences).

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)

The primary ground truth used in the clinical correlation studies was the measurements obtained from legally marketed predicate devices. For non-clinical tests like linearity in aqueous solutions, the "ground truth" was the gravimetrically prepared standards with known values.

8. The Sample Size for the Training Set

The document is a 510(k) summary for an in vitro diagnostic (IVD) device (a laboratory analyzer), not a machine learning/AI device that would typically have a distinct "training set" in the common sense. Therefore, no sample size for a training set is specified. The device is based on established principles of measurement (potentiometric, amperometric, photometric, spectrophotometric, conductance) rather than being trained on a large dataset.

9. How the Ground Truth for the Training Set Was Established

As explained in point 8, the concept of a "training set" for this type of device is not directly applicable. The device's principles of operation are based on validated chemical and physical measurement techniques, not on learning from a labeled dataset. Therefore, this information is not provided nor relevant in the context of this device's submission.

Summary

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JAN 29 1999

KG90092

Contact Person

Randy Byrd

Image /page/0/Picture/2 description: The image shows a logo with the letters AVL in a bold, sans-serif font. The letters are connected and form a single, solid shape. The logo is black and the background is white. The letters are stylized and have a modern look.

510(k) Summary

Submitter's name, address (a) (1)

AVL Scientific Corporation 33 Mansell Court Roswell, GA 30076

Date of preparation of this summary:

AVL OMNI™ Modular Analyzer

Quality Assurance Manager

(770) 587-4040 x 631

30 December 1998

Device trade or proprietary name: (2)

Device common or usual name or classification name

Fully automatic, modular analyzer for the analysis of: Itomatic, modular analyzer for the analysis cases of Chloride, ionized Calcium pri, Blood Gases, for selectric Bucclobin derivatives, Glucose and Lactate and Urea Nitrogen.

PRODUCT NOMENCLATURE	REGULATION	NUMBER	CLASS	PANEL
ELECTRODE, ION-SPECIFIC, POTASSIUM	862.1600	75 CEM	II	CHEMISTRY
ELECTRODE, ION-SPECIFIC, CALCIUM	862.1145	75 JFP	II	CHEMISTRY
ELECTRODE, ION-SPECIFIC, SODIUM	862.1665	75 JGS	II	CHEMISTRY
ELECTRODE, ION-SPECIFIC, CHLORIDE	862.1170	75 CGZ	II	CHEMISTRY
ELECTRODE, BLOOD GASES (PCO2, PO2) AND pH	862.1120	75 CHL	II	CHEMISTRY
SYSTEM, HEMOGLOBIN, AUTOMATED	864.5620	81 GKR	II	HEMATOLOGY
SYSTEM, HEMATOCRIT, AUTOMATED	864.5600	81 GKF	II	HEMATOLOGY
ASSAY, CARBOXYHEMOGLOBIN	864.7425	81 GHS	II	HEMATOLOGY
OXYHEMOGLOBIN	864.7500	81 GGZ	II	HEMATOLOGY
METHEMOGLOBIN		not known
SULFHEMOGLOBIN	864.7490	81 GJC	II	HEMATOLOGY
DEOXYHEMOGLOBIN		not known
ACID, LACTIC ENZYMATIC METHOD	862.1450	75 KHP	II	CHEMISTRY
GLUCOSE OXIDASE, GLUCOSE	862.1345	75 CGA	II	CHEMISTRY
ELECTRODE, ION-SPECIFIC, UREA NITROGEN	862.1770	75 CDS	II	CHEMISTRY

Substantial Equivalence (3)

The AVL OMNI is substantially equivalent in function, safety and efficacy to a number of currently marketed devices known as 'Combi Analyzers.' The Urea Nitrogen method is specifically equivalent to that employed in the NOVA Biomedical ULTRA H [K960120] and the i-STAT 200 Portable Clinical Analyzer (K940918). As demonstrated by the clinical tests included with the attached, the urea nitrogen value reported by the OMNT™ is equivalent to that obtained from analysis of the same sample by a photometric method on the Boehringer Mannheim/Hitachi 917 Analyzer (K953239).

