Placebo-controlled study of intravenous magnesium supplementation during large-volume leukapheresis in healthy allogeneic donors.

BACKGROUND: Marked decreases in ionized magnesium (iMg) levels occur during large-volume leukapheresis (LVL); however, the effect of intravenous (IV) magnesium supplementation in this setting has not been carefully studied. STUDY DESIGN AND METHODS: Thirty healthy allogeneic peripheral blood progenitor cell donors receiving citrate anticoagulant with IV calcium prophylaxis were randomized to receive either IV magnesium (0.2 mg Mg per mL acid citrate dextrose-A) or placebo during LVL, with a double-blind design. RESULTS: Thirty subjects underwent 75 LVL pro- cedures, 37 with magnesium and 38 with placebo. Group characteristics were similar for sex, weight, citrate infusion rate (1.36 mg/kg/min vs. 1.37 mg/kg/min), and volume processed (16 L vs. 17 L). Serum iMg levels remained within the reference range with magnesium supplementation, but decreased 39+/-11 percent below baseline (p<10(-10)) after placebo, with greater decreases after consecutive procedures. Subjects receiving magnesium had more vigorous parathyroid hormone responses and higher glucose levels and also tended to have higher serum potassium and ionized calcium levels. Mild paresthesias, coldness, and nausea occurred in 28, 20, and 7 percent of donors, respectively, with no significant differences between groups. Severe symptoms (chest tightness) occurred in only one subject receiving placebo. CONCLUSION: IV magnesium supplementation exerts a significant impact on serum magnesium levels, but does not reduce the frequency or severity of the relatively mild citrate-related effects observed in LVL performed with continuous IV calcium prophylaxis.

Randomized placebo-controlled study of oral calcium carbonate administration in plateletpheresis: I. Associations with donor symptoms.

BACKGROUND: The effect of oral calcium (Ca) supplements in preventing citrate-induced symptoms during plateletpheresis was evaluated in a randomized, blinded, placebo-controlled trial. STUDY DESIGN AND METHODS: Twenty-three donors (12 men, 11 women) underwent four plateletpheresis procedures each, ingesting either 1 or 2 g of oral Ca carbonate or an equivalent placebo 30 minutes before donation. Ten of these subjects subsequently ingested 4 g of open-label Ca before a fifth procedure. All procedures were conducted at the same citrate infusion rate (1.5 mg/kg/min) for 90 minutes. RESULTS: Ingestion of 2 g of oral Ca resulted in a significant reduction in the severity of paresthesias and a significant, though modest, increase in serum ionized calcium (iCa), but no significant improvement in total symptom scores, compared to placebo. Minimal effects were seen with the 1-g dose. The two factors most highly correlated with development of severe symptoms were decreased levels of iCa and ionized magnesium (iMg) at 30 minutes into apheresis. Lower preapheresis serum albumin, creatinine, vitamin D, iMg, and total Mg concentrations were also significantly associated with symptoms. Women experienced more frequent and severe symptoms than men, however, gender was not associated with symptoms after adjustment for lower serum albumin, creatinine, and Mg levels. Ingestion of 4 g of Ca offered no improvement in symptoms or iCa levels compared with the 2-g dose. CONCLUSION: Prophylactic oral Ca was associated with modest improvements in citrate-induced symptoms and laboratory parameters. Baseline albumin and Mg levels were strongly predictive of the development of symptoms. In donors with a prior history of uncomfortable citrate-related effects, a 2-g oral Ca dose before apheresis is recommended.

Randomized placebo-controlled study of oral calcium carbonate supplementation in plateletpheresis: II. Metabolic effects.

