Biomedical subjects
Publications and source records attributed to J Toffaletti.
Despite the many advantages of POCT, the biggest obstacle for the lab often becomes documentation and billing of tests performed at remote locations. To solve this problem, this lab took advantage of a wireless radiofrequency network that had been installed for the pharmacy to transmit and receive patient histories. They decided to use this same system to communicate between the analyzers and the LIS.
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Blood lactate measurements are being used clinically as an indicator of circulatory impairment and the overall state of oxygenation of patients in critical care. This report briefly covers the areas of usage of lactate testing, lactate biochemistry, appropriate sample handling, and clinical interpretation of lactate measurements in critical care monitoring including pediatric cardiac surgery and extracorporeal membrane oxygenation (ECMO).
For the purpose of demonstrating both the clinical value and economic advantages of using blood lactate as a marker for haemodynamic instability, we present the clinical guidelines for when to measure blood lactate and how these measurements are interpreted in two clinical settings: following open-heart surgery for complex congenital heart disease, and in determining both the need for and the effectiveness of extracorporeal membrane oxygenation (ECMO). Several case histories are presented that demonstrate the conditions which can elevate blood lactate concentrations and the resulting therapeutic interventions, based on use of volume support, inotropic support, vasodilators, and/or ventilation, that can lead to a successful outcome in these patients. In one of the case histories a greatly elevated blood lactate apparently indicated that intracranial hemorrhage had occurred in a patient who later expired.
The biochemical and physiologic bases for clinical use of ionized calcium, magnesium, or lactate measurements are described, with emphasis on the critical care setting. Ionized calcium or magnesium are usually measured to prevent hypocalcemia or hypomagnesemia, conditions that most affect cardiovascular function. Blood lactate measurements have been used more frequently in the last 5 years, despite decreases in overall laboratory test volume. Lactate measurements appear to have clinical value, particularly for children having major cardiac surgery or extracorporeal membrane oxygenation. The changes in test volumes in the past few years due to the changing economic climate in medical practice are also described.
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We describe the construction, the reaction principle and the performance of Reflotron K+, a new Reflotron test for the quantitative determination of potassium in serum and heparinized plasma. The reaction principle is based on the introduction of the potassium cation via valinomycin into a non-polar phase; the accompanying loss of protons from the non-polar phase is detected by the colour change of a pH indicator. The multicentre evaluation of the reagent carrier system showed in median CVs of < 0.9% (within-series in heparinized plasmas) and 1.3% (run-to-run in control sera). The recovery in control sera was +/- 4% for seven laboratories. In the method comparison with flame emission spectrometry, using sera and heparinized plasma samples, regression analysis yielded correlations with slopes of 1.00 +/- 0.04 (median slope 1.005) and negligible intercepts. The reagent carrier system showed a linear response in the measuring range 2-12 mmol/l. Bilirubin (up to 513 mumol/l), triacylglycerols (up to 5,7 mmol/l), sodium (135-189 mmol/l) and ammonium ions (up to 590 mumol/l) did not interfere with the test. Comparison with the results from flame atomic emission spectrometry shows that the recoveries of Reflotron K+ and the direct potentiometric method are slightly and similarly influenced by total protein. With a panel of 28 drugs tested, no interference could be detected. Reflotron K+ provides a precise and reliable procedure for the measurement of potassium in serum and heparinized plasma.
We evaluated a new analyzer that measures lactate in undiluted whole blood by direct (or undiluted) amperometry [Nova Stat Profile 7 Analyzer (SP7); Nova Biomedical, Waltham, MA] by comparing it with two other analyzers, one for measuring lactate in whole blood by indirect (or diluted) amperometry [Model 2300; Yellow Springs Instrument Co. (YSI), Yellow Springs, OH] and another for measuring lactate in plasma by enzymatic colorimetry (aca; Du Pont Co., Wilmington, DE). All between-method comparisons of the three methods showed that the results for plasma were comparable (Sy/x = 0.24-0.33 mmol/L). Within-method comparisons by the YSI differed substantially between plasma and whole blood (Sy/x = 0.48 mmol/L), but within-method comparisons by the SP7 produced better agreement between plasma and whole blood (Sy/x = 0.18 mmol/L). The difference between whole blood and plasma by YSI is related to hematocrit, with the greatest differences noted for samples with the highest hematocrit. Serum lactate measured by SP7 had between-day imprecision (CV) ranging from 12% at 0.5 mmol/L to 4.2% at 3.7 mmol/L, showed a linear standard curve to at least 11.5 mmol/L, and was independent of hematocrit. There was a mean bias of approximately 0.4 mmol/L for results in the reference range for both plasma and whole blood by SP7 compared with plasma results by either aca or YSI.