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Description of the new device (4)

The AVL OMNI™ Analyzer is a fully-automatic, microprocessor-controlled system that can perform up to 17 tests per sample.

Versions	Parameter
AVL OMNI™ 1	BG (pH, PO₂ and PCO₂)
AVL OMNI™ 2	BG and tHb
AVL OMNI™ 3	BG and COOX (ctHb, HHb, O₂Hb, COHb, MetHb, SulfHb)
AVL OMNI™ 4	BG, Hct and ISE (Na+, K+, Cl-, iCa++)
AVL OMNI™ 5	BG and tHb, Hct and ISE
AVL OMNI™ 6	BG and COOX, Hct and ISE
AVL OMNI™ 7	BG, Hct, ISE and MSS (Glu, Lac, BUN)
AVL OMNI™ 8	BG and tHb, Hct and ISE and MSS (Glu, Lac, BUN)
AVL OMNI™ 9	BG and COOX, Hct and ISE and MSS (Glu, Lac, BUN)

(ર) Intended use of the device.

(6) Technological characteristics of the device.

Principles of Measurement

The principles of measurement used in the AVL OMNI™ Combi Analyzer are essentially identical to those principles existing in the electrolyte analyzers to which substantial equivalence is claimed in paragraph (a)(3) above.

pH, PCO2	potentiometric
PO2	amperometric
Na, K, Cl, Ca	direct potentiometric
ctHb (AVL OMNITM 2, 5)	photometric
COOX (AVL OMNITM 3, 6)	spectrophotometric
Hct	conductance
Glu, Lac	amperometric
Urea Nitrogen	potentiometric

Image /page/1/Figure/11 description: The image contains the number 2.2. The number is written in a simple, handwritten style. The number is black against a white background.

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Calibration

The AVL OMNI™ Combi Analyzer uses a patented, liquid calibration system for all The AVE Overvir - Some of any gas supply system and thus, eliminating the disadvantages coupled with gas supplies.

(b) (1)Summary of non-clinical tests submitted with the premarket notification for the device.

Following is a summary of non-clinical testing performed with this submission for the I onowing is a saminary of new itformation is provided with previous submissions, K945915, K954018 and K972733.

Precision

Typical Within-Run (Swr), Between-Day (Sdd) and Total (ST) precision were 1 ypload within read ( ... ) .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . OMNT™ instruments using samples of each of the specimen types suitable for measurement on the AVL OMNI™. All assays available on the OMNI were evaluated as appropriate for the specimen type.

Linearity in Aqeuous Solutions

Aqueous standard solutions were gravimetrically prepared, then diluted serially to obtain I nearity standard solutions with a known range of values. These solutions were then measured on each of three AVL OMNI™ units.

Linearity in Serum

Patient-Sample Pool. The ideal sample matrix is a pool of patient specimens with an analyte level up to 30 % higher than the upper linear limit to be diluted with another patient-sample pool with an analyte level at or below the claimed lower linear limit. The aliquots were then mixed in varying ratios to provide a linear range of values for each of the metabolites, and measured in randomized order on two AVL OMNI™ instruments.

Interferences

The effects of various analytes or drugs on the measurement of urea nitrogen were considered, including exogenous and endogenous substances, and the results included with this submission. Additionally, substances with known interference to urea measurement for which compensation is made were evaluated. No significant effects on measurement were demonstrated at the concentrations evaluated.

3.3

1 NCCLS. Interference Testing in Clinical Chemistry, Proposed Guideline. NCCLS Document EP7-P. NCCLS, 771 East Lancaster Avenue, Villanova, Pennsylvania 19085, 1986.

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(b) (2) Summary of clinical tests submitted with the premarket notification for the device.

