Role of Ketamine as Part of the Anti-Hyperalgesic Approach in Opioid-Free Anesthesia (OFA) and Postoperative Analgesia (OFAA)

There is increasing evidence of the close relationship between persistent activation of the glutaminergic pathway, central sensitization, hyperalgesia and chronic pain. Opioids have long been the standard analgesics used in the perioperative. However, their side effects, namely opioid-induced hyperalgesia, opioid tolerance and post-operative dependence in patients with chronic pain that are to undergo aggressive surgeries have motivated anesthesiologists to develop alternative anesthetic techniques. They include analgesic and anti-inflammatory drugs that act by modulating the nociceptive pathways with an opioid-sparing effect and even opioid-free anesthesia (OFA). In OFA plus postoperative analgesia (OFAA) techniques, ketamine plays a fundamental role as an analgesic with its antagonist action on the N-Methyl-D-Aspartate-receptors (NMDAr). However, ketamine is limited to use at sub-anesthetic doses (“low-doses”) due to its dose-dependent side effects. Consequently, other analgesic drugs with anti-NMDAr effects like magnesium sulfate and other non-opioid analgesics such as lidocaine and alpha-2-adrenergic agonists are often used in OFAA techniques. The aim of this text is to present a summary of the importance of the use of ketamine in OFA based on nociceptive pathophysiology. Additionally, the perioperative protocol (OFAA) with the anti-hyperalgesic approach of ketamine, lidocaine and dexmedetomidine co-administration in our center will be described. Some of the main indications for the OFAA protocol will be mentioned