There are over 18,000 hospitalizations and 75,000 hospitalization days annually for children suffering vaso-occlusive crises secondary to sickle cell disease. The vast majority of these hospitalizations are for pain crisis, making pain one of the most significant morbidities for children with sickle cell disease. The acute treatment for these pain crises has changed little over the past three decades, mainly relying on intravenous fluids, opioids and non-steroidals. More recently, there has been a greater recognition of the role that nitric oxide plays in the pathogenesis of pain crises, and inhaled nitric oxide is being studied as a possible treatment. We have recently tested an alternative approach, intravenous magnesium, that produces vaso- dilation through both endothelium-dependent nitric oxide mechanisms, as well as direct action on the underlying vascular smooth muscle. The safety profile, ease of administration, and low cost of magnesium make its potential as a sickle cell therapy particularly exciting. In this application, we utilize the Pediatric Emergency Care Applied Research Network to develop a four-center collaboration between pediatric emergency medicine and pediatric sickle cell centers to test this novel therapy through a double-blind, randomized, placebo controlled trial assessing the impact of the addition of intravenous magnesium to standard therapy for sickle cell pain crisis. The primary clinical outcome is the decrease in length of hospital stay for pediatric sickle cell pain crisis, with a secondary clinical outcome measuring the effect of intravenous magnesium on the use of opioid pain medication during the hospitalization. In addition to the clinical outcomes, we will gain valuable insight into the pathophysiology of sickle cell crisis through the measurement of hemolysis, nitric oxide pathway metabolites, and markers of cellular injury and inflammation. At the conclusion of this study, we have the potential to improve the care of children with sickle cell disease using a low cost, low risk treatment.

Public Health Relevance

In the United States alone, there are over 18,000 hospitalizations and 75,000 hospitalization days annually for children suffering vasoocclusive pain episodes secondary to sickle cell disease;the vast majority of these children are African-American. With this application, we aim to decrease the pain children experience with these crises, thus shortening hospitalizations and decreasing the cost associated with caring for children with this painful disease.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-PSE-H (51))
Program Officer
Zajicek, Anne
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Medical College of Wisconsin
Schools of Medicine
United States
Zip Code
Hulbert, Monica L; Panepinto, Julie A; Scott, J Paul et al. (2017) Red blood cell transfusions during sickle cell anemia vaso-occlusive crises: a report from the magnesium in crisis (MAGiC) study. Transfusion 57:1891-1897
Brandow, Amanda M; Nimmer, Mark; Simmons, Timothy et al. (2016) Impact of emergency department care on outcomes of acute pain events in children with sickle cell disease. Am J Hematol 91:1175-1180
Brousseau, David C; Scott, J Paul; Badaki-Makun, Oluwakemi et al. (2015) A multicenter randomized controlled trial of intravenous magnesium for sickle cell pain crisis in children. Blood 126:1651-7
Xu, Hao; Wandersee, Nancy J; Guo, YiHe et al. (2014) Sickle cell disease increases high mobility group box 1: a novel mechanism of inflammation. Blood 124:3978-81
Badaki-Makun, Oluwakemi; Scott, J Paul; Panepinto, Julie A et al. (2014) Intravenous magnesium for pediatric sickle cell vaso-occlusive crisis: methodological issues of a randomized controlled trial. Pediatr Blood Cancer 61:1049-54