Ketorolac vs Morphine for Severe Vaso-Occlusive Crisis in Sickle Cell Disease: An Open-Label Randomized Controlled Trial (KISS Study).

Abstract

Objectives: To compare the efficacy and safety of intravenous (IV) ketorolac and IV morphine in the management of severe vaso-occlusive crisis (VOC) in children with sickle cell disease (SCD).

Method: An open-label, randomized controlled trial was conducted from January 2021 to July 2022 wherein children with SCD aged 3 to 15 years, presenting with severe VOC (score > 6 on the Wong-Baker Faces Pain scale) were included. Block randomization with minimization was done and participants received either IV ketorolac (intervention) or IV morphine infusion (standard). The pain score was reassessed three hourly and if the pain score exceeded 6, the drug dose was escalated every 3 hours, upto a maximum of three escalating doses. A pain score of ≤ 6 were regarded as response.

Results: The mean (SD) pain scores at admission in the ketorolac and morphine groups were 9.28 (0.89) and 9.12 (1.01), respectively (P = 0.636). At 3, 6, 9, and 12 hours of infusion, the mean pain scores in the ketorolac and morphine groups were 8.04 (1.24) vs 8.28 (1.24), P = 0.313; 7.04 (1.210) vs 7.28 (1.28), P = 0.331; 6.40 (1.26) vs 6.28 (1.17), P = 0.860; and 5.56 (1.00) vs 5.60 (1.04), P = 0.817, respectively. Five and eleven children developed minor side effects in the ketorolac and morphine groups, respectively (P = 0.069). Overall, one child in the ketorolac group and two in the morphine persisted to have severe pain even after 12 hours of therapy (P = 0.55).

Conclusion: Intravenous ketorolac may be considered as a good alternative to IV morphine in the management of severe VOC in SCD.