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Because the effects of specific changes in magnesium or protein-bound calcium on biologic processes in humans have not been clearly defined, we developed an experimental system to specifically lower either ionized calcium, protein-bound calcium, or ionized magnesium. As an indicator of the biological effect of these changes, we measured parathyroid hormone (PTH) in blood. To selectively dilute only one constituent, we infused one of four specially prepared solutions into each of six healthy blood donors following ordinary blood donation. Each donor received at random 450 mL of a different solution at four different blood donations. The respective concentrations of ionized calcium (mmol/L), total magnesium (mmol/L), and albumin (g/L) in these fluids were as follows: control fluid, 1.25, 1.20, 40; no calcium fluid, 0, 1.20, 40; no magnesium fluid, 1.25, 0, 40; no albumin fluid, 1.25, 1.00, 0. Using selective in vivo dilution of the volunteers' blood, we specifically lowered either (1) ionized calcium by 0.07 mmol/L (5.5%), (2) protein-bound calcium by 0.09 mmol/L (10%), or (3) ultrafiltrable magnesium by 0.03 mmol/L (4.8%). While measurements of intact PTH showed that concentrations of PTH in blood did not respond to either decreased ultrafiltrable magnesium or decreased protein-bound calcium, these measurements showed that PTH increased by 400% within 10 minutes in response to decreased ionized calcium.
By analyzing whole blood containing no anticoagulants (uncoagulated whole blood) immediately after collection, we evaluated the relative changes in the concentrations of ionized calcium and other electrolytes in whole blood collected in dry heparinized syringes and in serum prepared from blood collected in evacuated blood-collection tubes. Using these dry heparinized syringes, we collected and analyzed whole blood that contained either 33 or 13 int. units of lithium heparin or 40 int. units of electrolyte-balanced heparin per milliliter of blood. We evaluated the effects both of these heparins at different concentrations of ionized calcium and of the incomplete filling of the syringes. We conclude that: (a) when analyzed within 2-3 min after collection, uncoagulated whole blood provides ionized calcium results unaffected by anticoagulants or cellular metabolism; (b) the preparation of serum unpredictably changes ionized calcium; (c) the use of dry electrolyte-balanced heparin virtually eliminates the interference in ionized calcium concentrations between 0.9 and 1.6 mmol/L; and (d) incomplete filling of electrolyte-balanced heparinized syringes produces no effect in syringes two-thirds full (60 int. units/mL heparin concentration) and a small effect in syringes one-third full (120 int. units/mL heparin).
We compared relative increases in creatine kinase (EC 2.7.3.2) MB isoenzyme (CK-MB) after reperfusion in myocardial infarction for four popular methods: electrophoresis, immunoinhibition, the "Magic Lite" (Ciba-Corning) system, and the Stratus (Dade). In a method comparison study, we confirmed that all four methods correlated (r greater than 0.95). Electrophoresis demonstrated the greatest scatter about the regression line, immunoinhibition the least. For CK-MB quantities near each method's "positive cutoff" indicating myocardial infarction, results by all methods agreed in 95% of samples. To characterize relative increases in CK-MB, we computer-fitted data obtained from each method for serial specimens collected from six acute myocardial infarction patients during myocardial reperfusion. Although for each individual patient the four methods appeared to exhibit parallelism, the methods differed significantly in terms describing their appearance rate, peak-time & fall-off, and time-to-peak activity. Consistent with these data, we found that the relative CK-MB increases at various times after reperfusion, compared with baseline concentrations, are method-dependent. Therefore, when using CK-MB for indicating coronary patency, one must develop specific limits for each method utilized.
