Evaluation of ionized and total serum magnesium concentrations in hyperthyroid cats

Hyperthyroidism can increase the renal excretion of magnesium and thus cause hypomagnesemia in various species. Anaerobically collected blood samples from 15 hyperthyroid and 40 normal, healthy cats were analyzed with an ion-selective electrode analyzer and a serum biochemical analyzer. There was no significant difference in ionized or total serum magnesium concentration between the 2 groups, but there was a significant difference (P = 0.004) in the ratio of ionized to total serum magnesium concentrations between the healthy cats and the hyperthyroid cats with thyroxine (T4) concentrations at or above the median. There was a significant correlation (r = 0.894, P = 0.000) between the ionized and total magnesium concentrations in the hyperthyroid cats. The hyperthyroid cats had a significantly lower (P = 0.003) total serum protein concentration than the healthy cats. A significant negative correlation (r = -0.670, P = 0.006) was detected between the ionized magnesium and logarithmically transformed total T4 concentrations in the hyperthyroid cats, which suggests that the severity of hyperthyroidism may contribute to a decrease in the ionized magnesium concentration.     

Prediction of serum ionized calcium concentration by serum total calcium measurement in cats

Feline serum samples (n = 434) were classified as hypercalcemic, normocalcemic, or hypocalcemic based on both total calcium (tCa) and ionized calcium (iCa) concentrations. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive diagnostic likelihood ratio (PDLR), and negative diagnostic likelihood ratio (NDLR) were calculated for prediction of hypercalcemia and hypocalcemia in all samples, in hypoalbuminemic cats, and in those with chronic renal failure (CRF) as compared with cats that had other conditions. Diagnostic discordance in prediction of iCa using tCa was 40%. Sensitivity of tCa in prediction of ionized hypercalcemia was low and specificity was high. The PDLR for prediction of ionized hypercalcemia or hypocalcemia was low in all cats, especially in those with CRF. Due to the high level of diagnostic discordance, tCa should not be used to predict iCa concentration. Concentration of iCa should be measured directly when accurate assessment of calcium status is needed.     

Prediction of serum ionized calcium concentration by use of serum total calcium concentration in dogs

OBJECTIVE: To determine whether total serum calcium (tCa) or adjusted tCa concentrations accurately predict ionized calcium (iCa) status in dogs. SAMPLE POPULATION: 1,633 canine serum samples. PROCEDURE: The tCa concentration was adjusted for total protein (TP) or albumin concentration by use of published equations. Correlations between iCa and tCa or adjusted tCa, tCa and TP, and tCa and albumin were calculated. Diagnostic discordance between tCa or adjusted tCa and iCa was determined. Diagnostic discordance in predicting iCa was also determined for 490 dogs with chronic renal failure (CRF). Sensitivity, specificity, positive and negative predictive values, and positive and negative diagnostic likelihood ratios were calculated for tCa, tCa adjusted forTP, and tCa adjusted for albumin. RESULTS: Diagnostic discordance was 27% when tCa concentration was used to predict iCa status. Use of adjusted tCa increased diagnostic discordance to approximately 37% for all dogs and 55% for dogs with CRF. Positive predictive value and positive diagnostic likelihood ratios were poor when tCa concentration was used to predict iCa status. The tCa concentration overestimated normocalcemia and underestimated hypocalcemia. Adjusted tCa overestimated hypercalcemia and underestimated hypocalcemia. CONCLUSIONS AND CLINICAL RELEVANCE: Adjusted tCa or tCa concentrations are unacceptable for predicting iCa status in dogs. Use of adjustment equations is not recommended. Direct measurement of iCa concentration is necessary for accurate assessment of calcium status. Use of tCa or adjusted tCa concentrations to predict iCa status in dogs could cause serious mistakes in diagnosis and case management, especially in dogs with CRF.     

