Opioid-free anesthesia opioid side effects: Tolerance and hyperalgesia

Opioids are the most potent drugs used to control severe pain. However, neuroadaptation prevents opioids' ability to provide long-term analgesia and produces opposite effects, i.e., enhancement of existent pain and facilitation of chronic pain development. Neuroadaptation to opioids use results in the development of two interrelated phenomena: tolerance and "opioid-induced hyperalgesia" (OIH). Tolerance, a pharmacologic concept, and OIH, a clinical syndrome, have been mostly observed under experimental conditions in animals and in human volunteers. In contrast, their occurrence and relevance in clinical practice remain debated. In perioperative setting, intraoperative administration of high doses of opioids increases postoperative opioid requirements and worsens pain scores (acute tolerance or perioperative OIH). Further, preoperative chronic opioid intake and postoperative long-term use of opioid analgesics beyond the normal healing period have a negative effect on surgical outcome. Conversely, observations of improved patient's recovery after opioid-sparing anesthesia techniques stand as an indirect evidence that perioperative opioid administration deserves caution. To date, perioperative OIH has rarely been objectively assessed by psychophysics tests in patients. A direct relationship between the presence of perioperative OIH and patient outcome is missing and certainly deserves further studies.