The Efficacy and Safety of Ketamine or Ketorolac Compared to Opioids in Painful Vaso-Occlusive Crisis: A Systematic Review and Meta-Analysis

Abstract

Objective:

To evaluate the efficacy and safety of ketamine or ketorolac compared to opioids in painful vaso-occlusive crisis (VOC).

Data resources:

A systematic review and meta-analysis was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) criteria and used Embase, MEDLINE, and Cochrane Central to obtain data that evaluated the efficacy and safety of ketamine or ketorolac compared to opioids in acute painful VOC in July of 2025.

Study selection and data extraction:

The primary endpoints were meaningful reduction of pain on pain scales, reduction in opioid requirements, and the incidence of adverse effects reported in the studies. A P-value of <0.05 was considered statistically significant, and heterogeneity among the studies was reported as the I² value.

Data synthesis:

Eight randomized controlled trials were included. Ketorolac showed a statistically significant pain reduction compared to opioids (standard mean difference [SMD]: 0.58 [95% CI: 0.31-0.85, P < 0.0001]), whereas ketamine showed no statistically significant difference in pain reduction (MD: −0.17 [95% CI: −0.53 to 0.18, P = 0.34]). A statistically significant reduction in opioid requirements was demonstrated in both intervention groups (MD: 3.23 [95% CI: −4.40 to −2.06, P < 0.0001]). Regarding safety, ketorolac showed a lower risk of adverse effects compared to opioids (risk ratio [RR]: 0.54 [95% CI: 0.36-0.79, P = 0.0019]), while ketamine demonstrated a higher risk of adverse effects (RR: 9.90 [95% CI: 4.30-22.82, P < 0.0001]).

Relevance to patient care and clinical practice:

Ketamine or ketorolac demonstrated effective reduction in pain and opioid requirements, with ketorolac showing a greater pain relief and a favorable safety profile compared to ketamine. These findings demonstrate their use as either nonopioid analgesics or opioid-sparing agents.

Conclusion:

Ketamine or ketorolac may not only reduce opioid requirements but may also serve as nonopioid treatment options, supporting safer and individualized pain-management strategies in painful VOC.