Circadian variation in ionized calcium and intact parathyroid hormone: evidence for sex differences in calcium homeostasis.

The rate of bone loss with age and the incidence of osteoporosis are greater in women than men, which led us to question whether subtle sex differences may occur in the circadian variation of serum ionized calcium (iCa) and PTH. We measured iCa hourly and intact PTH every 2 h for 26 h in 25 women (21-69 yr) and 24 men (20-67 yr) consuming self-selected diets. Urine was collected at 0800-1600, 1600-2400, and 2400-0800 h. Serum iCa levels followed a circadian rhythm in both sexes (P less than or equal to 0.01), and the patterns differed between sexes, notably during early morning, when serum iCa levels were lower in women (P = 0.02). Urinary calcium excretion and fractional excretion of calcium declined in both sexes at night (2400-0800 h), but the decline in men was significantly greater (P = 0.02). Similarly, the percent reduction in urinary calcium excretion at night was greater in men than in women (34% vs. 17%; P less than or equal to 0.05). In women, 26-h mean serum iCa values correlated significantly with total daily calcium intake (r = 0.44; P = 0.03). Serum intact PTH levels showed a significant circadian pattern in both sexes (P less than or equal to 0.001). The patterns of serum intact PTH differed between the sexes (P = 0.05), with an earlier and greater increase at night in men. This blunted nocturnal rise in PTH in women may explain the poor nocturnal adaptation to fasting found in women who, despite lower calcium intake, did not reduce urinary calcium loss at night as effectively as men.

A defect in renal calcium conservation may contribute to the pathogenesis of postmenopausal osteoporosis.

Although all postmenopausal women are estrogen deficient, women who have postmenopausal osteoporosis may have a defect, in addition to estrogen deficiency, that accounts for their higher rates of bone resorption and greater bone loss, relative to those who do not. To test the hypothesis that one defect is an impairment in renal calcium conservation, we measured renal calcium transport in 19 osteoporotic and 19 normal postmenopausal women, whose ages (median and 25th-75th percentile range) were 70 yr (range, 67-72) and 72 yr (range, 69-74), respectively. There was no difference between groups in values for serum ionized calcium and PTH concentrations or in renal filtered load of calcium. However, before PTH infusion, the osteoporotic women had lower (P = 0.0046) values for tubular reabsorption of calcium (TRCa) of 96.8% (range, 96.0-97.1) vs. 98.0% (range, 97.2-98.3) and higher (P = 0.0154) urinary calcium excretion of 0.194 mg/dL of glomerular filtrate (GF) (0.154-0.239) vs. 0.125 mg/dL of GF (0.103-0.173) than the normal women. After infusion of 200 U of synthetic PTH (synthetic 1-34 analog of human PTH), TRCa increased and calcium excretion decreased comparably in both groups, so that the differences between groups after intervention remained: for TRCa, 98.3% (97.7-98.6) vs. 98.9% (98.4-99.3; P = 0.0042); and for calcium excretion, 0.099 mg/dL of GF (0.080-0.138) vs. 0.066 mg/dL of GF, (0.045-0.097, P = 0.0180). In conclusion, postmenopausal women with osteoporosis have a PTH-independent defect in renal calcium conservation. This defect is of sufficient magnitude to contribute to the greater negative calcium balance in post-menopausal women with osteoporosis vs. their postmenopausal peers.

Abnormalities of parathyroid hormone secretion in elderly women that are reversible by short term therapy with 1,25-dihydroxyvitamin D3.