Abnormalities of serum electrolyte concentrations in dogs with hypoadrenocorticism

BACKGROUND: The sensitivity and specificity of the sodium to potassium ratio (Na:K ratio) as a cutoff for recommendation of an adrenocorticotropic hormone (ACTH) stimulation test in dogs suspected of having hypoadrenocorticism (HA) is unknown. Additionally, abnormalities in plasma ionized calcium (iCa2+) and ionized magnesium (iMg2+) concentrations and venous pH of dogs with HA are incompletely documented. OBJECTIVES: To define the sensitivity and specificity of the Na:K ratio as a diagnostic aid for HA in dogs and to examine for associations between venous pH and the Na:K ratio, iCa2+ concentration, or iMg2+ concentration in dogs with HA. ANIMALS: Seventy-six dogs with HA and 200 dogs randomly selected from the general hospital population. METHODS: Retrospective study. Dogs were included in the study if results of an ACTH stimulation test confirmed a diagnosis of HA, the dog had a serum sodium concentration below the reference range or a serum potassium concentration above the reference range, and the dog was treated with mineralocorticoids. Receiver operating curve analysis was used to determine optimal cutoffs of sensitivity and specificity for the Na:K ratio in diagnosing HA. RESULTS: Use of Na:K ratios of 27 or 28 classified 95% of dogs correctly as diseased or not diseased. The sensitivity of a Na:K ratio of 28 was 93% (CI, 85-98%) and that of 27 was 89% (CI, 80-95%). The specificity of a Na:K ratio of 28 was 96% (CI, 92-98%) and that of 27 was 97% (CI, 93- 99%). The sensitivity and specificity of a Na:K ratio of 24 were 79% (95% CI, 67-86%) and 100% (98%, CI, 97%-100%), respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Na:K ratios of 27 or 28 identify the highest percentage of dogs with suspected mineralocorticoid and glucocorticoid deficiency correctly. In dogs with a Na:K ratio of 24 or less, the likelihood of confirming a diagnosis of HA with an ACTH stimulation test is high.     

Effects of storage on serum ionized calcium and pH from horses with normal and abnormal ionized calcium concentrations

It has been previously shown that Ca(I) concentration is stable in serum collected from healthy horses for 10 days if stored at 40 degrees C. This may not be true for horses with abnormal Ca(I) concentrations. Thus the stability of ionized calcium (Ca(I)) concentration and pH measurement in serum from horses with both normal and abnormal Ca(I) concentrations stored for various times at 40 degrees C and -10 degrees C was evaluated. Our results indicated that serum Ca(I) concentration was stable throughout 7 days of cold or frozen storage, after being received by the Clinical Chemistry Laboratory. Serum Ca(I) concentration showed a significant decrease by 14 days of frozen storage (-10 degrees C). Serum pH showed a statistically significant increase by 7 days of cold storage, and within 3 days of frozen storage. If equine serum is collected, handled and stored anaerobically, and kept cold or frozen, Ca(I) concentration can be accurately measured for approximately 7 days after collection, regardless of the health status of the animal. An accurate measurement of pH may be made within 3 days of cold or 1 day of frozen storage.     

Evaluation of a bench-top coagulation analyzer for measurement of prothrombin time, activated partial thromboplastin time, and fibrinogen concentrations in healthy dogs

OBJECTIVE: To evaluate a bench-top coagulation analyzer for determination of prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen concentration in healthy dogs. ANIMALS: 55 healthy adult dogs. PROCEDURES: PT, APTT, and fibrinogen concentration were determined by use of the coagulation analyzer. Values were compared with results obtained independently by a conventional laboratory. RESULTS: Correlations (with 95% confidence intervals) between the coagulation analyzer and conventional laboratory values were 0.760 (0.610 to 0.857), 0.700 (0.448 to 0.721), and 0.896 (0.878 to 0.918) for PT, APTT, and fibrinogen concentration, respectively. Using linear regression, comparison of data from the coagulation analyzer and the conventional laboratory provided equations relating the coagulation analyzer values with values from the conventional laboratory and suggested that APTT and fibrinogen values from the coagulation analyzer and conventional laboratory were approximately the same within expected random variation. Prothrombin time values for the coagulation analyzer were significantly offset from the PT values for the conventional laboratory but still were correlated reasonably well with the conventional laboratory values. CONCLUSIONS AND CLINICAL RELEVANCE: By use of the mechanical method of analysis, fibrinogen concentrations obtained with a bench-top coagulation analyzer correlated well with results for a conventional laboratory, indicating that the coagulation analyzer is a reliable instrument for determination of this coagulation variable. Coagulation analyzer results for PT and APTT correlated less strongly with those for the conventional laboratory, but they would still be considered clinically reliable.     

