A multicenter randomized controlled trial of intravenous magnesium for sickle cell pain crisis in children

Abstract

Magnesium, a vasodilator, anti-inflammatory, and pain reliever, could alter the pathophysiology of sickle cell pain crises. We hypothesized that intravenous magnesium would shorten length of stay, decrease opioid use, and improve health-related quality of life (HRQL) for pediatric patients hospitalized with sickle cell pain crises. The Magnesium for Children in Crisis (MAGiC) study was a randomized, double-blind, placebo-controlled trial of intravenous magnesium vs normal saline placebo conducted at 8 sites within the Pediatric Emergency Care Applied Research Network (PECARN). Children 4 to 21 years old with hemoglobin SS or Sβ(0) thalassemia requiring hospitalization for pain were eligible. Children received 40 mg/kg of magnesium or placebo every 8 hours for up to 6 doses plus standard therapy. The primary outcome was length of stay in hours from the time of first study drug infusion, compared using a Van Elteren test. Secondary outcomes included opioid use and HRQL. Of 208 children enrolled, 204 received the study drug (101 magnesium, 103 placebo). Between-group demographics and prerandomization treatment were similar. The median interquartile range (IQR) length of stay was 56.0 (27.0-109.0) hours for magnesium vs 47.0 (24.0-99.0) hours for placebo (P = .24). Magnesium patients received 1.46 mg/kg morphine equivalents vs 1.28 mg/kg for placebo (P = .12). Changes in HRQL before discharge and 1 week after discharge were similar (P > .05 for all comparisons). The addition of intravenous magnesium did not shorten length of stay, reduce opioid use, or improve quality of life in children hospitalized for sickle cell pain crisis. This trial was registered at www.clinicaltrials.gov as #NCT01197417.

© 2015 by The American Society of Hematology.

Figures

Figure 1

Consolidated Standards of Reporting Trials (CONSORT) diagram. *Exclusion criterion removed as a part of protocol version 1.04, dated January 11, 2012. †Exclusion criterion removed as a part of protocol version 1.03, dated July 5, 2011. ‡Exclusions with fewer than 10 occurrences included: intolerance to IV morphine and hydromorphone, known kidney/liver failure, pulmonary hypertension, pregnancy, diagnosis of hemodynamic instability or sepsis, taking oral magnesium, or current/planned use of neuromuscular blockers. §267 unique subjects; more than 1 exclusion possible on a visit; subjects may have had multiple visits. ǁReasons not approached with fewer than 5 occurrences included: physician request, inability to consent because of medical condition, language barrier, admitted to unit with untrained staff, unable to complete follow-up, research pharmacy closed, or patient refused to allow research team to speak with parents. ¶Reasons for not receiving all allocated doses included study withdrawal, hypotension, no 25-hour safety laboratory (blinded magnesium level), physician request, found to be ineligible, and site miscommunication.

Figure 2

Magnesium vs placebo length of stay for primary outcome. Primary outcome length of stay defined as time from first study drug infusion until 12 hours after last intravenous opioid or time of discharge, whichever occurred first.