This is for our readers who treat pain
Arginine administered intravenously resulted in changes in biomarkers that signalled less oxidative stress in patients with sickle cell disease who were hospitalised with vaso-occlusive pain, and arginine also led to a trend in decreased opioid use, according to a study presented at the 64th Annual Meeting of the American Society of Hematology (ASH).
“Ultimately, arginine replacement therapy is an excellent strategy to reverse at least some of the complications [associated with sickle cell disease and vaso-occlusive pain episodes],” said Claudia R Morris, MD, Emory University School of Medicine, and Children’s Healthcare of Atlanta, Atlanta, Georgia.
The study included 108 children, adolescents, and young adults with sickle cell disease aged 3 to 21 years who were hospitalised for vaso-occlusive pain and required intravenous opioids. Patients were randomised to receive arginine 100 mg/kg/dose (standard dose), a loading dose of arginine 200 mg/kg followed by the standard dose, or placebo.
The investigators found that patients in the placebo arm needed 45% greater parenteral opioid — the primary endpoint — and experienced more than 15 hours longer mean time to crisis resolution compared with combined arginine-treated arms after adjusting for hydroxyurea use, continuous age, and sex.
Among patients aged younger than 17 years, the placebo arm needed 80% more parenteral opioid compared with combined arginine arms (P = .075).
Mitochondrial complex IV and V activity increased significantly in both arms treated with arginine while there was no change in the placebo arm (P < .001). In addition, protein carbonyl levels in platelet rich plasma decreased in both arginine arms (P < .001). The biggest mitochondrial improvement occurred with the arginine loading dose.
“Given emerging data supporting a link between mitochondrial function and pain, improved mitochondrial activity may mechanistically contribute to decreased pain, and ultimately less opioid requirement with intravenous arginine treatment, as well as have further implications for improved metabolism and oxidative signalling in sickle cell disease,” said Dr. Morris.
The researchers are enrolling 360 children in an ongoing phase 3 randomised controlled trial to confirm these findings.
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