Blood gases and oximetry: calibration-free new dry-chemistry and optical technology for near-patient testing.

The first calibration-free Near-Patient-Testing instrument (NPT7) for blood gases, pH and oximetry has been developed. With cartridges of 30 single-use cuvettes, the NPT7 needs no preparation prior to sample aspiration, no manual calibration, and no maintenance apart from paper and cartridge changes and regulatory quality control. Each cuvette measures pCO2, pO2, pH, total hemoglobin (ctHb), oxygen saturation (sO2), fractions of carboxyhemoglobin (FCOHb) and methemoglobin (FMetHb) on 95 microl whole blood with a 110-s measuring cycle. The measurement principles are as follows: pCO2-three-wavelength infrared spectroscopy of dissolved CO2; pO2-measurement of O2-induced changes in the decay time of phosphorescence; pH-the absorbance spectra change of an azo-dye color indicator; and oximetry is performed with a 128-wavelength spectrophotometer. We determined the within and between instrument variations with tonometered whole blood on seven prototype instruments, using between one and five control levels per analyte. The 95% analytical performance limits: +/-(/Bias/ +2 xS(T)) in the NPT7 instrument matched the analytical performance criteria for the measured quantities as defined by AACC guidelines. The application of these optical measuring methods for blood gases, pH and oximetry in single-use devices introduces a new concept into point-of-care testing (POCT), where preanalytical activities otherwise associated with instrument preparation are eliminated.

Assessment of pH and oxygen status during hemodialysis using the arterial blood line in patients with an arteriovenous fistula.

BACKGROUND: In patients with arteriovenous fistulas, assessment of pH and oxygen status during hemodialysis (HD) using the extracorporeal dialysis arterial blood line is widely used both in daily routine and in most studies investigating hypoxia during HD. We designed this study to evaluate whether results of blood gas samples drawn from the extracorporeal arterial line were clinically acceptable in assessing oxygen status. METHODS: We compared samples drawn from the extracorporeal arterial line with conventionally arterial punctures during 18 routine HD sessions. The samples were drawn simultaneously and analyzed immediately for blood gases, pH and hemoximetry values. RESULTS: No significant difference was found between the values from the radial artery and the extracorporeal arterial blood line except for FMetHb. CONCLUSION: Thus, obtaining samples from the extracorporeal dialysis arterial blood line to evaluate the parameters of the oxygen status (pH, pO(2), pCO(2), ctHb, sO(2), FCOHb and ctO(2)) during routine HD is a clinically convenient and accurate sampling approach.

Quantifying pulmonary oxygen transfer deficits in critically ill patients.

The clinical picture describing oxygen transfer deficits in literature is complicated by inconsistent terminology, and a weak perception of the influence total errors of measured and estimated values have on clinical decision-making. Clinical and analytical terminology: Terms like hypoxia, hypoxaemia and tissue hypoxia in clinical literature are often used synonymously. In present terminology, arterial hypoxia (pO2(a)) is considered to be based on measurements of oxygen tension in arterial blood. On the other hand, arterial hypoxaemia (ctO2(a)) is considered to be based on measurements of both pO2, total haemoglobin (ctHb), saturation (sO2), carboxyhaemoglobin (FCOHb), and methaemoglobin (FMetHb). Arterial hypoxia is simply a low oxygen tension in arterial blood. Arterial hypoxaemia is thus simply a low oxygen concentration in arterial blood. Pulmonary indices: The tension-based indices. At the bedside, assessment of the oxygen uptake in the lungs has been evaluated by calculating indices like pO2(a)/FO2(I),pO2(A-a),pO2(a/A) and the respiratory index (RI = pO2(A-a)/pO2(a)). The different oxygen tension-based indices all require the calculation of the alveolar oxygen tension from the alveolar equation. These calculations involve many assumptions (exact analytical measurements of the respiratory quotient (RQ), FO2(I), etc.) to be fulfilled, and might include clinically unacceptable errors. The concentration-based index (FShunt). Considering a fixed arterio-mixed venous oxygen difference (3-5 mL/dL), this index is by some researchers indicated to be superior to the oxygen tension-based (the correlation coefficient to the true measured shunt being 0.94 for the FShunt compared to 0.72 for the best tension-based (RI = pO2(A-a)/pO2(a))). However, the scatter around the line is considerable and this index seems to fail, as well as the tension-based in the many cases where the assumed difference is not equal to the assumed (3-5 mL/dL). The intrapulmonary shunt: The best available means of outlining the extent to which the pulmonary system contributes to hypoxic hypoxaemia, is to calculate the intrapulmonary shunt. It reflects the degree to which the lung deviates from ideal as an oxygenator of pulmonary blood. Exact calculation of the intrapulmonary shunt requires measurements of oxygen concentration in both arterial and mixed-venous blood samples. Calculation of the intrapulmonary shunt at 100% inspired oxygen represents the term (Qs/Qt). Venous admixture or the physiologic shunt (Qsp/Qt) represents measurements of the intrapulmonary shunt at less than 100% inspired oxygen. Interpretative guidelines for (Qsp/Qt) in critically ill patients having a pulmonary catheter are: A calculated shunt less than 10% is clinically compatible with normal. A shunt of 10-19% seldom would require significant support. A calculated shunt of 20-29% may be life threatening in a patient with limited cardiovascular function. A calculated shunt greater than 30% usually requires significant cardiopulmonary support. The necessity of sampling mixed-venous blood seems to be the most limiting factor for a widespread clinical use of shunt calculations.