Validation of the Nova CRT8 for the measurement of ionized magnesium in feline serum

Background: Evaluation of serum magnesium (Mg) concentration is becoming important in human and veterinary critical care medicine. An ion‐selective electrode can measure the physiologically active ionized fraction. Objectives: The purpose of this study was to validate an ion‐specific electrode analyzer and assay for measuring ionized Mg in feline serum and to determine a reference interval for this analyte in cats. Methods: Venous blood samples were collected anaerobically from clinically healthy cats, and the serum was used to validate the analyzer and assay. This included investigating the stability of samples stored at different temperatures, intra‐ and interassay precision, linearity, analytical sensitivity, and potential interferences from bilirubin, lipemia, hemoglobin, or serum separator tubes. A reference interval was calculated. Results: Serum samples evaluated for ionized Mg concentrations can be stored at 20°C for ≤24 hours, at 4°C for ≤72 hours, and at ?20°C for ≤4 weeks, when samples are minimally exposed to air. Intra‐ and interassay precisions had coefficients of variation (CVs) of 1.23% and 2.02%, respectively. There was good linearity using serum (r= .998; y=?0.0057 + 1.0256x) and manufacturer‐supplied aqueous solutions and quality control materials (r= .999; y= 0.0110 + 0.9213x). Apparent analytical sensitivity was at least 0.015 mmol/L. Mean recovery was good for ionized Mg in samples with ≤1+ icterus (104%), 4+ lipemia (99.3%) and 1–4+ hemolysis (98.6%). There was no significant difference (P= .52) in ionized Mg concentrations in serum collected in tubes containing no additives compared with serum collected in glass separator tubes. The serum ionized Mg reference interval was 0.47–0.63 mmol/L (n = 40). Conclusions: The Nova CRT8 analyzer and assay provide a precise and reliable method of measuring ionized Mg concentration in feline serum. Strict adherence to sampling techniques, handling, and storage are necessary for reliable results.     

A comparison of total calcium,corrected calcium,and ionized calcium concentrations as indicators of calcium homeostasis among hypoalbuminemic dogs requiring intensive care

Objective – (1) To evaluate whether total calcium (tCa) correlates with ionized calcium (iCa) in hypoalbuminemic dogs; (2) to evaluate whether calcium adjusted for albumin (Alb), or total protein (TP), or both accurately predict iCa concentrations and hence can be used to monitor calcium homeostasis in critically ill hypoalbuminemic dogs; and (3) to evaluate factors associated with any potential discrepancy in calcium classification between corrected total and ionized values. Design – Prospective observational clinical study. Setting – Small animal intensive care unit in a veterinary medical teaching hospital. Animals – Twenty‐eight client‐owned dogs with hypoalbuminemia. Interventions – None. Measurements and Main Results – iCa was determined using ion‐specific electrode methodology, on heparinized plasma. The tCa concentration was adjusted for Alb and TP using published equations. In total 29% (8/28) of the hypoalbuminemic, critically ill dogs in this study were hypocalcemic at intensive care unit admission, as determined by iCa measurement. Corrected calcium values failed to accurately classify calcium status in 67.9% and 64.3% of cases, according to whether the Alb‐adjusted or TP‐adjusted values, respectively, were used. The sensitivity and specificity of the tCa to evaluate hypocalcemia was 100% and 47%, respectively. The sensitivity and specificity of the correction formulae were 37.5% and 79% for the Alb‐adjusted values and 37.5% and 74% for TP‐adjusted values. tCa overestimated the presence of hypocalcemia and underestimated the presence of normocalcemia, while corrected calcium values overestimated the presence of normocalcemia and underestimated the presence of hypocalcemia. Conclusions – Calcium homeostasis in hypoalbuminemic critically ill dogs should be evaluated by iCa concentrations rather than tCa or calcium adjusted for Alb or TP. Given that tCa has 100% sensitivity for detecting hypocalcemia in this population it is recommended that all hypoalbuminemic and critically ill patients with low tCa should be evaluated with an iCa measurement.     