BACKGROUND: The metabolic effects of oral calcium (Ca) supplementation during plateletpheresis were evaluated in a randomized, placebo-controlled trial. STUDY DESIGN AND METHODS: Twenty-three donors underwent four plateletpheresis procedures each, receiving in random order, elemental Ca (Ca) 1 or 2 g orally, or a corresponding placebo, 30 minutes before donation. Ten of these donors underwent a fifth procedure using a 4-g Ca dose. All procedures were performed at a fixed citrate infusion rate of 1.5 mg per kg per minute. RESULTS: Oral Ca induced dose-sensitive changes in parathyroid hormone (iPTH), total (tCa), and ionized (iCa) calcium levels. Compared to placebo, the greatest improvement in tCa and iCa levels occurred after the 2-g Ca dose (tCa of 73, 89, and 25% above placebo levels at 60 min, using 1, 2, and 4 g of oral Ca, respectively). Twenty-four hours after apheresis, serum tCa and iCa levels were higher, and iPTH levels lower, in donors who received oral Ca rather than placebo. Marked increases in urinary Ca and magnesium (Mg) excretion occurred at the completion of apheresis, were unaffected by Ca dose, and returned to baseline within 24 hours. Plateletpheresis also induced significant changes in serum alkaline phosphatase, 1,25-dihydroxyvitamin D, and osteocalcin levels immediately and at 24 hours after apheresis. CONCLUSION: Plateletpheresis induces marked acute metabolic effects, with sustained changes evident up to 24 hours after the completion of apheresis. Oral Ca supplementation exerts a significant but clinically modest impact on selected laboratory variables associated with these effects. Further studies are indicated to examine the long-term impact of plateletpheresis, with or without Ca supplementation, on donor Ca balance and bone density.

Controlled study of citrate effects and response to i.v. calcium administration during allogeneic peripheral blood progenitor cell donation.

BACKGROUND: Leukapheresis procedures are generally performed at citrate anticoagulation rates extrapolated from shorter plateletpheresis procedures. However, neither the metabolic effects nor the management of associated symptoms have been critically evaluated during leukapheresis in healthy donors. STUDY DESIGN AND METHODS: Symptom assessments (n = 315) and laboratory analyses (n = 49) were performed during 244 procedures performed with and 71 without prophylactic calcium (Ca) chloride or Ca gluconate given at a dose linked to the citrate infusion rate (1.0-2.2 mg/kg/min). RESULTS: During leukapheresis of 12 to 25 L processed, ionized Ca and ionized magnesium (Mg) decreased as much as 35 and 56 percent, respectively, each exhibiting a tight negative correlation with marked increases in serum citrate levels. Significant increases in urinary Ca and Mg excretion accompanied the renal excretion of a large citrate load. Serum divalent cation levels remained depressed 24 hours after leukapheresis. Symptoms were more frequent in donors who were women, had low initial total Mg levels, and underwent procedures in which larger volumes were processed at higher citrate infusion rates. Ca infusions reduced clinically significant paresthesias by 96 percent and also attenuated decreases in serum potassium. Ca chloride maintained higher Ca levels than Ca gluconate. CONCLUSIONS: Prophylactic Ca infusions safely attenuate the marked metabolic effects of citrate administration and promote faster, more comfortable, leukapheresis procedures.

Effects of interleukin 2 therapy on lymphocyte magnesium levels.

Interleukin 2 (IL-2) can cause partial or complete tumor regression in approximately 20% of patients with renal cell carcinoma. Among the many physiologic effects of IL-2, decreased serum levels of the divalent cations magnesium (Mg) and calcium have been demonstrated, with corresponding decreases in their urinary excretion. We investigated the effect of IL-2 on lymphocyte Mg levels among patients receiving three different dosing regimens. Twenty-eight patients with metastatic renal cell carcinoma were treated with high-dose intravenous, low-dose intravenous, or subcutaneous IL-2 therapy. Serum ionized Mg, urinary Mg, and peripheral blood mononuclear cell Mg levels were measured in samples from patients during treatment and compared with pretreatment levels. Serum Mg and ionized Mg levels decreased for all patients within 12 hours of treatment (P <.005) and remained low for the duration of therapy. Urinary Mg decreased in parallel with serum levels in all patients (P <.005). The peripheral blood mononuclear cell Mg content per cell increased within 24 hours of treatment (P <.005). The magnitude of these changes was similar during the first week of treatment for patients receiving intravenous or subcutaneous administration of IL-2. During IL-2 therapy, lymphocyte Mg increases coincident with serum Mg depletion. Mg availability may have functional implications for lymphocyte proliferation and integrin function.