Chapter Outline
What Can We Test? 271
Blood Gases and Electrolytes 271
Hematologic Parameters 274
Coagulation Tests 276
Regulatory Issues 280
Conclusions 281
Point of care testing (POCT), also known as near patient or bedside testing, is one of the most rapidly growing areas in the diagnostics industry. The key objective of POCT is the generation of a result quickly, so that treatment decisions can be made to improve medical or economic outcomes. The operating room presents unique opportunities to achieve both of these goals, particularly in rapidly changing medical situations, and when a rapid result may reduce the use of the expensive operating room time and resources. In addition, there are blood tests required during surgical procedures that must necessarily be performed at the point of care, such as activated clotting time. For some analytes, POCT is more accurate than core laboratory testing because of the delay in transport of the specimen or because of the transport process itself. Red blood cell metabolism can significantly change blood gases and glucose in a sample over time, and even small air bubbles in a sample sent through a pneumatic tube can alter blood gas results.
Utility and cost of point of care testing, compared with central laboratory testing, have been the subject of many studies over the past 20 years. In general, it has been shown that the per test cost of POCT is higher than the same test performed in a central lab, but the savings in terms of the entire hospital experience has been difficult to quantify. Point of care coagulation testing has been shown to reduce blood product use in cardiac surgery, and intraoperative parathyroid hormone testing has been shown to reduce operative time, but benefits of other forms of POCT are largely intuitive. For example, in a case of rapid hemorrhage, we would expect that a hemoglobin test that produces a result in 60 seconds would make management easier and safer than a result that takes 20 minutes from a central lab, and might prevent unnecessary, prophylactic transfusion.
There are several ways in which laboratory testing can be brought to or close to the point of care. A satellite laboratory may be placed in the operating suite, a testing device may be placed on a cart that is then taken into the operating room, or hand-held or small desk top device may be brought literally to the patient’s bedside. This chapter will focus on the latter two categories, those devices which are brought into the operating room and used by direct care givers, rather than by laboratory technicians.
What Can We Test?
Blood Gases, Electrolytes, and Metabolites
For the purpose of this discussion, these analytes are grouped together because most of the POCT devices measure them as part of a menu determined by the cartridge or device chosen. Most portable and hand-held instruments test whole blood samples, using electrodes or sensors and reagents, which are built into disposable cartridges or cuvettes. The number of tests available is determined by the reagents, chemicals, and enzymes on the cartridge and in the device. Cartridges may be single or multiple sample use, in some cases up to several hundred samples. Expiration dates are often several weeks after the cartridge is opened, so choosing the appropriate device and cartridge for expected testing volume is important for cost control. Figure 20–1 shows some of the many currently available POCT instruments for testing blood gases, electrolytes, metabolites, and other analytes.
Portable instruments range in size from larger desktop instruments to those to approaching the size of hand-held devices, which are somewhat larger than hand-held glucose meters. The larger devices may be brought to the patient’s bedside on a cart. If a cart based system is used, it is important to make sure the device will run on batteries without interruption or require repeat calibration or quality control (QC) if unplugged from AC power.
Some POCT systems require that the operator manually place the sample in the cartridge using a syringe or capillary tube, while others aspirate the sample automatically from a syringe or tube. Manual entry may be a source of testing error, from either over or under filling or introduction of air bubbles, though the devices will in many cases give an error message and require repeat testing.
Common analytic principles used in POCT instruments include potentiometry, amperometry, and optical methods. In addition, conductometry is used to measure hematocrit, and will be discussed later.
Potentiometry is the measurement or electrical potential difference between two electrodes in an electrochemical cell. The potential difference is logarithmically proportional to the electrolyte concentration. One electrode is a reference, the other is specific for the ion being measured, an ion specific electrode (ISE). The ISE has a membrane that attracts the ion, creating a potential difference which can then be measured through the circuit of the reference and ISE. Potentiometry is used to measure pH, PCO 2 , Na, Ca, Cl, K, and Mg.
Amperometry is measurement of the electric current flowing through an electrochemical sensor circuit when a constant potential is applied to the electrodes. The electrochemical sensor consists of an anode and a cathode, surrounded by a selectively permeable membrane, which prevents entry of proteins and other oxidants. When a sample is applied, the substrates and analyte diffuse through the membrane, an oxidation-reduction reaction occurs, electrons form a current under the electric potential applied. The amplitude of the current is proportional to the substrate level in the cell, and is measured by the device. Amperometry is used to measure PO 2 , BUN, glucose, lactate, creatinine, and ketones.
