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O Siggaard-Andersen

Publications and source records attributed to O Siggaard-Andersen.

At least 19 recordsLinked to original sources

International Federation of Clinical Chemistry (IFCC). Recommendation on mean molar activity coefficients and single ion activity coefficients of solutions for calibration of ion-selective electrodes for sodium, potassium and calcium determination.

In principle, flame photometry measures substance concentration, and ion-selective electrodes (ISEs) measure ion activity. However, the situation regarding the comparison of results from the two techniques when applied to blood plasma is complex. The problem can be approached experimentally from the point of view of calibration of ion-selective electrodes with concentration calibrators, and similar procedures are adopted for commercial ISE-based clinical analysers. Nevertheless, there is interest in the evaluation of single ion activities in blood plasma and solutions simulating its ionic composition. Solutions are proposed for calibrating ion-selective electrodes for the determination of sodium, potassium and calcium. It is recommended that the values for single ion activities derived from the Pitzer treatment of mixed electrolyte solutions be adopted, because, although this has some empirical features, it has a sounder theoretical basis than the previously used Stokes-Robinson-Bates hydration approach.

Calcium

The Oxygen Status Algorithm on-line with the pH-blood gas analyzer.

BACKGROUND: The Oxygen Status Algorithm is a computer program for interpretation of pH-blood gas measurements. Recently the facility for on-line transfer of measured data from the pH-blood gas analyzer (ABL 520) to the computer with instant calculation, graphical display, and print-out of the oxygen status and the acid-base status of the blood has been implemented. OBJECTIVE: To describe experiences with routine application of the Oxygen Status Algorithm in an intensive care unit and to describe recent improvements of the program. DATA SOURCES: Routine pH-blood gas analyses during a two year period with an average of 40 analyses per day. RESULTS: Several unexpected results were disclosed, especially with respect to abnormal haemoglobin-oxygen affinity, causing suspicion of low 2,3-diphosphoglycerate concentration and hypophosphatemia. The criteria for routine administration of oxygen could be revised on the basis of the oxygen extraction tension. The program was expanded to allow the printing of a cumulated patient report, and modified to allow calculation of the oxygen consumption rate on the basis of simultaneous measurements on the arterial and the mixed venous blood. The program and the computer hardware functioned well in continuous operation during the whole study. It proved to be difficult, however, to ensure that all measurements were supplemented by information on the patient temperature and the fraction of inspired oxygen. CONCLUSION: The Oxygen Status Algorithm provides a more detailed description of the oxygen status and the acid-base status of the blood than currently employed. The interaction between the arterial oxygen tension, the haemoglobin oxygen capacity and the haemoglobin oxygen affinity is displayed graphically and the degree of compensation among these three properties is expressed in terms of a single quantity: the oxygen extraction tension. The program also provides an interactive interpretation, allowing a rapid prediction of the expected effect of therapeutic intervention. Nevertheless, implementation of the program in the daily routine requires an intensive educational effort among physicians as well as nurses and laboratory technicians.

Acid-Base Equilibrium

Erythrocyte 2,3-diphosphoglycerate depletion associated with hypophosphatemia detected by routine arterial blood gas analysis.

OBJECTIVE: To describe a clinical case where an extremely low erythrocyte 2,3-diphosphoglycerate concentration (2,3-DPG) was discovered by routine blood gas analysis supplemented by computer calculation of derived quantities. The finding of a low 2,3-DPG revealed a severe hypophosphatemia. DESIGN: Open uncontrolled study of a patient case. SETTING: Intensive care observation during 41 days. PATIENT: A 44 year old woman with an abdominal abscess. INTERVENTIONS: Surgical drainage, antibiotics and parenteral nutrition. MEASUREMENTS AND RESULTS: daily routine blood gas analyses with computer calculation of the hemoglobin oxygen affinity and estimation of the 2,3-DPG. An abrupt decline of 2,3-DPG was observed late in the course coincident with a pronounced hypophosphatemia. The fall in 2,3-DPG was verified by enzymatic analysis. CONCLUSION: 2,3-DPG may be estimated by computer calculation of routine blood gas data. A low 2,3-DPG which may be associated with hypophosphatemia causes an unfavorable increase in hemoglobin oxygen affinity which reduces the oxygen release to the tissues.

2,3-Diphosphoglycerate

Changes in plasma ionized calcium and magnesium in blood donors after donation of 450 mL blood. Effects of hemodilution and Donnan equilibrium.