Ionized calcium in blood: studies on patients with pulmonary disease.

A new automatic ionized calcium analyser ICA 2 (Radiometer, Copenhagen, Denmark) was used for studies of ionized calcium (cCa2+) in the arterial blood of patients with a compensated respiratory acidosis due to chronic lung disease. The data for 16 patients showed an unexpectedly high level of variation in cCa2+ (range, 1.01-1.25 mmol l-1) despite the fact that there was only a small degree of variability in pH (range, 7.38-7.51). cCa2+ was not correlated with pH as has been observed in acute respiratory disturbances. A highly significant negative correlation was found between cCa2+ and base excess (BE) (r = -0.81, P less than 0.0001), and between cCa2+ and carbon dioxide tension (PCO2) (r = 0.71, P less than 0.002). These correlations differed from those reported previously in acute respiratory disturbances. CCa2+ showed a significant positive correlation with oxygen tension (PO2) (r = 0.71, P less than 0.002). It is concluded that cCa2+ in arterial blood from patients with chronic lung disease is correlated with acid-base and gas quantities in an entirely different manner to that observed in acute acid-base disturbances in normal adults.

Critical analytical and clinical aspects of ionized calcium in neonates.

Clinical diagnosis in neonates is often based primarily on biochemical data, because clinical symptoms are difficult to assess and inconclusive. A knowledge of the validity of the data would therefore seem very important. Practical technical assessments lead me to conclude that measurement of ionized calcium at actual pH in anaerobic capillary samples of whole blood, currently practicable, is an easy and optimal laboratory analysis when biologically significant data are required for assessment of acute disturbances in calcium homeostasis of neonates. Values are given for ionized calcium, describing the relations in cord and maternal blood in uncomplicated pregnancies at term. Recent published cross-sectional and longitudinal reference values for ionized calcium, measured during the first weeks in healthy full-term and preterm neonates, seem to provide a new basis for the diagnosis and management of early neonatal hypocalcemia.

"Stat" measurements of L-lactate in whole blood and cerebrospinal fluid assessed.

A first-generation semi-automatic amperometric lactate analyzer (Yellow Springs Instrument Co.) was assessed for urgent ("stat"), rapid laboratory measurements in whole blood and cerebrospinal fluid. For whole blood, measured lactate concentration and hematocrit were linearly correlated. An improved equation is presented for estimating the concentration of lactate in plasma from measurements in whole blood. The 95% reference range for the concentration of lactate in paired samples of capillary and venous whole blood from 40 healthy laboratory adults was found to be 0.4-1.5 mmol/L and 0.3-1.5 mmol/L, respectively. The 95% ranges for lactate in whole blood from 24 uncomplicated vaginal deliveries at term were established for cord venous blood, 1.2-5.0 mmol/L; cord arterial blood, 1.6-5.5 mmol/L; and maternal venous blood, 1.7-6.6 mmol/L. The 95% paired ranges were established for 20 lumbar-anaesthetized urological patients without neurological disorders after induction of anaesthesia for venous whole blood and cerebrospinal fluid (venous blood, 0.5-1.3 mmol/L; cerebrospinal fluid, 1.1-2.4 mmol/L).