Characteristics of CK-MB, the MB1 and MB2 isoforms, and the MB2/MB1 ratio are described in six acute myocardial infarction (AMI) patients in whom the infarct-related artery was identified and, after intervention, normal coronary flow was re-established. After myocardial reperfusion, washout of CK-MB and the MB2 isoform occurred in parallel, with CK-MB peaking between 5.75 and 10.0 h, and MB2 peaking between 4.50 and 8.00 h. In five of the six patients, MB1 peaked between 8.75 and 15.5 h; the MB2/MB1 ratio demonstrated the earliest peak from 0.75 to 2.25 h. When we compared this study group to an additional 10 AMI patients who had achieved myocardial reperfusion earlier, we found a significant difference (P less than 0.005) for all tests, except MB1 isoform activity, as early as 50 min after reperfusion. This same comparison, by logistic-regression analysis, showed that the MB2/MB1 ratio discriminated between the groups 50 min after reperfusion (P less than 0.05); MB2 showed near-significance at 100 min (P less than 0.057); and CK-MB achieved significance after 200 min (P less than 0.05). CK-MB, the MB2 isoform, and especially the MB2/MB1 ratio show potential for the early, noninvasive detection of myocardial reperfusion.
We have studied, both in vitro and in vivo, the quantitative effects of lactic acid production on concentrations of ionized calcium, bound calcium, pH, bicarbonate, and albumin. To do so, we examined the effects of addition of aqueous solutions of either hydrochloric acid, lactic acid, or lithium lactate to blood; we studied in vitro accumulation by storing blood sealed in tubes at room temperature for 5 h, then exposing the blood to air; and we induced in vivo production of lactic acid in healthy individuals who climbed stairs for 10 min. Lactic acid evidently affects the ionized, protein-bound, and complex-bound calcium concentrations in the following ways: (a) hydrogen ions from lactic acid bind to protein, which decreases protein-bound calcium; (b) lactate chelates calcium ions from free ionized calcium and protein-bound calcium about equally; and (c) the loss of a millimole of bicarbonate, either by exposure of blood to air or by respiratory alkalosis, results in the release of about 7 mumol of calcium ions, which re-equilibrate with both the protein-bound and ionized calcium. Because lactate apparently removes calcium ions directly from albumin, our study indicates that protein-bound calcium readily provides calcium ions that buffer changes in the concentration of ionized calcium.
We evaluated an automated method for measuring total magnesium in serum, plasma, or urine that utilizes dry multilayered thin-film reagents and reflectance photometry for use on the Kodak Ektachem 400 analyzer. Comparison of magnesium results by this method and by atomic absorption revealed the following: the results on samples from a variety of patients agreed closely, the thin-film methodology was not affected by icteric, hemolyzed, or lipemic samples, and over 100 drugs studied did not interfere. Only very high concentrations of citrate and calcium affected magnesium results by this method. Both the accuracy and versatility of the thin-film method are well suited to routine, fast response, and pediatric testing in the clinical laboratory.
To determine if bias between different ionized calcium analyzers could be decreased, we analyzed 10 control fluids during a study in which ionized calcium was measured in more than 150 serum and whole-blood samples. After calibrating three ionized calcium analyzers (Radiometer ICA 1, Nova 8, and AVL 980) with the manufacturers' respective calibrators, we used the between-instrument differences of the control fluids to simulate recalibration of the analyzers during each analytical run. A filtered human serum pool containing ionized calcium at 1 mmol/L concentration, with CO2 removed and having no added buffer, was the only material that consistently decreased between-analyzer bias of both serum and whole blood. Another human serum pool containing about 1.3 mmol of ionized calcium and about 10 mmol of bicarbonate per liter was even better at minimizing analyzer biases for serum samples, but was not as effective for whole-blood samples. Some additives used to buffer pH apparently adversely affected both the accuracy and precision of some, but not other, calcium ion electrodes. We conclude that if a reference material is developed for calibration of ionized calcium analyzers, it should be tested on several analyzers for use with both serum and whole blood, and it should be at least as effective as a human serum material, such as that used here.
We studied 16 patients undergoing open-heart surgery and heart-lung bypass, to examine the relationship between ionized calcium and lactate. Blood was sampled at successive stages of the operation for measurement of ionized and total calcium, lactate, blood gases, pH, hematocrit, and other constituents. We found that correlations between ionized calcium and lactate were positive and statistically significant (p less than 0.05), both among and within patients. The linear regression of ionized calcium on lactate remained highly significant (p less than 0.0001) after adjustment for variability among patients and across operative stages as well as after correction for pH and hemodilution. The significant regressions between calcium and lactate, both before and after administration of calcium, indicate a relationship for calcium and lactate in patients undergoing open-heart surgery.