CLN’SCLN’S LABORATORYLABORATORY TESTING:TESTING: EVOLVINGEVOLVING INTOINTO THETHE 2121ST CENTURY SERIES Gases and Other Critical Care Analytes Weighing All the Options When Selecting New Instrumentation ROBERT F. MORAN,PHD, FCCM, FAIC

uring the past several decades,pH/blood gas and measurements have been among the

primary STAT analytes needed to assess the status of critically ill patients. Recent reports have sug-

gested (1–8) that the addition of other analytes to blood gas systems would be advantageous. For

example,technology advances have made it possible to include lactate,,and other analytes

on the same analytical instruments that perform blood gases. Unfortunately, the issues surround- Ding this area of laboratory testing are easily blurred in a maelstrom of competing marketing claims.Furthermore, techno- logical feasibility does not necessarily equate with clinical need.

As clinicians become increasingly critical analytes, careful analysis of the lo- budget allowances, must all be considered. aware of new STAT testing technologies gistics and cost issues for these analytes This article reviews some of the factors and begin to demand quicker turnaround must include numerous details to provide that laboratorians should take into ac- of more and more analytes, many hospi- a true picture of overall cost/benefit. count when deciding whether to include tal laboratories have turned to faster pneu- Additionally, each group involved in the additional analytes on near-patient test matic tube systems for sample transport selection process—the laboratory, man- systems that also measure blood gases. and dedicated analyzers for use in the agement, finance, and direct caregivers— near-patient testing environment. has a different perspective, each of which What is a Critical Analyte? In management of clinical laboratory test- ing, the word “critical” connotes clinical importance and short turnaround time. However, different institutions have dif- ferent, and sometimes seemingly arbitrary, definitions of what “critical” means. More than a decade ago, AACC’s Quality Assurance Committee recognized the need for a more principled approach to these sometimes-contentious issues and developed a set of guidelines for provid- ing quality STAT laboratory services (9). Although the STAT test list included in the AACC publication needs updating in the light of new analytical and therapeutic ap- proaches that have evolved, the principles behind that list remain valid (Table 1).The use of these criteria, combined with in- formation about the institution’s typical patient population and therapeutic pos- sibilities, can be very useful in deciding which analytes should be classified as ur- gent and important. In today’s reimbursement and regula- tory environment, a new third category called “Responsible and Responsive,” may also be needed. This category would take into account the strict clinical require- ments noted in the original AACC guide- lines, and it adds two new perspectives: laboratory management in today’s health However, it is the laboratorian that must is legitimate in its own right. care environment and analytical capabil- weigh all the options—analytical, finan- The laboratorian’s job is to deliver an- ities of new instruments. In addition, cial, and operational—when selecting an- alytically accurate test results that meet third-party payers may find this new cat- alytical instruments that incorporate new the needs of patients and clinicians. In or- egory useful for determining reimburse- critical care analytes. der to accomplish this, clinical laborato- ment policies. In critical care situations, Hospital administrators expect clini- rians must consider the range of available legitimate physician orders and ordering cal laboratory scientists to make these de- instrumentation, as well as its analytical patterns may not always fit the predeter- cisions based on resources, staffing, and operational reliability. In addition, mined criteria developed by insurers who reliability of systems, cost, and clinical and test frequency, sample collection require- have little understanding of critical care operational measures of outcome. While ments, and the economics of care, in- analyses. clearly there is a clinical need for certain cluding reimbursement policies and