Serum PTH concentrations increase with aging and may play an important causal role in age-related bone loss. To better define possible PTH secretory abnormalities with aging, we studied 10 young (aged 27-34 yr) and 10 elderly (aged 71-77 yr) women using sequential infusions of calcium and EDTA. To assess possible age-related resistance of PTH secretion to modulation by 1,25-dihydroxyvitamin D [1,25-(OH)2D], the infusions were repeated after 1 week of oral 1,25-(OH)2D3 therapy (1 microgram/day). Baseline serum intact PTH concentrations were higher in the elderly compared to the young women (mean +/- SEM, 3.8 +/- 0.5 vs. 2.7 +/- 0.4 pmol/L; P = 0.03). In addition, the elderly women had a significantly higher maximal PTH response to hypocalcemia compared to the young women (16.6 +/- 1.1 vs. 12.8 +/- 1.0 pmol/L; P = 0.03). The elderly women also had a greater nonsuppressible component of PTH secretion (0.8 +/- 0.1 vs. 0.4 +/- 0.1 pmol/L; P < 0.001). The set-point for PTH secretion, however, was identical in the elderly and young women (1.18 +/- 0.01 vs. 1.19 +/- 0.01 mmol/L; P = NS). After 1,25-(OH)2D3 administration, both groups had similar reductions in baseline and maximally stimulated PTH levels, indicating that elderly women have normal responsiveness to 1,25-(OH)2D3 suppression of PTH secretion. In addition, maximally stimulated PTH levels in the 1,25-(OH)2D3-treated elderly women decreased to the pretreatment values of young women (13.3 +/- 1.1 vs. 12.8 +/- 1.0 pmol/L; P = NS). thus, elderly women have greater basal, maximal, and nonsuppressible levels of PTH secretion, without alterations in the set-point. These abnormalities are similar to those found in patients with secondary hyperparathyroidism and parathyroid hyperplasia. Further, the abnormal PTH secretory dynamics in elderly women are reversible by short term 1,25-(OH)2D3 therapy.

Abnormalities in circadian patterns of bone resorption and renal calcium conservation in type I osteoporosis.

We compared changes over 24 h in 15 postmenopausal normal women (mean [+/- SD] age, 64 +/- 7 yr) with those in 15 postmenopausal women with type I osteoporosis and vertebral fractures (mean age, 64 +/- 5 yr). The serum osteocalcin concentration, a sensitive index of bone formation, increased by about 5% at night in both groups. Urinary deoxypyridinoline excretion, a sensitive index of bone resorption, increased by 48% at night (P less than 0.01) in the normal women, whereas in the osteoporotic women it was 62% higher overall (P less than 0.05), and the increase persisted into the morning. At night, urinary fractional excretion of calcium decreased by 20% (P less than 0.001) in the normal women, but was unchanged in the osteoporotic women; this circadian pattern differed between groups (P less than 0.05). The serum ionized calcium concentration did not change at night in either group. There was a trend (P = 0.07) for blunting of the nocturnal increase in the serum intact PTH level in osteoporotic women. Thus, the nocturnal serum ionized calcium level is maintained by decreased urinary calcium excretion and increased bone resorption in postmenopausal normal women, but almost entirely by increased resorption in postmenopausal osteoporotic women. This greater dependence on bone resorption during the nocturnal fast may account in part for the greater bone loss in osteoporotic women.

Skeletal responsiveness to endogenous parathyroid hormone in postmenopausal osteoporosis.

To test the hypothesis that increased sensitivity of bone to PTH may be a major cause of bone loss in postmenopausal osteoporosis, we induced acute calcium deprivation and measured bone responsiveness to endogenous PTH under physiological conditions. Eighteen osteoporotic and 17 normal postmenopausal women with similar dietary calcium intakes were studied before and after 4 days of calcium deprivation (dietary calcium 230 mg/day and treatment with a calcium-binding agent). Despite decreased serum PTH values, the baseline indices of bone turnover (serum osteocalcin level and 24-h urinary excretions of total deoxypyridinoline/creatinine and pyridinoline/creatinine corrected for total body bone mineral content), were higher in the osteoporotic women. During calcium deprivation, the changes in bone markers from baseline were similar in both groups, except for serum osteocalcin and serum type I procollagen carboxy-terminal propeptide. Changes in the normal and the osteoporotic women were, respectively: serum ionized calcium concentration decreased 3.3% and 2.1%; serum intact PTH increased 65% and 56%; plasma 1,25-dihydroxyvitamin D3 increased 29% and 39%; pyridinoline/creatinine increased 12% and 11%; and deoxypyridinoline/creatinine increased 27% and 12%. Serum osteocalcin increased 2.3% and serum procollagen carboxy-terminal propeptide decreased 9.4% in the normal women but did not change in the osteoporotic women. We conclude that women with postmenopausal osteoporosis do not have increased skeletal responsiveness to PTH compared with age-comparable normal postmenopausal women. Therefore, the higher bone turnover in postmenopausal osteoporosis, despite lower serum intact PTH concentration, must be due to other factors. Assessment of acute changes in bone turnover during physiological alterations in endogenous PTH secretion is a useful test in metabolic bone diseases.

Role of parathyroid hormone in mediating nocturnal and age-related increases in bone resorption.

