Phosphate Infusion Research Articles

Impact of different hemodiafiltration solutions on ionemia in long-term CRRT.

Critical patients with Acute Kidney Injury (AKI) requiring renal replacement therapy are in most cases eligible only for continuous modalities where the electrolyte balance control is a critical issue. The standard solutions used for hemodiafiltration, containing potassium at 2 mmol/L and no phosphorus, determines during the extended renal replacement therapy hypokalemia and hypophosphatemia. Therefore, solutions containing potassium and phosphate in physiological concentrations were formulated to avoid electrolyte imbalances and reduce ion alterations in prolonged treatments, these solutions are not routinely used in the standard clinical practice. To avoid electrolyte imbalances, we have first introduced in our practice two different solutions and then we have retrospectively analyzed the electrolyte balance upon these two solutions in order to identity the impact of these solutions on potassium and phosphate according to our clinical practice. We retrospectively analyzed 96 patients treated with Continuous Renal Replacement Therapy (CRRT) in the intensive care units (ICU) at Padua's University Hospital to evaluate the role on electrolyte balance of Phoxilium® and Prismasol 2® that differ in their composition and the need for electrolytes infusions. In the Phoxilium group the frequency of hypokalemia, hypophosphatemia, and the need of potassium and phosphate replacement were significantly reduced resulting in a reduction in complications, workload, and clinical risk associated with infusions of electrolytes. Our data demonstrated that the use of these two different hemodiafiltration solutions can reduce the occurrence of hypokalemia and hypophosphatemia during CRRT performing personalized treatments without the use of potassium and phosphate infusions.

Ferric carboxymaltose (Ferinject®) associated hypophosphataemia: case report illustrating the need for increased awareness to minimise incidence and risk

Ferric carboxymaltose (Ferinject®) is an infusion administered for the treatment of iron deficiency anaemia. A number of previous case reports have shown the occurrence of hypophosphataemia after Ferinject® treatment, supposedly managed though high dose phosphate therapy. This case report highlights the risk associated with, and futility of, managing this adverse effect through high dose phosphate infusion. A review of the available literature suggests that if hypophosphataemia develops as a result of Ferinject®, through upregulation of the renal protein Fibroblast Growth Factor-23, it cannot be readily reversed and on average persists for circa 50 days. Acute medical units should be aware of this – likely underreported – adverse effect, and avoid treating these hypophosphataemic patients with high dose phosphate since it can compound symptoms.

The duration of fetal antenatal steroid exposure determines the durability of preterm ovine lung maturation

Antenatal corticosteroids (ACS) are the standard of care for maturing the fetal lung and improving outcomes for preterm infants. Antenatal corticosteroid dosing remains nonoptimized, and there is little understanding of how different treatment-to-delivery intervals may affect treatment efficacy. The durability of a lung maturational response is important because the majority of women treated with antenatal corticosteroids do not deliver within the widely accepted 1- to 7-day window of treatment efficacy. We used a sheep model to test the duration of fetal exposures for efficacy at delivery intervals from 1 to 10 days. For infusion studies, ewes with single fetuses were randomized to receive an intravenous bolus and maintenance infusion of betamethasone phosphate to target 1-4 ng/mL fetal plasma betamethasone for 36 hours, with delivery at 2, 4 ,or 7 days posttreatment or sterile saline solution as control. Animals receiving the clinical treatment were randomised to receive either a single injection of 0.25 mg/kg with a 1:1 mixture of betamethasone phosphate+ betamethasone acetate with delivery at either 1 or 7 days posttreatment, or 2 treatments of 0.25 mg/kg betamethasone phosphate+ betamethasone acetate spaced at 24 hours (giving ∼48 hours of fetal steroid exposure) with delivery at 2, 5, 7, or 10 days posttreatment. Negative control animals were treated with saline solution. All lambs were delivered at 121 ± 3 days gestational age and ventilated for 30 minutes to assess lung function. Preterm lambs delivered at 1 or 2 days post-antenatal corticosteroid treatment had significant improvements in lung maturation for both intravenous and single-dose intramuscular treatments. After 2 days, the efficacy of 36-hour betamethasone phosphate infusions was lost. The single dose of 1:1 betamethasone phosphate+ betamethasone acetate also was ineffective at 7 days. In contrast, animals treated with 2 doses had significant improvements in lung maturation at 2, 5, and 7 days, with treatment efficacy reduced by 10 days. In preterm lambs, the durability of antenatal corticosteroids treatment depends on the duration of fetal exposure and is independent of the intravenous or intramuscular maternal route of administration. For acute 24- to 48-hour posttreatment deliveries, a 24-hour fetal antenatal corticosteroids exposure was sufficient for lung maturation. A fetal exposure duration of at least 48 hours was necessary to maintain long-term treatment durability. A single-dose ACS treatment should be sufficient for women delivering within <48 hours of antenatal corticosteroids treatment.

