Early vs late initiation of sodium glycerophosphate: Impact on hypophosphatemia in preterm infants <32 weeks.

BACKGROUND & AIMS: Early electrolyte and mineral imbalances have emerged as a conspicuous problem in very preterm babies since the revision of nutrition guidelines and the eventual implementation of early aggressive parenteral nutrition (PN). We opted to carry out a study with the introduction of phosphorus as sodium glycerophosphate in PN from the first day onward to reveal the impact on serum phosphorus and calcium levels following the surge in the incidence of hypercalcemia and hypophosphatemia. METHODS: In this single-center, prospective, observational cohort study, inborn babies <32 gestational weeks and <1500 g between August 2017 and July 2018 were enrolled consecutively. Infants born in the first 6-month of this period were initiated PN (Early phosphorus group) containing phosphorus (1 mmol P as sodium glycerophosphate/100 ml PN) immediately after birth, and in the latter six-months, mineral-free standard PN (Control group) was commenced up until 48 h of life. Parenteral nutritional prescriptions of both groups were similar in terms of macro and micronutrient intakes except for early phosphorus, calcium, and sodium. Serum mineral and electrolyte levels were measured on Days 1-3-7 and compared between the groups. The primary outcome was the presence of hypophosphatemia in the first week of life. The secondary outcome was hypercalcemia, preterm morbidity, and mortality. RESULTS: A total of 261 infants were included in this study. There were 130 babies in Early phosphorus group and 131 in control group. Gestational ages (28.79 ± 2.1 vs 28.46 ± 2.2 weeks, respectively) and birth weights (1138 ± 273 vs 1090 ± 274 g, respectively) were similar in the groups. Mean serum phosphorus levels were higher on all days in Early phosphorus group (p < 0.001). Early phosphorus group had a lower incidence of hypophosphatemia on days 1-3 and 7 (p < 0.001). The percentage of hypercalcemic infants was significantly lower in Early phosphorus group on day 3 (p < 0.001). No difference was noted in terms of hypernatremia in the groups. CONCLUSIONS: Adding phosphorus to PN in the first hours of life reduced the frequency of hypophosphatemia and hypercalcemia without any surge in hypernatremia or morbidity. Nutrition guidelines need to be revised accordingly in terms of early mineral/electrolyte supplementation.

Poly(ethylene glycol)/chitosan/sodium glycerophosphate gel replaced the joint capsule with slow-release lubricant after joint surgery.

Body fluid is normally the only lubricant after joint replacement surgery, but wear problems have occurred because body fluid has poor lubrication ability. However, traditional lubricant would be diluted by body fluids and then absorbed by the human body. Therefore, an injectable gel with the ability to slow-release lubricant was designed to replace the joint capsule. The proposed gel, poly(ethylene glycol)/chitosan/sodium glycerophosphate (PEG/CS/GP) composite gel was then tested. The tribology results showed that the PEG/CS/GP gel had excellent slow-release properties, especially under pressure, and the PEG played an important role in improving the gel's rheological and mechanical properties. Moreover, this study revealed that the release solution had a good lubrication effect because the PEG and GP could crosslink via the hydrogen bond effect.

In situ mucoadhesive-thermosensitive liposomal gel as a novel vehicle for nasal extended delivery of opiorphin.

Previous studies proved the effectiveness of an intravenous PEGylated liposomal formulation of opiorphin (1mg/mL) in protecting the drug from enzymatic degradation, and improving intensity and duration of its painkilling effect. Therefore, considering the advantages of nasal administration, the aim of this work was the development of a liposomal mucoadhesive thermo-sensitive in situ gel for the extended nasal delivery of opiorphin. With this purpose, the potential of a series of combinations of different polymers (i.e. chitosan, hydroxypropylmethylcellulose, Poloxamer, Carbopol) in forming solutions able to rapidly gel at the nasal cavity temperature (34 °C) has been investigated. The best formulations were further characterized for gel strength and mucoadhesion properties. The selected formulation, composed by Poloxamer 407 (26.5%) and Carbopol 934P (1%), showed short gelation time at 34 °C (10s) and suitable mucoadhesion duration (5.5h) and strength (27g/cm2). Due to the low volume administrable via the nasal route, a concentrated liposomal formulation of the peptide (16.5mg/mL) was developed and loaded in the selected in situ gel formulation. Ex-vivo permeation studies, by excised nasal porcine mucosa, showed that the liposomal hydrogel formulation enabled a sustained and controlled delivery of opiorphin over more than 5h, and highlighted the role of the liposomal carrier in enhancing up to 6 times permeability coefficient and permeation rate of the peptide through the lipophilic nasal mucosa compared to a free peptide-loaded gel.

Aluminum Content of Neonatal Parenteral Nutrition Solutions.

INTRODUCTION: Calcium chloride (CaCl2) has been the only calcium additive available in the United States that has a low aluminum (Al) content. Calcium gluconate in glass vials (CaGluc-Gl) has a high Al content while calcium gluconate in plastic vials (CaGluc-Pl) has a low Al content. The purpose of this study was to measure Al concentrations in neonatal parenteral nutrition (PN) solutions prepared using various calcium additives. METHODS: Samples of solutions compounded with CaCl2 or CaGluc-Gl and sodium phosphate (NaPhos) as well as CaGluc-Pl and sodium glycerophosphate (NaGP) with and without cysteine were analyzed for Al content. Samples of the cysteine and calcium gluconate additives were also sent for analysis. RESULTS: Solutions containing CaCl2 and CaGlu-Pl had mean Al concentrations of 1.2-2.3 mcg/dL, while those with CaGlu-Gl had mean concentrations of 14.6-15.1 mcg/dL. Solutions made with NaGP were low in Al content. The measured Al content of 2 lots of the cysteine additive were 168 ± 23 mcg/L and 126 ± 5 mcg/L. The Al concentration equalled 2730 ± 20 mcg/L for the CaGlu-Gl additive and 310 ± 80 mcg/L for the CaGlu-Pl additive. CONCLUSION: The study indicates that solutions containing CaCl2 or CaGluc-Pl and NaPhos or NaGP are low in Al content. Using these options for calcium and phosphate additives can limit aluminum intake from neonatal PN to levels within the Food and Drug Administration guideline of ≤5 mcg/kg/d.

