Integration and innovative development of enhanced recovery after surgery and anesthesiology. Enhanced recovery after surgery and rational use of opioids

1. The development history of enhanced recovery after surgery (ERAS) Enhanced recovery after surgery (ERAS) is a multimodal perioperative care approach that has evolved over the past 2 decades since its inception. In 1997, Professor Henrik Kehlet, also known as the “father of ERAS”, from the University of Copenhagen in Denmark first proposed the ERAS concept and discovered its clinical feasibility and superiority, achieving remarkable results. ERAS was initially applied in colorectal surgery; subsequently, the concept gradually gained popularity and application worldwide. Originating from the concept of fast-track surgery, ERAS has been increasingly recognized for its ability to reduce postoperative complications, shorten hospital stay, and improve patient outcomes. In fact, concepts encompassed by ERAS were applied clinically by Chinese doctors as early as the 1960s. Tongji Hospital utilized the “two reductions and one preservation” concept in 1965 for 33 patients undergoing subtotal gastrectomy, achieving excellent clinical results.[1] Professor Fazu Qiu, who was instrumental in this pioneering work, was considered the “father of ERAS” in China. The philosophy of ERAS is grounded in evidence-based medicine and involves collaborative efforts from various disciplines, including surgery, anesthesia, nursing, nutrition, and physiotherapy. Since its introduction in China, the application of ERAS has gradually increased and expanded to multiple medical specialties, such as orthopedics, cardiothoracic surgery, obstetrics and gynecology, and urology. ERAS has been gaining momentum with a growing body of clinical research supporting its effectiveness and advocating for its broader application in clinical practice. 2. Anesthesia: A vital component of enhanced recovery after surgery (ERAS) Anesthesia is a cornerstone of ERAS and influences patient recovery through preoperative, intraoperative, and postoperative management. Anesthesiologists play a crucial role in patient education, assessment, and optimization preoperatively. Traditional fasting guidelines have been revised to allow clear fluids up to 2 hours before surgery, which helps maintain hydration and reduces the stress response. This aligns with the ERAS philosophy of minimizing preoperative fasting and dehydration. During surgery, anesthesiologists manage the patients' physiological responses to ensure optimal surgical conditions. This includes maintaining normal body temperature, which is essential for reducing surgical site infections and improving outcomes. Goal-directed fluid therapy improves postoperative outcomes by minimizing fluid overload and maintaining appropriate tissue perfusion. Effective postoperative pain management is a pivotal aspect of ERAS that ensures patient comfort and enables early mobilization. The traditional reliance on opioids has been replaced by multimodal analgesia to reduce side effects and improve recovery. This approach often includes acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), selective cyclooxygenase-2 inhibitors, and the patient-controlled analgesic morphine. Anesthesiologists also play a role in reducing postoperative nausea and vomiting (PONV), which is crucial for early ambulation and oral intake. 3. The role of opioids in pain management Postoperative pain management is a crucial measure for achieving the ultimate goal of ERAS, and opioids have traditionally played a significant role in postoperative pain management. However, with the advent of ERAS protocols, there has been a shift toward minimizing opioid use due to the associated side effects such as nausea, vomiting, constipation, and potential respiratory depression. The ERAS approach advocates low-opioid or non-opioid anesthesia, utilizing the shortest duration and lowest effective doses of opioids. In cases where non-opioid analgesics are insufficient, opioids are considered the last resort for acute pain management. The goal was to reduce opioid-related adverse events and promote faster recovery by employing alternative methods such as local and regional anesthesia techniques. The real culprit is not the opioids themselves, but the way people are accustomed to using them. Surgeons and anesthesiologists have different concerns about opioid medications. Surgeons, considering the side effects of opioids, the impact on postoperative outcomes, and the issue of opioid abuse, choose to use them as little as possible, whereas anesthesiologists use them selectively and rationally based on the anesthesia medication combination plan. Instead of continuously focusing on the “nots” of opioids, should we shift our attention more toward how to better utilize opioids? First, the importance of opioids in perioperative pain management should be recognized. Opioids have strong analgesic effects, rapid and accurate efficacy, and stress-reducing properties, making them the foundation of perioperative pain management. Opioids also have side effects, such as addiction and respiratory depression, which require rational use. Recently, there has been a serious opioid