Clinical testing was conducted to demonstrate the correlation of AVL OMNI™ to legally marketed predicate devices in a clinical setting, operated by personnel trained to perform and report these analyses. Specimens analyzed in these tests were remnant from patient specimens of both whole blood and serum or plasma collected for routine analysis on existing instrumentation. Patient populations were selected which included extreme ranges of clinical values. All assays available on the OMNI Modular Analyzer were evaluated in at least one of the seven clinical trials.

In all evaluations, there was no significant difference in mean values (P<0.05) obtained on measurement by the AVL OMNI™ .

(b) (3) Conclusions drawn from the clinical and nonclinical trials.

Analysis of the comparative measurement presented in the 510(k) for this device, together with the linearity and precision data collected during these clinical and non-clinical trials demonstrates that the AVL OMNI™, with the additional analyte, Urea Nitrogen, is safe and effective, and equivalent to those predicate devices to which it is compared.

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Image /page/4/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle or bird-like figure with flowing lines, representing movement or progress. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the bird figure.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JAN 2 9 1999

Randy Byrd Quality Assurance Manager AVL Scientific Corporation 50 Mansell Court Roswell, GA 30076

Re: K990092 Trade Name: AVL OMNI™ Modular Analyzer Regulatory Class: II Product Code: 75 CHL, JFP, CGZ, CGA, KHP, CEM, JGS, CDS 81 GKR, GKF, GLY Dated: January 8, 1999 Received: January 11, 1999

Dear Mr. Byrd:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770)488-7655.

This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll free number (800) 638-2041 or at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"

Sincerely vours.

Steven Sutman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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510(k) Number (if known): K960092

Device Name: AVL OMNI™ Modular Analyzer

The AVL OMNI™ is a modular Critical Care Analyzer intended to be used for the measurement of pH, PCO2, PO2, ctHb, HHb, O2Hb, COHb, MetHb, SulfHb, Na', K. Cl. ionized Cat. Hematocrit, glucose, lactate and urea nitrogen in whole blood, serum, plasma, dialysate and QC materials as appropriate by minimally trained personnel qualified to perform and to report these values in a clinical laboratory setting.

Indications for Use1,2

The pH value of the blood may be the single most valuable factor in the evaluation of the acid-base status of a patient. The pH value is an indicator of the balance between the buffer (blood), renal (kidney) and respiratory (lung) systems, and one of the most tightly controlled parameters in the body. The causes of abnormal blood pH values are generally classified as:

• primary bicarbonate deficit	metabolic acidosis
-------------------------------	--------------------

· primary bicarbonate excess metabolic alkalosis
· primary hypoventilation respiratory acidosis
· primary hyperventilation respiratory alkalosis

An increase in blood, serum or plasma pH (alkalemia) may be due to increased plasma bicarbonate, or a feature of respiratory alkalosis due to an increased elimination of CO2 due to hyperventilation.

A decrease of pH value (acidemia) in blood, serum or plasma may occur due to an increased formation of organic acids, an increased excretion of H -ions in certain renal disorders, an increased acid intake such as in salicylate poisoning or loss of alkaline body fluids. Respiratory acidosis is the result of a decreased alveolar ventilation and may be acute, as the result of pulmonary edema, airway obstruction or medication, or maybe be chronic, as the result of obstructive or restrictive respiratory diseases.

The composition of serous body fluids: pleural, pericardial, ascitic and cerebrospinal fluid, is similar to serum and plasma in electrolyte content and pH. The AVL OMNI™ may be used for the analysis of these fluids, limited to a pH in the range between 6 and 8, as long as care is taken to ensure the specimen to be analyzed is clear of fibrin clots or other debris which may block the sample transport system.

1 Tietz, Norbert W., Ed., Clinical Guide to Laboratory Tests, 2nd Ed., (Philadelphia: W.B.Saunders, Co., 1990) p.436.

2 Burtis C, Ashwood E (Eds.), Tietz Textbook of Clinical Chemistry, 2nd Ed., (Philadelphia: W.B.Saunders, Co., 1994) pp.1354-1360,2180-2206.

