Paramedic Initiation of Neuroprotective Agent Infusions: Successful Achievement of Target Blood Levels and Attained Level Effect on Clinical Outcomes in the FAST-MAG Pivotal Trial (Field Administration of Stroke Therapy - Magnesium)

Stroke. 2017 Jul;48(7):1901-1907. doi: 10.1161/STROKEAHA.116.015664. Epub 2017 Jun 5.

Abstract

Background and purpose: Paramedic use of fixed-size lumen, gravity-controlled tubing to initiate intravenous infusions in the field may allow rapid start of neuroprotective therapy for acute stroke. In a large, multicenter trial, we evaluated its efficacy in attaining target serum levels of candidate neuroprotective agent magnesium sulfate and the relation of achieved magnesium levels to outcome.

Methods: The FAST-MAG phase 3 trial (Field Administration of Stroke Therapy - Magnesium) randomized 1700 patients within 2 hours of onset to paramedic-initiated, a 15-minute loading intravenous infusion of magnesium or placebo followed by a 24-hour maintenance dose. The drug delivery strategy included fixed-size lumen, gravity-controlled tubing for field drug administration, and a shrink-wrapped ambulance kit containing both the randomized field loading and hospital maintenance doses for seamless continuation.

Results: Among patient randomized to active treatment, magnesium levels in the first 72 hours were assessed 987 times in 572 patients. Mean patient age was 70 years (SD±14 years), and 45% were women. During the 24-hour period of active infusion, mean achieved serum level was 3.91 (±0.8), consistent with trial target. Mg levels were increased by older age, female sex, lower weight, height, body mass index, and estimated glomerular filtration rate, and higher blood urea nitrogen, hemoglobin, and higher hematocrit. Adjusted odds for clinical outcomes did not differ by achieved Mg level, including disability at 90 days, symptomatic hemorrhage, or death.

Conclusions: Paramedic infusion initiation using gravity-controlled tubing permits rapid achievement of target serum levels of potential neuroprotective agents. The absence of association of clinical outcomes with achieved magnesium levels provides further evidence that magnesium is not biologically neuroprotective in acute stroke.

Keywords: Allied Health Personnel; ambulances; magnesium sulfate; neuroprotection; stroke.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Intravenous
  • Aged
  • Aged, 80 and over
  • Emergency Medical Technicians*
  • Female
  • Follow-Up Studies
  • Humans
  • Magnesium / blood*
  • Magnesium Sulfate / administration & dosage
  • Magnesium Sulfate / pharmacology*
  • Male
  • Middle Aged
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology*
  • Outcome Assessment, Health Care*
  • Stroke / drug therapy*

Substances

  • Neuroprotective Agents
  • Magnesium Sulfate
  • Magnesium