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

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Abrupt Analgesic Offset

The plasma concentration of remifentanil decreases by 50% to 80% within 3 minutes to 15 minutes of stopping its infusion.1, 10 The fast elimination of remifentanil is accompanied by an abrupt analgesic offset, which may leave residual pain unopposed and underlie the onset of moderate to severe pain. Abrupt analgesic offset as a source of significant pain after the intraoperative administration of remifentanil is a well-documented phenomenon.11 An example is provided by the study of Derrode et

Increased Postoperative Pain And/Or Opioid Consumption

A series of studies in patients undergoing surgery suggest that the administration of a high rather than a low intraoperative opioid dose (including a zero dose) is associated with increased pain and/or opioid consumption in the postoperative period (Table 1).3, 4, 6, 15, 20, 23, 25, 26 For example, patients undergoing major abdominal surgery and randomized to an infusion rate of 0.3 µg/kg/min of remifentanil for about 4 hours experienced 50% higher pain levels during the first 4 hours and

Tolerance Versus Oih

The onset of acute tolerance could explain why patients exposed to a high intraoperative opioid dose experience aggravated pain and/or have higher opioid requirements in the postoperative period. However, an alternative explanation is that these patients may have developed acute OIH. While tolerance and OIH are pharmacologically distinct, they both impose a clinical need to increase the opioid dose to maintain a desired analgesic effect. This is illustrated in Figure 3. Tolerance results from a

Hyperalgesia And Persistent Pain After Surgery

Several studies indicate that the intraoperative use of high doses of remifentanil can aggravate postoperative wound hyperalgesia. An important study by Joly et al randomized patients undergoing major abdominal surgery to an infusion rate of 0.05 or 0.4 μg/kg/min for about 4 hours. Patients assigned to the higher infusion rate suffered from aggravated wound hyperalgesia on postoperative days 1 and 2.6 Wound hyperalgesia was quantified by assessing the mechanical pain threshold in close

Remifentanil Versus Other Opioids

It has been suggested that acute tolerance and/or OIH are more likely to occur with remifentanil than with other types of opioids.5, 12, 35 However, clinical data supporting or rejecting this notion are sparse. Several considerations should be taken into account when discussing the propensity of remifentanil to induce acute tolerance and/or OIH. First, the abrupt analgesic offset shortly after stopping the administration of remifentanil could readily be confounded with the development of acute

Practical Implications

Abrupt analgesic offset should be the first consideration in patients who received remifentanil as the sole or main opioid during surgery and report the onset of moderate-to-severe pain shortly after surgery. Importantly, an abrupt analgesic offset can occur despite bridging from remifentanil to a longer-acting opioid towards the end of surgery.11, 12 Consequently, rapid titration to adequate pain relief with a fast-acting opioid such as fentanyl is a reasonable first step in managing these

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