Calcium gluconate injection is available as a 100-mg/mL (10%) concentrate for injection in preservative-free 10- and 50-mL single-dose vials and 100-mL pharmacy bulk packages.3289 Each mL contains 100 mg of calcium gluconate (equivalent to 94 mg of calcium gluconate with 4.5 mg of calcium saccharate tetrahydrate) and hydrochloric acid and/or sodium hydroxide for pH adjustment in water for injection, providing 9.3 mg (0.465 mEq) of elemental calcium.3289 Aluminum also is present.3289
For direct intravenous injection, the calcium gluconate dose should be diluted in dextrose 5% or sodium chloride 0.9% to a concentration of 10 to 50 mg/mL.3289 For continuous intravenous infusion, the calcium gluconate dose should be diluted in dextrose 5% or sodium chloride 0.9% to a concentration of 5.8 to 10 mg/mL.3289
Calcium gluconate also is available as a premixed, ready-to-use solution at concentrations of 10 or 20 mg/mL in single-dose flexible plastic containers.3917; 3918 Each mL of the 10-mg/mL solution contains calcium gluconate monohydrate 10 mg (equivalent to 9.4 mg of calcium gluconate anhydrous with 0.45 mg calcium saccharate tetrahydrate) with sodium chloride 8 mg in water for injection, and provides 0.93 mg (0.0465 mEq) of elemental calcium.3918 Each mL of the 20-mg/mL solution contains calcium gluconate monohydrate 20 mg (equivalent to 18.8 mg of calcium gluconate anhydrous and 0.9 mg of calcium saccharate tetrahydrate) with sodium chloride 6.75 mg in water for injection, and provides 1.86 mg (0.093 mEq) of elemental calcium.3917; 3918 The solutions also contain hydrochloric acid and/or sodium hydroxide for pH adjustment.3917; 3918 Aluminum also is present.3917; 3918
pH
From 6 to 8.2.3289; 3917; 3918
Osmolarity
The osmolarity of a 100-mg/mL solution is stated to be 680 mOsm/L.3313
Osmolality
The osmolality of a calcium gluconate 10% solution was determined by osmometer to be 276 mOsm/kg.1233
Aluminum Content
Aluminum content may vary depending on the product; specific product labeling should be consulted.
Calcium gluconate injection (Fresenius Kabi) contains up to 512 mcg of aluminum per L.3289
Calcium gluconate premixed injection solution from WG Critical Care or Fresenius Kabi contains up to 25 or 100 mcg of aluminum per L, respectively.3917; 3918
Calcium gluconate is administered intravenously by slow intravenous injection or by continuous infusion through a secure intravenous line.3289; 3917 The 100-mg/mL concentrate should be diluted in dextrose 5% or sodium chloride 0.9% prior to administration.3289 Premixed, ready-to-use solutions should not be further diluted.3917 When administered by direct intravenous injection, the infusion rate should not exceed 200 mg of calcium gluconate per minute in adults or 100 mg of calcium gluconate per minute in pediatric patients, including neonates.3289; 3917
Intramuscular or subcutaneous injection of the drug is not recommended because of possible severe necrosis and sloughing.183; 184; 185; 359; 3313 If extravasation occurs or if clinical manifestations of calcinosis cutis are present, administration at that site should be discontinued and appropriate treatment should be instituted.3289
Calcium gluconate injection is a supersaturated solution that has been stabilized by the addition of calcium saccharate.3313 Intact vials and solutions in flexible plastic containers should be stored at controlled room temperature and not frozen.3289; 3917; 3918 The 100-mg/mL concentrate is a clear and colorless to slightly yellow solution.3289 The premixed, ready-to-use solutions should appear clear and colorless.3917; 3918 Solutions should not be used if particulate matter or discoloration is present.3289; 3917
The manufacturer states that doses dispensed from the pharmacy bulk package and diluted solutions must be used immediately.3289 Unused portions of single-dose vials should be discarded immediately, and pharmacy bulk packages should be discarded after 4 hours of initial puncture.3289
Precipitation
Calcium gluconate injection is a supersaturated solution, and such solutions are susceptible to precipitation.3289 If precipitates have formed, they may be dissolved by warming affected vials to 60 to 80°C with occasional agitation until a clear solution results, followed by vigorous shaking of the vials.3289 Warmed vials should be allowed to cool to room temperature prior to dispensing.3289 Contents of such vials should only be used if they are clear immediately prior to use.3289
Drugs in Syringe Compatibility
Y-Site Injection Compatibility (1:1 Mixture)
Additional Compatibility Information
Calcium and Phosphate
UNRECOGNIZED CALCIUM PHOSPHATE PRECIPITATION IN A 3-IN-1 PARENTERAL NUTRITION MIXTURE RESULTED IN PATIENT DEATH.
