Continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodiafiltration are common modes of continuous renal-replacement therapy (CRRT) performed in intensive care units (ICUs).1,2 Hemofiltration has often required the use of replacement fluids that traditionally have been prepared by hand or by an automated compounding device. However, in recent years the marketing of bicarbonate-buffered replacement solutions (PrismaSol [Gambro, Lakewood, CO] and Normocarb HF [Dialysis Solutions Inc., Whitby, Ontario, Canada]) has been approved by the Food and Drug Administration for use during CRRT.3,4 While premixed solutions provide increased convenience and improved patient safety,5 there is still a need for hemofiltration fluids customized for individual patients. Unfortunately, published information on the compatibility of magnesium sulfate and sodium bicarbonate in these solutions is limited. It is critical to understand the compatibility of additives in hemofiltration solutions, as they are given intravenously to patients during CRRT. For example, precipitates created by the mixing of magnesium and bicarbonate salts might have serious clinical consequences if a solution containing them is infused.
The purpose of this study was to assess the physical compatibility of magnesium sulfate and sodium bicarbonate in a pharmacy-compounded, bicarbonate-buffered hemofiltration solution.
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Methods
Two bicarbonate-buffered hemofiltration solutions (low- and high-magnesium formulations) were compounded in triplicate with an automated compounding devicea under a laminar airflow hood using aseptic technique (Table 1). The low- magnesium solution resembled one that might be used clinically whereas the high-magnesium solution was studied to determine whether a very high magnesium concentration— higher than would be used in practice—might result in precipitation. The concentrations of magnesium (15 meq/L) and sodium bicarbonate (50 meq/L) in the high-magnesium formulation were chosen to be somewhat below the concentrations (magnesium sulfate 16 meq/L and sodium bicarbonate 80 meq/L in 5% dextrose injection) reported as being incompatible in a popular reference.6 The solutions were compounded following the normal procedures of our pharmacy’s i.v. additive service. The additive sequence of the stock solutions used to compound the hemofiltration fluids is shown in Table 1. The six hemofiltration bags were stored at 22-25 °C in our pharmacy’s i.v. room without protection from light and with the clear side of the bags facing upward for 48 hours.
The physical compatibility of the solutions was assessed by our pharmaceutical development section. At 48 hours, visual analysis for precipitation was performed on solutions in the bags with a perpendicular high-intensity lamp against a black and white background. In addition, the entire volume of each bag was filtered through a 37-mm, 0.45-μm gridded filter.b The filter was then removed from the casing and observed for particulate matter under a 125-1000× power microscope. The pH of these hemofiltration solutions was measured 3-4 and 52-53 hours after preparation using a pH meterc that was calibrated before use with buffer solutions of pH 7 and 10. In addition, the osmolality of the solutions was measured with an osmometerd 3-4 hours after solution preparation.
Xem thêm : Al + Cl2 → AlCl3 | Al ra AlCl3
Another set of six hemofiltration solutions, compounded as described previously, was stored at 22-23 °C and assessed for physical compatibility as described above. One sample from each bag was assayed by our department of laboratory medicine with a Synchron LX20 Clinical Systeme for sodium, chloride, carbon dioxide, magnesium, potassium, and glucose concentrations 3-4 and 50-51 hours after solution preparation.
Results
No particulate matter was observed by visual or microscopic inspection in the compounded hemofiltration solutions. The mean ± S.D. pH values of the low-magnesium solutions at 3-4 and 52-53 hours after compounding were 8.01 ± 0.02 and 8.04 ± 0.02, respectively. The mean ± S.D. pH values of the high- magnesium solutions at 3-4 and 52-53 hours after compounding were 7.96 ± 0.02 and 7.98 ± 0.01, respectively. The electrolyte and glucose concentrations in the low- and high-magnesium solutions were similar at 3-4 and 50-51 hours after preparation (Table 2). The mean ± S.D. osmolality of the low- and high-magnesium solutions was 270 ± 2.08 and 279 ± 2.65 mOsm/kg, respectively.