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Pleural fluid3

The pH measurement of pleural fluid can be a clinically useful tool in the management of patients with parapneumonic effusions. Patients with pneumonia may develop effusions when the infectious process extends to the visceral pleura, causing exudation of fluid into the pleural space. Fluids are divided into potentially benign and complicated effusions on the basis of pH. Fluids with a pH greater than 7.30 resolve spontaneously, whereas a pH less than 7.20 is an indication of tube drainage.

PCO2

The PCO2 value of arterial blood is used to assess how well the body eliminates carbon dioxide in relation to the metabolic rate of CO2 production

An arterial PCO2 below the normal range is termed respiratory alkalosis and indicates hypocapnia, a condition caused by increased alveolar ventilation such as hyperventilation. An arterial PCO2 above the normal range is termed respiratory acidosis and indicates hypercapnia, a sign of hypoventilation and failure, resulting from cardiac arrest, chronic obstructive lung disease, drug overdose, or chronic metabolic acid-base disturbances.

PCO2

The PO2 value of arterial blood has become the primary tool for the evaluation of arterial oxygenation status. Values below the normal arterial PO2 (arterial hypoxemia) are usually caused by pulmonary, circulatory, or respiratory abnormalities (e.g. bronchial obstruction, vascular problems, decrease in cardiac output, increased oxygen demand, anatomical heart defect, low inspired O2 content). Generally, PO2 levels above 100 mmHg do not contribute significantly to the oxygen content since, with normal hemoglobin concentrations, 80 - 100 mmHg, PO2 provides a 97 % saturation level, and a level greater than 100 % cannot be achieved.

3 Kaplan LA, Pesce AJ. Clinical Chemistry: Theory, analysis and correlation, 2nd Ed. (St.Louis: C.V.Mosby Co. 1989) p 590-591.

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Sodium

Sodium is the major cation of extracellular fluid. Its primary functions in the body are to chemically maintain osmotic pressure and acid-base balance and to transmit nerve impulses. Sodium functions at the cell membrane level by creating an electrical potential between different cell membranes causing the transmission of nerve impulses and neuromuscular excitability to be maintained. Sodium is involved in some enzyme catalyzed reactions as a cofactor. The body has a strong tendency to maintain a total base content, and only slight changes are found even under pathologic conditions.

Low sodium values, hyponatremia, usually reflect a relative excess of body water rather than a low total body sodium. Reduced sodium levels may be associated with: low sodium intake; sodium losses due to vomiting or diarrhea with adequate water and inadequate salt replacement, diuretics abuse, or salt-losing nephropathy; osmotic diuresis, metabolic acidosis; adreocortical insufficiency; congenital adrenal hyperplasia; dilution type due to edema, cardiac failure, hepatic failure; and hypothyroidism.

Elevated sodium values, hypernatremia, are associated with conditions with water loss in excess of salt loss through profuse sweating, prolonged hyperpnea, severe vomiting or diarrhea, diabetes insipidus or diabetic acidosis; increased renal sodium conservation in hyperaldosteronism, Cushing's syndrome; inadequate water intake because of coma or hypothalamic diseases, dehydration; or excessive saline therapy.

The sodium value obtained may be used in the diagnosis or monitoring of all disturbances of the water balance, infusion therapies, vomiting, diarrhea, burns, heart and kidney insufficiencies, central or renal diabetes insipidus, endocrine disturbances and primary or secondary cortex insufficiency of the adrenal gland or other diseases involving electrolyte imbalance.

Potassium

Potassium is the major cation in the intracellular fluid and functions as the primary buffer within the cell itself. Ninety percent of potassium is concentrated within the cell, and damaged cells release potassium into the blood. Potassium plays an important role in nerve conduction, muscle function, and helps maintain acid-base balance and osmotic pressure.