The potential for the formation of a calcium phosphate precipitate in parenteral nutrition solutions is well studied and documented,1771; 1777 but the information is complex and difficult to apply to the clinical situation.1770; 1772; 1777 The incorporation of lipid emulsion in 3-in-1 parenteral nutrition solutions obscures any precipitate that is present, which has led to substantial debate on the dangers associated with 3-in-1 parenteral nutrition mixtures and when or if the danger to the patient is warranted therapeutically.1770; 1771; 1772; 2031; 2032; 2033; 2034; 2035; 2036 Because such precipitation may be life-threatening to patients,2037; 2291 FDA issued a Safety Alert containing the following recommendations:1769
Calcium Phosphate Precipitation Fatalities
Fatal cases of paroxysmal respiratory failure in 2 previously healthy women receiving peripheral vein parenteral nutrition were reported. The patients experienced sudden cardiopulmonary arrest consistent with pulmonary emboli. The authors used in vitro simulations and an animal model to conclude that unrecognized calcium phosphate precipitation in a 3-in-1 total nutrition admixture caused the fatalities. The precipitation resulted during compounding by introducing calcium and phosphate near to one another in the compounding sequence and prior to complete fluid addition. This resulted in a temporarily high concentration of the drugs and precipitation of calcium phosphate. Observation of the precipitate was obscured by the incorporation of 20% lipid emulsion, intravenous, into the nutrition mixture. No filter was used during infusion of the fatal nutrition admixtures.2037
In a follow-up retrospective review, 5 patients were identified who had respiratory distress associated with the infusion of the 3-in-1 admixtures at around the same time. Four of these 5 patients died, although the cause of death could be definitively determined for only 2.2291
Calcium and Phosphate Conditional Compatibility
Calcium salts are conditionally compatible with phosphate in parenteral nutrition solutions. The incompatibility is dependent on a solubility and concentration phenomenon and is not entirely predictable. Precipitation may occur during compounding or at some time after compounding is completed.
NOTE: Some amino acid solutions inherently contain both calcium and phosphate, which must be considered in any projection of compatibility.
A study determined the maximum concentrations of calcium (as chloride and gluconate) and phosphate (as sodium phosphates) that can be maintained without precipitation in a parenteral nutrition solution consisting of FreAmine II 4.25% and dextrose 25% for 24 hours at 30°C. It was noted that the amino acids in parenteral nutrition solutions form soluble complexes with calcium and phosphate, reducing the available free calcium and phosphate that can form insoluble precipitates. The concentration of calcium available for precipitation is greater with the chloride salt compared to the gluconate salt, at least in part because of differences in dissociation characteristics. Consequently, a greater concentration of calcium gluconate than calcium chloride can be mixed with sodium phosphate.608
In addition to the concentrations of phosphate and calcium and the salt form of the calcium, the concentration of amino acids and the time and temperature of storage altered the formation of calcium phosphate in parenteral nutrition solutions. As the temperature was increased, the incidence of precipitate formation also increased. This finding was attributed, at least in part, to a greater degree of dissociation of the calcium and phosphate complexes and the decreased solubility of calcium phosphate. Therefore, a solution possibly may be stored at 4°C with no precipitation, but on warming to room temperature a precipitate will form over time.608
The compatibility of calcium and phosphate in several parenteral nutrition formulas for newborn infants was evaluated. Calcium gluconate 10% (Cutter) and potassium phosphate (Abbott) were used to achieve concentrations of 2.5 to 100 mEq/L of calcium and 2.5 to 100 mmol/L of phosphorus added. The parenteral nutrition solutions evaluated were as shown in Table 1. The results were reported as graphic depictions.