An appraisal of the in vivo role of phosphate as a modulator of urinary ammonium and titratable acid excretion in the acidotic rabbit.

Previous studies have shown that the intravenous infusion of inorganic phosphate increased urinary ammonium excretion 8- to 10-fold in the acidotic rabbit. This was considered to be a very important observation at the time and to be unique to the rabbit. While investigating this finding, we discovered that the formol titration procedure, used to measure urinary ammonium by this research group, is subject to interference by phosphate, casting doubt on the validity of the urinary ammonium excretion data reported by them in the literature. In order to re-assess the importance of phosphate as a potential modulator of urinary ammonium excretion in the acidotic rabbit, renal net acid excretion studies were carried out in phosphate-loaded acidotic animals. We observed that while urinary ammonium excretion increased significantly (p<0.05) after 50min of phosphate infusion, the maximum concentrations excreted were substantially less than previously reported in the literature. However, through its urinary buffering capacity, we observed that inorganic phosphate, via an experimentally induced phosphaturia, could substantially enhance titratable acid excretion. Contrary to earlier reports, we demonstrated that phosphate plays a relatively minor in vivo modulator role in enhancing renal net acid excretion through the vehicle of ammonium during acute metabolic acidosis in the hyperphosphataemic rabbit. The findings reported in this study constitute an important update on ammonia metabolism in the acidotic rabbit.

Increased acute vascular deposition of radioactive phosphate is an index of calcification

Mineral bone disorder and vascular calcification (VC) are substantial contributors to the elevated cardiovascular disease (CVD) burden in chronic kidney disease patients. The degree to which the uremic milieu and mineral dysregulation individually contribute to this CVD is poorly understood. Calcitriol, the active form of vitamin D, is a key regulator of mineral metabolism. In this study, we present a model of rapid calcitriol‐induced VC in rats with normal kidney function, with findings that point to active and non‐active processes of calcification being fundamentally different phenotypes.Male Sprague Dawley rats (n=17, 15 weeks) were injected with 0.5 μg/kg/day calcitriol SQ for 8 days. On the 9th day, half of the animals were sacrificed (n=8, CxE), and the remainder were sacrificed 14 days after the cessation of calcitriol (n=9, CxL). Control animals (n=6) followed the same protocol. Circulating calcium, phosphate, and hormones regulating mineral metabolism (parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF‐23)) were measured every two days. At sacrifice, animals underwent an IV infusion of 300μmol PO4 spiked with radioactive 33PO4. Forty body tissues, including 14 across the vascular tree, were harvested and analyzed for mineral content/VC (calcium and phosphate) as well as acute phosphate deposition (33PO4 accrual).Daily administration of high‐dose calcitriol significantly elevated FGF‐23 and calcium, and suppressed PTH after only 2 doses, however, 14 days after calcitriol withdrawal, the analytes had fully normalized (Figure 1). Substantial VC was generated over the 8 days of treatment (7.8±4.2 v. 166±142 nmol Ca/mg tissue, p&lt;0.001) and persisted 14 days after stopping treatment (540±492 nmol Ca/mg tissue). Following IV infusion of phosphate labelled with 33PO4, animals sacrificed directly following calcitriol treatment (CxE) had greater accrual of phosphate acutely in the vascular bed compared to those sacrificed 14 days after the cessation of treatment (CxL; −50.4%, p&lt;0.001), despite having sustained levels of resident VC (Figure 2).Despite the similar magnitude of VC, acute deposition of phosphate following the IV load, a potential measure of calcification activity, was significantly greater during calcitriol treatment (CxE) than after stopping it (CxL). This suggests that the VC itself does not mediate the increased accrual of phosphate, but rather the cellular phenotype of the tissue. Also, it was this acute activity, not the resident VC, that aligned with dysregulated mineral metabolism markers. The transcriptional, cellular, and physiological differences of these two states, as well as their differential associations with circulating analytes are not currently differentiated in VC research. These differences likely have an important role in VC present in humans.Support or Funding InformationThis research was funded by Canadian Institutes of Health Research and Vanier Canada Graduate Scholarships.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The efficacy of antenatal steroid therapy is dependent on the duration of low-concentration fetal exposure: evidence from a sheep model of pregnancy