Elevated potassium levels, hyperkalemia, can be found in oligouria, anemia, urinary obstruction, renal failure due to nephritis or shock, metabolic or respiratory acidosis. renal tubular acidosis with the K /H exchange and hemolysis of the blood. Low potassium levels, hypokalemia, can be found in excessive loss of potassium through diarrhea or vomiting, inadequate intake of potassium, malabsorption, severe burns and increased secretion of aldosterone. High or low potassium levels may cause changes in muscle irritability, respiration and myocardial function.

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The potassium value obtained may be used to monitor electrolyte imbalance in the diagnosis and treatment of infusion therapies, shock, heart or circulatory insufficiency, acid-base imbalance, therapy with diuretics, all kinds of kidney problems, diarrhea and hyper- and hypo-function of adrenal cortex and other diseases involving electrolyte imbalance.

Chloride

Chloride is an anion that exists predominantly in extracellular spaces. It maintains cellular integrity through its influence on osmotic pressure. It is also significant in monitoring acid-base balance and water balance. In metabolic acidosis, there is a reciprocal rise in chloride concentration when the bicarbonate concentration drops.

Decreased levels are found in severe vomiting, severe diarrhea, ulcerative colitis, pyloric obstruction, severe burns, heat exhaustion, diabetic acidosis, Addison's disease, fever and acute infections such as pneumonia.

Increased levels are found in dehydration, Cushing's syndrome, hyperventilation, eclampsia, anemia, cardiac decompensation.

ionized Calcium

Calcium in blood is distributed as free calcium ions (50 %), bound to protein, mostly albumin (40 %) and 10 % bound to anions such as bicarbonate, citrate, phosphate and lactate. However, only ionized calcium can be used by the body in such vital processes as muscular contraction. cardiac function, transmission of nerve impulses and blood clotting. The AVL OMNI™ measures the ionized portion of the total calcium. In certain disorders such as pancreatitis and hyperparathyroidism, ionized calcium is a better indicator for diagnosis than total calcium.

Elevated calcium, hypercalcemia, may be present in various types of malignancy, and calcium measurements may serve as biochemical markers. In general, while ionized calcium may be slightly more sensitive, either ionized or total calcium measurements have about equal utility in the detection of occult malignancy. Hypercalcemia occurs commonly in critically ill patients with abnormalities in acidbase regulation and losses of protein and albumin, which gave clear advantages to monitoring calcium status by ionized calcium measurements.

Patients with renal disease caused by glomular failure often have altered concentrations of calcium, phosphate, albumin, magnesium and pH. Since these conditions tend to change ionized calcium independently of total calcium, ionized calcium is the preferred method for accurately monitoring calcium status in renal disease .

Ionized calcium is important for diagnosis or monitoring of: hypertension management, parathyroidism, renal diseases, inadequate calcium intake, vitamin D

4 Burritt MF, Pierides AM, Offord KP: Comparative studies of total and ionized serum calcium values in normal subjects and in patients with renal disorders. Mayo Clinic Proc. 55:606, 1980.

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monitoring, dialysis patients, cancer, pancreatitis, effect of diuretics, malnutrition, kidney stones, multiple myeloma and diabetes mellitus.

total Hemoglobin concentration (ctHb)

The hemoglobin is the main component of erythrocytes. It serves as the vehicle for transportation of oxygen within the bloodstream and each gram/dL of hemoglobin can carry 1.39 mL of oxygen. The oxygen combining capacity of the blood is directly proportional to the hemoglobin concentration rather than to the number of red blood cells (RBC), because some red cells contain more hemoglobin than the others.

Although oxygen transport is the main function of hemoglobin, it also serves as an important buffer in the extracellular fluid. Decreases in the amount of hemoglobin can come about as a result of a decreased concentration of hemoglobin in the erythrocytes, or a decreased number of erythrocytes that contain a normal concentration of hemoglobin.

Decreased levels are found in anemia states, hyperthyroidism, severe hemorrhage and hemolytic reactions due to transfusions of incompatible blood, reaction to chemical, infectious and physical agents as well as various systemic diseases. Increased levels are found in hemoconcentration of the blood, chronic obstructive pulmonary disease and congestive heart failure.