Optical technologies used in POCT devices include optical reflectance, absorbance, fluorescence, and multilength spectrophotometry, which is used for co-oximetry testing. Optical reflectance and absorbance measure the change in color between incident light and absorbed or reflected light. As an analyte is oxidized by an oxidation-reduction reaction, electrons are generated, which oxidize a dye to create a color, the intensity of which is proportional to the concentration of the analyte. The device measures the reflectance or absorbance of a known incident wavelength of light. Optical reflectance has been used to measure glucose, PO 2 , PCO 2, and pH. Optical fluorescence and luminescence technologies measure the photons emitted from molecules when exposed to light of a particular wavelength. For example, Na and K can be measured with fiber-optic optodes encased in a membrane that contains selective recognition elements, ionophores, linked to fluorescent dye. As the ions pass through the membrane, they bind the ionophores, and once exposed to light, fluoresce with an intensity that is proportional to the concentration of the ions.
The i-STAT (Abbott) device deserves particular mention because it uses microfabricated chip-based technology in its cartridges. i-STAT cartridges are approximately 1-inch square, 0.25-inch thick plastic. Channels are etched in the surface to draw the sample from a well to the sensors and electrodes. There are a number of cartridge types that allow a menu of testing, including blood gases, electrolytes, metabolites, cardiac markers, and hematologic parameters, using a variety of the technologies described above.
Most POCT devices measure some of the reported parameters and calculate others. For example, the instrument may measure PCO 2, pH, and electrolytes, and then calculate and display bicarbonate, total CO 2 base excess and anion gap.
Portable and handheld POCT instruments use a variety of methods for calibration and QC. Calibration for single use cartridges is usually automatically performed by the device just before use, while calibration on multiuse cartridges is performed periodically at intervals between sample measurements using reagent packages with the cartridge. Unlike larger laboratory instruments that use gas tanks to calibrate blood gas measurements, cartridges for POCT devices are packaged with pretonometered calibration solutions, or perform gas calibration using room air.
Liquid QC is performed on representatives from each cartridge lot as it is first used; typically known samples in a range over which testing will be performed are tested. In addition, many POCT systems are tested periodically using electronic QC, using a surrogate cartridge to assess the response of the sensors and to detect internal system failures.
Table 20–1 shows characteristics and specifications of a number of currently available and widely used POCT devices with capability of testing blood gases, electrolytes, and metabolites.
| Device | Abbott i-STAT | IL Gem Premier 4000 | Siemens Rapidpoint 405 | Radiometer ABL80 Flex | Epocal Epoc |
|---|---|---|---|---|---|
| Test menu ∗ | P o 2 , P co 2 , pH, Na, K, Cl, iCa, Cl Glu, lactate, BUN, Hct, Crea, ACT, PT/INR, cardiac markers | P o 2 , P co 2 ,pH, Na, K, Ca, Cl Glu, lactate, Hct, tHb, O 2 Hb, COHb, MetHb, HHb (co-ox) | P o 2 , P co 2 ,pH, Na, K, iCa, Cr, Glucose, Hct, Hb (co-ox)) | P o 2 , P co 2 , pH, Na, K, iCa, Cl, Glu, Hct, tHb, O 2 Hb, COHb, MetHb, HHb (co-ox) | P o 2 , P co 2 , pH, Na, K, iCa, Hct |
| Sample size | 17-95 μL | 150 μL | 100-200 μL | 105 μL | 100 μL |
| Report time | 130-200 sec except for ACT, PT | 95 sec | 60 sec | 140 sec | 35 sec |
| Cartridge size | Single use | 75-450 tests | 250-750 tests | 25-300 tests | Single use |
| Cartridge life | Two weeks once at room temp | 30 days in use | 28 days in use | 15-30 days in use | |
| Dimensions/size | 3 × 9.2 × 2.8 in 22.9 oz | 44 lb | 11.5 × 16 × 21.5 inches, 34 lb | 9 × 11 × 16 in, 19 lb | 8.5 × 3.3 × 2 inches, 1.1 lb |
| Device memory | 5000 patient results, L QC and E QC | 80 gigabyte hard drive, 1-yr retention of data | Information unavailable | 500 patient test 500 system cycle 500 manual QC unlimited user ID | No memory in meter |
| Operation temperature | 15-40 o C | 12-32 o C | 15-32 o C | 12-28 o C | 15-30 o C |
| Operation humidity | Up to 90% | 5%-85% | 5- 85% | Up to 85% | Up to 85% |
| Operationaltitude | 300 – 1000 mmHg | Not applicable | 523-800 mm Hg | Up to 7513 ft. | 400-835 mm Hg |
| QC | Automatic QC and Calibration unless glucose test strips use, then liquid QC | AutomaticQC and calibration | Automatic QC and calibration | Automatic | |
| Comments | Cartridges must be refrigerated, brought to room temp prior to use May use Abbott Glucose test strips | Data transferred to mobile computer, uses test cards, more analyte cards under development |
∗ Test menu varies depending on cartridge chosen for some devices. For example, iSTAT offers 18 different cartridges with various combinations of parameters.