Discussion
Two bicarbonate-buffered hemofiltration solutions were physically compatible, with no particulate matter seen by microscopy, when stored at room temperature without protection from light for 48 hours. These observations are supported by the pH values, which showed no appreciable change over the course of the study. The low-magnesium solution contained the maximum amount of additives that we may use in clinical practice at our ICU. In clinical practice, these solutions are stored at room temperature and given an expiration of 28 hours after preparation for sterility reasons. While the high-magnesium solution would never be used in a clinical setting, as it would cause severe hypermagnesemia, we studied this formulation to investigate if a higher magnesium concentration would lead to the formation of magnesium carbonate precipitates. The electrolyte and glucose concentrations in both formulations were similar at 3-4 and 50-51 hours after preparation. There was a small decrease in the carbon dioxide concentration in both formulations at 50-51 hours, possibly due to carbon dioxide loss from the monolayer Exacta-Mix i.v. bags. The mean magnesium concentration of 1.3 meq/L in the low-magnesium solution (Table 2) was lower than expected, which may have been due to precipitate formation, assay variability, and inaccuracy of the automated compounding device when measuring the small volume of magnesium. Precipitate formation, however, was unlikely, as particulate matter would have been visible under a microscope.
Bicarbonate has become the preferred buffer over lactate in hemofiltration solutions. In a study by Barenbrock et al.,7 hypotensive episodes occurred more frequently in patients receiving lactate-buffered than bicarbonate-buffered replacement fluids during CVVH. However, the use of bicarbonate increases the risk of incompatibility with divalent cations, such as calcium and magnesium. While precipitate formation is a well-recognized problem with the addition of calcium to bicarbonate solutions, magnesium has not been extensively studied as an additive. In our ICUs, the incompatibility of calcium and bicarbonate has been handled by running a separate, adjustable calcium chloride infusion during CRRT. The ability to add physiological concentrations of magnesium sulfate to bicarbonate-buffered replacement fluids obviates the need for a second infusion or frequent intermittent doses of magnesium and improves convenience and safety.
Xem thêm : NaNO3 → NaNO2 + O2 ↑ | NaNO3 ra NaNO2 | NaNO3 ra O2
The potential incompatibility of sodium bicarbonate and magnesium sulfate is a concern for hospital pharmacies that compound hemofiltration solutions. Clinical studies of bicarbonate-buffered replacement solutions have used lower concentrations of bicarbonate, with some solutions containing lactate for stability.2,7-10 As mentioned before, magnesium sulfate 16 meq/L and sodium bicarbonate 80 meq/L in 5% dextrose injection are reportedly incompatible,6 but no particulate matter was observed in the solution containing magnesium 15 meq/L and bicarbonate 50 meq/L. In further support of this solution’s compatibility, the magnesium sulfate was added to the sodium bicarbonate before dilution with sterile water for injection (Table 1).
The theoretical formation of precipitate in combining magnesium sulfate and sodium bicarbonate may be understood through the following two formulas: (1) MgSO4 + 2NaHCO3 ⇌ Mg(HCO3)2 + Na2SO4 and (2) MgSO4 + NaHCO3 ⇌ ↓MgCO3 + NaHSO4. We found no solubility coefficient for magnesium bicarbonate, but the solubility coefficients for magnesium sulfate and magnesium carbonate are 35.7 g/100 g water and 0.18 g/100 g water, respectively.11 As no precipitate was observed in either low- or high- magnesium solutions, magnesium carbonate seems unlikely to form under hospital pharmacy conditions.
Chapter 788 of the United States Pharmacopeia recommends the use of light obscuration or microscopy to detect particulate matter in parenteral infusions or solutions for injection.12 Recent studies of parenteral nutrition have used both tests to assess calcium and phosphate compatibility.13-15
Conclusion
Magnesium sulfate 1.5 meq/L and sodium bicarbonate 50 meq/L were physically compatible in a pharmacy-compounded hemofiltration solution for 48 hours when stored at 22-25 °C without protection from light.
Tables
Footnotes
References
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This post was last modified on Tháng ba 22, 2024 8:42 chiều