Antenatal corticosteroids are among the most important and widely used interventions to improve outcomes for preterm infants. Antenatal corticosteroid dosing regimens remain unoptimized and without maternal weight-adjusted dosing. We, and others, have hypothesized that, once a low concentration of maternofetal steroid exposure is achieved and maintained, the duration of the steroid exposure determines treatment efficacy. Using a sheep model of pregnancy, we tested the relationship among steroid dose, duration of exposure, and treatment efficacy. The study was conducted to investigate the relative importance of duration and magnitude of fetal corticosteroid exposure to mature the preterm fetal ovine lung. Ewes with single fetuses at 120 days gestation received an intravenous bolus (loading dose) followed by a maintenance infusion of betamethasone phosphate to target 12-hour fetal plasma betamethasone concentrations of (1) 20 ng/mL, (2) 10 ng/mL, or (3) 2ng/mL. In a subsequent experiment, fetal plasma betamethasone concentrations were targeted at 2 ng/mL for 26 hours. Negative control animals received sterile saline solution. Positive control animals received 2 intramuscular injections of 0.25 mg/kg Celestone Chronodose (betamethasone phosphate+ betamethasone acetate) spaced at 24 hours. Preterm lambs were delivered surgically and ventilated 48 hours after treatment commenced. Maternal and fetal plasma betamethasone concentrations were confirmed by mass spectrometry in a parallel study of chronically catheterized, corticosteroid-treated ewes and fetuses. The loading and maintenance doses were achieved and maintained the desired fetal plasma betamethasone concentrations of approximately 20, 10, and 2 ng/mL for 12 hours. Compared with the 12-hour infusion-treated animals, lambs from the positive control (2intramuscular doses of 0.25 mg/kg Celestone Chronodose) group had the greatest functional lung maturation (compliance, gas exchange, arterial pH) and molecular evidence of maturation (glucocorticoid receptor signaling activation), despite having maximum fetal plasma betamethasone concentrations 2.5 times lower than animals in the 20 ng/mL betamethasone infusion group. Lambs from the 12-hour 2-ng/mL betamethasone infusion group had little functional lung maturation. In contrast, lambs from the 26-hour 2-ng/mL betamethasone infusion group had functional lung maturation equivalent to lambs from the positive control group. In preterm lambs that were exposed to antenatal corticosteroids, high maternofetal plasma betamethasone concentrations did not correlate with improved lung maturation. The largest and most consistent improvements in lung maturation were in animals that were exposed to either the clinical course of Celestone Chronodose or a low-dose betamethasone phosphate infusion to achieve a fetal plasma betamethasone concentration of approximately 2 ng/mL for 26 hours. The duration of low-concentration maternofetal steroid exposure, not total dose or peak drug exposure, is a key determinant for antenatal corticosteroids efficacy. These findings underscore the need to develop an optimized steroid dosing regimen that may improve both the efficacy and safety of antenatal corticosteroids therapy.

Regional citrate anticoagulation for continuous renal replacement therapy without post-filter monitoring of ionized calcium

Continuous renal replacement therapy (CRRT) modalities are usually preferred in hemodynamically unstable patients in the intensive care units (ICU) but perceived expense and complexity slows broad acceptance. Heparin remains a problematic choice for CRRT anticoagulation due to the risk of bleeding in ICU patients and concerns about heparininduced thrombocytopenia. In this paper, we are describing our simplified regional citrate anticoagulation protocol, utilizing commercially available, premixed solutions exclusively and minimized laboratory monitoring. The protocol is employing Anticoagulant Citrate Dextrose-A (ACD-A) solution for citrate delivery, calcium-free dialysate or replacement fluids and separate calcium infusion, all commercially available in the United States. ACD-A is being infused pre-filter with an hourly rate of 1.5:1 to blood flow rate per minute without specific monitoring of post-filter ionized calcium concentration. Separate infusions of calcium-chloride, sodium phosphate and magnesium chloride are employed via triple lumen catheter to normalize peripheral ionized calcium, phosphate and magnesium concentrations, respectively. The protocol can be conveniently applied in both continuous veno-venous hemofiltration and hemodiafiltration regimens with several of the commercially available CRRT platforms. Built-in features of the protocol are the tendency alkalization and mild hypernatremia, which may be advantageous under select circumstances.