Comparison of serum parathyroid hormone and ionized calcium and magnesium concentrations and fractional urinary clearance of calcium and phosphorus in healthy horses and horses with enterocolitis

OBJECTIVE: To evaluate calcium balance and parathyroid gland function in healthy horses and horses with enterocolitis and compare results of an immunochemiluminometric assay (ICMA) with those of an immunoradiometric assay (IRMA) for determination of serum intact parathyroid hormone (PTH) concentrations in horses. ANIMALS: 64 horses with enterocolitis and 62 healthy horses. PROCEDURES: Blood and urine samples were collected for determination of serum total calcium, ionized calcium (Ca2+) and magnesium (Mg2+), phosphorus, BUN, total protein, creatinine, albumin, and PTH concentrations, venous blood gases, and fractional urinary clearance of calcium (FCa) and phosphorus (FP). Serum concentrations of PTH were measured in 40 horses by use of both the IRMA and ICMA. RESULTS: Most (48/64; 75%) horses with enterocolitis had decreased serum total calcium, Ca2+, and Mg2+ concentrations and increased phosphorus concentrations, compared with healthy horses. Serum PTH concentration was increased in most (36/51; 70.6%) horses with hypocalcemia. In addition, FCa was significantly decreased and FP significantly increased in horses with enterocolitis, compared with healthy horses. Results of ICMA were in agreement with results of IRMA. CONCLUSIONS AND CLINICAL RELEVANCE: Enterocolitis in horses is often associated with hypocalcemia; 79.7% of affected horses had ionized hypocalcemia. Because FCa was low, it is unlikely that renal calcium loss was the cause of hypocalcemia. Serum PTH concentrations varied in horses with enterocolitis and concomitant hypocalcemia. However, we believe low PTH concentration in some hypocalcemic horses may be the result of impaired parathyroid gland function.     

Circadian changes in blood ionized calcium, sodium, potassium, and chloride concentrations and pH in cattle.

OBJECTIVE: To explore diurnal variation in blood ionized calcium, sodium, potassium, and chloride concentrations and pH in pregnant dairy cows. ANIMALS: 14 dairy cows in their third or later pregnancy approximately 6 weeks before expected parturition. PROCEDURE: Throughout a 24-hour period, blood samples were taken at 2-hour intervals and analyzed for ionized calcium (iCa2+), potassium (K+), sodium (Na+), and chloride (Cl-) concentrations and pH. Paired t-tests were used to compare initial and final values. Circadian changes were tested by use of repeated-measures ANOVA. Additionally, a nonparametric analysis was performed for each animal to determine minimal and maximal values for the variables. RESULTS: Significant differences were not detected between initial and final values of any variable. Repeated-measures ANOVA indicated significant diurnal fluctuations in all variables. With the exception of Cl- concentration, nonparametric analysis of individual values also revealed significant changes over time. CONCLUSIONS AND CLINICAL RELEVANCE: The magnitude of daily fluctuations does not make it necessary to standardize time of sample collection for routine diagnostic examination of blood iCa2+, Na+, and Cl-concentrations and pH. However, it may be important to standardize time of sample collection in comparative studies in which more discrete differences may be identified.     

