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The Goldilocks Principle of Perioperative Opioid Administration

Op-Med is a collection of original articles contributed by Doximity members.

Every year, over ten thousand anesthesiologists travel to the American Society of Anesthesiologists annual meeting in the United States to gain exposure to contemporary practices and maintain a finger on the pulse of cutting-edge medical science. Recognizably, the field of healthcare data science is expanding as researchers discuss new methods for acquiring and interpreting an ever-expanding amount of healthcare data. Often, this data acquisition, however, leaves providers with more questions than answers. Debates rage over the optimal, most ideal, or best practice for the specialty. Within this framework exists the ongoing debate pertaining to opioid-free anesthesia. The pendulum of medicine tends to swing to extremes, and this case may be no different. Opioids are certainly not the panacea of analgesia due to their well-recognized side effect profile. Symptoms such as nausea, vomiting, dizziness, disorientation, and respiratory depression are readily observed and are not unanticipated side effects identified long before the opioid epidemic. However, new studies over the past decade have further elucidated the potential for other effects, such as increased tolerance. Though traditionally, this may have been considered for patients with a history of chronic opioid consumption, it is now known that this may manifest even within the short perioperative period of a single anesthetic (i.e., with greater 24-hour postoperative pain scores and opioid consumption in those patients that received higher doses of intraoperative opioid). Additionally, opioid-induced hyperalgesia (OIH) has been elucidated as a well-known phenomenon associated with opioid administration. Furthermore, it would be remiss to forget that many institutions do not offer pharmacogenomic testing. Providers are left to use their best judgment in selecting the most efficacious opioid and determining the appropriate amount of opioid to administer, without overdose, to supplement natural neurotransmitter release in patients with recognizably variable neurophysiologic function. That said, pain is notably a subjective experience and does not reliably correlate with intraoperative hemodynamic perturbation, so appreciating the severity of perceived pain and the adequacy of pain treatment is difficult. Researchers continue to pursue reliable technologies for pain evaluation, including cerebral optical spectrometry, fNIRS, pupillometry, and EEG. Unfortunately, continuous EEG monitoring does not have a reliable EEG biomarker to identify pain. Perhaps one of these technologies will become a reliable tool for intraoperative pain evaluation in the future. In the absence of identifiable evidence as to a patient’s perceived pain, physicians are using opioid analgesics as sympatholytics for the interpreted likelihood that temporally relevant events may correlate and often denote potential pain intraoperatively. Since administering too much opioid during the perioperative period may increase the risk for adverse postoperative effects, including the debatable potential for abuse, and since patients would prefer to experience pain over other symptoms of nausea, vomiting, and dizziness, should anesthesiologists not avoid opioid administration at all costs to avoid this potentially significant detriment to our patients?

The counterargument, however, paints a different picture with a different cost. Providing opioid-free anesthesia requires an increasingly complex anesthetic. Where anesthesiologists would historically provide a single relatively hemodynamically stable intraoperative analgesic (e.g., methadone, hydromorphone, etc.), newer efforts at opioid-free anesthesia may require a multitude of additional adjuncts (i.e., gabapentinoids, acetaminophen, ketorolac, steroids, magnesium, dexmedetomidine, esmolol, ketamine, etc.). These adjuncts are not without their side effects (e.g., sedation and synergistic respiratory depression (gabapentinoids), bradycardia and hypotension (dexmedetomidine and beta-blockers), arrhythmia (local anesthetics), salivation and psychotomimetic effects (ketamine), immunomodulation, etc.). A relatively recent clinical trial investigating opioid-free anesthesia was halted secondary to adverse medication side effects and safety concerns (i.e., increasing bradycardia was observed in the dexmedetomidine arm). Also of note, is a recent meta-analysis and systemic review that further reported the absence of a significant reduction in postoperative pain and opioid consumption when opioid-free anesthesia was performed, suggesting a limited benefit. There is further evidence that the provision of certain opioids (e.g., methadone) may have postoperative benefits in the prevention of chronic pain when administered intraoperatively. Processing this information potentiates additional concerns regarding potentially inadequate postoperative pain control in our surgical patients. As our non-opioid analgesics have a ceiling effect with narrow therapeutic indices, their administration in isolation is unlikely to match the adequacy of opioid analgesia and may contribute to this undertreatment. Since it is known that pain is an unpleasant sensory and emotional experience with neurophysiologic implications, does this undertreatment not result in additional adverse neurophysiologically driven symptomatology such as postoperative nausea and vomiting? Or worse, it is recognized that inadequately treated intraoperative pain may contribute to increased arousal and the potential for recall under anesthesia. In the absence of a nociceptive monitor, should anesthesiologists not, therefore, limit anesthetic complexity, decrease anesthetic side effects, reduce pain-related symptomatology, ensure adequate hypnosis, and potentially decrease the incidence of chronic pain by targeting the provision of opioids to all patients intraoperatively?

As always, the answer is that it depends. While there may be undeniable benefits from implementing an Enhanced Recovery After Surgery pathway, the idea that one size fits all continues to plague medicine. While certain patients may benefit from an opioid-free anesthetic, anesthesiologists should use caution in the blanket application of this technique. A better approach, and perioperative goal, targets opioid-sparing anesthesia. As anesthesiologists continue to engage in the greater perioperative arena of patient care, we must strive to promote individualized care. Preoperative patient evaluation and optimization should strive to include individualized pharmacogenomic testing. We should continue to focus on minimizing intraoperative opioids, as able, and pursuing regional anesthetic techniques while deliberately and selectively administering various analgesic adjuncts as indicated. Anesthesiologists, recognizing the dynamic and fluid nature of the perioperative environment, must not perseverate on any single technique but instead focus on an ultimate objective that targets patient comfort and satisfaction. Our anesthetic must be made-to-order. Not too hot, not too cold, but just right. If it was easy, anyone could do it.  


Dr. Carness has no conflicts of interest to report.

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