The efficacy of oral L-arginine therapy for the treatment of vaso-occlusive pain episodes in children with sickle cell disease.

Abstract

Pain is the clinical hallmark of sickle cell disease (SCD), with painful Vaso-occlusive episodes (VOEs) being the common medical emergencies associated with an increased mortality rate. The current study aimed to evaluate the efficacy of L-arginine as an adjuvant therapy for children with SCD and VOE, as well as its effect on Tricuspid Regurgitant Jet Velocity (TRJV) during VOE. The primary outcome was to evaluate the efficacy of L-arginine on pain intensity. This double-blind, randomized, controlled, and parallel prospective study was carried out on 40 SCD children who presented with VOE and met the inclusion criteria. The mean ± SD of age was 8.8 ± 3.2 years, and 62.5% were males. They were randomized into two groups; Group 1 included 20 patients who received L-Arginine (100 mg/kg/dose three times/day for 15 doses or until their discharge) plus standard therapy. Group 2 consisted of 20 patients who received a placebo in addition to standard therapy. Total analgesic use, daily pain score, time to crisis resolution, and length of hospital stay were recorded. Routine laboratory investigations, serum L-Arginine, asymmetric dimethyl-arginine (ADMA) levels and the Arginine/ADMA ratio were assessed. Moreover, Echocardiography was performed to assess TRJV. All these parameters were assessed at baseline (during painful crisis), at discharge, and during the clinically asymptomatic state. As regards the age, sex, consanguinity, or family history there were no statistically significant difference between all of the studied groups. L-arginine therapy significantly decreased pain score at the 3rd day of admission(p-value 0.036), total analgesic use (p-value <0.001), time to crisis resolution (p-value 0.011), length of hospital stays (p-value 0.016), and TRJV (p-value < 0.001). Additionally, serum L-arginine level and Arginine/ADMA ratio (p-value <0.001) were increased upon arginine treatment. Additionally, statistically significant differences in the serum L-arginine level, serum ADMA level, Arginine/ADMA ratio, and TRJV were reported during painful crisis compared to the asymptomatic state. L-arginine Supplementation improved painful VOE symptoms in SCD children and decreased TRJV in those children. Oral arginine could be a promising adjuvant therapy for SCD-VOE management.