Table 1. Parenteral Nutrition Solutions609
| Solution Number | ||||
|---|---|---|---|---|
| Component | #1 | #2 | #3 | #4 |
| FreAmine III | 4% | 2% | 1% | 1% |
| Dextrose | 25% | 20% | 10% | 10% |
| pH | 6.3 | 6.4 | 6.6 | 7a |
aAdjusted with sodium hydroxide.
The pH dependence of the phosphate-calcium precipitation has been noted. Dibasic calcium phosphate is very insoluble, while monobasic calcium phosphate is relatively soluble. At low pH, the soluble monobasic form predominates; but as the pH increases, more dibasic phosphate becomes available to bind with calcium and precipitate. Therefore, the lower the pH of the parenteral nutrition solution, the more calcium and phosphate can be solubilized. Once again, the effects of temperature were observed. As the temperature is increased, more calcium ion becomes available and more dibasic calcium phosphate is formed. Therefore, temperature increases will increase the amount of precipitate.609
Similar calcium and phosphate solubility curves were reported for neonatal parenteral nutrition solutions using TrophAmine (McGaw) 2, 1.5, and 0.8% as the sources of amino acids. The solutions also contained dextrose 10%, with cysteine and pH adjustment being used in some admixtures. Calcium and phosphate solubility followed the patterns reported previously.609 A slightly greater concentration of phosphate could be used in some mixtures, but this finding was not consistent.1024
Using a similar study design, 6 neonatal parenteral nutrition solutions based on Aminosyn-PF (Abbott) 2, 1.5, and 0.8%, with and without added cysteine hydrochloride and dextrose 10% were studied. Calcium concentrations ranged from 2.5 to 50 mEq/L, and phosphate concentrations ranged from 2.5 to 50 mmol/L. Solutions sat for 18 hours at 25°C and then were warmed to 37°C in a water bath to simulate the clinical situation of warming prior to infusion into a child. Solubility curves were markedly different than those for TrophAmine in the previous study.1024 Solubilities were reported to decrease by 15 mEq/L for calcium and 15 mmol/L for phosphate. The solutions remained clear during room temperature storage, but crystals often formed on warming to 37°C.1211
However, these data were questioned by Mikrut, who noted the similarities between the Aminosyn-PF and TrophAmine products and found little difference in calcium and phosphate solubilities in a preliminary report.1212 In the full report,1213 parenteral nutrition solutions containing Aminosyn-PF or TrophAmine 1 or 2.5% with dextrose 10 or 25%, respectively, plus electrolytes and trace metals, with or without cysteine hydrochloride, were evaluated under the same conditions. Calcium concentrations ranged from 2.5 to 50 mEq/L, and phosphate concentrations ranged from 5 to 50 mmol/L. In contrast to the previous results,1024 the solubility curves were very similar for the Aminosyn-PF and TrophAmine parenteral nutrition solutions but very different from those of the previous Aminosyn-PF study.1211 The authors again showed that the solubility of calcium and phosphate is greater in solutions containing higher concentrations of amino acids and dextrose.1213