Aggressive Treatment of Life-Threatening Hypophosphatemia During Recovery From Fulminant Hepatic Failure: A Case Report

Acute liver failure secondary to acetaminophen overdose can be a life-threatening condition, characterized by severe electrolyte derangements. Hepatocyte regeneration is associated with phosphorous utilization and is a known complication of liver recovery following injury. We report the case of profound, life-threatening hypophosphatemia following recovery from acute fulminant liver failure. As the liver enzymes normalized, serum phosphorous levels plummeted. Our patient required an aggressive, individualized phosphorus replacement regimen, which resulted in a continuous infusion of intravenous (IV) sodium phosphate, titrated to a maximum rate of 30 mmol/h or 0.5 mmol/kg/h. The patient required over 400 mmol of total IV and oral phosphorous over the course of 48 hours. An aggressive approach to phosphorous replacement was done safely and effectively. Traditional replacement protocols are not adequate to sustain patients with this degree of hypophosphatemia. This is the first report to utilize a continuous infusion of phosphate with a maximum reported rate (0.5 mmol/kg/h). Our report summarizes a novel and safe approach for clinicians to maximally support these patients through high-dose, continuous infusion phosphorous administration.

Unexpected acute renal injury after high-dose etoposide phosphate and total body irradiation in children undergoing hematopoietic stem cell transplantation.

High-dose etoposide phosphate, a water-soluble prodrug of etoposide, may be used after total body irradiation (TBI) in pediatric allogeneic bone marrow transplantation for lymphoblastic leukemia. In a retrospective study of 21 children treated at the Nancy University Hospital (2000-2014), we identified unprecedentedly an unexpectedly high incidence (57%) of acute renal injury following etoposide phosphate infusion. Patients who developed renal function impairment experienced more severe mucositis but had outcomes similar to those who did not. No risk factors were identified. We speculate that the etoposide phosphate diluent, dextran 40, may have been the causative agent in these post-TBI renal toxicity cases.

The effects of fructose and phosphate infusions on dry matter intake of lactating cows

The objective of this study was to examine the effects of fructose and phosphate (Pi) infusions on dry matter intake by dairy cows to further understand the mechanisms controlling feed intake related to hepatic energy status. We performed 3 experiments in which we infused fructose and Pi intravenously or abomasally to Holstein cows. The first experiment used 8 cows (4-8 d postpartum) in a duplicated 4 × 4 Latin square experiment with 1 square of multiparous and 1 square of primiparous cows. A 2 × 2 factorial arrangement of treatments was used including jugular infusions of solutions (1 L/h) containing fructose or glucose (0.6 mol/h) and Pi (NaH2PO4) or NaCl (0.3 mol/h). Periods were 24 h, including 2 h for infusions and 22 h for recovery. The second experiment used 4 multiparous cows (74-81 d postpartum) in a 4 × 4 Latin square design and infused fructose or glucose and either Pi or no Pi at the same rates as experiment 1. Periods were 24 h, including 1 h for infusions and 23 h for recovery. The third experiment used 4 ruminally cannulated multiparous cows (15-26 d postpartum) in a 4 × 4 Latin square design and infused fructose or glucose and either Pi or NaCl at the same rates as experiment 1 but to the abomasum. Periods were 24 h, including 1 h for infusions and 23 h for recovery. In each experiment, feed intake was recorded by a computerized data acquisition system; blood was analyzed for the concentrations of glucose, nonesterified fatty acids, and Pi; and the liver was analyzed for the concentration of Pi (experiments 2 and 3 only). Overall, fructose infusion increased DMI by fresh cows when infused intravenously and abomasally, but it did not affect DMI by mid-lactation cows. Fructose infusion also reduced hepatic Pi, and Pi infusion increased hepatic Pi when infused abomasally but not intravenously. These results suggest that fructose increases feed intake, likely by sequestering Pi and preventing ATP production. When infused intravenously to multiparous cows, Pi increased DMI and did not affect hepatic Pi content. However, when infused abomasally, Pi reduced DMI and increased hepatic Pi content. These results suggest that although Pi infusion prevents the effect of fructose loading and reduces DMI, it also increases intake through a competing mechanism. Examining long-term effect of Pi infusion on DMI could determine if competing mechanisms complicate the determination of P requirement for dairy cows. These results are consistent with the control of feed intake by hepatic energy status in dairy cows.

