Opioid-sparing effects of ketorolac in palliative care patients receiving opioids for chronic cancer-related pain: A systematic literature review

Palliat Med. 2022 Jan;36(1):71-80. doi: 10.1177/02692163211045310. Epub 2021 Oct 11.

Abstract

Background: Standard of care in treatment of cancer-related pain involves opioids in combination with non-steroidal anti-inflammatory drugs (NSAID). Ketorolac, a NSAID, has demonstrated opioid-sparing effects in other clinical settings.

Aim: This systematic literature review investigated ketorolac's opioid-sparing effects in patients receiving opioids for chronic, cancer-related pain.

Design: The primary outcome was total daily dose of opioids. Secondary outcomes included frequency of opioid use, use and frequency of 'rescue' medication and adverse events. Outcomes were described, and meta-analysed where possible. PROSPERO registration CRD42019130894.

Data sources: Articles included original research, from any study phase or methodology, published in English in a peer-reviewed journal or conference between 1990 and 2020; included subjects >18 years; had chronic cancer-related pain and described the use of opioid-sparing effect of ketorolac.

Results: Nine articles were included. While there was significant heterogeneity, ketorolac may have an opioid-sparing effect, with significant reductions in total daily dose of morphine observed in a single randomised controlled trial (SMD -4.30 mg, 95% CI -5.36 to -3.25), but the changes in the before and after studies were not statistically significant -0.46 mg (95% CI -1.14 to 0.22). Ketorolac was associated with greater likelihood of complete pain relief, but the data were heterogeneous. Insufficient data were available to analyse frequency of opioid use, or rescue medication requirements.

Conclusions: Given the heterogeneity of the data, adequately powered, randomised controlled trials are required to establish any opioid-sparing effect of ketorolac. For patients not responding to conventional pain management, ketorolac may have a role in treatment augmentation.

Keywords: Palliative care; analgesics; cancer pain; ketorolac; opioid-sparing; opioids.

Publication types

  • Systematic Review

MeSH terms

  • Analgesics, Opioid / therapeutic use
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Cancer Pain* / drug therapy
  • Humans
  • Ketorolac / therapeutic use
  • Neoplasms* / complications
  • Neoplasms* / drug therapy
  • Pain, Postoperative / chemically induced
  • Pain, Postoperative / drug therapy
  • Palliative Care
  • Randomized Controlled Trials as Topic

Substances

  • Analgesics, Opioid
  • Anti-Inflammatory Agents, Non-Steroidal
  • Ketorolac