12 CLINICAL LABORATORY NEWS AUGUST 2000 The basic blood gas panel includes the Other analytes such as ionized magne- Table 1. Principles of Test Categorization* most important indicator of oxygenation sium, which are analytically feasible and status for many patients: the oxygen ten- available on some STAT analyzers, may AACC Test Category 1: Urgent sion of arterial blood [PO2(aB)]. need to be reconsidered for appropriate- Molecular oxygen—O —is present in the ness in the future. ® Analyte is a cause or effect marker for immediate life-threatening 2 air we breathe, and it is this form of oxy- condition. gen in combination with products of glu- Making the Choices ® Specific and immediate therapeutic action is based on analyte level. cose that fuels cellular In order to make the best choices when ® Timeliness and reliability are crucial. mitochondria to manufacture the bioen- selecting urgent care instrumentation, lab- AACC Test Category 2: Important ergy storage compound adenosine oratorians need to seek the expertise of a ® Analyte levels are necessary for diagnosis, triage, follow-on therapy. triphosphate (ATP). multidisciplinary group: clinicians, sci- Other aspects of oxygenation—oxygen entists, engineers, and marketing staff, as ® Timeliness is a key factor. transport, uptake, and utilization—man- well as economic and regulatory experts. Suggested New Test Category: Responsible and Responsive date measurement of total , The availability of multiple analytes on ® The quantities are considered clinically related. oxygen content, and saturation. Also, the same analytical system certainly pro- ® The frequency of need for one quantity is nearly “simultaneous”with many clinical situations can justify inclu- vides some real operational and even clin- others. sion of hemoglobin derivatives such as ical advantages, but at the same time may carboxyhemoglobin along with the blood require re-education on issues such as ® A single blood specimen is required using analytically related or gas determinations. sample processing, costs, availability of the compatible technology. The addition of potassium to the ba- measurements, and billing practices. Table ® The cost of treatment vs. no treatment vs. total costs based on the sic set of measurements is most appro- 4 presents some important points to con- test is significant and related to the test performed. priate in the critical care setting, sider when making this decision. Overall, ® Timeliness is significant, but not critical. considering potassium’s effect on cardiac it is important to look at the clinical and efficiency and output. In critically ill pa- *Modified from AACC Guidelines (9) tients, parenteral therapy that involves also supports the addition of Table 3. Important Using the Fundamentals other electrolytes such as sodium and ties are combined with base excess of chloride, which are frequently needed in Blood Analytes* Homeostasis, the dynamic balance be- blood [BE(aB)] and/or base excess of ex- the same time frame as the blood gases. ® All analytes from the Urgent tween opposing systems or within syner- tra cellular fluid [BE(ecf)], an assessment Ionized may be required in the AACC Category 1 list gistic systems, is a characteristic that can of the non-respiratory component of any critical care setting as well, albeit in some- ® Urea, , Fe, NH4 , be applied to a number of areas in human acid-base disturbance can be calculated. what more restricted clinical conditions , Ketones, ALT, AST, physiology, including hematopoiesis, he- There is a long-standing controversy than those that justify sodium and potas- , HCG, mostasis, and acid-base/bioenergetic bal- among the experts regarding which BE sium. For example, in patients receiving ® Leukocytes, Differential, ance. While the individual characteristics value to use. BE(aB) is by far the most massive transfusions of citrated blood, cal- Fibrinogen of each of these systems can reach a crit- commonly used and in fact could be mea- cium is chelated by the citrate, causing sig- New Important Blood ical state and thus deserve urgent atten- sured directly. On the other hand, BE(ecf) nificant lowering of the ionized calcium Analytes tion by testing facilities, there are three is more representative of long-term clin- level. The resulting cardiac and neuro- ® Oxygen Saturation and systems that stand out as fundamental ical conditions, but cannot be measured. muscular effects can have profound im- Content homeostatic systems: acid-base, blood gas- An algorithm based on a standard model pact on patient morbidity. ® COHb, MetHb es, and electrolytes as well as the determi- of extra-cellular fluid must be used to cal- There is a well-documented need for ® Lactate nants, mediators, and substrates of those culate BE(ecf). The reference values for monitoring sodium and chloride during ® CK-MB, T and I systems. both BE quantities are the same, and in parenteral therapy and the analytical com- Using the AACC criteria for defining clinical conditions they both change in the patibility of the electrolytes makes the *Based on AACC Test Category 2 (9) urgent testing, an updated list of urgent same direction—the only difference is in measurement of all electrolytes, along tests would contain a combination of an- the amount of change with the blood gases, an operationally and alytes from the original AACC list along clinically prudent course of action in a operational compatibility of the timing with new analytes that also fit the criteria wide range of clinical testing environ- and urgency related test groups when (Table 2). Table 2. STAT Testing ments. making a decision on the purchase of new As markers of fundamental homeo- 2000—An Updated List critical care instrumentation. static mechanisms, the classic blood gas Which Tests Should Be Even considering all of these factors, of Urgent Analytes Considered Important? measurements—PCO2 and PO2—have there are a number of commercially avail- been and clearly remain the best labora- Traditional Urgent Blood Taking into account current analytical able instruments that meet the clinical and tory-based test profile for assessing Analytes* technologies and therapies, a new list of operational requirements for urgent, im- acid–base status and gas exchange in he- ® Blood Gases : PO2,PCO2 analytes based on the criteria for AACC portant, and responsible testing. Most of modynamically stable patients. The mea- ® Hydrogen Ion Concentration: test category 2 might contain the addi- these systems allow for flexibility based on sured blood gas quantities and their pH (cH+) tional determinations listed in Table 3.For the needs of a care unit’s patient popula- derivatives (e.g., base excess) provide the ® Hemoglobin: Hb or example, new measurement technologies, tion and specialties, although some sys- basis of understanding for acid–base bal- Hct/Packed Cell Volume such as direct “whole blood” lactate or tems are more flexible than others. ance and oxygenation status, but overlook (PCV) ionized magnesium using ion-selective Another important consideration some physiologically key elements such as ® Electrolytes: Na+,K+, electrodes (ISEs), make it possible to read- when deciding on a STAT test menu is the actual amount of oxygen being trans- Ionized Ca++ ily obtain quantitative information on what the Health Care Financing ported and used. In some situations, the ® Glucose these analytes that was not feasible in the Administration (HCFA) allows in terms lack of this information can impact clin- ® Prothrombin (PT) past. Similarly, significant new therapeu- of test profiles. Laboratorians must con- ical decision-making. ® Partial Thromboplastin ( PTT) tic intervention for heart attack patients sider that the operational convenience of Measurement of pH or hydrogen ion ® Platelets warrants the addition of CK-MB and the any device may be limited by government concentration (cH+) provides a current as- cardiac troponins I and T to this list. regulation. Without the availability of in- New Urgent Blood Analytes sessment of acid–base level, but does not Unfortunately, the remaining analytes clusive profiles on a patient-to-patient ba- ® Base Excess of Blood (BE) or give an indication of the cause. The addi- on the list of important blood analytes do sis, adding STAT analytes to the test menu of Extra-cellular tional measurement of not pass the test for clinical, analytical, and could push the limits of operational and Fluid/ tension of arterial blood, PCO (aB) pro- operational compatibility with the other economic responsibility, especially when 2 ® Activated Clotting Time vides an ability to assess the extent of the analytes on either the urgent or impor- considering some of the third-party re- (ACT) respiratory or ventilatory component of tant lists. Current technology for mea- imbursement criteria enforced by HCFA’s any acid–base disorder. *Based on AACC Criteria (9) suring them is not readily compatible with Office of the Inspector General. However, when these analyte quanti- the technology for the other analytes.