The effect of propofol infusion with topical epinephrine on cochlear blood flow and hearing: An experimental study

Background and objectivePropofol is the most commonly used intravenous (IV) anesthetic agent and is associated with hypotension upon induction of anesthesia. Intravenous propofol infusion has several properties that may be beneficial to patients undergoing middle ear surgery. Topical application of concentrated epinephrine is a valuable tool for achieving hemostasis in the middle ear and during mastoid surgery. The purpose of the present study was to determine the effects of propofol infusion with topical epinephrine on cochlear blood flow (CBF) and hearing in rats. Materials and methodsTwenty one male Sprague-Dawley rats were divided into three groups. The rate of intravenous infusion of propofol was 4–6 ml/kg/hour. The first group (control group, n = 7) was given IV infusion of phosphate buffered saline (PBS) with topical application of PBS in the round window. In study group A (n = 7), the effect of topical phosphate buffered saline with IV infusion of propofol on CBF and hearing was evaluated. In study group B (n = 7), additional effects of topical epinephrine with IV infusion of propofol on CBF and hearing were evaluated. The laser Doppler blood flowmeter, CBF, and the mean arterial blood pressure (MAP) were measured and analyzed. Additionally, hearing test using auditory brainstem response (ABR) was performed in both groups. ResultsIn both groups, infusion of propofol induced a time-dependent decrease in MAP. Approximately 30 min after the start of the propofol infusion, the CBF started to decrease slowly. The decrease in CBF was significantly greater in the study group compared to the control group. The threshold was elevated in the study group relative to the control group. ConclusionDuring middle ear surgery, use of IV infusion of propofol with topical epinephrine cotton ball or cottonoid application is not recommended.

Maternofetal pharmacokinetics and fetal lung responses in chronically catheterized sheep receiving constant, low-dose infusions of betamethasone phosphate

Antenatal steroids are standard of care for cases of anticipated preterm labor to improve neonatal outcomes. However, steroids are potent drugs, and their use in pregnancy remains largely unoptimized. The objective of the study was to measure the maternofetal pharmacokinetics of constant, low-dose intravenous betamethasone phosphate infusions and correlate these data with the transcriptional effect exerted by subclinical betamethasone exposures on the ovine fetal lung. Thirty-two ewes carrying a single fetus had surgery to catheterize fetal and maternal jugular veins at 116 days of gestation (term, 150 days). Animals were recovered for 2 days and then were randomized to receive 2 sequential maternal intravenous infusions of either (n= 4/group) of the following: 1) saline, 0.125, 0.04, or 0.0125 mg/kg betamethasone phosphate over 3 hours; or 2) saline, 0.25, 0.08, or 0.025 mg/kg betamethasone phosphate over 12 hours. Each infusion was separated by 2 days. Fetal lung tissue was collected for analysis using quantitative polymerase chain reaction and an ovine-specific microarray. Plasma betamethasone levels from time-course catheter samples were determined by mass spectrometry. Data were assessed for distribution, variance, and tested by an analysis of variance. Betamethasone was detectable (>1 ng/mL) in fetal plasma only in animals randomized to 0.125 mg/kg 3 hour or 0.250 mg/kg 12 hour infusions. Fetal betamethasone half-lives were 1.7-2.8 times greater than maternal values. At maximum concentration, fetal plasma betamethasone levels were approximately 10% of maternal levels. Compared with saline control, all animals, other than those receiving 0.0125 mg/kg 3 hour betamethasone phosphate infusions, had evidence of dose-dependent glucocorticoid transcriptional responses in the fetal lung. Constant maternal betamethasone infusions delivering substantially lower fetal and maternal betamethasone maximal concentrations than those achieved with current clinical treatment protocols were associated with dose-dependent changes in glucocorticoid-response markers in the fetal lung. Further studies to determine the minimally efficacious dose of steroids for improving outcomes in preterm infants should be viewed as a priority.