Blood Glucose
A large segment of the worldwide POCT market involves blood glucose testing, including the home, self-test devices, and the in-hospital devices. As ever increasing numbers of the patients who present for surgery are diabetic, and with relatively recent interest in intensive insulin therapy for some patient populations, the need for blood glucose monitoring is increasing. Many hospitals now have widespread POCT programs for blood glucose. Testing can be done with hand-held devices that use disposable strip technology, which will be discussed here, or on multianalyte machines that use cartridges, such as the i-STAT and Gem (Instrumentation Laboratories) systems, which will be discussed later.
Glucose itself is very difficult to measure, so it is usually done by indirect methods, whereby glucose is converted enzymatically to a substance that is easily measured. Current blood glucose monitoring systems use one of two methods, reflectance photometry, which measures a colored product or dye, or electrochemistry, which measures electrical current. Hand-held glucose measurement systems consist of a meter and a disposable strip, or in the case of the HemoCue device a cuvette, which is inserted in the meter. A tiny sample of whole blood, between 0.5 and 5 μL, is then applied to the strip, which is impregnated with dry enzymes and coenzymes that allow the analysis to occur. Examples of meters and strips are shown in Figure 20–2 .
Glucose meters are approximately 3 × 7 × 2 inches, have a display window, a slot on the top or side for a test strip, a key board for data and selection entry, a battery compartment, a laser window for bar code scanning, and an infrared window for data transfer. They often come with a docking station or base unit for charging, data transfer, or both. Meters have built in memory to store results, quality control, and operator data. Like other POCT devices, most now have software programs that allow centralized management of competency, operator access, transfer of results to laboratory information systems, and billing programs. Meters allow scanning and in some cases manual entry of patient identification, operator ID, and strip or cuvette bar codes.
Dry reagent glucose strips or cuvettes come in either individual sealed packets or multicontainer jars. The HemoCue cuvettes must be refrigerated until used. Other strips are kept at room temperature. They all have expiration dates, usually contained along with a lot number and calibration information in the bar code information on the package. Quality control levels are run on the meters at an interval that is determined by the testing site, recommended by the manufacturer, using commercially available samples at two to four glucose levels.
Three enzyme systems are currently used in measuring blood glucose: glucose oxidase, glucose dehydrogenase, and hexokinase. Each then uses a coenzyme to create an end product which either generates electrons and a current, or a colored product, either of which is proportional to the amount of glucose in the specimen. The HemoCue (HemoCue Diagnostics AB) cuvette adds a step: red blood cells are lysed by saponin so that a true whole blood glucose level is measured. The enzyme system used and the method of measuring the end product are of interest to anesthesiologists because of the potential for interference from other substances in the sample. For example, reactions that use glucose dehydrogenase and pyrroloquinoline quinone (GDH-PQQ) are not glucose specific, and cannot distinguish between glucose, maltose, galactose, or xylose. Maltose is in intravenous immunoglobulin solutions and in peritoneal dialysis solutions, such that blood glucose measurement for those patients with a device that uses the GDH-PQQ method may give falsely high readings. The enzyme system used is described in the package insert that comes with the test strips, and should be a factor considered when choosing a device.