The plasma concentration of ionized calcium and ionized magnesium in 26 blood donors decreased 0.01 mmol/L during blood donation. The changes could be explained by admixture of interstitial fluid. About 162 mL or 36% of the donated blood was replaced by interstitial fluid during blood donation. From the changes in concentration and hematocrit we could estimate the composition of the added fluid. The concentration of protein was much lower than in plasma. The concentration of protein-bound and free cations was also lower, in accord with the Donnan theory. We conclude that blood donors immediately after blood donation are unsuited as a reference population for proteins and ions.

Albumins

Oxygen status of arterial and mixed venous blood.

OBJECTIVES: To describe system requirements for determination of the oxygen status of the blood using the oxygen status algorithm, a computer program. To define the oxygen extractivity, a term we propose, of the arterial blood and the oxygen extraction tension. To describe the different causes of tissue hypoxia, and the clinical interpretation of mixed venous oxygen tension and oxygen consumption rate. DATA SOURCES: Previous physiological and clinical studies related to oxygen status of the blood. DATA SYNTHESIS: The oxygen status algorithm calculates the oxygen extraction tension and generates the oxygen graph as an aid in interpreting oxygen status of the patient. A cybernetic scheme explains the causes of tissue hypoxia and forms the basis for the interpretation of changes in the mixed venous oxygen tension. A diagram with the mixed venous oxygen tension on the abscissa and the oxygen consumption rate on the ordinate illustrates the oxygen flux dependent oxygen consumption rate. A graph shows the relationship between mixed venous oxygen tension and oxygen delivery. CONCLUSIONS: The oxygen status of arterial blood comprises three groups of quantities related to arterial oxygen tension, hemoglobin oxygen capacity, and hemoglobin oxygen affinity. Disturbances in one of these groups may be compensated by opposite changes in one or both of the other. The oxygen extraction tension indicates the degree of compensation, and mixed venous oxygen tension is the key parameter in evaluating the presence of a state of oxygen flux-dependent oxidative metabolism.

Algorithms

Oxygen status algorithm, version 3, with some applications.

The Oxygen Status Algorithm is a computer program which uses measurements from a pH & blood gas analyser and a hemoximeter to calculate the oxygen status and the acid-base status of the arterial blood. Version 3 features on-line data collection from the analyser; storage of up to 2000 patient cases in a Lotus 123 file format; printing of a Cumulated Patient Report in addition to the Patient Status Report; combination of arterial and mixed venous data for calculation of the shunt and the oxygen consumption rate (when cardiac output is keyed in); calculation of reference values for fetal haemoglobin for newborns (when gestational age is keyed in). Examples of applications answer the following questions: 1) Does hyperventilation improve the oxygen supply to the tissues? No, for a normal person a slight hypoventilation with a pCO2 of 8.5 kPa provides a maximal oxygen extraction tension. 2) What is the optimal hyperventilation at the top of Mt. Everest (ambient pressure 33 kPa)? Hyperventilation to a pCO2 of about 1.4 kPa provides a maximal oxygen extraction tension of 2.4 kPa for an unacclimatized person. 3) Which change in haemoglobin oxygen affinity would be equivalent to a decrease in arterial pO2 to 6.3 kPa? The oxygen extraction tension would decrease to 4.0 kPa and the same value would be caused by a decrease in half-saturation tension to 2.8 kPa, a decrease which could be due to a moderate alkalaemia (pH = 7.54) combined with a moderately decreased 2,3-diphosphoglycerate concentration (3.4 mmol/L). 4) Is temperature correction of the measured pO2 and pCO2 to the actual body temperature needed? Yes, for example, omitting temperature correction even when the patient temperature is only slightly decreased to 36 degrees C would result in a negative value for the calculated arterio-venous shunt fraction when the actual value, using temperature correction, is 11%. 5) Does the alpha-stat approach of pCO2 and pH regulation in hypothermia, where pH is allowed to rise as in blood in vitro, cause a fall in mixed venous pO2 below the critical value? No, although the mixed venous pO2 will be lower than with the pH-stat approach (constant pH at body temperature), it remains above the critical mixed venous pO2 level. The program is intended for clinical routine use as well as teaching purposes. It has context sensitive help as well as an extensive help index. A number of "demo" cases are provided with annotations in a separate file.

2,3-Diphosphoglycerate

Oxygen and acid-base parameters of arterial and mixed venous blood, relevant versus redundant.

