I’ll Have a Serving of Anesthesia, but Hold the Opioids

By Adaora M. Chima, MBBS, MPH, from the IARS, AUA and SOCCA 2019 Annual Meetings*

The Society for Neuroscience in Anesthesiology and Critical Care (SNACC) panel, Opioid-Free Anesthesia: Biologic Basis and Potential Applications in Neurosurgical Anesthesiology, moderated by Dhanesh Gupta, MD (Duke University), held on Sunday, May 20, focused on the biologic mechanisms and clinical evidence that set the stage for developing anesthetic techniques to minimize the use of opioids for intracranial and spine surgery.

The session began with a presentation by Jianren Mao, MD, PhD, of Harvard Medical School. His talk titled, “Mechanisms of Opioid-Induced Hyperalgesia and Possible Future Therapeutic Approaches,” described findings of hyperalgesia in lab rats treated intrathecally with opioids. In these animals, a decrease in nociceptive receptors and inverse increase in pain sensitivity was noted.

He described the phenomenon of hyperalgesia, which is often mistaken for tolerance as an apparent reduction in the effect of the same dose of opioid, that often results in opioid dose escalation. Unlike tolerance though, there is increased sensitivity to pain. There is no tool to tell the difference between tolerance and opioid-induced hyperalgesia.

Dr. Gupta shared schematic illustrations of pathways through which opioid use can either result in desensitization, causing tolerance or increased sensitization of pronociceptive receptors, resulting in hyperalgesia. Further administration of opioids result in a vicious cycle if the hyperalgesia pathway is activated, causing increasing sensitivity and increasing pain, in the absence of procession of inciting disease process. Although the findings indicate that opioids appear to be able to cause neuroplastic changes in the central nervous system (CNS), resulting in increased pain, the mechanism is not well understood. He however described opioid mechanisms of presynaptic inhibition of membrane excitation, postsynaptic receptor hyperpolarization of pain pathways, opioid interactions with protein kinase C and N-methyl-d-aspartate (NMDA) receptors downstream.

Studies have shown increased pain sensitivity in opioid addicts, with heightened sensitivity in addicts on methadone maintenance therapy. Multiple studies indicate that intraoperative opioid administration is associated with an increase in postoperative opioid use and increased incidence of postoperative pain. A thermal stimulation study showed a decrease in thermal pain threshold in the chronic opioid group compared to their controls. These and other similar findings call for a change in the approach to opioid administration in the perioperative period.

Strategies to opioid sparing anesthetic techniques include the use of neuraxial anesthesia, avoiding neuraxial opioids as this might be counterproductive in patients with suspected tolerance/hyperalgesia. Reduction of pre-operative opioid dose may also be beneficial in these patients.

Helene Beloeil, MD, PhD, University Rennes, France, discussed alternative non-opioid pharmacologic agents by reviewing available literature on trials regarding non-opioid analgesics for intraoperative use. She reminded the audience about the distinction between pain (a conscious sensation) and nociception, which can occur in the absence of pain such as under general anesthesia. The myriad of mediators and receptors involved in the pain pathway can be targeted for perioperative pain management.

Multimodal approaches to anesthesia care are necessary to avoid opioid administration perioperatively. This may involve regional anesthesia techniques, intravenous local anesthetics, alternate or adjunct pharmacotherapy such as NMDA antagonists, alpha 2 agonists, magnesium, and beta blockers (e.g., esmolol). Intravenous lidocaine has shown benefits in reducing morphine consumption, postoperative nausea and vomiting (PONV), and ileus. It has also shown opioid-sparing effects in complex spine surgeries for up to one month postoperatively.

Ketamine has shown similar results in abdominal, thoracic and spine procedures. The feared hallucinogenic effect is predominantly seen in high doses. Intraoperative esmolol infusion has also been associated with reduced opioid consumption. Dexmedetomidine, an alpha-2 agonist, has been studied extensively and has been shown to provide hypnosis, sedation and analgesia. Concerns with its use are a delay in extubation and discharge time (if in an ambulatory center), and hemodynamic effects of hypotension. A study comparing dexmedetomidine and remifentanil intraoperative use demonstrated a better hemodynamic profile with dexmedetomidine but extubation time was delayed.  

Dr. Gupta rounded off the panel discussion by examining the role of remifentanil in neuroanesthesiology. He distilled the goals of neuroanesthesia to include amnesia/hypnosis, immobility, hemodynamic stability as well as provision of neuroprotection, neuromonitoring and rapid emergence as indicated. These goals are predominantly achieved with balanced anesthesia, including opioids, of which remifentanil is a popular choice. He reviewed relevant regional techniques and adjuvant agents previously described by Dr. Beloeil, their potential roles in achieving the neuroanesthesia care goals, and their potential disadvantages. Examples include delayed extubation with alpha-2 agonists, unpredictable recovery from ketamine, the effect of antihypertensives on the stress response relative to antinociception, hypotension associated with magnesium, and logistical difficulties with scalp blocks.

In conclusion, opioid-sparing techniques and neuroanesthesia goals can be achieved through multimodal anesthesia using the armamentarium available to the anesthesiologist. However, unique characteristics of the patient, potential medication interactions and side effects, and specific surgical procedure goals, should steer every anesthesia plan.

*Coverage from the SNACC Panel: Opioid-Free Anesthesia: Biologic Basis and Potential Applications in Neurosurgical Anesthesiology during the IARS 2019 Annual Meeting