abuse crisis in the United States and other countries, raising concerns regarding the use of opioids. From 2010 to 2017, the number of deaths from fentanyl and other synthetic opioids increased nearly tenfold, from approximately 3000 (14.3% of opioid-related deaths) to over 28,466 (59.8%). Synthetic opioids are now almost twice as commonly involved in overdose deaths as prescription opioids or heroin,[2] and this crisis is referred to as the “opioid epidemic”. A high-level consultation between China and the United States reached an important consensus to strengthen the management of opioid drugs. However, in China, opioids are strictly regulated, and there is a severe shortage in their clinical use, with a low rate of abuse. In China, the perioperative management of opioids has 3 major features. The first is the wide variety of opioid drugs available. With a deeper understanding of the scope and degree of adverse events related to opioids, the development of opioid drugs for the treatment of pain has continued. The second feature is the broad scope of application, and there is a significant demand for analgesia among the Chinese population given its large population size. The third feature is stringent management of opioids. In China, potent opioids have always been classified as specially controlled drugs with strict measures in place to prevent abuse. There are stringent regulatory systems at every stage, including raw material production, manufacturing, sales, prescriptions, and applications. At present, opioids in China are mainly used for the treatment of acute pain, and there is a serious lack of analgesics for the treatment of chronic pain, especially cancer pain. A rational strategy should be formulated for the use of opioids based on China's national conditions, optimally utilizing their analgesic effects, while minimizing their side effects. It is essential to strive to implement medical order systems in anesthesiology and intelligent management of the entire narcotic drug process, strictly controlling occupational exposure to narcotic drugs. Opioid-free anesthesia (OFA) is a novel concept representing a multimodal anesthesia strategy that combines multiple non-opioid drugs and/or techniques to achieve high-quality anesthesia without the use of opioid medications. Published studies have aimed to achieve OFA using a combination of one or more adjuncts apart from known analgesic components, including acetaminophen, NSAIDs, cyclooxygenase-2–specific inhibitors, and locoregional analgesia.[3] The adjuncts included ketamine, lidocaine, α-2 agonists (dexmedetomidine), magnesium, and beta-blockers. However, compared to opioid-based anesthesia, OFA is less effective, and a rigorously designed randomized controlled trial (RCT) was prematurely halted owing to serious adverse events occurring in the OFA group.[4] In that study, patients undergoing elective moderate-to-large noncardiac surgeries were administered balanced anesthesia with either remifentanil or dexmedetomidine infusions. Although postoperative opioid consumption and nausea/vomiting were less frequent, patients undergoing dexmedetomidine-based OFA had higher rates of intraoperative severe bradycardia and hypoxemia in the Post-Anesthesia Care Unit (PACU), as well as longer extubation times and prolonged stays in the PACU. OFA is theoretically more advantageous than disadvantageous and is feasible; however, its efficacy and safety in different types of surgery remain controversial. In another study[5] where esketamine was used as a substitute for opioids, researchers investigated whether OFA could reduce the incidence of chronic postoperative pain in patients undergoing video-assisted thoracoscopic surgery (VATS). The results showed that the OFA group, which received general anesthesia combined with a thoracic epidural block using esketamine, showed an improvement in mild chronic postoperative pain at 3 and 6 months, but there was no difference in severe or moderate pain. Additionally, the OFA regimen had an improved side effect profile at the expense of increased acute pain. Currently, evidence-based data confirming the benefits of OFA are lacking. In another recent large-scale RCT,[6] among eligible male and female patients undergoing elective major surgery (excluding orthopedic surgery), patients in the intervention group received a combination of at least 2 drugs, ketamine, lidocaine, clonidine, and magnesium sulfate. The primary outcome was assessed using the Quality of Recovery-15 (QoR-15) score 24 hours after surgery. Compared to standard anesthesia, OFA improved the early postoperative quality of recovery after major elective surgery in a statistically but not clinically significant manner. There is no good reason to suggest that patients not exposed to opioids will require fewer opioids after surgery compared with the judicious use of opioids during general anesthesia. Rebound pain and higher consumption of opioids in the short term have been observed even after interscalene blockade in shoulder surgeries.