sickle cell disease
Credit: St. Jude Hospital
SAN FRANCISCO—Magnesium does not improve outcomes in children hospitalized for sickle cell pain crises, results of the MAGiC study suggest.
Researchers hypothesized that magnesium—a known vasodilator, anti-inflammatory, and pain reliever—could alter the pathophysiology of pain crises.
However, when compared to normal saline, intravenous (IV) magnesium did not shorten hospital stays, lessen opioid use, or improve patients’ quality of life.
David C. Brousseau, MD, of the Medical College of Wisconsin and the Children’s Hospital of Wisconsin in Milwaukee, presented the results of this study at the 2014 ASH Annual Meeting (abstract 88).
Dr Brousseau noted that vasoocclusive crises are the most common acute complication of sickle cell disease and the most frequent cause of acute care or emergency department visits and hospitalizations. But recent changes in treatment have been minimal, with the judicious use of IV fluid and IV opioids being the mainstays of therapy.
“There have been few multicenter clinical trials evaluating new treatments, in part, due to a long history of difficulty with enrollment in interventional trials for sickle cell crises,” he continued. “These enrollment difficulties have been due to an inability to consent or to consent in a timely manner, leading to delayed initiation of study drug.”
With the MAGiC trial, Dr Brousseau and his colleagues sought to overcome this problem through a collaboration between pediatric emergency medicine physicians and pediatric hematologists.
In this randomized, double-blind trial, the researchers compared IV magnesium to normal saline. They enrolled children ages 4 to 21, with hemoglobin SS or hemoglobin SB° thalassemia, who were hospitalized after failing emergency department management for pain.
A total of 208 children were enrolled at 8 study sites over 3 years. Four children were excluded before receiving treatment, so 101 were randomized to receive magnesium and 103 to saline.
The children received 40 mg/kg of IV magnesium every 8 hours for a total of 6 doses or normal saline of an equivalent volume (1 mL/kg).
The treatment groups were well-balanced, with similar baseline age, sex, genotype, weight, history of acute chest syndrome or asthma, previous hospitalizations within the past 3 years, use of hydroxyurea, and days of pain prior to arrival.
The median time from the first emergency department opioid to the first study drug infusion was 7.3 hours in the magnesium group and 7.5 hours in the saline group.
For the study’s primary outcome, the researchers assessed patients’ length of stay from the first study drug infusion until 12 hours after the last IV opioid dose or the time of discharge, whichever came first.
“Approximately 50% of children [overall] met the study endpoint within 52 hours, and 25% met the study endpoint within 24 hours of the first drug infusion,” Dr Brousseau noted.
And there was no significant difference in the median length of stay between the treatment arms—56 hours in the magnesium arm and 47 hours in the placebo arm (P=0.264).
A secondary outcome was opioid use, recorded as morphine equivalents. There was no significant difference with this outcome, either. Patients in the magnesium arm received 1.46 mg/kg of morphine equivalents, compared to 1.28 mg/kg in the saline arm (P=0.12).
The researchers also assessed quality of life using the PedsQL sickle cell disease-specific module, fatigue module, and generic module. At 48 hours after the first infusion, there was no significant difference in quality of life scores between the treatment groups for any of the modules (P=0.17, 0.26, and 0.94, respectively). The same was true 1 week after discharge (P=0.55, 0.82, and 0.36, respectively).
As for safety, there was no significant difference between the treatment arms for most measures. However, patients in the magnesium arm were more likely to experience warmth upon infusion, at 26%, compared to 2% in the saline arm (P<0.01).
Acute chest syndrome occurred in 16% of patients in the magnesium arm and 14% in the saline arm (P=0.78). Hypotension occurred in 4% and 1%, respectively (P=0.39). And rehospitalization within 7 days occurred in 12% and 7%, respectively (P=0.11).
In closing, Dr Brousseau noted that, although the researchers did not prove their hypothesis correct, the MAGiC study was a success in one respect.
“Intravenous magnesium does not shorten length of stay, lessen opioid use, or improve quality of life in children hospitalized for sickle cell pain crises,” he said. “[However,] a collaboration between pediatric emergency department medicine physicians and pediatric hematologists allowed for successful enrollment in an acute intervention trial with a median time to first study drug of 7.5 hours.”
