About this item:

651 Views | 323 Downloads

Author Notes:

Author correspondence: Claudia R. Morris (claudia.r.morris@emory.edu)

The authors would like to thank the attending staff and nurses of the emergency department and hematology clinic for their assistance in this study, as well as the staff from the Children’s Hospital & Research Center Oakland (CHRCO) Pediatric Clinical Research Center.

We also thank Jane van Warmerdam CNP for her assistance with enrollment of patients.

Finally, we thank our patients with sickle cell disease and their families for their participation.

Information on authorship, contributions, and financial & other disclosures was provided by the authors and is available with the online version of this article at www.haematologica.org.


Research Funding:

This study was supported in part by NIH-NHLBI grant K23 HL 04386-05, FDA grant 1R01FD003531-04 and CTSA grant UL1 RR024131 (to CRM).

A Randomized, Placebo-Controlled Trial Of Arginine Therapy For The Treatment Of Children With Sickle Cell Disease Hospitalized With Vaso-Occlusive Pain Episodes

Journal Title:



Volume 98, Number 9


, Pages 1375-1382

Type of Work:

Article | Final Publisher PDF


Painful episodes of vaso-occlusion are the leading cause of hospitalizations and emergency department visits in sickle cell disease, and are associated with increased mortality. Low nitric oxide bioavailability contributes to vasculopathy in sickle cell disease. Since arginine is the obligate substrate for nitric oxide production, and an acute deficiency is associated with pain, we hypothesized that arginine may be a beneficial treatment for pain related to sickle cell disease. Thirty-eight children with sickle cell disease hospitalized for 56 episodes of pain were randomized into this double-blinded placebo-controlled trial. Patients received L-arginine (100 mg/kg tid) or placebo for 5 days or until discharge. A significant reduction in total parenteral opioid use by 54% (1.9±2.0 mg/kg versus 4.1±4.1 mg/kg, P=0.02) and lower pain scores at discharge (1.9±2.4 versus 3.9±2.9, P=0.01) were observed in the treatment arm compared to the placebo one. There was no significant difference in hospital length of stay (4.1±01.8 versus 4.8±2.5 days, P=0.34), although a trend favored the arginine arm, and total opioid use was strongly correlated with the duration of the admission (r=0.86, P<0.0001). No drug-related adverse events were observed. Arginine therapy represents a novel intervention for painful vaso-occlusive episodes. A reduction of narcotic use by >50% is remarkable. Arginine is a safe and inexpensive intervention with narcotic-sparing effects that may be a beneficial adjunct to standard therapy for sickle cell-related pain in children. A large multi-center trial is warranted in order to confirm these observations.

Copyright information:

© Ferrata Storti Foundation

Export to EndNote