PTH has been postulated to play a role in both nocturnal and age-related increases in bone resorption. We tested this hypothesis directly in 10 young (ages 24-35 yr) and 10 elderly (ages 71-78 yr) normal women by measuring the cross-linked N-telopeptide of type I collagen (NTx), a marker for bone collagen breakdown, in 4-h urine collections before and during suppression of PTH secretion by a 24-h iv infusion of calcium. Serum ionized calcium and PTH levels were also measured every 2 h before and during the infusion. In both groups of women, serum PTH levels and urinary NTx excretion followed a circadian pattern before calcium infusion (analysis of variance, P = 0.0001) with peaks in the afternoon and at night for PTH and at night for urinary NTx. During the calcium infusion, the nocturnal urinary NTx excretion peak persisted (P = 0.0001), despite elimination of both PTH peaks. Urinary 24-h NTx excretion (nanomoles per millimoles of creatinine) at baseline was higher in the elderly women (mean +/- SEM, 25.7 +/- 2.1) than in the young women (19.3 +/- 1.7) (P < 0.01), and the decrease during calcium infusion was greater (7.5 +/- 1.9 vs. 4.1 +/- 1.5, P < 0.05). Therefore, the increase in serum PTH levels with age is one of the major factors responsible for the age-related increase in bone resorption. PTH does not mediate the circadian pattern of bone resorption but does play a role in setting the absolute level of bone resorption at which this pattern occurs.

Role of calcium intake in modulating age-related increases in parathyroid function and bone resorption.

Serum parathyroid hormone (PTH) and bone resorption increase in elderly women and contribute to age-related bone loss. Whether these abnormalities are caused by calcium deficiency resulting from age-related decreases in absorption and renal conservation is unclear. We studied 28 normal elderly women (mean +/- SD, age 69.3 +/- 2.7 yr) who were maintained for 3 yr on usual calcium intake levels (20.4 +/- 7.2 mmol/day [815 +/- 289 mg/day]; n = 15) (known as the usual calcium group) or high calcium intake levels (60.4 +/- 6.5 mmol/day [2414+/260 mg/day]; n = 13) (known as the high calcium group) and a reference group of 12 normal young adult women (age 30.1 +/- 4.4 yr), whose calcium intake was 23.0 +/- 4.8 mmol/day (918 +/- 193 mg/day) (known as the young group). Serum PTH was measured every 2 h, and urinary excretion of deoxypyridinoline (Dpd), a new marker for bone resorption, was measured in 4 h collections. Parathyroid gland secretory capacity was assessed during induced hypocalcemia. The mean 24 h serum PTH was 40% lower (P < 0.001), and the mean 24 h urinary Dpd was 35% lower (P < 0.005) in the high than in the usual calcium group. Mean parathyroid gland secretory capacity also was 47% lower (P < 0.005) in the high calcium group than in the usual calcium group. However, the usual calcium group had a mean 24 h serum PTH level that was 70% higher (P < 0.001) and a mean 24 h urinary Dpd level that was 30% higher (P < 0.005) than the young group, whereas the high calcium group was indistinguishable from the young group. Thus, failure of elderly women to increase their calcium intake to offset age-related increases in calcium requirement contributes substantially to their development of increased parathyroid activity and increased bone resorption, whereas a high calcium intake can reverse both abnormalities.

Mechanism of renal calcium conservation with estrogen replacement therapy in women in early postmenopause--a clinical research center study.

To assess the mechanism by which estrogen replacement therapy (ERT) enhances renal calcium conservation in perimenopausal women, we studied 18 normal women in early postmenopause before and after 6 months of ERT (cyclic treatment with transdermal estradiol at 100 micrograms/day and medroxyprogesterone acetate at 10 mg/day for the first 12 days of each cycle). The changes after ERT were: serum ionized calcium and ultrafiltrable calcium, no change; serum intact PTH, 38.2% increase (P < 0.0001); serum 1,25-dihydroxyvitamin D, 23.8% increase (P < 0.0001); urinary calcium excretion, 33.3% decrease (P < 0.001); and deoxypyridinoline (a marker for bone resorption), 19.5% decrease (P < 0.0001). Also, ERT increased tubular reabsorption of calcium (TRCa; 97.6% +/- 0.2% to 98.7% +/- 0.1%; P < 0.0001), and this increase correlated with that in serum PTH (r = 0.49; P < 0.05). After the infusion of human PTH-(1-34), the TRCa maximum was greater after ERT than at baseline (99.4% +/- 0.1% vs. 99.0% +/- 0.1%; P < 0.0001), resulting in decreased calcium excretion (0.9 +/- 0.20 vs. 1.43 +/- 0.20 mumol/dL glomerular filtrate; P < 0.001). Thus, in early postmenopause, the major mechanism of increased renal calcium conservation after ERT is an increase in TRCa due to an increase in serum PTH because of estrogen-induced inhibition of bone resorption. However, ERT also may directly increase the TRCa maximum in response to PTH.