Calcium and phosphate solubility curves for TrophAmine 1 and 2% with dextrose 10% and electrolytes, vitamins, heparin, and trace elements were reported. Calcium concentrations ranged from 10 to 60 mEq/L, and phosphorus concentrations ranged from 10 to 40 mmol/L. Calcium and phosphate solubilities were assessed by analysis of the calcium concentrations and followed patterns similar to those reported previously.608; 609 The higher percentage of amino acids (TrophAmine 2%) permitted a slightly greater solubility of calcium and phosphate, especially in the 10 to 50-mEq/L and 10 to 35-mmol/L ranges, respectively.1614
The maximal product of the amount of calcium (as gluconate) times phosphate (as potassium) that can be added to a parenteral nutrition solution, composed of amino acids 1% (Travenol) and dextrose 10%, for preterm infants was reported. Turbidity was observed on initial mixing when the solubility product was around 115 to 130 mmol2 or greater. After storage at 7°C for 20 hours, visible precipitates formed at solubility products of 130 mmol2 or greater. If the solution was administered through a barium-impregnated silicone rubber catheter, crystalline precipitates obstructed the catheters in 12 hours at a solubility product of 100 mmol2 and in 10 days at 79 mmol2, much lower than the in vitro results.1041
The solubility characteristics of calcium and phosphate in pediatric parenteral nutrition solutions composed of Aminosyn 0.5, 2, and 4% with dextrose 10 to 25% were reported. Also present were electrolytes and vitamins. Sodium phosphate was added sequentially in phosphorus concentrations from 10 to 30 mmol/L. Calcium gluconate was added last in amounts ranging from 1 to 10 g/L. The solutions were stored at 25°C for 30 hours and examined visually and microscopically for precipitation. The authors found that higher concentrations of Aminosyn increased the solubility of calcium and phosphate. Precipitation occurred at lower calcium and phosphate concentrations in the 0.5% solution compared to the 2 and 4% solutions. For example, at a phosphorus concentration of 30 mmol/L, precipitation occurred at calcium gluconate concentrations of about 1, 2, and 4 g/L in the 0.5, 2, and 4% Aminosyn mixtures, respectively. Similarly, at a calcium gluconate concentration of 8 g/L and above, precipitation occurred at phosphorus concentrations of about 13, 17, and 22 mmol/L in the 0.5, 2, and 4% solutions, respectively. The dextrose concentration did not appear to affect the calcium and phosphate solubility significantly.1042
The solubility of calcium and phosphorus in neonatal parenteral nutrition solutions composed of amino acids (Abbott) 1.25 and 2.5% with dextrose 5 and 10%, respectively, was evaluated. Also present were multivitamins and trace elements. The solutions contained calcium (as gluconate) in amounts ranging from 25 to 200 mg/100 mL. The phosphorus (as potassium phosphate) concentrations evaluated ranged from 25 to 150 mg/100 mL. If calcium gluconate was added first, cloudiness occurred immediately. If potassium phosphate was added first, substantial quantities could be added with no precipitate formation in 48 hours at 4°C (Table 2). However, if stored at 22°C, the solutions were stable for only 24 hours, and all contained precipitates after 48 hours.1210
Table 2. Maximum Calcium and Phosphorus Concentrations Physically Compatible for 48 Hours at 4°C1210
| Phosphorus (mg/100 mL) | ||
|---|---|---|
| Calcium (mg/100 mL) | Amino Acids 1.25% + Dextrose 5%a | Amino Acids 2.5% + Dextrose 10%a |
| 200b | 50 | 75 |
| 150 | 50 | 100 |
| 100 | 75 | 100 |
| 50 | 100 | 125 |
| 25 | 150b | 150b |
aPlus multivitamins and trace elements.bMaximum concentration tested.