A complete pH and blood gas analysis of arterial and mixed venous blood may comprise more than forty different quantities. We have selected sixteen, including patient temperature. The arterial oxygen tension group includes the oxygen tension, fraction of oxygen in inspired air, and fraction of mixed venous blood in the arterial (total physiological veno-arterial shunting). The haemoglobin oxygen capacity group includes effective haemoglobin concentration and fractions of carboxy- and methaemoglobin. The haemoglobin oxygen affinity group includes half-saturation tension and estimated 2,3-diphosphoglycerate concentration of erythrocytes. In a neonatal care unit fraction of fetal haemoglobin needs to be included. The arterial oxygen extra-activity is measured as the oxygen extraction tension, which indicates the degree of compensation among the oxygen tension, capacity, and affinity. The mixed venous group includes mixed venous oxygen tension, and, when measured, cardiac output, and oxygen consumption rate. The acid-base status includes blood pH, arterial carbon dioxide tension, and extracellular base excess. Other quantities such as haemoglobin oxygen saturation, respiratory index, total oxygen concentration (oxygen content), oxygen extraction fraction, oxygen delivery, and several others, provide no essential additional clinical information and are therefore redundant.

2,3-Diphosphoglycerate

Base excess or buffer base (strong ion difference) as measure of a non-respiratory acid-base disturbance.

Stewart in 1983 (Can J Physiol Pharmacol 1983: 61: 1444) reintroduced plasma buffer base under the name "strong ion difference" (SID). Buffer base was originally introduced by Singer and Hastings in 1948 (Medicine (Baltimore) 1948: 27: 223). Plasma buffer base, which is practically equal to the sum of bicarbonate and albuminate anions, may be increased due to an excess of base or due to an increased albumin concentration. Singer and Hastings did not consider changes in albumin as acid-base disorders and therefore used the base excess, i.e., the actual buffer base minus the buffer base at normal pH and pCO2, as measure of a non-respiratory acid-base disturbance. Stewart and followers, however, consider changes in albumin concentration to be acid-base disturbances: a patient with normal pH, pCO2, and base excess but with increased plasma buffer base due to increased plasma albumin concentration get the diagnoses metabolic (strong ion) alkalosis (because plasma buffer base is increased) combined with metabolic hyperalbuminaemic acidosis. Extrapolating to whole blood, anaemia and polycytaemia should represent types of metabolic alkalosis and acidosis, respectively. This reveals that the Stewart approach is absurd and anachronistic in the sense that an increase or decrease in any anion is interpreted as indicating an excess or deficit of a specific acid. In other words, a return to the archaic definitions of acids and bases as being the same as anions and cations. We conclude that the acid-base status (the hydrogen ion status) of blood and extracellular fluid is described in terms of the arterial pH, the arterial pCO2, and the extracellular base excess. It is measured with a modern pH-blood gas analyser. The electrolyte status of the plasma is a description of the most important electrolytes, usually measured in venous blood with a dedicated electrolyte analyser, i.e., Na+, Cl-, HCO3-, and K+. Albumin anions contribute significantly to the anions, but calculation requires measurement of pH in addition to albumin and is usually irrelevant. The bicarbonate concentration may be used as a screening parameter of a nonrespiratory acid-base disturbance when respiratory disturbances are taken into account. A disturbance in the hydrogen ion status automatically involves a disturbance in the electrolyte status, whereas the opposite need not be the case.

Acid-Base Equilibrium

The oxygen status of fetal blood.

OBJECTIVE: To estimate the acid-base and oxygen status of fetal blood and compare with maternal placental venous blood. DATA SOURCES AND CALCULATIONS: We selected pH and blood gas data from the literature pertaining to umbilical vein and artery blood obtained by cordocentesis and estimated values for the 30th and 40th gestational week. Average values for maternal venous blood leaving the placenta were estimated on the assumption of equal maternal arterio-venous and umbilical veno-arterial total oxygen concentration differences. RESULTS: pH and pCO2 of maternal blood leaving the placenta and umbilical vein blood are almost identical at week 30. A small pCO2 and pH difference may exist at week 40. The pO2 of the maternal placental venous blood and umbilical vein blood are almost identical at week 30, but at week 40 a pO2 difference indicates an umbilical arterio-venous shunting of as much as 30%. The fetal mixed venous pO2 falls from 2.6 kPa to 2.2 kPa from the 30th to the 40th gestational week. CONCLUSION: More accurate measurements are needed to confirm our results. Future measurements should be performed with a combined pH-blood gas analyser and haemoximeter to allow determination of the complete oxygen status of the blood.