OtHb gives valuable information in an emergency situation if interpreted not in an isolated fashion but in conjunction with other pertinent laboratory data. CtHb is used to screen for disease associated with anemia, to determine the severity of anemia, to follow the response to treatment for anemia and to evaluate polycythemia.

Hemoglobin derivatives

Each hemoglobin molecule is composed of four heme groups, each containing

an iron atom. These iron atoms may exist in either a ferrous (reduced) or ferric (oxidized) state. In their ferrous state, each iron atom of reduced hemoglobin (HHb) may be reversibly associated with molecular oxygen (O2Hb) or carbon monoxide (COHb) or irreversibly with sulfur as sulfhemoglobin (SulfHb). In its ferric, oxidized state it is termed methemoglobin (MetHb), and may be associated with hydroxyl ions, cyanide or sulfur compounds. The fraction of the total hemoglobin content which is bound to oxygen is the oxyhemoglobin fraction, FO2Hb, and used to assess the amount of oxygen available to the tissues and, together with tHb and PO2, is used to calculate the oxygen content. The degree of association between oxygen and hemoglobin is determined by the PO2 and the affinity of hemoglobin for oxygen and is quantified as oxygen saturation. The plot of oxygen saturation (SO2) against PO2 results in a sigmoidal curve known as the O2 dissociation curve, and the shape of this curve arises as a function of the affinity of the hemoglobin in the blood for O2.

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The affinity of hemoglobin for oxygen is dependent on five factors: temperature, pH PCO2, concentration of 2,3-DPG and the type of hemoglobin. Hemoglobin which is capable of combining with oxygen is termed functional hemoglobin, and decreased amounts of functional hemoglobin can occur when quantities of hemoglobin are converted into nonfunctional, carboxyhemoglobin, methemoglobin, sulfhemoglohin or cyanmethemoglobin. Impairment of the ability to transfer oxygen from the lung to the hemoglobin, inadequate circulation or shunt, may result in a decrease in PO2, a decrease in oxygen saturation, and ultimately a decrease in the delivery of oxygen to the tissues. Clinically, it is important to distinguish between hypoxia (decrease oxygen availability due to a decrease in PO2 and oxygen saturation) and cyanosis (decrease in oxygen saturation because of abnormally high concentrations of deoxyhemoglobin or the dysfunctional hemoglobin derivatives, methemoglobin or sulfhemoglobin). Cyanosis is generally described to occur when the capillary content of deoxyhemoglobin exceeds 5 g/100 mL. This may occur when the arterial hemoglobin is not saturated, or when tissue extraction of oxygen from the blood is high. However, due to the altered color characteristics of sulfhemoglobin and methemoglobin, comparable degrees of cyanosis may occur with 1.5 g MetHb/dL of blood or 0.5 g SulfHb/dL of blood. The presence of abnormally high concentrations of MetHb or SulfHB generally result from reactions to drugs or chemicals, although congenital methemoglobinanemia does occur infrequently.

Oxyhemoglobin (O2Hb)

When each heme group of the hemoglobin molecule is associated with one molecule of oxygen, the hemoglobin is referred to as oxyhemoglobin (O2Hb). The amount of oxyhemoglobin, expressed as a fraction of the total hemoglobin is termed, oxyhemoglobin fraction of total hemoglobin (FO2Hb). The largest portion (about 98%) of blood oxygen content is the oxygen bound to hemoglobin. The reference interval for arterial blood from healthy adults is typically 94 to 98% .

Deoxyhemoglobin (HHb)

Deoxyhemoglobin is the hemoglobin with the iron molecule in the heme group in its ferrous state and not associated with any other molecule, thus, capable of carrying one oxygen molecule. The sum of deoxyhemoglobin and oxyhemoglobin, those derivatives capable of oxygen transport within the blood, is termed, functional hemoglobin.

