Hypophosphatemia is Associated with the Serial Administration of Triple-Dose Gadolinium to Patients for Brain MRI

J Neuroimaging. 2015 May-Jun;25(3):379-83. doi: 10.1111/jon.12241. Epub 2015 Apr 13.

Abstract

Background and purpose: The purpose of this study is to report a metabolic abnormality associated with frequent, triple-dose Gadolinium (TdGd) use in MS patients during BECOME trial.

Methods: Potential clinical adverse events and lab abnormalities were monitored at each monthly MRI visit. Hypophosphatemia was defined as phosphate <2.5 mg/dL. Statistical analysis included McNemar's test for pairwise comparisons across visits and generalized estimating equations (GEE) to fit models over time.

Results: Eight hundred seventy seven phosphate values were analyzed from the first 12 months. Compared with 4% of subjects at screening, an average of 15.1% (95% confidence interval (CI): 11.4%-19.7%) of patients had hypophosphatemia at visits from months 1 to 12, during which subjects received serial TdGd. Forty four of seventy five (59%) patients developed hypophosphatemia at least once. We also found a significant increasing trend in hypophosphatemia by visit when treatment groups were evaluated together or separately (p < .001). There was a statistically significant decrease in frequency to 9.8% (95% CI: 4.6-19.8%) by month 24 (p = .005) coinciding with a period of less frequent gadolinium administration.

Conclusions: Serial TdGd in MS patients, unrelated to immunomodulatory treatment, was associated with increased frequency of hypophosphatemia that progressed with cumulative triple-dose and markedly decreased in second year, with less frequent triple-dose administration.

Keywords: Multiple sclerosis; adverse effects; gadolinium; hypophosphatemia; phosphate.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Contrast Media / administration & dosage
  • Contrast Media / adverse effects
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Gadolinium DTPA / administration & dosage*
  • Gadolinium DTPA / adverse effects*
  • Humans
  • Hypophosphatemia / blood
  • Hypophosphatemia / chemically induced*
  • Hypophosphatemia / diagnosis*
  • Magnetic Resonance Imaging / adverse effects*
  • Male
  • Middle Aged
  • Multiple Sclerosis / pathology*
  • Phosphates / blood
  • Young Adult

Substances

  • Contrast Media
  • Phosphates
  • Gadolinium DTPA