Accuracy Of Point Of Care Blood Glucose Measurements
Accuracy of point of care testing of blood glucose is determined by comparison with samples run in the core laboratory. To obtain approval for a medical device from the Food and Drug Administration), the manufacturer must provide data showing correlation with acceptable standard methods of measurement, but this testing is done under ideal conditions. A number of factors have been shown to affect the accuracy of POCT for glucose, shown in Table 20–2 , and many of them can apply to patients undergoing surgery and anesthesia. Importantly, glucose metabolism occurs in red blood cells during transport of a sample from the point of care to the laboratory, which builds in a variable difference between even very accurate point of care testing, depending on temperature, time of transport, and absolute level of glucose. Manufacturers specify that blood should be tested as soon as possible after collection, and always within 30 minutes.
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POCT devices measure glucose on whole blood, whereas laboratories routinely measure glucose in plasma or serum. Plasma values can be as much as 12% higher than whole blood values because of lower water content of red blood cells. Thus most meters mathematically correct the result to simulate plasma, generally calibrated using normal hematocrits. Many meters have been shown to exhibit positive bias (read too high) at lower hematocrits, and negative bias at higher hematocrits. To address this issue, the Multi-Well StatStrip (Nova Biomedical) measures both hematocrit and glucose and corrects for hematocrit interference, though the device only reports glucose.
Though arterial and venous blood can be used with glucose strips, often capillary or fingerstick testing is done because it is convenient and uses less blood. However, hypoperfusion states, such as hypotension, use of vasopressors, and vasoconstriction because of cold have all been shown to introduce error. Because venous blood glucose in the nonfasting state is approximately 8% lower than arterial or capillary blood glucose, meters compensate mathematically for this and require the user to select the type of sample being used. Running a venous sample in the capillary/arterial mode can thus result in falsely high results.
Anesthesiologists should keep in mind that with the exception of the HemoCue device, POCT glucose meters are approved by the FDA as screening devices; they are not approved for the diagnosis of diabetes or determination of treatment. Despite this fact, in most hospitals (and certainly in the hands of diabetic patients at home) POCT glucose meters are used as part of sliding scale insulin administration.
Manufacturers of glucose testing systems continue to work on improvements, particularly in areas of increased accuracy, and most recently, continuous glucose monitoring. Devices which continually measure blood glucose via subcutaneous and intravascular catheters are under development. Table 20–3 shows the specifications for five currently available hand-held glucose monitoring devices.
| Device | Abbott Precision Xceed Pro/Precision Pcx Plus Test Strips | Nova Biomedical StatStrip | Lifescan SureStepFlexx/Sure Step Test Strips | Roche Accu-chek Inform/Comfort Curve Test Strip | HemoCue Glucose 201/Microcuvettes |
|---|---|---|---|---|---|
| Chemistry | GDH-NAD , amperometric | 4 well modified glucose oxidase, amperometric | Glucose oxidase amperometric | Glucose dehydrogenase with potassium ferricyanide/PQQ | Saponin hemolysis, GDH/NAD photometric |
| Reportable range | 20-500mg/dL | 10-600 mg/dL | 0-500 mg/dL | 10-600 mg/dL | 0-444 mg/dL |
| HCT range | 20%-70% | 25%-60% | 20-65% for results <200, 20-55% for >200 | “Care should be taken when…hematocrit may be extreme” | |
| Sample size | 1.2 μL | 1.2 μL | 10 μL | 1.2 μL | 5 μL |
| Operation Temperature | 15-40 ° C | 15-40 ° C | 15-40 ° C | 14-40 ° C | 18-30 ° C |
| Operation altitude | Up to 7200 ft | Up to 15,000 ft | Up to 10,000 ft | Up to 10,000 ft | Not applicable |
| Operation humidity | 10%-90% | 10%-90% | 30%-70% | <85% | <90% |
| Meter memory | 2500 results 1000 control test results 6000 user ID | 1000 tests 500 QC 4000 user ID | 1500 tests 4000 user ID | 4000 tests | 4000 tests 500 analyzer logs |
| Report time | 20 sec | 6 sec | 30 sec | 26 sec | 40-240 sec |
| Comments | Two well system corrects for HCT | Interference by maltose, galactose | Approved for diagnosis, screening, monitoring, cuvettes must be refrigerated |
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