Siggaard-Andersen O, Durst RA, Maas AHJ, IFCC/IUPAC approved recommendation (1984) on phyicochemical quantities and units in clinical chemistry. J Clin Chem Clin Biochem. 25:369-391, 1987.

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Carboxyhemoglobin (COHb)

Hemoglobin has the capacity to combine with carbon monoxide in the same proportion as with oxygen, that is, one heme group can associate with one carbon monoxide molecule. However, the hemoglobin molecule has an affinity for carbon monoxide 200-300 times greater than its affinity for oxygen. Due to this high affinity of carbon monoxide to the oxygen binding site, it successfully competes with oxygen to form carboxyhemoglobin. This explains why a spurious concentration of carbon monoxide may result in life-threatening levels of COHb. Levels of approximately 6% are seen in the blood of moderate smokers. Blood concentrations of 10 to 20 % are associated with headaches and mild dyspnea. 30 to 40 % COHb causes weakness, nausea, vomiting and visual disturbances, at a 40 to 50 % level the clinical findings are characterized by tachypnea, tachycardia, ataxia and syncopes. Between 50 and 70 % seizures, coma and compromized overall heart and lung functions become apparent, higher levels usually cause death. Clinical diagnosis requires CO-Oximetry, since calculated oxygen saturation from blood gas and acid base measurements are misleadingly high . Small amounts of carbon monoxide are produced in the body in the conversion of heme to biliverdin and, this small amount of endogenous carbon monoxide production is accelerated in hemolytic anemias. 7

Methemoglobin (MetHb)

In methemoglobin, the central iron atom is oxidized to its ferric state. Because of the loss of an electron, methemoglobin is incapable of reversibly binding oxygen or carbon monoxide. It is formed spontaneously especially from deoxyhemoglobin, which is more readily subject to rapid autooxydation. Therefore it is found increased in chronic hypoxemia and in residents at high altitude. Methemoglobin is also formed by a number of organic and inorganic oxidants and may be induced by drugs such as primaquine, dapsone, aniline and nitrates . It also occurs in natients with hereditary structural abnormalities of the hemoglobin. MetHb levels up to 20% are usually well tolerated, levels of 30 to 40% cause dyspnea and headaches, levels above 40% require therapy, usually with intravenous methylene blue treatment, which acts as an activator of the NADPH dehydrogenase. In patients with certain enzyme deficiencies, methemoglobin can rise up to 70%.

6 Meigs JW, Hughes JPW (1952) Acute carbon monoxide poisoning- an analysis of five hundred cases. AMA Arch Ind Hvg 6: 344

7 Burtis C, Ashwood E (Eds.), Tietz Textbook of Clinical Chemistry, 2nd Ed.,

(Philadelphia: W.B.Saunders, Co., 1994) pp.1178-1179.

8 Jaffe ER (1981) Methemoglobinemia. J Clin Haematol 10: 99

3 Shapiro BA, Peruzzi WT, Kozelowski-Templin R. Clinical Application of Blood Gases, 5th Ed.,(Chicago: Mosby, 1994), pp.200-201.

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Sulfhemoglobin (SulfHb)

Sulfhemoglobin is formed as the product of sulphur ligand binding to the heme Sumiemogioum is formed as in prith toxic side effects of drugs such as iron in sulphuce intoXoanoiis and with with with the frequently misdiagnosed sunonamides, dapsons, accumina and proventive CO- Oximeters to separate it from other derivatives, especially MetHb10

from other derivatives, especially 1 and does not disappear from the circulation Sulfro is irreversiony and completed their life cycle and SulfHb is metabolized.

Hematocrit

Hematocrit, sometimes denoted as packed cell volume (PCV), is the Henatoorit, somethines action the red blood cells. The Hct is expressed either in percentage or fraction.

Citier in porcomtung an indicator for anemia (a condition where there is a reduction in Hct, tHb and RBCs), leukemia, hyperthyroidism, cirrhosis, acute massive blood loss as well as hemolytic reactions due to transfusions of incompatible blood, reaction to chemical, infectious and physical agents. Increased levels are found in polycythemia, erythrocytosis, severe dehydration and shock.

