Evaluating the Therapeutic Effects of Amino Acid Treatment on Vaso-Occlusive Pain in Sickle Cell Disease: A Systematic Review and Meta-Analysis Protocol

Introduction: Sickle Cell Disease (SCD) affects over 100,000 individuals in the United States and 20 million globally, causing acute and chronic pain. The disease is characterized by misshapen red blood cells caused by mutations in beta-hemoglobin genes. SCD leads to multiorgan damage, chronic anemia, and severe pain crises, with a median life expectancy of 43 years. Current treatments involve opioids, blood transfusions, and hydroxyurea. Amino acids, especially L-Glutamine, have shown promise in managing SCD pain. This systematic review aims to comprehensively analyze the effects of amino acid treatments on vaso-occlusive pain crises in SCD patients. Methods: Following the Cochrane Handbook and PRISMA-P guidelines, this systematic review will include studies comparing amino acid treatment to placebo or standard care for SCD pain crises. Eligible studies of all age ranges, settings, and amino acid types will be considered. A comprehensive search strategy will be employed in PubMed, Embase, and Scopus databases. Studies will be assessed for risk of bias using Cochrane's RoB2 tool. Primary outcomes include a reduction in pain, measured quantitatively through pain scales. Secondary outcomes encompass quality of life, hospital length of stay, and opioid equivalents used. Discussion: Existing literature underscores the therapeutic potential of amino acids, yet there still lacks a systematic review comparing the overall effects of different amino acid treatments for vaso-occlusive crises in patients with SCD. This review aims to serve as a valuable resource for clinicians, offering insights into amino acid interventions as alternatives or supplements to opioid treatments. Additionally, it seeks to encourage further randomized clinical trials, contributing to an informed clinical use of amino acids for pain management in SCD. Ultimately, the findings aim to enhance the understanding of the therapeutic effects of essential amino acids on pediatric patients with SCD, facilitating evidence-based clinical decisions.