Background Inherently dangerous, anesthesia has matured into an essentially safe practice due to major advancements in the field. Over the decades, even since the 1950s, the field of anesthetic and perioperative care has witnessed a continuous decline in mortality rates.1 These advancements can be attributed to the utilization of safer anesthetic agents, the development of advanced technical instruments and techniques, and comprehensive training programs, among other pivotal factors. Despite these remarkable progressions, challenges and gaps in our understanding persist. The evolution of drug use in anesthesiology is particularly noteworthy. Initially focused on facilitating surgical procedures and enhancing patient health outcomes, in the current landscape of 2023, anesthetics have expanded their applications well beyond the confines of the operating room. They are now integral in diverse medical contexts, including trauma care, resuscitation, sedation, intensive care, and the management of acute and chronic pain.2 Furthermore, the exploration of unconventional agents, such as psychedelics for pain, and the use of anesthetic agents in other disciplines, underscores the dynamic nature of modern medical practice and interdisciplinary research.3 For instance, consider ketamine, an N-methyl-D-aspartate receptor (NMDAR) blocker, introduced as an intravenous anesthetic in 1965. Since the 1990s its applications have extended to include the management of acute and chronic pain. More recently, since the early 2000s, nasal S-ketamine marketed as Spravato, has also found utility in psychiatry, offering an alternative treatment for therapy-resistant depression and post-traumatic stress disorder. This presents a potential replacement for traditional treatments like electroconvulsive therapy or antipsychotic therapy in specific cases.4,5 Studies on this fascinating drug can be advantageous for both the fields of psychiatry and anesthesiology. One persistent challenge of drugs in anesthesiology revolves around the efficacy and side-effect profile of contemporary analgesics. Both non-opioid and opioid analgesics, while indispensable in pain management, exhibit limitations in certain patient groups, particularly those suffering from chronic pain. Conversely, these drugs have adverse effects, including the potential for abuse, as observed with ketamine and opioids, as well as the life-threatening risk of opioid-induced respiratory depression. The combination of addiction and respiratory depression stands at the core of the current opioid epidemic in the United States, characterized by more than 100,000 deaths from opioid overdose in 2022.6 Both the efficacy and side-effect profile of these analgesics are intertwined with the critical role played by the patient’s phenotype.”One Size Fits All” is a thing of the past and research and guidelines are increasingly tailored to 2
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