Acid-Base Equilibrium

Classes of tissue hypoxia.

We identify eight causes of tissue hypoxia, falling into three classes, A, B, and C, depending upon the effect on the critical mixed venous pO2 and the optimal oxygen consumption rate. The critical mixed venous pO2 is the value above which the oxygen consumption rate is optimal and independent of the mixed venous pO2 and below which the oxygen consumption rate decreases towards zero. Class A hypoxia: primary decrease in mixed venous pO2. Causes: 1) ischaemic hypoxia (decrease in cardiac output), 2) low-extractivity hypoxia (decrease in oxygen extraction tension, px). Class B hypoxia: primary increase in critical mixed venous pO2. Causes: 1) shunt hypoxia (increased a-v shunting), 2) dysperfusion hypoxia (increased diffusion length from erythrocytes to mitochondria and/or decreased total capillary endothelial diffusion area, e.g., tissue oedema, microembolism), 3) histotoxic hypoxia (inhibition of the cytochrome chain). Class C hypoxia: primary increase in optimal oxygen consumption rate. Causes: 1) uncoupling hypoxia (uncoupling of the ATP formation associated with O2 reduction), 2) hypermetabolic hypoxia (increased energy metabolism, e.g., due to hyperthermia).

Adenosine Triphosphate

International Federation of Clinical Chemistry (IFCC), Committee on pH, Blood Gases and Electrolytes: approved IFCC recommendation on definitions of quantities and conventions related to blood gases and pH.

Terminology in blood pH and gas analysis can be confusing, both because more than one name has been used for the same quantity, and because the same name has been used for more than one quantity. In addition, several calculated quantities are commonly used, but in some cases many different algorithms have been published for a single quantity. This document contains definitions of the most useful quantities in blood pH and gas analysis, and presents algorithms for the most useful calculated quantities. Use of these should lessen confusion among users and should also result in data that are more comparable among laboratories.

Algorithms

Composition of interstitial fluid.

In several previous experiments to determine the composition of interstitial fluid, the results varied depending on the collecting technique, and the electrolyte concentrations differed from those of a hypothetical ultrafiltrate of plasma. In our approach, since a change of position from standing to supine is accompanied by hemodilution with interstitial fluid, we used the changes in hematocrit and composition of plasma in 20 subjects before and after lying down to calculate the composition of added interstitial fluid. The estimated protein concentration was 20.6 g/L, and the concentrations of total calcium and magnesium were low, in accord with a lower concentration of protein-bound calcium and magnesium. The activity of free cations was also lower, in agreement with a Donnan equilibrium potential of 1 mV across the endothelium. The concentration of leukocytes and platelets decreased according to the hemodilution, implying no escape or mobilization of these elements.

Adult

International Federation of Clinical Chemistry (IFCC). Scientific Division. Committee on pH, Blood Gases and Electrolytes. Approved IFCC recommendations on whole blood sampling, transport and storage for simultaneous determination of pH, blood gases and electrolytes.

Pre-analytical variables, e.g., specimen collection, transport, and storage, can contribute significantly to inaccurate pH, blood gas, and electrolyte values. The International Federation of Clinical Chemistry (IFCC), through its Committee on pH, Blood Gases and Electrolytes, has developed specific recommendations to minimize the undesirable effects of pre-analytical variables. The Committee has drawn upon the experiences of its own members as well as published data by others. Specifically, the Committee has included pertinent guidelines and suggestions by the IFCC Working Group on Selective Electrodes (WGSE), the National Committee on Clinical Laboratory Standards (NCCLS), and the Electrolyte/Blood Gas Division of the American Association for Clinical Chemistry (AACC). This paper will familiarize the reader with the effect of different types of specimen containers and anticoagulants. It discusses important aspects of specimen collection procedures including patients status and special precautions during specimen collection from indwelling catheters or cannulae. The paper also identifies different requirements in storage and transport of specimens for blood gas and electrolyte analysis.

Anticoagulants

Biosensors and bioprobes in anaesthesia and intensive care. From in vitro to in vivo monitoring.

