Routine daily quality control on blood gas instruments
Most current blood gas/electrolyte/metabolite analyzers have onboard internal quality control (QC) systems that automatically monitor the stability and performance of reagents, electrodes, and electronics of the analyzer. These control systems make these “hybrid” analyzers well-suited to use in both laboratory and Point-of-Care Testing (POCT) areas. Two such analyzers use easily replaced multiuse packs that contain controls, calibrants, rinse solution, and waste. Some also have the flow system and analyte sensors within the pack. They are described in the following.
One model of a hybrid blood gas analyzer measures pH, p CO 2 , p O 2 , Na + , K + , Cl − , Ca 2+ , glucose, lactate, total hemoglobin (Hb), and several forms of Hb including oxy-Hb, carboxy-Hb, and met-Hb. Part of its QC system utilizes four process control solutions (PCS) all contained within a multiuse test pack to monitor the stability of the analytical responses. PCS A and B are run at least every 4 h and after every sample. PCS C is run once per 24 h, and PCS D is run every 12 h. Once the test pack is validated, an active QC program monitors the analytical process before, during, and after sample measurement, with automatic error detection. During the analysis, the sensor response is continually evaluated for abnormal responses that might indicate microclots, microbubbles, or some chemical interferences. If an error is detected in the analysis, the system automatically tries to correct the system error and will either document any corrective actions or disable that test channel if the problem cannot be fixed.
Another brand of hybrid blood gas analyzer measures pH, p CO 2 , p O 2 , Na + , K + , Ca 2+ , Cl − , glucose, lactate, bilirubin, and Hb with cooximetry. This analyzer utilizes a replaceable cassette of solid-state amperometric and potentiometric ion-selective sensors, optical p O 2 detection, and spectrophotometric measurements for oximetry. QC solutions are contained within a multiuse pack containing three calibrant solution pouches (with one also used for rinse), one gas mixture pouch, three QC solution pouches, a flow selector, pump tubing, and a waste pouch. To compensate for drift, a calibrant solution is run to bracket every test measurement. Every 8 h, one level of each of three levels of liquid internal QC solutions is automatically run. All controls enter through the sample probe and flow through the entire system. Clots are usually trapped by a clot catcher near the sample inlet, plus pressure sensors detect any blockage of flow along the analysis path. If abnormal pressure is detected, the analyzer initiates a clot removal process to rid the offending clot from the flow path. To ensure that accurate results are reported, a question mark appears next to any invalid result that may be caused by an inhomogeneous sample, insufficient sample, or some problem with the calibration.
Hand-held portable blood gas analyzers utilize both a liquid calibrant contained within a single-use test card, and an external multiuse electronic simulator card that checks the acceptability of the electronic sensors within the instrument. This simulator is often referred to as providing equivalent quality control (EQC) in place of external control solutions. By itself, it verifies only the electronic function of the analyzer, but does not check the reagent or sensor stabilities of the test card. Every 24 h when cartridges are being tested, the external electronic simulator is used to verify any internal electronic failures. Twice per year, this simulator performs the required thermal probe check. The electronic simulator sends signals that are below and above the measurement ranges of the tests to simulate signals of a test cartridge during an actual analysis of a sample and these simulator results are stored in the instrument’s memory. However, these electronic checks typically have almost no variation and do not represent the more realistic precision results obtained with either liquid controls or patient samples.
Another single-use disposable cartridge contains microsensors, a calibrant solution, flow system, and a waste chamber. Sensors for analysis of total CO 2 , sodium, potassium, chloride, ionized calcium, glucose, creatinine, urea as blood urea nitrogen (BUN) and hematocrit are available in a variety of panel configurations. Approximately two–three drops (100–150 μL) of anticoagulated blood are dispensed into the cartridge sample well, which is sealed before inserting the cartridge into the analyzer. Inserting a test card brings the card’s sensors into contact with the instruments electrical contacts. This contact activates a heater assembly to bring the measurement region to 37°C. This also opens the fluidic valve in the card to deliver calibrant fluid from the reservoir to the measurement region.
After calibration, and upon a prompt by an LED and an audio beep, the user introduces a blood sample for measurement through the blood sample port to the card’s measurement region. When blood contacts the analyte sensors, an electrical signal is generated that is proportional to analyte concentrations in the blood sample.
Individualized Quality Control Plan
Many current blood gas instruments have some type of internal onboard QC. Some analyzers use internal liquid control solutions that flow through the analyzer system making contact with the analyte sensors. Other analyzers use an electronic simulator device that is inserted into the analyzer to check only the electronics of the analyzer. For many years, there has been debate about whether these internal controls fulfill the requirements for external controls as per CLIA 88. For internal liquid controls the issue is whether the daily QC solution is introduced into the system through the sample probe and flows through the entire system, or enters the sample flow path immediately after the sample probe. Manufacturers claim the analysis of these internal controls, along with other quality checks of the system, satisfy the CLIA requirements for external QC.