The physical compatibility of calcium gluconate 10 to 40 mEq/L and potassium phosphates 10 to 40 mmol/L in 3 neonatal parenteral nutrition solutions (TPN #123 to #125 in Appendix), alone and with retrograde administration of aminophylline 7.5 mg diluted with 1.5 mL of sterile water for injection was reported. Contact of the alkaline aminophylline solution with the parenteral nutrition solutions resulted in the precipitation of calcium phosphate at much lower concentrations than were compatible in the parenteral nutrition solutions alone.1404
The maximum allowable concentrations of calcium and phosphate in a 3-in-1 parenteral nutrition mixture for children (TNA #192 in Appendix) were reported. Added calcium was varied from 1.5 to 150 mmol/L, while added phosphate was varied from 21 to 300 mmol/L. The mixtures were stable for 48 hours at 22 and 37°C as long as the pH was not greater than 5.7, the calcium concentration was below 16 mmol/L, the phosphate concentration was below 52 mmol/L, and the product of the calcium and phosphate concentrations was below 250 mmol2/L2.1773
Additional calcium and phosphate solubility curves were reported for specialty parenteral nutrition solutions based on NephrAmine and also HepatAmine at concentrations of 0.8, 1.5, and 2% as the sources of amino acids. The solutions also contained dextrose 10%, with cysteine and pH adjustment to simulate addition of lipid emulsion used in some admixtures. Calcium and phosphate solubility followed the hyperbolic patterns previously reported.609 Temperature, time, and pH affected calcium and phosphate solubility, with pH having the greatest effect.2038
The maximum sodium phosphate concentrations were reported for given amounts of calcium gluconate that could be admixed in parenteral nutrition solutions containing TrophAmine in varying quantities (with cysteine hydrochloride 40 mg/g of amino acid) and dextrose 10%. The solutions also contained magnesium sulfate 4 mEq/L, potassium acetate 24 mEq/L, sodium chloride 32 mEq/L, pediatric multivitamins, and trace elements. The presence of cysteine hydrochloride reduces the solution pH and increases the amount of calcium and phosphate that can be incorporated before precipitation occurs. The results of this study cannot be safely extrapolated to TPN solutions with compositions other than the ones tested. The admixtures were compounded with the sodium phosphate added last after thorough mixing of all other components. The authors noted that this is not the preferred order of mixing (usually phosphate is added first and thoroughly mixed before adding calcium last); however, they believed this reversed order of mixing would provide a margin of error in cases in which the proper order is not followed. After compounding, the solutions were stored for 24 hours at 40°C. The maximum calcium and phosphate amounts that could be mixed in the various solutions were reported tabularly and are shown in Table 3.2039 However, these results are not entirely consistent with another study.2196 See below.
Table 3. Maximum Amount of Phosphate (as Sodium) (mmol/L) Not Resulting in Precipitation2039 See CAUTION Below.a
| Amino Acid (as TrophAmine) with Cysteine HCl 40 mg/g of Amino Acid | |||||
|---|---|---|---|---|---|
| Calcium (as Gluconate) | 0% | 0.4% | 1% | 2% | 3% |
| 9.8 mEq/L | 0 | 27 | 42 | 60 | 66 |
| 14.7 mEq/L | 0 | 15 | 18 | 30 | 36 |
| 19.6 mEq/L | 0 | 6 | 15 | 27 | 30 |
| 29.4 mEq/L | 0 | 3 | 6 | 21 | 24 |
aCAUTION: The results cannot be safely extrapolated to solutions with formulas other than the ones tested. See text.
The temperature dependence of the calcium-phosphate precipitation has resulted in the occlusion of a subclavian catheter by a solution apparently free of precipitation. The parenteral nutrition solution consisted of FreAmine III 500 mL, dextrose 70% 500 mL, sodium chloride 50 mEq, sodium phosphate 40 mmol, potassium acetate 10 mEq, potassium phosphate 40 mmol, calcium gluconate 10 mEq, magnesium sulfate 10 mEq, and Shil’s trace metals solution 1 mL. Although there was no evidence of precipitation in the bottle, tubing and pump cassette, and filter (all at approximately 26°C) during administration, the occluded catheter and Vicra Loop Lock (next to the patient’s body at 37°C) had numerous crystals identified as calcium phosphate. In vitro, this parenteral nutrition solution had a precipitate in 12 hours at 37°C but was clear for 24 hours at 26°C.610
Similarly, a parenteral nutrition solution that was clear and free of particulates after 2 weeks under refrigeration developed a precipitate in 4 to 6 hours when stored at room temperature. When the solution was warmed in a 37°C water bath, precipitation occurred in 1 hour. Administration of the solution before the precipitate was noticed led to interstitial pneumonitis due to deposition of calcium phosphate crystals.1427