Calcium and other biochemical alterations induced by masseter spasm following suxamethonium.

Calcium and other biochemical disturbances are reported from the plasma of a child which presented masseter spasm following the administration of suxamethonium during the induction of halothane anesthesia. After masseter spasm, the ionized calcium concentration decreased whereas the total calcium level remained unchanged despite the occurrence of metabolic and respiratory acidosis. Throughout the rest of anesthesia, the total and ionized calcium concentrations continued to decrease. These variations may indicate that complex metabolic and biochemical events influenced the calcium binding to albumin and the calcium transfer into the muscle cells.

Age-related reference values for ionized calcium in the first week of life in premature and full-term neonates.

Reference values for ionized calcium were measured in anaerobic samples of capillary blood from 22 healthy premature neonates, gestational age 33-36 weeks, birth weight 1660-2480 g. Reference values (mean +/- 2SE) for premature neonates aged 5-12, 13-19, 25-48, 51-72, 77-99, 108-140, 150-185 h were: 1.21 +/- 0.16, 1.17 +/- 0.12, 1.21 +/- 0.16, 1.28 +/- 0.18, 1.34 +/- 0.14, 1.38 +/- 0.13, 1.40 +/- 0.16 mmol/l, respectively. Ionized calcium in 59 full-term neonates with mild pathological hyperbilirubinaemia (no phototherapy needed) and 28 neonates born by section (no neonatal complications) showed no statistical difference (unpaired t-test) in age-related values compared with matching healthy neonates with no clinical remarks. Data for full-term neonates were pooled and age-related reference values (mean +/- 2SE) for ionized calcium in capillary whole blood for 168 full-term neonates, gestational age 38-41 weeks, birth weight 2550-4700 g, aged 1-12, 13-24, 25-48, 49-72, 73-99, 99-120, 121-144, 146-168, 178-264 h were: 1.24 +/- 0.11, 1.19 +/- 0.12, 1.21 +/- 0.13, 1.22 +/- 0.14, 1.29 +/- 0.17, 1.35 +/- 0.12, 1.37 +/- 0.12, 1.38 +/- 0.16, 1.40 +/- 0.10 mmol/l, respectively.

Ionized calcium and acid-base status in arterial and venous whole blood during general anaesthesia.

Ionized calcium, pH, pCO2 and base excess (BE) have been measured in paired samples of anaerobically collected arterial (aB) and venous whole blood (vB) from patients under general anaesthesia and during recovery. A statistically significant decrease was found in the concentration of ionized calcium in anaerobic arterial and venous blood during induction of anaesthesia and during surgery partly due to variations in pH. Statistically significant correlations were found between logcCa2+ and pH (r = -0.67, p less than 0.001), and between cCa2+ and pCO2 (r = 0.66, p less than 0.001) in anaerobic arterial blood. The in vivo slope (dlogcCa2+/dpH) was found to be -0.15 +/- 0.08 and -0.14 +/- 0.06 for arterial and venous blood, respectively (mean +/- SE). The in vitro slope estimated by equilibrating arterial and venous serum at two pCO2 values was -0.22 +/- 0.03, and -0.21 +/- 0.03, respectively (mean +/- SE). Because of a considerable variability in slope we believe that the best clinical evaluation of ionized calcium is achieved by taking measurements from anaerobically collected whole blood. Interpolating or extrapolating ionized calcium to a standard pH of 7.40 on the basis of a standard slope may introduce unnecessary errors.

Plasma ionized calcium during paediatric anaesthesia: effects of pH and succinylcholine.