Effects of the circadian variation in serum cortisol on markers of bone turnover and calcium homeostasis in normal postmenopausal women.

Bone turnover has a circadian pattern, with bone resorption and, to a lesser extent, bone formation increasing at night. Serum cortisol also has a circadian pattern and is a potential candidate for mediating the circadian changes in bone turnover. Thus, we measured bone formation and resorption markers before (study A) and after (study B) elimination of the morning peak of cortisol. We also assessed effects of the circadian cortisol pattern on serum calcium, PTH, and urinary calcium excretion. Ten normal postmenopausal women, aged 63-75 yr (mean, 69 yr), were studied. Metyrapone was administered to block endogenous cortisol synthesis and either a variable (study A) or a constant (study B) infusion of cortisol was given to reproduce and then abolish the morning cortisol peak. Blood was sampled every 2 h for serum cortisol, ionized calcium, PTH, and bone formation markers [osteocalcin and carboxyl-terminal propeptide of type I collagen (PICP)], and timed 4-h urine samples were collected for measurement of calcium, phosphorus, sodium, potassium, and bone resorption markers (N-telopeptide of type I collagen and free deoxypyridinoline). During study A, serum osteocalcin had a circadian pattern, with a peak at 0400 h and a nadir at 1400 h. During study B, however, the afternoon nadir of serum osteocalcin was eliminated (P < 0.001 and P < 0.005 for the difference in the patterns of peak and nadir, respectively, on the 2 study days). In contrast, the circadian patterns of serum PICP and urinary N-telopeptide of type I collagen and free deoxypyridinoline were virtually identical during the two studies. Urinary calcium excretion declined after the cortisol peak, without differences between the 2 study days in phosphorus or sodium excretion or in serum PTH. We conclude that the circadian variation in serum cortisol is responsible for the circadian pattern of serum osteocalcin, but not that of PICP or bone resorption markers. The physiological variation in serum cortisol may also reduce urinary calcium excretion.

Comparative studies of total and ionized serum calcium values in normal subjects and patients with renal disorders.

One hundred fourteen nondialyzed azotemic adult patients (creatinine connentration 1.2 to 17.6 mg/dl), 78 stable renal transplant recipients (creatinine less than 1.9 mg/dl), 50 patients with idiopathic nephrolithiasis, 36 patients with surgically proven primary hyperparathyroidism, and 62 normal volunteers were studied with simultaneous serum ionized calcium, total calcium, parathyroid hormone (PTH), phosphorus, and creatinine measurements. Ionized calcium could not be reliably predicted from total calcium. Although in all patient groups values for serum ionized calcium correlated significantly with those for total calcium, the scatter around the regression line was such that a direct interpretation was not precise. With respect to reference values, significant differnces were found between ionized and total calcium in 26% of all studied patients. When compared with total serum calcium, ionized calcium appeared to be a more sensitive index of calcium metabolism. All correlations with ionized calcium had a higher r value compared with those with total serum calcium. Two findings were particularly rewarding. In patients with chronic renal failure, serum PTH showed a negative correlation with serum ionized calcium, indicating that the latter may have been largely responsible for the secondary increase in PTH; in patients after a successful transplant, serum PTH showed a positive correlation with serum ionized calcium, indicating that in the presence of normal kidney function the previously hypertrophied parathyroid glands may be largely responsible for the daily study of a large number of specimens, determinations of serum ionized calcium should be encouraged in all patients suspected of having abnormalities of renal calcium metabolism.

The sensitivity and specificity of nutrition-related variables in relationship to the duration of hospital stay and the rate of complications.