A 2-mL fluid barrier of dextrose 5% in a microbore retrograde infusion set failed to prevent precipitation when used between calcium gluconate 200 mg/2 mL and sodium phosphate 0.3 mmol/0.1 mL.1385
Calcium phosphate precipitation phenomena was evaluated in a series of parenteral nutrition admixtures composed of dextrose 22%, amino acids (FreAmine III) 2.7%, and fat emulsion (Abbott) 0, 1, and 3.2%. Incorporation of calcium gluconate 19 to 24 mEq/L and phosphate (as sodium) 22 to 28 mmol/L resulted in visible precipitation in the fat-free admixtures. New precipitate continued to form over 14 days, even after repeated filtrations of the solutions through 0.2-µm filters. The presence of the amino acids increased calcium and phosphate solubility, compared with simple aqueous solutions. However, the incorporation of the fat emulsion did not result in a statistically significant increase in calcium and phosphate solubility. The authors noted that the kinetics of calcium phosphate precipitate formation do not appear to be entirely predictable; both transient and permanent precipitation can occur either during the compounding process or at some time afterward. Because calcium phosphate precipitation can be very dangerous clinically, the use of inline filters was recommended. The authors suggested that the filters should have a porosity appropriate to the parenteral nutrition admixture—1.2 µm for fat-containing and 0.2 or 0.45 µm for fat-free nutrition mixtures.2061
Laser particle analysis was used to evaluate the formation of calcium phosphate precipitation in pediatric TPN solutions containing TrophAmine in concentrations ranging from 0.5 to 3% with dextrose 10% and also containing L-cysteine hydrochloride 1 g/L. The solutions also contained in each liter sodium chloride 20 mEq, sodium acetate 20 mEq, magnesium sulfate 3 mEq, trace elements 3 mL, and heparin sodium 500 units. The presence of L-cysteine hydrochloride reduces the solution pH and increases the amount of calcium and phosphate that can be incorporated before precipitation occurs. The results of this study cannot be safely extrapolated to TPN solutions with compositions other than the ones tested. The maximum amount of phosphate that was incorporated without the appearance of a measurable increase in particulates in 24 hours at 37°C for each of the amino acids concentrations is shown in Table 4.2196 These results are not entirely consistent with previous results.2039 See Table 3. The use of more sensitive electronic particle measurement for the formation of subvisual particulates in this study may contribute to the differences in the results.
Table 4. Maximum Amount of Phosphate (as Potassium) (mmol/L) Not Resulting in Precipitation2196 See CAUTION Below.a
| Amino Acid (as TrophAmine) plus Cysteine HCl 1 g/L | ||||||
|---|---|---|---|---|---|---|
| Calcium (as Gluconate) (mEq/L) | 0.5% | 1% | 1.5% | 2% | 2.5% | 3% |
| 10 | 22 | 28 | 38 | 38 | 38 | 43 |
| 14 | 18 | 18 | 18 | 38 | 38 | 43 |
| 19 | 18 | 18 | 18 | 33 | 33 | 38 |
| 24 | 12 | 18 | 18 | 22 | 28 | 28 |
| 28 | 12 | 18 | 18 | 18 | 18 | 18 |
| 33 | 12 | 12 | 12 | 12 | 12 | 12 |
| 37 | 12 | 12 | 12 | 12 | 12 | 12 |
| 41 | 9 | 9 | 9 | 12 | 12 | 12 |
| 45 | 0 | 9 | 9 | 12 | 12 | 12 |
| 49 | 0 | 9 | 9 | 9 | 12 | 12 |
| 53 | 0 | 9 | 9 | 9 | 9 | 9 |
aCAUTION: The results cannot be safely extrapolated to solutions with formulas other than the ones tested. See text.
The solubility of calcium acetate versus calcium gluconate with sodium phosphates was evaluated in pediatric parenteral nutrition solutions following storage for 30 hours at 25°C followed by 30 minutes at 37°C. Concentrations of Aminosyn PF studied varied from 1 to 3%, dextrose from 10 to 25%, calcium from 5 to 60 mEq/L, and phosphate from 1 to 60 mmol/L. L-Cysteine hydrochloride at a dose of 40 mg/g of Aminosyn PF, magnesium 3.2 mEq/L, and pediatric trace elements-4 at 2.4 mL/L of pediatric parenteral nutrition solution were also added. Calcium acetate was found to be less soluble than calcium gluconate when prepared under these concentrations. The maximum concentrations of the calcium salts and sodium phosphates are shown in Table 5. Polarized light microscopy was used to identify the calcium acetate and sodium phosphate crystals adherent to the container walls because simple visual observation was not able to identify the precipitates. The authors recommended the use of calcium acetate to reduce the iatrogenic aluminum exposure often seen with calcium gluconate in the neonatal population receiving parenteral nutrition.2466 However, care must be taken to avoid inadvertent calcium phosphate precipitation at the lower concentrations found with calcium acetate if it is substituted for the gluconate salt to reduce aluminum exposure.