Variations of plasma ionized calcium and pH were studied in 16 children anaesthetized with halothane and succinylcholine for minor surgery. During anaesthesia, a close negative correlation was noted between pH and ionized calcium. Intubation was followed by a fall of the ionized calcium concentration. A mean decrease of 0.04 mmol X L-1 was noted, without pH change. The acute elevation of carbon dioxide following extubation allowed the in vivo effects of pH on ionized calcium to be studied. For each pH unit decrease, a mean rise of 0.60 mmol X L-1 of ionized calcium was found. During the study, no significant variations of plasma total calcium concentration were observed. The variations in the hydrogen ion concentration and the administration of succinylcholine were accompanied by changes of the free calcium ion concentration, due probably to alterations in calcium binding to proteins, and perhaps to the formation of a calcium complex with anions. Our results emphasize the importance of knowledge of the pH for the interpretation of ionized calcium variations in the presence of acid-base disturbances.

The effects of plasma volume variations on the calcium concentration during epidural anaesthesia.

The plasma variations of the ionized and total calcium concentration in relation to protein concentration and plasma volume were studied in 12 patients during epidural anaesthesia for transurethral prostatectomy. The most significant changes were noted during the onset of anaesthesia. From arrival in the operating theatre to start of operation, the plasma concentration of ionized calcium decreased from 1.28 (s.d. = 0.05) mmol/l to 1.22 (s.d. = 0.04) mmol/l and total calcium decreased from 2.39 (s.d. = 0.11) mmol/l to 2.17 (s.d. = 0.10) mmol/l. At the same time, however, the decrease in ionized calcium concentration and the increase in plasma volume were associated with a rise of 10.3% in the pool of free calcium ion in plasma. After the start of surgery, the plasma ionized calcium concentration remained almost unaffected throughout the rest of the study period. The total plasma calcium concentration as well as the total protein concentration remained stable during operation, only increasing after the end of surgery. The preoperative changes in the plasma calcium concentration may have been the result of both haemodilution and mobilization of calcium ions from its bone stores. Postoperatively, an increased urinary loss of calcium must have followed the administration of furosemide at the end of surgery.

Nuclear thyroxine binding in human mononuclear blood cells from hyperthyroid and hypothyroid patients before and after treatment.

Nuclear binding of [125I]T4 in human mononuclear blood cells was examined in six hyperthyroid and six hypothyroid patients before and after treatment. In hypothyroid patients the nuclear T4 binding was initially increased and subsequently normalized as the patients became euthyroid suggesting a homeostatic counter-regulation. The thyroid state did not affect the nuclear T4 binding in hyperthyroid patients. Treatment with methimazol however increased the nuclear T4 binding, suggesting either a direct effect of methimazol on the hormone-receptor interaction or that the patients had become slightly hypothyroid during the treatment. The TSH was shown not to affect nuclear T4 binding. The thyroid state of the patients did not significantly affect the nuclear accumulation of the T3 produced intracellularly by deiodination of T4.

Complex biochemical syndrome of hypocalcemia and hypoparathyroidism during cytotoxic treatment of an infant with leukemia.

Patients with cancer are especially vulnerable to the development of hyper- and hypocalcemia. These disorders may be the basic clinical manifestation of cancer or may result from vigorous cancer treatment. During cytotoxic treatment of a child with leukemia we describe the longitudinal course of ionized calcium in a complex syndrome of hypocalcemia and hypoparathyroidism. The results suggest that the development of severe hypocalcemia can be explained on the basis of hypoparathyroidism in relation to hyperphosphatemia, hypomagnesemia, and acute renal failure. The low ionized calcium was unsuccessfully treated with several doses of calcium levulinate but successfully treated with 1 alpha-hydroxycholecalciferol.

Plasma magnesium during epidural anaesthesia. A study in patients undergoing transurethral prostatectomy.

