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Ketorolac delivers greater pain reduction and a safer adverse-effect profile than opioids, and both ketorolac and ketamine effectively lower opioid requirements, supporting their role as opioid-sparing options in painful vaso-occlusive crisis.
Ketorolac and ketamine may reduce opioid dependence in the management of painful vaso-occlusive crisis (VOC) in sickle cell disease, according to a new systematic review and meta-analysis of randomized controlled trials.
Conducted as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the review analyzed evidence from Embase, MEDLINE, and Cochrane Central databases. In total, 8 randomized controlled trials were included, comparing ketamine or ketorolac versus opioid therapy for acute pain care in sickle cell VOC. Primary outcomes included clinically meaningful pain reduction, opioid-sparing effects, and the incidence of adverse events, with statistical significance defined as P < 0.05 and heterogeneity assessed via I² statistics.
As found, ketorolac considerably improved pain scores compared with opioids, showing a standardized mean difference of 0.58. In contrast, ketamine did not attain a prominent reduction in pain intensity relative to opioids (mean difference [MD] −0.17). Despite this difference in analgesic potency, both ketorolac and ketamine diminished opioid requirements, confirming their role as opioid-sparing agents in VOC pain management (MD: −3.23).
Safety outcomes further differentiated the two therapies. Ketorolac was linked with a substantially lower risk of adverse effects than opioids, minimizing complication rates by nearly 46% (risk ratio [RR]: 0.54). Conversely, ketamine was linked to a substantially higher incidence of adverse events, with nearly 10-fold heightened risk compared with opioid treatment (RR: 9.90). The results support ketorolac as an effective non-opioid alternative or adjunct to opioids for acute VOC, offering improved pain control with fewer safety risks.
While ketamine may contribute to opioid reduction, its higher adverse-event burden underscores the requirement for careful patient selection. Overall, the study reinforces a growing shift toward non-opioid analgesics and individualized pain-management strategies in sickle cell disease, with ketorolac emerging as a leading option for safer and more beneficial treatment of painful vaso-occlusive crises.
Annals of Pharmacotherapy
The Efficacy and Safety of Ketamine or Ketorolac Compared to Opioids in Painful Vaso-Occlusive Crisis: A Systematic Review and Meta-Analysis
May M. Shehata et al.
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