In vitro monitoring is inherently invasive with discrete measurements on blood samples and the results are often delayed an hour or more when the analyses are performed in the central laboratory. The delay may be greatly reduced if the analyses are performed near the patient. In vivo monitoring may be non-invasive and may provide continuous real-time data but the accuracy usually does not match that of in vitro measurements. In vivo monitoring therefore finds its application in the detection of trends of change, and it is needed only for quantities that change rapidly and unpredictably and where a suitable therapeutic action is available. In critically ill patients, this applies to the arterial pO2, pCO2, and pH, and the mixed venous pO2. Ideal in vivo monitoring techniques are not available for all these quantities. In the newborn, the arterial pO2 may be monitored with a transcutaneous pO2 electrode. In the adult, the arterial pO2 may be monitored indirectly by monitoring the arterial oxygen saturation with a pulse oximeter and the mixed venous pO2 by monitoring the mixed venous oxygen saturation with a catheter tip sensor. The arterial pCO2 may be monitored with a transcutaneous pCO2 electrode or by capnography, i.e., by monitoring the end-expiratory pCO2. Other in vivo monitoring techniques such as gastric tonometry for the gastric mucosal pH and thoracic impedance measurement have found some routine application, whereas near-infrared spectrometry for oxy- and deoxyhaemoglobin in the brain, and magnetic resonance spectroscopy for tissue ATP are at the stage of research and development.

Adult

Standardizing and reporting results from Mg2+ ISEs, with some notes on sample handling.

Mg2+ by ion-selective electrode (ISE) is a direct measure of the reactivity of magnesium ions in plasma, which may be clinically and physiologically more relevant than the concentration of total magnesium. The Mg(2+)-ISE will build up an electric potential which exactly matches the chemical potential of Mg2+ in the sample. Chemical potential (= chemical work per unit of Mg2+) has no absolute value and is difficult to visualize. The results must be standardized, either to the magnesium concentration in a protein-free calibrator or to the concentration of total magnesium in plasma. The constant factor relationship will assure identical clinical discrimination, no matter how the Mg(2+)-ISE results are reported. The general opinion of a conference held in Orlando, Florida in March of 1993 was to define free Mg2+ in plasma as the concentration of magnesium in a saline standard with the same magnesium activity as the sample, and report it in SI units (mmol/L). The small differences in liquid junction potential and water concentration will provide a value for free Mg2+ in plasma of approximately 103% of the true concentration, or 96% of the true molality. Differences between plasma and interstitial fluid and Donnan equilibria across the vascular endothelium will effect the result, so sampling should take place with the patient at rest to assure a stable plasma volume. Since heparin binds magnesium, it is preferable to use serum or plasma with a minimum of heparin which has been titrated with magnesium. Binding of Mg2+ depends on pH, and pH of circulating plasma is not constant.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Proteins

The TANH-equation modified for the hemoglobin, oxygen, and carbon monoxide equilibrium.

The model of the hemoglobin-oxygen equilibrium represented by the TANH-equation is incorporated in the Oxygen Status Algorithm, a computer program for calculating and displaying the oxygen status and the acid-base status of the blood. In the presence of carbon monoxide it is necessary to take the Haldane equation into account. We here describe the necessary equations and methods for iterative solutions. The validity of the Haldane equation has previously been demonstrated by Zwart et al. (J Appl Physiol 1984; 57: 14-20). We have performed a few experiments to confirm this. Like Zwart et al. we find a small deviation from the theory, but in the opposite direction, i.e. the measured p50 values are slightly higher than predicted. We conclude that the Haldane equation adequately accounts for the carbon monoxide effect up to 30% carboxy-hemoglobin, but further studies are needed to confirm or exclude any minor deviation from the Haldane relationship which may be significant at higher carboxy-hemoglobin fractions.

Carbon Monoxide

Ionic binding, net charge, and Donnan effect of human serum albumin as a function of pH.

The ionic activities and total molalities of sodium, potassium, calcium, lithium, and chloride in a solution of human serum albumin were measured at different values of pH between 4 and 9. The same quantities were measured simultaneously in a protein-free electrolyte solution in membrane equilibrium with the albumin solution. Taking the residual liquid-junction potential and bias from unselectivity of the electrodes into account, we determined the own, bound, and net charges of albumin. Chloride was amply bound at low pH, and calcium at high pH. The varying charge of ions bound to albumin opposed the effect of acid or base on the net charge. All ions were distributed across the membrane according to the same electric potential difference, which equalled the Donnan potential. The high concordance between observation and theory favors the Donnan theory and furthermore implies that the electrodes are as accurate in a solution with albumin as in a protein-free solution.

Calcium