Glucose

Hyperglycemia can be due to a number of causes which can be sub-divided into those due to diabetes mellitus or those due to non-diabetic causes. Diabetes mellitus is a syndrome of chronic hyperglycemia which is due to either absolute insulin deficiency or reduced tissue response to insulin, or both. It is a common misulii donelelly of a diagnosed according to strict criteria that rely upon measurement of the blood glucose level. Nondiabetic causes of hyperglycaemia include or the otoo's immediately after a carbohydrate-containing meal), factitious (blood taken from an arm where glucose is being infused), drugs (produce a tissue (previsitivity to insulin), non-pancreatic endocrine disease (excessive production of anti-insulin hormones), pancreatic disorders (secondary diabetes mellitus), and stress (physical and psychogenic types causing excess secretion of cortisol and catecholamines.

Hypoglycemia is an acute medical condition with a number of characteristic signs and symptoms which are accompanied by biochemical hypoglycamia and which are relieved by the administration of glucose. The causes of hypoglycaemia can be divided into three groups: Medication/Toxins, Reactive Hypoglycemia; Fasting Hypoglycemia. Hypoglycemia due to excessive amounts of certain Medications or Toxins include insulin overdose is the commonest cause of hypoglycemia), oral hypoglycaemics or suphonylureas, ethanol and other drugs such as salicylate and propanalol. Reactive Hypoglycemia occur, within 5-hours of a carbohydrate meal in otherwise normal subjects, in patients with early adult-onset diabetes

10 Park CM, Nagel RL (1984) Sulfhemoglobinemia. N Engl J Med 310:1579

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mellitus and in patients who have had gastric surgery. Fasting Hypoglycemia can be due to insulinomas, non-pancreatic tumors, endocrine disorders, liver failure, sepsis, renal failure or autoimmune disorders

Lactate

Causes of an increased lactate or lactic acidosis can be divided into two general groups:

Type A causes are those in which there is overt evidence of hypoxia and are the most causes of a lactic acidosis. Insufficient tissue oxygenation to meet the metabolic needs of the patient can arise due to severe exercise; poor tissue perfusion such as in shock; or due to reduced arterial oxygen content such as in asphyxia or hypoxemia.

Type B causes are those where there is no overt evidence of hypoxia and can occur in association with a wide variety of discases and toxins/chemicals. In these cases the mechanism is unclear but it is thought to be due to impaired tissue oxygen utilisation. Causes include drugs and toxins such as ethanol, methanol and phenformin; predisposing diseases such as respiratory alkalosis and diabetes mellitus, liver failure and sepsis; inborn or congenital errors in carbohydrate metabolism.

In all of the above cases the excess lactate is of the laevo or L-form. Dextro or Dlactic acidosis can occur when there is overgrowth of certain bacteria in a gut which has been shortened through surgery. The bacteria produce excessive quantities of D-lactate.

Urea Nitrogen

Urea is produced in the liver as a by-product from the breakdown of amino acids. These are transaminated and deaminated to ammonia which is a toxin. Detoxification of ammonia occurs in the urea cycle where two molecules of ammonia are joined to a molecule of carbon dioxide to form urea. Approximately 1120-1680 mg/dL of urea nitrogen are produced per day but the production depends upon protein intake and liver function. A wide variety of renal diseases with different permutations of glomerlular, tubular, interstitial or vascular damage can effect azotemia (increased urea concentration).

Jean Couzen

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Regulation Number and Section

§ 862.1120 Blood gases (P

CO2 , PO2 ) and blood pH test system.(a)
Identification. A blood gases (PCO2 , PO2 ) and blood pH test system is a device intended to measure certain gases in blood, serum, plasma or pH of blood, serum, and plasma. Measurements of blood gases (PCO2 , PO2 ) and blood pH are used in the diagnosis and treatment of life-threatening acid-base disturbances.(b)
Classification. Class II.