Rate of Infusion for Intravenous Magnesium Replacement in Hematopoietic Cell Transplant Patients

Amber B. Clemmons, PharmD BCOP
Clinical Associate Professor, University of Georgia College of Pharmacy
Hematology/Hematopoietic Cell Transplantation Clinical Pharmacy Specialist
Augusta University Medical Center
Augusta, GA

Hypomagnesemia is a frequent occurrence after hematopoietic cell transplantation (HCT). Correction of electrolyte disturbances is required to prevent neuromuscular and cardiac manifestations. Magnesium replacement is often provided via the intravenous (IV) route after HCT because of gastrointestinal disturbances from nausea or vomiting, mucositis, or diarrhea. Significant doses are often required to maintain therapeutic levels during concomitant receipt of magnesium-wasting therapies such as calcineurin inhibitors. However, administration of IV magnesium can be challenging because renal handling in a high-peak serum concentration leads to increased excretion and decreased tubular reabsorption. It has therefore been postulated that slowing the infusion rate can improve magnesium retention. A paucity of data exists to support this theory and any impact on clinical outcomes. Potential detrimental effects of prolonged infusion rates include labor and temporal factors, as well as the possibility for increased issues related to IV access availability and incompatibility with other medications.

In the first study to assess magnesium infusion rate in HCT patients, Snyder and colleagues evaluated 103 allogeneic HCT patients in an ambulatory care setting.¹ In this study, prolonging the rate of infusion did not change the primary endpoint of grams of magnesium replaced per clinic visit. However, this study compared administering 4 grams over 1 hour (4 g/hr rate) versus administering 4 grams over 2 hours (2 g/hr rate). The authors acknowledged that the study did not address the potential utility of giving higher doses over a longer duration.

To further address the impact of prolonged magnesium infusion rates in HCT recipients, a postgraduate-year-1 pharmacy residency research project was performed by Ku and colleagues at the Augusta University Medical Center in Augusta, GA.² In this study, researchers retrospectively examined two groups of HCT recipients. One group received prolonged magnesium infusions (0.5 g/hr; n = 41), and the second group received shorter magnesium infusions (>0.5 g/hr [median rate 2.07 g/hr, range 0.8–6 g/hr; n = 41]). The primary endpoint was percent of days with serum magnesium within the goal range (2–2.7 g/dL). Other endpoints included percent of days with serum magnesium within the therapeutic range (1.3–2.7 g/dL), total amount of IV magnesium administered, total number of days of IV magnesium replacement, and incidence of hypomagnesemia and hypermagnesemia. Both autologous and allogeneic HCT patients were included to allow generalizability to a transplant program or medical ward protocol. Baseline characteristics including receipt of magnesium-wasting therapies (44% vs. 32%; p = .25), presence of magnesium in IV fluids (2.4% vs. 4.9%; p = .56), receipt of parenteral nutrition (19.5% vs. 17.1%; p = .78), type of transplant (allogeneic HCT 49% vs. autologous HCT 32%; p = .11), and incidence of graft-versus-host disease (25% vs. 46%; p = .14) were similar between prolonged versus short infusion groups.

Overall, the mean age was 57 years with 54% male patients. Sixty percent received an autologous HCT, and 41% received high-dose melphalan conditioning chemotherapy. The percent of days in goal range (32.2% vs. 28.1%; p = .3) was not different between cohorts. Notably, the vast majority (>97%) of patients in both groups were in technical therapeutic range for most days. No difference existed in total amount of IV magnesium administered (22.5 g vs. 21.4 g, p = .81) or days of IV magnesium replacement (7.2 days vs. 6.2 days, p = .41). Incidence of hypomagnesemia and hypermagnesemia was low overall and not significantly different between cohorts (p = .43 each).

Nine patients (two patients from the prolonged-infusion-rate group and seven patients from the short-infusion-rate group) experienced at least one episode of hypomagnesemia (median level 1.2 mg/dL, range 0.9–1.2 mg/dL); notably, eight of these nine patients received allogeneic HCT. Seven patients (five patients from the prolonged-infusion-rate group and two from the short-infusion-rate group) experienced one episode of hypermagnesemia (median level 2.9 mg/dL, range 2.8–2.9 mg/dL, for the prolonged-infusion-rate group vs. median level 3 mg/dL, range 2.8–3.2 mg/dL, for the short-infusion-rate group). Notably, six of these seven patients received allogeneic HCT. Because of the retrospective design, researchers were unable to assess other safety outcomes for different infusion rates. On the basis of these data, we advised our hospital to abandon the prolonged-infusion-rate policy, and this recommendation was accepted.

Although this study was limited by its small sample size and retrospective design, no difference in practical outcomes was demonstrated between infusion rates. Further prospective studies would provide definitive information about using the optimal infusion rate for safety and efficacy outcomes while balancing practical concerns about administration. Prospective studies should include assessment of renal function, all sources of magnesium (e.g., dietary), and clinical outcomes such as potassium replacement and symptoms that are often difficult to assess and quantify from retrospective reviews.

Providers should carefully weigh the potential benefit of prolonged infusion rates with the administration challenges. Using a short infusion rate of 2–4 g/hr in HCT populations is a reasonable approach, given the limited available data.

References

1. Snyder M, Shillingburg A, Newton M, et al. Impact of intravenous magnesium infusion rate during ambulatory replacements on serum magnesium concentrations after allogeneic stem cell transplant. Support Care Cancer. 2016;24(10):4237-4240.
2. Ku PM, Waller JL, Sportès C, Clemmons AB. Prolonged versus short infusion rates for intravenous magnesium sulfate administration in hematopoietic cell transplant patients. Support Care Cancer. 2018;26(8):2809-2814.