Table 5. Maximum Concentrations of Sodium Phosphates and Calcium as Acetate and as Gluconate Not Resulting in Precipitation2466
| Aminosyn PF (%) | Sodium Phosphates (mmol/L) | Calcium Acetate (mEq/L) | Calcium Gluconate (mEq/L) |
|---|---|---|---|
| 1 | 10 | 25 | 50 |
| 1 | 15 | 15 | 25 |
| 2 | 10 | 30 | 45 |
| 2 | 25 | 10 | 12.5 |
| 3 | 20 | 10 | 15 |
| 3 | 25 | 15 | 17.5 |
Calcium and phosphate compatibility was evaluated in a series of adult formula parenteral nutrition admixtures composed of FreAmine III, in concentrations ranging from 1 to 5% (TPN #258 through #262). The solutions also contained dextrose ranging from 15% up to 25%. Also present were sodium chloride, potassium chloride, and magnesium sulfate in common amounts. Cysteine hydrochloride was added in an amount of 25 mg/g of amino acids from FreAmine III to reduce the pH by about 0.5 pH unit and thereby increase the amount of calcium and phosphates that can be added to the TPN admixtures as has been done with pediatric parenteral nutrition admixtures. Phosphates as the potassium salts and calcium as the gluconate salt were added in variable quantities to determine the maximum amounts of calcium and phosphates that could be added to the test admixtures. The samples were evaluated at 23 and 37°C over 48 hours by visual inspection in ambient light and using a Tyndall beam and electronic measurement of turbidity and microparticulates. The addition of the cysteine hydrochloride resulted in an increase of calcium and phosphates solubility of about 30% by lowering the solution pH 0.5 pH unit. The boundaries between the compatible and incompatible concentrations were presented graphically as hyperbolic curves.2469
A 2-in-1 parenteral nutrition admixture with final concentrations of TrophAmine 0.5%, dextrose 5%, L-cysteine hydrochloride 40 mg/g of amino acids, calcium gluconate 60 mg/100 mL, and sodium phosphates 46.5 mg/mL was found to result in visible precipitation of calcium phosphate within 30 hours stored at 23 to 27°C. Despite the presence of the acidifying L-cysteine hydrochloride, precipitation occurred at clinically utilized amounts of calcium and phosphates.2622
The presence of magnesium in solutions may also influence the reaction between calcium and phosphate, including the nature and extent of precipitation.158; 159
The interaction of calcium and phosphate in parenteral nutrition solutions is a complex phenomenon. Various factors play a role in the solubility or precipitation of a given combination, including:608; 609; 1042; 1063; 1210; 1234; 1427; 2778
Enhanced precipitate formation would be expected from such factors as high concentrations of calcium and phosphate, increases in solution pH, decreases in amino acid concentrations, increases in temperature, addition of calcium before phosphate, lengthy standing times or slow infusion rates, and use of calcium as the chloride salt.854
Even if precipitation does not occur in the container, it has been reported that crystallization of calcium phosphate may occur in a Silastic infusion pump chamber or tubing if the rate of administration is slow, as for premature infants. Water vapor may be transmitted outward and be replaced by air rapidly enough to produce supersaturation.202 Several other cases of catheter occlusion also have been reported.610; 1427; 1428; 1429
Aluminum
Calcium gluconate injection in glass vials is a significant source of aluminum, which has been associated with neurological impairment in premature neonates. Aluminum is leached from the glass vial during the autoclaving of the vials for sterilization. The use of calcium gluconate injection in polyethylene plastic vials in countries where it is available has been recommended to reduce the aluminum burden for neonates.2322
For a list of references cited in the text of this monograph, search the monograph titled References.