Abstract W P215: Validation of Achievement of Target Blood Drug Levels by Paramedic Infusion Start in a Large, Pivotal Prehospital Stroke Trial

Abstract

Background: Paramedic start of research stroke therapies in the ambulance is a promising approach to accelerating treatment for acute ischemic stroke. However, intravenous (IV) infusions are not a standard element of paramedic practice, so prehospital IV regimens require innovations in care processes. Methods: In the Field Administration of Stroke Therapy - Magnesium (FAST-MAG) phase 3 trial, 1700 patients were randomized within 2 hours of symptom onset to receive IV magnesium sulfate (Mg) or placebo, with field initiated 15 minute loading dose and 24 hour maintenance infusion upon hospital arrival. The drug delivery regimen included paramedic use of fixed lumen size, gravity-controlled tubing in the field, providing controlled delivery without setting an infusion pump, and a shrink-wrapped study kit carried in the ambulance including the randomized hospital maintenance dose in addition to the field loading dose. Results: Among the patients randomized to active treatment, Mg levels in the first 72 hours were assessed 987 times in 572 patients. Mean patient age was 70 (SD ±14), and 45% were female. During the period of active infusion (first 24 hours), treatment arm mean Mg level was 3.88 (SD ±1.1) in contrast with placebo arm mean level of 1.92 (SD ±0.3), achieving the study target of doubling of serum Mg (Figure). Mg levels rapidly increased with the field bolus and climbed minimally during next 24 hours. Mg levels declined steadily during hours 25-48 and normalized in hours 49-72. In the first 24 hours, Mg levels were not affected by patient age, race-ethnicity, weight, or BMI, but were affected by sex, with higher levels in women, 4.42 vs 3.82, p=0.02. Conclusion: In this large-scale ambulance trial, the combined prehospital and hospital treatment regimen achieved targeted levels for the magnesium intervention. Intravenous delivery of therapeutic agents by paramedic personnel is a viable strategy for future stroke hyperacute treatment trials.