Opioid-induced Hyperalgesia: An Analgesic Paradox in Modern Anaesthetic Practice. Narrative Review

Resumo

Opioid-induced hyperalgesia (OIH) is a paradoxical increase in pain sensitivity associated with opioid exposure. Its perioperative incidence remains unknown because validated diagnostic criteria are lacking and surgical pain, tolerance, withdrawal and central sensitisation produce overlapping clinical manifestations. The most consistent human evidence concerns remifentanil. Studies in healthy volunteers show modest reductions in pain thresholds and expansion of hyperalgesic areas after discontinuation, whereas surgical meta-analyses associate higher doses with small increases in postoperative pain and analgesic consumption. These surrogate outcomes are not equivalent to a clinical diagnosis of OIH. Proposed mechanisms include NMDA receptor-dependent glutamatergic potentiation, descending facilitation, loss of inhibitory tone, glial activation and altered mu-opioid receptor signalling; none currently provides a clinically validated biomarker. OIH should be suspected when pain becomes diffuse or disproportionate, allodynia or spread beyond the expected surgical territory develops, and symptoms worsen after opioid escalation, once surgical complications and withdrawal have been excluded. Prevention rests on opioid exposure proportionate to the nociceptive stimulus, a planned analgesic transition and evidence-based multimodal analgesia. When OIH is considered likely, reflex dose escalation should be avoided, the opioid should be reduced or rotated safely, and ketamine may be considered in selected patients. Opioid-free anaesthesia is not a universal objective, but an individualised option within opioid-sparing care.