Aluminum Content of Neonatal Parenteral Nutrition Solutions: Options for Reducing Aluminum Exposure.

INTRODUCTION: Calcium chloride (CaCl2 ) has been the only calcium additive available in the United States that has a low aluminum (Al) content. Calcium gluconate in glass vials (CaGluc-Gl) has a high Al content while calcium gluconate in plastic vials (CaGluc-Pl) has a low Al content. The purpose of this study was to measure Al concentrations in neonatal parenteral nutrition (PN) solutions prepared using various calcium additives. METHODS: Samples of solutions compounded with CaCl2 or CaGluc-Gl and sodium phosphate (NaPhos) as well as CaGluc-Pl and sodium glycerophosphate (NaGP) with and without cysteine were analyzed for Al content. Samples of the cysteine and calcium gluconate additives were also sent for analysis. RESULTS: Solutions containing CaCl2 and CaGlu-Pl had mean Al concentrations of 1.2-2.3 mcg/dL, while those with CaGlu-Gl had mean concentrations of 14.6-15.1 mcg/dL. Solutions made with NaGP were low in Al content. The measured Al content of 2 lots of the cysteine additive were 168 ± 23 mcg/L and 126 ± 5 mcg/L. The Al concentration equalled 2730 ± 20 mcg/L for the CaGlu-Gl additive and 310 ± 80 mcg/L for the CaGlu-Pl additive. CONCLUSION: The study indicates that solutions containing CaCl2 or CaGluc-Pl and NaPhos or NaGP are low in Al content. Using these options for calcium and phosphate additives can limit aluminum intake from neonatal PN to levels within the Food and Drug Administration guideline of ≤5 mcg/kg/d.

Does Adding Intravenous Phosphorus to Parenteral Nutrition Has Any Effects on Calcium and Phosphorus Metabolism and Bone Mineral Content in Preterm Neonates?

The use of parenteral nutritional supplementation of phosphorus may lead to exhibit higher plasma phosphate concentrations and less radiological features in premature neonates susceptible to osteopenia. The present study aimed to assess the beneficial effects of adding intravenous phosphorus to total parenteral nutrition (TPN) on calcium and phosphorus metabolism in preterm neonates by measuring bone mineral content. This open-labeled randomized clinical trial was conducted on premature neonates who were hospitalized at NICU. The neonates were randomly assigned to two groups received TPN with intravenous sodium glycerophosphate or Glycophos (1.5 mmol/kg/day) or TPN without sodium glycerophosphate. At the end of the four weeks of treatment, the presence of osteopenia was examined using DEXA Scan. After completing treatment protocols, the group received TPN with intravenous Glycophos had significantly lower serum alkaline phosphatase (360±60 versus 762±71, P<0.001), as well as higher serum calcium to creatinine ratio (1.6±0.3 versus 0.44±0.13, P<0.001) compared to the control group received TPN without Glycophos. Those who received TPN with intravenous Glycophos experienced more increase in bone mineral density than those in control group (0.13±0.01 versus 0.10±0.02, P<0.001). There was no significant difference in serum calcium and serum vitamin D between the case and control groups. Adding intravenous sodium glycerophosphate to TPN in premature neonates can compensate the lack of bone mineral content and help to prevent osteopenia.

Physical Compatibility of Sodium Glycerophosphate and Calcium Gluconate in Pediatric Parenteral Nutrition Solutions.

BACKGROUND: The solubility of inorganic calcium and phosphate in parenteral solutions can be complicated in pediatrics due to the dosing of calcium and phosphorus at the saturation point. The purpose of this study was to test the solubility of sodium glycerophosphate (NaGP) with calcium gluconate in pediatric parenteral nutrition (PN) solutions. METHODS: Five PN solutions were compounded by adding calcium gluconate at 10, 20, 30, 40, and 50 mEq/L and corresponding concentrations of NaGP at 10, 20, 30, 40, and 50 mmol/L. Each of the 5 solutions was compounded using 1.5% and 4% amino acids, cysteines, and lipids. Compatibility was evaluated by visual inspection (precipitation, haze, and color change). Solutions were evaluated microscopically for any microcrystals and measured by a turbidimeter for changes in turbidity. Solutions were further analyzed using United States Pharmacopeia 788 standards. Six hundred seventy-one PN solutions were compounded at various concentrations and evaluated for visual stability. RESULTS: Compatibility testing showed no changes in the PN solution in any of the concentrations tested. Microscopically, no microcrystals were detected. The turbidimeter measurements had changes of ≤ 0.14 nephelometric turbidity units for all test solutions. There were no visual changes in any of the 671 PN solutions. CONCLUSION: It is recommended that NaGP replace sodium phosphate in PN solutions. This would eliminate the concern of calcium and phosphorus precipitation and the need of any saturation curves.