Intravenous Phosphate Loading Increases Fibroblast Growth Factor 23 in Uremic Rats

Oral phosphate loading and calcitriol stimulate Fibroblast growth factor 23 (FGF23) secretion, but the mechanisms underlying the stimulation of FGF23 remain to be studied. We compared the effect of intravenous phosphate loading with that of oral loading on FGF23 levels in normal and 5/6 nephrectomized uremic rats. Uremic rats (Nx) and sham-operated rats were fed a normal phosphate diet for 2 weeks and then divided into 3 groups: 1) with the same phosphate diet (NP), 2) with a high phosphate diet (HP), and 3) NP rats with intravenous phosphate infusion using a microinfusion pump (IV). Blood and urine were obtained 1 day (early phase) and 7 days (late phase) after the interventions. In the early and late phases, serum phosphate levels and fractional excretion of phosphate (FEP) were comparable in the HP and IV groups in both Sham and Nx rats. Serum phosphate levels in the HP and IV groups were equally and significantly higher than those in the NP group only in the late phase in Nx rats. In the early phase, FGF23 levels were comparable in the NP, HP, and IV groups, but were significantly higher in the HP and IV groups compared to the NP group in the late phase in Nx rats. 1α-hydroxylase and sodium dependent phosphate co-transporter 2a expression levels in the kidney in Nx rats were equally and significantly decreased in the HP and IV groups compared with the NP group, while 24-hydroxylase expression was equally and significantly increased. These results show that chronic intravenous phosphate loading increases bioactive FGF23, indicating that an alternative pathway for FGF23 regulation, in addition to the dietary route, may be present. This pathway is clearer under conditions produced by a kidney injury in which phosphate is easily overloaded.

Abstract 543: Local Uterine Ang-(1-7) Infusion Augments Expression of Cannabinoid Receptors and Differentially Alters Endocannabinoid Metabolizing Enzymes in the Decidualized Uterus of Pseudopregnant Rats

Endocannabinoids (ECs) are important contributors to implantation and decidualization and are suppressed in early pregnancy. Elevated levels of anandamine (AEA), the endogenous ligand for the CB 1 and CB 2 receptor (R), interfere with receptivity of the blastocyst. Ang-(1-7) is present in the decidualized zones of the implantation site (IS) at early pregnancy and is down-regulated in the IS in normal pregnancy. We determined the effects of intra-uterine Ang-(1-7) on the EC system in the decidualized uterus. Ovariectomized rats were sensitized for the decidual cell reaction by steroid treatment. Decidualization was induced by infusion of phosphate buffered saline into the left horn (infused); the right horn was non-infused. Ang-(1-7) (24 μg/kg/hr) or vehicle was given into one of the two uterine horns. CB 1 R mRNA was reduced by decidualization but increased in the presence of Ang-(1-7) . CB 2 R mRNA was increased by decidualization and by Ang-(1-7) ( Figure). The enzyme metabolizing AEA, fatty acid amide hydrolase (FAAH), was reduced by decidualization (1.0 ± 0.07 vs. 0.13 ± 0.03 U, p&lt;0.01) and remained reduced by Ang-(1-7), whereas the enzyme metabolizing 2-arachidonylglycerol, monoacyl glycerol lipase (MAGL), was unchanged by decidualization (1.06 ± 0.11 vs. 1.34 ± 0.13 U, ns) and increased by Ang-(1-7) (1.32 ± 0.19 vs. 2.27 ± 0.23 U, p&lt;0.01). These findings report for the first time that Ang-(1-7) augments the expression of CB 1 R, CB 2 R and MAGL in the decidualized uterus. The effects of Ang-(1-7) to disrupt regulation of the EC system may interfere with the early events of decidualization, including alterations in angiogenesis, apoptosis, permeability, and receptivity.

Is Parenteral Phosphate Replacement in the Intensive Care Unit Safe?

