Opioid-induced Hyperalgesia in Patients With Chronic Pain: A Systematic Review of Published Cases

Introduction: Opioid-induced hyperalgesia (OIH) remains an issue in patients with chronic pain. Multiple cases of OIH in patients with chronic pain exposed to opioids have been reported worldwide. The objective of this systematic review was to summarize the evidence of OIH from clinical reports.

Methods: We searched the PubMed, Cochrane, EMBASE, and LILACS databases for case reports and case series of OIH published up to December 2020, with the aim to summarize the evidence for OIH in patients with chronic pain from clinical reports and to discuss issues relevant to the clinical diagnosis and management of OIH.

Results: We retrieved and reviewed 41 articles describing 72 cases. Clinical features of OIH were observed in patients of both sexes, all ages, and with various types of pain treated with different classes of opioids. OIH was reported at all doses, but most published studies reported a pattern of OIH following treatment with very high daily doses of opioids (median oral morphine equivalent dose of 850 mg). OIH was diagnosed clinically in all cases. Three different strategies for OIH management were described: opioid rotation, opioid cessation, and the use of adjuvant pharmacotherapies. All had statistically similar success rates for OIH treatment: 72%, 57%, and 79%, respectively. The decrease in pain was achieved rapidly (mean: 8 d; range: 1 to 28 d). Adjuvant therapies resulted in the largest decrease in dose. Ketamine and dexmedetomidine were the most widely used adjuvant drugs.

Conclusion: The key finding is that clinical symptoms of OIH can be resolved when this condition is diagnosed and managed.