We assessed the nutritional status at the time of hospital admission of 74 patients who were admitted for elective gynecologic or urologic operations. Nutritional assessment included measurement of serum albumin, thyroxine-binding prealbumin, retinol-binding protein, weight-change history, estimate of daily protein and total calorie intake, and a global estimate of nutritional risk. The sensitivity, specificity, false-positive rate, likelihood ratio, and positive predictive value of these nutrition-related variables were analyzed in patients who stayed in the hospital for longer than 10 days and in those patients with recognized complications. In the analysis of patients who remained in the hospital longer than 10 days, the finding of a low serum protein concentration or a low protein intake was most sensitive, and a low serum albumin concentration was the most specific. A receiver-operating-characteristic diagram that depicts the sensitivity and false-positive rates for the single variables and the combinations of variables is probably the most clinically useful summary of our study. Using the information in such a diagram, a clinician might choose variables that are more sensitive to identify hospitalized patients who should receive special nutritional attention in comparison with another clinician who might need fewer false-positive results for a prospective study of nutritional intervention.

Artifactual hypercalcemia in multiple myeloma.

A calcium-binding IgG K monoclonal protein in a patient with multiple myeloma and asymptomatic hypercalcemia was recognized, isolated, and characterized. In addition to binding by the whole IgG molecules, calcium was bound by purified Fab fragments and recombined heavy and light chains. In a competitive binding study, the isolated myeloma protein did not bind magnesium. Recognition of calcium-binding myeloma proteins is important in order to avoid therapy for hypercalcemia.

Pediatric reference intervals for 19 biologic variables in healthy children.

We defined age- and sex-specific reference intervals for 19 biologic variables in serum samples from healthy children, 1 to 22 years of age, using common laboratory equipment. Upper and lower reference intervals were defined as the estimated 2.5 and 97.5 percentiles of the distribution. For variables (y) that varied with age, the relationship of y to age was modeled with polynomial regression. Parametric percentile estimates specific to each age were then calculated as the predicted y value +/- 1.96 . SD, in which SD = the standard deviation of the residuals. For variables not associated with age, the nonparametric 2.5 and 97.5 sample percentiles were used to define the reference intervals. No significant age or sex differences were found for serum sodium, total protein, glucose, direct bilirubin, or albumin. Potassium, chloride, and urea showed constant values in children that were higher than adult values in the case of potassium and chloride and lower than adult values in the case of urea. No sex-related differences were seen for these analytes. Creatinine, uric acid, and bicarbonate showed an upward trend in values with increasing age, whereas aspartate aminotransferase, phosphorus, and total and ionized calcium showed a downward trend with increasing age. Sex-related differences were noted for these analytes. The immunoglobulins (IgG, IgA, and IgM) showed an upward trend with increasing age, with no sex-related differences except for IgM in children.

Macroenzyme as a cause of unexplained elevation of aspartate aminotransferase.

Aspartate aminotransferase (AST) can exist as a macroenzyme by forming a complex with an immunoglobulin. This immunoglobulin-complexed macromolecule can cause an elevation in serum AST activity, which may be detected on routine blood chemistry analysis and erroneously considered to indicate the presence of liver disease. Clinicians should be aware of this phenomenon so patients are not subjected to unnecessary procedures. In patients with unexplained AST elevation, liver and muscle disease can be biochemically excluded by the finding of normal serum levels of alanine aminotransferase and creatine kinase. The presence of macro-AST can be determined by exclusion chromatography, electrophoresis, and activation assays with pyridoxal 5-phosphate. The elevated AST values can persist for many years.

Anesthesia approach to hepatic transplantation.

Anesthesia support for patients undergoing orthotopic liver transplantation can be complicated because of multiple medical problems in such patients and rapid hemodynamic, metabolic, and coagulation changes intraoperatively. Preoperative assessment should include careful review of the cardiovascular, respiratory, and hematologic systems. Use of isoflurane as the main anesthetic agent will minimize toxicity to the liver. During liver transplantation, hemodynamic monitoring and immediate laboratory studies should be available. In our experience during the first 100 liver transplantations performed at our institution, use of a rapid infusion pump and venovenous bypass has helped normalize hemodynamic and renal function.

Hemodynamic and metabolic changes in hepatic transplantation.

In this study, we retrospectively analyzed the intraoperative hemodynamic, laboratory, and coagulation data on the first 83 patients who underwent an initial liver transplantation procedure at our institution. The major hemodynamic changes at the time of reperfusion of the donor liver were significant decreases in arterial blood pressure, systemic vascular resistance, and pulmonary artery temperature and significant increases in cardiac output and pulmonary capillary wedge pressure. The alterations in laboratory values reflected intraoperative therapeutic manipulations. Citrate toxicity is a concern, and the amount of calcium chloride administered reflected the volume of blood transfused. On reperfusion, the fibrinogen concentration decreased and both the prothrombin time and the activated partial thromboplastin time increased. This coagulopathy was also evident in the thromboelastographic values. Aggressive monitoring and prompt intervention are necessary to maintain hemodynamic and metabolic homeostasis in these patients.