Hypophosphatemia is well recognized in the intensive care setting, associated with refeeding and continuous forms of renal replacement therapy (CCRT). However, it is unclear as to when and how to administer intravenous phosphate supplementation in the general intensive care setting. There have been recent concerns regarding phosphate administration and development of acute kidney injury. We therefore audited our practice of parenteral phosphate administration. We prospectively audited parenteral phosphate administration (20 mmol) in 58 adult patients in a general intensive care unit in a University tertiary referral center. Fifty-eight patients were audited; mean age 57.2 ± 2.0 years, 70.7% male. The median duration of the infusion was 310 min (228-417), and 50% of the patients were on CRRT. 63.8% of patients were hypophosphatemic (<0.87 mmol/L) prior to the phosphate infusion, and serum phosphate increased from 0.79 ± 0.02 to 1.07 ± 0.03 mmol/L, P < 0.001. Two patients became hyperphosphatemic (>1.45 mmol/L). There was no correlation between the change in serum phosphate and the pre-infusion phosphate. Although there were no significant changes in serum urea, creatinine or other electrolytes, arterial ionized calcium fell from 1.15 ± 0.01 to 1.13 ± 0.01 mmol/L, P < 0.01. Although infusion of 20 mmol phosphate did not appear to adversely affect renal function and corrected hypophosphatemia in 67.7% of cases, we found that around 33% of patients who were given parenteral phosphate were not hypophosphatemic, and that the fall in ionized calcium raises the possibility of the formation of calcium-phosphate complexes and potential for soft tissue calcium deposition.

Hyperglycemic Emergencies in Adults

Hyperglycemic Emergencies in Adults

Regional citrate anticoagulation in CVVH: A new protocol combining citrate solution with a phosphate‐containing replacement fluid

Regional citrate anticoagulation (RCA) is a valid anticoagulation method in continuous renal replacement therapies (CRRT) and different combination of citrate and CRRT solutions can affect acid-base balance. Regardless of the anticoagulation protocol, hypophosphatemia occurs frequently in CRRT. In this case report, we evaluated safety and effects on acid-base balance of a new RCA- continuous veno-venous hemofiltration (CVVH) protocol using an 18 mmol/L citrate solution combined with a phosphate-containing replacement fluid. In our center, RCA-CVVH is routinely performed with a 12 mmol/L citrate solution and a postdilution replacement fluid with bicarbonate (protocol A). In case of persistent acidosis, not related to citrate accumulation, bicarbonate infusion is scheduled. In order to optimize buffers balance, a new protocol has been designed using recently introduced solutions: 18 mmol/L citrate solution, phosphate-containing postdilution replacement fluid with bicarbonate (protocol B). In a cardiac surgery patient with acute kidney injury, acid-base status and electrolytes have been evaluated comparing protocol A (five circuits, 301 hours) vs. protocol B (two circuits, 97 hours): pH 7.39 ± 0.03 vs. 7.44 ± 0.03 (P < 0.0001), bicarbonate 22.3 ± 1.8 vs. 22.6 ± 1.4 mmol/L (NS), Base excess −2.8 ± 2.1 vs. −1.6 ± 1.2 (P = 0.007), phosphate 0.85 ± 0.2 vs. 1.3 ± 0.5 mmol/L (P = 0.027). Protocol A required bicarbonate and sodium phosphate infusion (8.9 ± 2.8 mmol/h and 5 g/day, respectively) while protocol B allowed to stop both supplementations. In comparison to protocol A, protocol B allowed to adequately control acid-base status without additional bicarbonate infusion and in absence of alkalosis, despite the use of a standard bicarbonate concentration replacement solution. Furthermore, the combination of a phosphate-containing replacement fluid appeared effective to prevent hypophosphatemia.

