Nalbuphine vs sufentanil as effective analgesics for postoperative pain management in gastric cancer resection

Abstract

This editorial highlights the randomized controlled trial by Qian et al evaluating the efficacy of nalbuphine in managing postoperative pain and associated inflammatory factors in patients undergoing radical gastrectomy for gastric cancer. Utilizing a multimodal analgesic approach with a controlled analgesia pump and a transverse abdominis muscle plane block, the study compared nalbuphine against sufentanil. Results indicate that nalbuphine significantly reduces pain scores at various postoperative intervals, decreases consumption and patient-controlled analgesia presses, and lowers levels of pain markers such as prostaglandin E2, serotonin, and substance P. While both agents demonstrated effective pain control, nalbuphine was associated with a lower incidence of adverse effects, suggesting its potential as a valuable alternative in appropriate clinical scenarios. This study offers valuable insights into nalbuphine’s clinical applicability, underscoring its benefits for pain management and enhancing patient recovery in the postoperative setting.

Key Words: Nalbuphine; Sufentanil; Postoperative pain management; Radical gastrectomy; Multimodal analgesia; Enhanced recovery after surgery

Core Tip: Enhanced recovery after surgery (ERAS) protocols emphasize optimal pain management while minimizing opioid-related complications. This editorial highlights the comparative efficacy and safety profile of nalbuphine vs sufentanil in postoperative pain management following radical gastrectomy. The study demonstrates nalbuphine's advantages in terms of pain control, reduced inflammatory response, and fewer adverse events. Particularly noteworthy is its potential role in multimodal analgesia within ERAS protocols, offering a promising alternative for optimizing postoperative recovery while minimizing opioid-related complications.

INTRODUCTION

Gastric cancer remains one of the most prevalent malignancies worldwide[1,2], with approximately one million new cases diagnosed annually. For patients undergoing radical gastrectomy, effective postoperative pain management represents a significant clinical challenge. Inadequate pain control not only affects patient comfort and recovery but also potentially influences postoperative outcomes and length of hospital stay[3].

Traditional postoperative pain management has relied heavily on pure μ-opioid agonists like sufentanil, which, while effective, can be associated with significant side effects[4,5]. In this context, nalbuphine, as a mixed κ-agonist/μ-antagonist, offers an alternative approach that may provide adequate pain control with a potentially better safety profile.

The integration of multimodal analgesia approaches, particularly within enhanced recovery after surgery (ERAS) protocols, has become increasingly important in optimizing postoperative outcomes[6,7]. These protocols emphasize the need for effective pain control while minimizing opioid-related complications, making the evaluation of alternative analgesic agents particularly relevant.

The concept of multimodal analgesia has emerged as a promising approach to optimize postoperative pain control while minimizing opioid-related complications[8,9]. This strategy combines different analgesic techniques and medications, targeting various pain pathways to achieve superior pain relief with fewer side effects. The integration of regional anesthetic techniques, such as transverse abdominis plane blocks, with systemic analgesics represents a significant advancement in this field.

Furthermore, with the widespread implementation of ERAS protocols, the optimization of postoperative pain management has become increasingly crucial. ERAS programs emphasize multimodal analgesia and opioid-sparing strategies to facilitate early recovery and improve surgical outcomes[10,11].

In this context, the exploration of alternative analgesics like nalbuphine, which offers potent pain relief with a potentially better safety profile, becomes particularly relevant. The study by Qian et al[12] provides valuable insights into the role of nalbuphine in multimodal postoperative pain management following gastric cancer surgery. It was a randomized controlled trial comparing nalbuphine with sufentanil in 108 patients under a standardized analgesia regimen, offering robust evidence for nalbuphine’s benefits. Notably, this is one of the first studies to directly evaluate nalbuphine against a traditional opioid in the context of gastric cancer surgery within an ERAS framework, filling a significant gap in evidence for opioid-sparing strategies.

CLINICAL SIGNIFICANCE OF NALBUPHINE

Nalbuphine represents a unique class of opioid analgesics with a distinct pharmacological profile that makes it particularly suitable for postoperative pain management[13-15]. As a mixed κ-opioid receptor agonist and partial μ-opioid receptor antagonist, nalbuphine offers several advantages over traditional pure μ-opioid agonists like sufentanil[16,17].

The drug's dual mechanism of action contributes to its favorable clinical profile. While the κ-receptor agonism provides effective analgesia, particularly for visceral pain commonly experienced after abdominal surgery, the partial μ-receptor antagonism results in a ceiling effect for respiratory depression, potentially offering a wider safety margin compared to conventional opioids. This characteristic is especially valuable in the postoperative setting, where respiratory complications remain a significant concern.