CLINICAL LABORATORY NEWS AUGUST 2000 13 Making It Work glycemic brain damage. Stroke Robert F. Moran, PhD, 1986;17:699–708. The laboratory testing paradigm contin- FCCM, FAIC, is chief ues to shift as clinicians’ needs for faster Table 4. Points to 3. Berger L, Hakim AM. The association executive officer of mvi turnaround time increases, as acceptable Consider When of with cerebral edema Sciences, an educational and sample sizes get smaller, and as technolo- Selecting New Critical in stroke. Stroke 1986;17:865–71. consulting organization gy takes some of the art and science from Care Analytical Systems 4. Friedman G, Berlot G, Kahn RJ, based in Mass. A fellow in the American laboratory measurement and makes it Vincent JL. Combined measurements of College of Critical Care Medicine and in ® Similar ordering situations possible to move it outside the laborato- blood lactate concentrations and gastric the American Institute of Chemists, he ry. How are the seemingly incompatible and frequency of ordering has been a member of AACC since 1965. intramucosal pH in patients with severe demands of highest accuracy in patient ® Compatible degree of He is also active in NCCLS, currently . Crit Care Med 1995;23:1184–93. testing reconciled with requirements that urgency serving as an officer of the NCCLS seem to push accuracy in the opposite di- ® Usually “simultaneous”need 5. Gutierrez G, Wulf ME. Lactic Executive Committee. rection? How should laboratorians and for profile elements in sepsis: a commentary. Intensive Care clinicians reconcile quality patient care ® Critical or critical and Med 1996;22:6–16. with economic and the requirements of important analytes 6. Hovda DA. Effect of hyperglycemia This article is available as the authorities that pay for the care? These ® NOT routine/experimental after cortical injury. Crit Care Med are difficult questions to answer, but if we ® Compatible sample handling 1997;25:1267–8. an 8 1/2" x 11" reprint on remain aware of the basic issues, we can and anticoagulants 7. Kessler KM, Kozlovskis P, Trohman better assess individual situations and ar- ® the AACC web site rive at workable solutions. Measurement technology RG, Myerburg RJ. lactate: prog- ® Compatible maintenance nostic marker for recurrent cardiac ar- (www.aacc.org/cln/ REFERENCES intervals rest? Am Heart J 1987;113:1540–4. 1. Aduen J, Bernstein WK, Miller J, et al. ® Sensor life 8. Maley TC, D’Orazio P. Biosensors for clninput.stm).Click on Relationship between blood lactate con- ® Reagents blood glucose: a new question of what is centrations and ionized calcium, glu- ® Calibration and calibrators measured and what should be reported. Clinical Laboratory News cose, and acid-base status in critically ill ® Appropriate levels of Clin Lab News 1995;21(1):12–13. and then “Feature and noncritically ill patients. Crit Care analytes measured 9. Guidelines for providing quality stat ® Med 1995;23:246–52. Matching reference methods laboratory services, AACC Press, Articles.” 2. Auer RN. Progress review: hypo- Washington, DC, 1987. CLN

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