Remifentanil-induced postoperative hyperalgesia: current perspectives on mechanisms and therapeutic strategies

Abstract

The use of remifentanil in clinical practice offers several advantages and it is used for a wide range of procedures, ranging from day-surgery anesthesia to more complex procedures. Nonetheless, remifentanil has been consistently linked with development of opioid-induced hyperalgesia (OIH), which is described as a paradoxical increase in sensitivity to painful stimuli that develops after exposure to opioid treatment. The development of OIH may cause several issues, delaying recovery after surgery and preventing timely patient’s discharge. Moreover, it causes patient’s discomfort with higher pain scores, greater use of analgesics, and associated side effects. Remifentanil is the opioid most convincingly associated with OIH, and hereby we provide a review of remifentanil-induced hyperalgesia, describing both the underlying mechanisms involved and the available studies investigating experimental and clinical pharmacologic approaches aiming at reducing its incidence and degree.

Opioid-Mediated Modulation of Acid-Sensing Ion Channel Currents in Adult Rat Sensory Neurons

“…That is, with the continued use of opioid medication and possibly the increased E-2 release at the ischemic site, patients exhibit sensitization to painful stimuli. This has been documented with Rem and Fen (Lee et al, 2011;Kim et al, 2014;Santonocito et al, 2018).…”

Perioperative opioid analgesia—when is enough too much? A review of opioid-induced tolerance and hyperalgesia

“…Consideration of a gradual tapering of remifentanil at the end of surgery may also reduce OIH, possibly by reducing withdrawal induced long term potentiation at the first central synapse in the spinal cord(71, 72) (73). Other suggested strategies to reduce this problem include limiting the dose of remifentanil, or specifically targeting putative mechanisms using novel approaches (74).…”

“…These include simple analgesics such as paracetamol and NSAIDs, dexmedetomidine, NMDA receptor antagonists (e.g. ketamine), and opioid dose reduction (74)(75)(76)(77). Opioid free multimodal analgesia may be a laudable aim, but the number of patients presenting for surgery who are not opioid naïve will pose a challenge.…”

Randomized, double-blind, placebo-controlled study of the analgesic effect of intraoperative esmolol for laparoscopic gastroplasty

“…Remifentanil was used for intraoperative supplementation because although it is liposoluble, its degradation is rapid, and does not enter the lipophilic compartment. It is used safely in obese patients, with the volume of distribution and clearance being similar to that of the non-obese population [21].…”