Intraoperative Use of Remifentanil for TIVA: Postoperative Pain, Acute Tolerance, and Opioid-Induced Hyperalgesia.

Abstract

REMIFENTANIL IS frequently the opioid of choice when relying on total intravenous anesthetic (TIVA) protocols. The unique pharmacokinetic properties of remifentanil afford a fast onset of action and a predictable and rapid recovery independent of the infusion duration. The high lipid solubility and low ionization of remifentanil at physiological pH allow for its quick transfer from blood to central nervous system binding sites as mirrored by its fast onset of action. The very short elimination half-life and stable context-sensitive half time reflect the exceptionally high clearance of remifentanil by plasma and tissue esterases. In the context of TIVA, these pharmacokinetic properties are ideal to meet anesthetics needs with the rapid up-and-down titration of remifentanil and the exposure to relatively high cumulative doses, as such use hardy affects recovery time. While the advantageous pharmacokinetic properties of remifentanil favor its liberal use, significant concern exist among clinicians that such use may negatively affect postoperative pain. More specifically, severe postoperative pain after the intraoperative use of remifentanil has repeatedly been linked to the development of acute tolerance and/or opioidinduced hyperalgesia (OIH). The claim has also been made that remifentanil, compared to other opioids, is particularly prone to induce acute tolerance and OIH due to its high potency and specific pharmacokinetic properties. The purpose of this topical review is to examine whether or not the intraoperative use of remifentanil has a unique negative impact on postoperative pain by inducing acute tolerance and/or OIH. The review will highlight 3 distinct phenomena associated with the intraoperative use of remifentanil: (1) the impact of an abrupt analgesic offset on spontaneous pain, (2) the development of acute tolerance and/or OIH as indicated by an aggravation of spontaneous pain, and (3) the development of OIH as indicated by an aggravation of wound hyperalgesia. Distinguishing between spontaneous pain and wound hyperalgesia is important as these phenomena are mechanistically distinct and lack a strong correlation. However, it is not uncommon that