The variations of plasma magnesium concentration in relation to protein concentration and plasma volume were studied in 12 patients during epidural anaesthesia for transurethral prostatectomy. The most significant changes in plasma magnesium concentration were observed during the onset of anaesthesia. From the arrival in the operating theatre to the start of operation, the concentration of plasma magnesium decreased from 0.88 (SD 0.10) mmol/l to 0.82 (SD 0.10) mmol/l. At the same time, the increase of 16 per cent in plasma volume was associated with a rise of 8.4 per cent in the total amount of magnesium in plasma. After commencement of surgery, the plasma magnesium concentration was unchanged throughout the remainder of the study period. The total plasma protein concentration and the erythrocyte volume fraction decreased during the onset of anaesthesia, remained stable during surgery and returned to initial values one hour postoperatively. The pre-operative changes in the plasma magnesium concentration may have been the result of haemodilution and mobilisation of magnesium ion from its bone stores. Postoperatively, an increased urinary loss of magnesium must have followed the injection of frusemide at the end of surgery. The consequences of these variations in plasma magnesium concentration are unlikely to be of clinical significance, except in patients with pre-existing subclinical magnesium deficiency.

Patterns of ionized and total calcium in serum of children following suxamethonium.

Serum ionized and total calcium levels of forty children, aged 3 to 18 years, were studied before and after the administration of suxamethonium during halothane inhalation in 20 children under the age of 10 (group I) and 10 children over the age of 10 (group II), and during intravenous induction of anesthesia with pancuronium and thiopentone in 10 children over the age of 10 (group III). In all groups suxamethonium was followed by a small but significant (p less than 0.02) decrease in the serum ionized calcium concentration. The fall was greater in group I. The serum total calcium concentration was lowered in groups II and III. But the decrease was only significant (p less than 0.001) in group III. In group I, there was a great discrepancy in the changes in serum total calcium concentration ranging from a fall of 0.535 mmol.l-1 to a rise of 0.680 mmol.l-1. The decrease in the total calcium concentration may have been caused by the depolarizing action of suxamethonium leading to the migration of the calcium ions into the muscle cells. But the changes in the ionized calcium concentration are more complex and may involve the movements of this ion in the cells, its binding to the proteins and its complexion to anions.

Potentiometric measurements of ionized calcium in anaerobic whole blood, plasma, and serum evaluated.

The measurements of ionized calcium and pH in paired samples of anaerobic capillary whole blood, venous whole blood, venous plasma, and venous serum have been evaluated with a modified ICA 1 analyzer and compared with those of an unmodified ICA 1 analyzer. The unmodified instrument showed a significant difference between measurements in anaerobic venous whole blood, venous plasma, and venous serum, but the modified instrument did not. Statistically significant differences between the two instruments were found for whole blood (magnitude of mean difference magnitude of = 0.053 mmol/L) and for venous serum (0.016 mmol/L), but not for venous plasma. The error of residual liquid junction potential due to blood cells, previously found in the unmodified ICA 1 (salt bridge: KCl, 2.68 mol/kg) was eliminated and independent of the erythrocyte volume fraction in the modified ICA 1 (salt bridge: sodium formate, 4.56 mol/kg). From studies of procedures for measurements of ionized calcium in anaerobically handled samples, we recommend the use of anaerobic whole blood for measuring ionized calcium.

Amniotic fluid analysis in prenatal diagnosis of neural tube defects: a comparison between six biochemical tests supplementary to the measurement of amniotic fluid alpha-fetoprotein.

Concanavalin A (con A) and lens culinaris agglutinin (LCA) microheterogeneity pattern of AFP (crossed affinity immunoelectrophoresis), alpha-2-macroglobulin and synaptic membrane protein D-2 (rocket immunoelectrophoresis) and qualitative (polyacrylamide gel electrophoresis) and quantitative (enzyme kinetic reaction rate) acetylcholinesterase were analysed in 87 consequtive samples from normal pregnancies and 37 abnormal samples (fetal neural tube defect or abdominal wall defect). Very few false positive results were obtained in normal pregnancies with any of the tests. In all cases of neural tube defects the correct result was obtained with qualitative acetylcholinesterase analysis, whereas only 2/3 of the abdominal wall defects were correctly predicted. Testing with con A or LCA was less optimal in neural tube defects, whereas all abdominal wall defects could be predicted correctly. Acetylcholinesterase in the quantitative test and protein D-2 did not decrease the rate of false results. Determination of the alpha-2-macroglobulin concentration performed well in the present study, but is not recommended because of the very high susceptibility to contamination of amniotic fluid with fetal or maternal blood.