Laboratory assessment of nutritional status.

Malnutrition is one of the major causes of increased morbidity and mortality among hospitalized patients. The availability of nutritional therapy for these patients has made clinicians aware of the need for reliable methods of nutritional assessment. A variety of anthropometric, biochemical, and immunologic parameters has been used as indicators of protein-calorie malnutrition. Recently, the concentration of several rapid-turnover visceral proteins (transferrin, thyroxine-binding prealbumin and retinol-binding protein) has been shown to be a very sensitive parameter for indicating both the efficiency of nutritional therapy and conditions of borderline protein intake in apparently healthy children. Likewise, several immunologic parameters (including T cells, delayed hypersensitivity response, and complement components) have been shown to correlate with morbidity, mortality risk, sepsis, and death.

Airborne and rescue point-of-care testing.

The prehospital environment has not been studied for point-of-care testing. Therefore, the authors' helicopter program evaluated the performance of the i-STAT Portable Clinical Analyzer, a rapid point-of-care, hand-held instrument. The primary aim of the study was to determine if the i-STAT Portable Clinical Analyzer could be used in the field to assess patient status in flight, and to allow the flight crew to intervene immediately, thus delivering a more stable patient to the emergency room. Imprecision and initial split-sample comparative studies with the Portable Clinical Analyzer were completed in the hospital satellite laboratory and clinical chemistry laboratory. Comparison studies were performed on patient samples drawn and analyzed in the helicopter and subsequently analyzed in the satellite and clinical chemistry laboratories. The only significant differences observed were with glucose. The glucose discrepancies were probably due to the time delay between collection of the specimen in the helicopter and subsequent analysis in the laboratory. Following this initial validation, the i-STAT Portable Clinical Analyzer was used on 81 patients transported by the flight crew. The tests performed in the helicopter include sodium, potassium, glucose, and hematocrit/hemoglobin concentrations. Fifteen (18.5%) of the patients were treated with transfusions, glucose, or insulin based on the Portable Clinical Analyzer results. Other identified needs include blood gas analysis (in process) and use of point-of-care testing in the fixed-wing environment.

Stability of heparin anticoagulant activity over time in parenteral nutrition solutions.

BACKGROUND: Heparin added to parenteral nutrition solutions may decrease the incidence of central venous thrombosis in patients receiving home parenteral nutrition. However, there are little data regarding the stability of heparin over time under conditions similar to those associated with home parenteral nutrition: low concentrations of heparin stored in solutions containing amino acids and high concentrations of dextrose for more than 24 hours. METHODS: The activity of porcine mucosal heparin was measured over time using an antifactor Xa assay in six IV solutions: four parenteral nutrition solutions containing 25% dextrose; 5% amino acids; trace elements; electrolytes; and 3000, 5000, 10,000, or 20,000 units/L of heparin; one solution of 25% dextrose and 5000 units/L heparin; and one solution of 0.9% saline and 5000 units/L heparin. RESULTS: In all solutions except 25% dextrose (without amino acids and additives), heparin activity remained stable within 4% of baseline up to 28 days. In the 25% dextrose solution, heparin activity declined by 3%, 6%, and 11% at 14, 21, and 28 days, respectively. CONCLUSION: Heparin activity was stable over time in the normal saline and parenteral nutrition solutions and decreased slightly from 2 to 4 weeks in the dextrose-containing solution. Based on these data, when home parenteral nutrition is administered containing components similar to the solutions used in this study, heparin may be added at the time of preparation of the home parenteral nutrition solution rather than just before administration, with no resultant loss of heparin activity over time [corrected].

Ionized calcium monitoring during liver transplantation.

Ionized calcium concentration was measured in five patients undergoing liver transplantation. Varying degrees of decreased ionized calcium were observed in all cases and can be attributed to the chelation of calcium by the citrate added during blood transfusions, the inability of the patient to metabolize citrate by the liver during the anahepatic phase of the transplant, and hemodilution of the blood volume with the perfusion prime during venovenous bypass. Calcium chloride was administered when necessary as guided by ionized calcium measurements to restore concentrations to levels that maintain adequate cardiac output. Because of the serious hemodynamic consequences of severe hypocalcemia, regular monitoring of ionized calcium concentration is necessary during this procedure. Total calcium levels are not reliable for this because they do not reflect the extent of anion binding.