Creatine and creatine analogues in hypertension and cardiovascular disease

The creatine kinase system, the central regulatory system of cellular energy metabolism, provides ATP in situ at ATP-ases involved in ion transport and muscle contraction. Furthermore, the enzyme system provides relative protection from tissue ischaemia and acidosis. The system could therefore be a target for pharmacologic intervention. To systematically evaluate evidence regarding the effectiveness of interventions directly targeting the creatine kinase system as compared to placebo control in adult patients with essential hypertension or cardiovascular disease. Electronic databases searched: Medline (1950 - Feb 2011), Embase (up to Feb 2011), the Cochrane Controlled Trials Register (issue 3, Aug 2009), Latin-American/Caribbean databank Lilacs; references from textbooks and reviews; contact with experts and pharmaceutical companies; and searching the Internet. There was no language restriction. Randomized controlled trials comparing creatine, creatine phosphate, or cyclocreatine (any route, dose or duration of treatment) with placebo; in adult patients with essential hypertension, heart failure, or myocardial infarction. We did not include papers on the short-term use of creatine during cardiac surgery. The outcomes assessed were death, total myocardial infarction (fatal or non-fatal), hospitalizations for congestive heart failure, change in ejection fraction, and changes in diastolic and systolic blood pressure in mm Hg or as percent change. Full reports or abstracts from 1164 papers were reviewed, yielding 11 trials considering treatment with creatine or creatine analogues in 1474 patients with heart failure, ischemic heart disease or myocardial infarction. No trial in patients with hypertension was identified. Eleven trials (1474 patients, 35 years or older) comparing add-on therapy of the creatine-based drug on standard treatment to placebo control in patients with heart failure (6 trials in 1226 / 1474 patients ), or acute myocardial infarction (4 trials in 220 / 1474 patients) or 1 in ischemic heart disease (28 / 1474 patients) were identified. The drugs used were either creatine, creatine phosphate (orally, intravenously, or intramuscular) or phosphocreatinine. In the trials considering heart failure all three different compounds were studied; creatine orally (Gordon 1995, Kuethe 2006), creatine phosphate via intravenous infusion (Ferraro 1996, Grazioli 1992), and phosphocreatinine orally (Carmenini 1994, Maggi 1990). In contrast, the acute myocardial infarction trials studied intravenous creatine phosphate only. In the ischemic heart disease trial (Pedone 1984) creatine phosphate was given twice daily through an intramuscular injection to outpatients and through an intravenous infusion to inpatients. The duration of the study intervention was shorter for the acute patients, from a two hour intravenous infusion of creatine phosphate in acute myocardial infarction (Ruda 1988, Samarenko 1987), to six months in patients with heart failure on oral phosphocreatinine therapy (Carmenini 1994). In the acute myocardial infarction patients the follow-up period varied from the acute treatment period (Ruda 1988) to 28 days after start of the symptoms (Samarenko 1987) or end of the hospitalization period (Zochowski 1994). In the other trials there was no follow-up after discontinuation of treatment, except for Gordon 1995 which followed the patients until four days after stopping the intervention.Only two out of four trials in patients with acute myocardial infarction reported mortality outcomes, with no significant effect of creatine or creatine analogues (RR 0.73, CI: 0.22 - 2.45). In addition, there was no significance on the progression of myocardial infarction or improvement on ejection fraction. The main effect of the interventions seems to be on improvement of dysrhythmia. This review found inconclusive evidence to decide on the use of creatine analogues in clinical practice. In particular, it is not clear whether there is an effect on mortality, progression of myocardial infarction and ejection fraction, while there is some evidence that dysrhythmia and dyspnoea might improve. However, it is not clear which analogue, dose, route of administration, and duration of therapy is most effective. Moreover, given the small sample size of the discussed trials and the heterogeneity of the population included in these reports, larger clinical studies are needed to confirm these observations.

Beeinflussung der Blutkonzentration von Glukose und anorganischem Phosphat durch Infusion 5- und 20%iger Glukoselösung bei Milchkühen

The study was performed to evaluate the influence of an intravenous infusion of 5% and 20% dextrose solution on the plasma concentration of glucose and inorganic phosphate in healthy, dairy cows. Ten healthy, lactating, nonpregnant 3 to 6 year-old Holstein-Friesian cows were included in this investigation. The daily milk yield was 20.3±2.7 liters. Blood plasma concentrations of inorganic phosphate and glucose were determined before, during, immediately and 60 minutes after infusion of 0.9% physiological saline, 5% or 20% dextrose solution. A statistically significant influence of dextrose infusion on blood glucose concentration was observed. After 20% dextrose infusion (200 g dextrose) the blood glucose concentration increased by approximately 13.26 mmol/l. The administration of 5% dextrose solution (50 g dextrose) yielded an increase of blood glucose concentration by 3.31 mmol/l. There was no significant correlation between plasma inorganic phosphate concentrations and infusion of 0.9% saline, 5% or 20% dextrose solution. Intravenous administration of 1000 ml of 5% or 20% dextrose solution does not induce a lasting plasma phosphate reduction and is suitable for elevating the blood glucose concentration.

The Treatment of Osteomalacia by the Intravenous Phosphate Infusion

The Treatment of Osteomalacia by the Intravenous Phosphate Infusion