Effect of sodium bicarbonate infusions on ionized calcium and total calcium concentrations in serum of clinically normal cats

The effects of sodium bicarbonate (0.5 mEq/kg of body weight, 1.0 mEq/kg, 2.0 mEq/kg, and 4.0 mEq/kg) on ionized and total calcium concentrations were determined in clinically normal cats. Also, serum pH, whole blood pH, and serum albumin, serum total protein, and serum phosphorus concentrations were measured. Intravenous administration of sodium bicarbonate to awake cats decreased serum ionized calcium and serum total calcium concentrations. All dosages of sodium bicarbonate were associated with significant decreases of serum ionized calcium concentration. This effect lasted for greater than 180 minutes when cats were given 2.0 mEq/kg or 4.0 mEq/kg. When cats were given 4 mEq of sodium bicarbonate/kg, serum ionized calcium concentration was significantly decreased, compared with that when cats were given lower doses, but only at 10 minutes after infusion. After sodium bicarbonate infusion, serum total calcium concentration, measured by ion-specific electrode and colorimetry, was lower than baseline values at most of the times evaluated. Decreases in serum ionized calcium and serum total calcium concentrations can be attributed only in part to an increase in serum or whole blood pH and to a decrease in serum protein concentration. Serum total calcium concentrations measured by ion-specific electrode and by colorimetry were positively correlated, but the variability was high. Only 44% of the variability in serum ionized calcium concentration could be predicted when serum total calcium, albumin, total protein, phosphorus, and bicarbonate concentrations and pH were considered.     

Determination of lactate concentrations in blood plasma and peritoneal fluid in horses with colic by an Accusport analyzer

BACKGROUND: Intestinal hypoperfusion can lead to increased lactate concentrations in plasma and peritoneal fluid of horses with colic. HYPOTHESIS: The purposes of this study were to (1) evaluate the reliability of the Accusport analyzer to assess peritoneal fluid lactate (PFL) concentrations in healthy horses and those with colic, (2) identify clinical features associated with abnormal blood plasma lactate (BPL) and PFL concentrations, and (3) evaluate the prognostic value of BPL and PFL. ANIMALS: BPL and PFL were determined in 20 healthy horses and in 106 horses with colic. RESULTS: The Accusport was reliable for determining BPL concentrations < 13 mM and PFL concentrations < 20 mM. Multivariate analysis indicated that PCV and the need for intestinal resection were independently associated with the BPL; pulse, PCV, venous pO2, the presence of necrotic intestine, an increased amount of peritoneal fluid, and fluid total protein content were independently associated with PFL. With a 1 mM increase in BPL or PFL, the respective odds ratios for required abdominal surgery increase to 1.23 (BPL) and 1.58 (PFL), odds ratios for a required intestinal resection increase to 1.20 (BPL) and 1.41 (PFL), and odds ratios for developing ileus increase by 1.33 (BPL) and 1.36 (PFL). PFL concentrations of 1, 6, 12, and 16 mM correspond to a probability of death of 11, 29, 63, and 82%, respectively, in horses without strangulating obstruction and of 25, 52, 82, and 92%, respectively, in horses with strangulating obstruction. CONCLUSION: PFL is more useful and sensitive than BPL for prognostic purposes in horses with colic.     

Evaluation of plasma inflammatory cytokine concentrations in racing sled dogs

In human athletes significant changes in cytokine concentrations secondary to exercise have been observed. This prospective study evaluated the effect of a multi-day stage sled dog race on plasma concentrations of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10). Samples from 20 dogs were harvested prior to and on days 2 and 8 of an 8-day race. Exercise resulted in significantly decreased TNF-α and IL-8 as well as increases of MCP-1, IL-6, and IL-10 concentrations (P-value between 0.01 and < 0.0001 for all parameters). The proportion of values for IL-2 that were below the detection limit increased from 40% on day 0 to 75% on day 2 and decreased on day 8 to 40% (P = 0.04). Racing sled dogs show cytokine-concentration changes that are different from those in humans.