Arginine supplementation significantly reduces pain in kids with sickle cell anemia

South Africa: Arginine supplementation may be significantly beneficial for sickle cell anaemia (SCA) children hospitalized with severe vaso-occlusive pain episodes (VOE), suggest findings presented at the American Society of Hematology (ASH) 2019 Annual Meeting in Orlando.

Arginine deficiency plays a role in acute pain requiring hospitalization in children with SCA. This recent study demonstrated that plasma arginine levels increased significantly with arginine supplementation. It also improved global arginine bioavailability, inversely associated with total analgesia and opioids used in vaso-occlusive pain episodes management. The supplementation also reduced the length of hospital stay (LOS) compared to placebo and there were no adverse events.

Previous findings have shown the benefit of the amino acid therapy for severe vaso-occlusive pain episodes versus placebo. Richard Onalo, Department of Pediatrics, University of Abuja, Nigeria, Abuja, Nigeria, and colleagues conducted this double-blind, randomized, controlled trial to determine the role of oral arginine as an adjuvant in the management of SCA-VOE.

A double-blinded RCT of L-arginine (100 mg/kg/dose every 8 hours until discharge; up to 5 days/15 doses maximum) was performed in SCA children hospitalized with severe VOE -- defined as Numerical Pain Scale Score (PS) of at least 7 on a scale of 0-10, at one of two hospitals in Abuja, Nigeria. All the patients received pain management (both opioids and non-opioid analgesics) per institutional practice.

The researchers obtained Demographics, clinical characteristics, length of hospital stay (LOS), pain scores, time-to-crisis-resolution (time-to-PS<4), analgesia medications required, and plasma amino acids levels before and after supplementation.

Mean total analgesic medication quantification scale score (MQS), a sensitive measure to quantify analgesic use in patients with SCA, was utilized as previously described (Jacob et al, 2007). Opioid doses were calculated based on morphine equivalents in milligrams (mg).

Sixty-eight children with SCA were recruited, aged 5-17 years (mean: 10.6±0.4 years; 35 children randomized into the arginine arm & 33 into the placebo arm).

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Key findings of the study include:

• Baseline characteristics were similar between arms (arginine arm versus placebo arm).


• MQS was significantly lower in the arginine group vs. placebo (73 vs. 120).


• By day 5, 54% of children treated with arginine had been discharged compared to 24% in the placebo arm.


• Although PS were similar in both groups prior to study drug delivery (8.7±1.1 vs. 8.4±1.2, arginine vs placebo), worst reported PS on day 5 were lower in children treated with arginine compared to placebo (1.2±0.4 vs. 3.0±0.5).


• The mean rate of PS decline was also greater in the arginine arm vs. placebo (1.5 vs. 1.1 cm/day).


• Plasma arginine levels increased by 125% vs 29% in the arginine arm vs. placebo; per cent increase in arginine bioavailable inversely correlated with MSQ.


• There was a non-statistically significant decrease in the mean total opioid dose used in the arginine group vs. placebo (3.8 vs 5.1 mg/kg).


• Patients receiving arginine had shorter time-to-crisis-resolution, shorter LOS and had no serious adverse events.


• There was 1 death in the placebo group on the second day of admission.


• There were no differences between groups in the development of adverse events, however, there was a trend towards more vomiting in the arginine arm compared to placebo (20% vs. 3%).

"The oral supplement therapy is a promising add-on to the sickle cell anemia-VOE management regimen," concluded the authors.

The study, “Oral Arginine Therapy As a Novel Adjuvant in the Management of Acute Pain in Children with Sickle Cell Anemia in Nigeria: A Randomized Placebo-Controlled TrialClinically Relevant Abstract,” was presented at ASH 2019.