For hand-held portable analyzers that use an external electronic simulator to verify the electronic functions of the analyzer, a liquid calibrant is contained within the single-use test card. Use of this calibrant provides a type of one-point calibration of the test cards to help ensure acceptable performance of the analyte sensors in the test card.
In 2013, the Centers for Medicare and Medicaid Services issued a “voluntary” option for meeting CLIA quality control standards, which was called Individualized Quality Control Plan (IQCP) that went into effect January 2016 ( ) . It applied to all labs with analyzers that use EQC. CLIA QC regulations remained the same as published in 2003. All of the preanalytical, analytical, and postanalytical systems requirements in the CLIA regulations remained in effect ( ) .
Much has been written about IQCP, so this section will only cover brief aspects of IQCP for clinical laboratories. The aim of IQCP was to monitor all phases of testing by developing a plan that assesses potential risks for (1) specimen handling, (2) personnel who test the specimens, (3) instrument reliability, (4) reagent reliability, and (5) environmental factors that could affect results ( ) . Developing and implementing an IQCP that addresses these potential risks could potentially overcome the limitations of an electronic simulator used as a control device.
The logic of IQCP is apparently that the laboratory runs the risk of error by utilizing internal QC as its external QC requirement. If a blood gas instrument introduces the internal QC sample automatically, it does not check the quality of sample handling by personnel, which is a mandatory area of risk assessment. Because no QC material tests the preanalytic phase of sample transport and handling, the IQCP requires a risk assessment of potential errors during this phase, particularly when time from patient draw to introducing the sample is a critical factor in testing samples, as with blood gas testing. While IQCP attempts to address all phases of testing, it still allows use of electronic simulators as controls, which of themselves provide minimal assurance of test quality.
To be considered an external control material, the control material must have a similar matrix to that of patient specimens, be treated in the same manner as patient specimens, and go through all elements of the analytical process. It must also be a different control or from a different lot number than used to calibrate the instrument (42CFR493.1256(d)(9)). Because electronic simulator controls only verify electronic and mechanical functions of the instrument, they do not meet the definition of an external control material.
Laboratories should evaluate their QC processes to determine if they monitor the entire analytical testing process. If the control process does not meet the criteria described for external control materials, the laboratory must either perform additional QC testing, such as analyzing appropriate external control materials once per 8 h, or implement an IQCP to meet requirements for daily QC. If onboard QC solutions meet the above definition of an external control material, an IQCP is not required. The laboratory can periodically verify proper sampling technique through proficiency testing, competency assessment, the use of other types of external control materials, and following processes defined in the manufacturer’s instructions.
The minimum guidelines according to CLIA 88 (2003) require laboratories to perform external QC at least one time per 8-h shift ( ) . In addition to the daily QC requirement for all nonwaived moderate-to-high complexity test systems, the laboratory must also perform and document calibration verification at least twice per year, as well as when any of the following occur: (1) after major maintenance; (2) when replacing significant parts that could affect an instrument’s performance; (3) when lot numbers of reagents are changed; and (4) whenever the laboratory identifies a trend or shift in its control material with results falling outside acceptable limits.
With the IQCP regulation now in effect, laboratories should develop a QC plan that includes the use of control materials that resemble patient samples. To eliminate the question of internal QC material qualifying as an external control, some suggest having personnel introduce at least one QC sample every 8-h ( ) .
Between-lab and between-instrument QC
To verify comparability of multiple instruments testing the same analyte, CAP regulation COM.04250 requires that labs verify comparability of results at least twice a year, preferably using human samples. As part of our routine between-laboratory QC survey, every 2 weeks we pool heparinized blood gas samples destined for discard that remain after testing and reporting ( ) . Leftover blood samples are randomly selected based on having sufficient volume remaining after testing, with no effort made to select any concentrations of analyte. Before testing, all pooled blood is checked for hemolysis by centrifugation. Twenty-five milliliter of blood is pooled into a plastic medicine cup, mixed, then aliquoted into several 3 mL syringes that are sealed then laid on ice as they are taken on a rotating basis to each laboratory and POCT location for analysis. The results are compiled in a report that is sent to each laboratory for review by the laboratory manager and director.
For evaluating results on this between-lab QC program, the mean of all results for each analyte is calculated, with acceptable analytical limits set for each test done on our blood gas analyzers, as shown in Table 11.1 . These ranges of acceptable differences for each analyte are based on, but usually more rigorous than, CLSI guidelines ( , ) .