[7] If the goal is to avoid the use of opioids during surgery but results in increased opioid consumption postoperatively, such a strategy is undesirable. An attempt for OFA, simply for the sake of avoidance without appropriate equipotent analgesia, could lead to worse pain outcomes, as noted in a large cohort study of 61,249 patients in whom intraoperative fentanyl and hydromorphone administration led to decreased pain in the recovery unit with decreased new chronic pain diagnoses at 3 months.[8] The complete avoidance of intraoperative opioids remains questionable as it does not necessarily ensure the avoidance of postoperative opioids. Multimodal analgesia, including local/regional anesthesia, may allow OFA for selected minimally invasive surgeries; however, further research is necessary for surgeries with high postoperative opioid requirements. While awaiting further evidence, it is prudent to practice the opioid-sparing approach in the intraoperative period rather than completely avoid opioids during general anesthesia.[9] The principles of ERAS and the rational use of opioids are as follows. The role and position of opioids in the perioperative period are irreplaceable. For postoperative analgesia, a multimodal analgesic strategy should be adopted, which includes neuraxial or peripheral nerve blocks, combined with opioid-sparing approaches and NSAIDs. Based on the pharmacological characteristics of opioids, the selection of opioid receptor agonists, such as the clinical application of the new generation G protein–biased μ-opioid receptor agonist oliceridine, is promising. The analgesic effects and adverse reactions of opioids are mediated by 2 different signaling pathways: the G-protein pathway, which is primarily associated with analgesia and triggers some adverse reactions; and the β-arrestin pathway, which is mainly related to adverse reactions such as respiratory and gastrointestinal issues, and has a certain attenuating effect on analgesic responses. Oliceridine[10] is a G-protein–biased μ-opioid receptor agonist that selectively activates the G-protein signaling pathway and significantly reduces activation of the β-arrestin pathway. It retains its analgesic potency while significantly reducing opioid-related adverse reactions rather than eliminating them. Compared to traditional opioids, oliceridine has a better safety profile, which is conducive to the implementation of ERAS. In addition to the development of novel opioids, another novel drug, bupivacaine liposome (Exparel),[11] has also contributed to the innovative development of postoperative pain management in ERAS. Bupivacaine offers an analgesic effect lasting up to 72 hours, addressing the limitation of the single-dose local analgesic effect of bupivacaine, which does not exceed 7 hours. This fulfills the clinical need for continuous pain treatment. 4. The impact of new anesthetic techniques and services on ERAS development The integration of new anesthetic techniques and services has been instrumental in the evolution of ERAS. Intelligent anesthesia management, which leverages modern information technology and artificial intelligence, has become a key component in enhancing the precision and safety of anesthesia care. Real-time monitoring and data analysis allow the optimization of anesthetic plans, leading to reduced surgical risks and improved patient comfort. For example, the use of regional anesthesia has been associated with improved pain control, reduced opioid consumption, and improved patient satisfaction. Additionally, the implementation of closed-loop anesthesia delivery systems and less-invasive monitoring technologies has improved the precision and safety of anesthesia care, aligning with the ERAS goals of minimal stress and early recovery. These technological innovations support the ERAS goals of minimizing postoperative stress and facilitating early recovery. The department of anesthesiology plays a crucial role in the development of hospitals, not only because it reflects the comprehensive strength of the hospital as a clinical specialty, but also because it serves as a platform for the development of various clinical disciplines. Recognition of the status of the anesthesiology profession in medical science is continuously increasing, and it has the potential to become “the largest department in future hospitals”. Anesthesia is not only used in the operating room but also routinely required for labor analgesia, painless gastrointestinal endoscopy, various pediatric examinations, interventional and minimally invasive surgeries, etc. The demand for anesthesia for comfortable medical care has become much broader. Moreover, owing to the need for improved hospital quality and efficiency, the rapid growth of day surgery, the increase in the number of elderly patients with complex and critical conditions, and the implementation of ERAS (where perioperative pain management is an important measure to achieve the ultimate goal of ERSA), the value of anesthesiologists is increasingly recognized. In practice, multimodal analgesia during the perioperative period should be implemented using a patient-centered approach. By combining different drugs, administering them through various routes, and collaborating across departments, a true full-course, standardized, multimodal analgesia can be achieved, providing better treatment experiences and outcomes for surgical patients.