Furthermore, nalbuphine demonstrates several practical advantages in clinical applications. Its moderate duration of action (3-6 hours) allows for flexible dosing schedules, while its lower potential for dependence and abuse makes it an attractive alternative in the current climate of opioid crisis. The drug's stability in solution and compatibility with other commonly used medications in multimodal analgesia protocols add to its practical utility.

In the context of gastric cancer surgery, nalbuphine's effectiveness in managing both somatic and visceral pain, combined with its favorable side effect profile, positions it as a promising agent for postoperative pain management. The integration of nalbuphine into multimodal analgesic protocols, as demonstrated in the current study, represents a rational approach to optimizing postoperative pain control while minimizing adverse effects.

KEY FINDINGS AND IMPLICATIONS

The study's findings provide compelling evidence for nalbuphine's efficacy in postoperative pain management following radical gastrectomy. Several key observations merit particular attention and have significant implications for clinical practice.

First, the superior pain control achieved with nalbuphine is particularly noteworthy. The significantly lower pain scores observed at multiple time points (6 hours, 12 hours, 24 hours, and 48 hours postoperatively) during both rest and movement suggest consistent and reliable analgesic efficacy. The reduced frequency of patient-controlled analgesia demands and lower total analgesic consumption in the nalbuphine group not only indicates better pain control but also suggests potential cost-effectiveness and reduced risk of medication-related complications.

Second, the study's examination of pain-related inflammatory markers provides valuable mechanistic insights. The observed reductions in prostaglandin E2, substance P, and serotonin levels at 24 hours postoperatively suggest that nalbuphine may modulate the inflammatory response to surgical trauma. This finding extends beyond simple pain control, potentially indicating broader benefits in the overall stress response to surgery and recovery process. Nevertheless, the clinical significance of these reductions warrants further investigation to determine whether they translate into improved patient outcomes-such as enhanced immune function, faster wound healing, or reduced postoperative complications.

Perhaps most significantly, the marked difference in adverse event rates between nalbuphine (5.56%) and sufentanil (22.22%) groups represents a substantial clinical advantage. This safety profile, combined with effective pain control, addresses one of the primary challenges in postoperative pain management-balancing analgesic efficacy with patient safety. The lower incidence of adverse effects may contribute to improved patient satisfaction, earlier mobilization, and potentially shorter hospital stays.

The implications of these findings extend well beyond immediate pain management. The demonstrated efficacy and safety profile of nalbuphine strongly supports its integration into multimodal analgesic protocols for major abdominal surgery. Moreover, its potential role in modulating the surgical stress response suggests broader applications in perioperative care. This evidence provides a strong foundation for healthcare institutions to develop and optimize their pain management protocols, particularly for patients who may be at higher risk for traditional opioid-related complications. However, it is also important to acknowledge that sufentanil’s role is not entirely supplanted. As a full μ-opioid agonist, sufentanil may offer superior analgesia in certain high-intensity pain scenarios where nalbuphine’s ceiling effect could limit efficacy. Therefore, rather than completely phasing out sufentanil, nalbuphine should be regarded as a valuable addition to the analgesic arsenal-one that can be preferentially used in contexts where its safety advantages improve patient outcomes.

FUTURE PERSPECTIVES

The integration of nalbuphine into ERAS protocols represents a particularly promising direction for future research. As ERAS programs continue to evolve and gain widespread adoption, understanding how nalbuphine-based analgesia can be optimally incorporated into these comprehensive care pathways becomes increasingly important. The potential of nalbuphine to support key ERAS principles-including early mobilization, reduced opioid consumption, and faster recovery-warrants detailed investigation.

Understanding the optimal dosing strategy remains another key area for future research. While the current study demonstrated efficacy with a standardized dosing protocol, individualized dosing approaches based on patient characteristics, surgical complexity, and genetic factors could potentially enhance outcomes. Additionally, investigating the potential synergistic effects between nalbuphine and other analgesic agents could lead to more refined multimodal pain management strategies.

The long-term implications of nalbuphine use also deserve attention. Future studies should focus on extended follow-up periods to evaluate the potential impact on chronic post-surgical pain development, a significant concern following major abdominal surgery. In addition, prolonged postoperative use of nalbuphine should be monitored to assess any late-arising adverse effects or dependence potential, thereby ensuring the therapy’s safety over weeks to months of recovery. Moreover, investigating the economic implications of nalbuphine-based protocols, including their impact on length of hospital stay and overall healthcare costs, would provide valuable information for healthcare systems.

Another promising avenue for research lies in identifying specific patient populations who might particularly benefit from nalbuphine-based protocols. This includes patients with a high risk for respiratory complications, those with a history of opioid sensitivity, and elderly patients who may be more susceptible to traditional opioid-related side effects. Finally, further studies should determine whether the advantages of nalbuphine observed in gastric cancer surgery can be generalized to other surgical contexts, such as less invasive procedures or different patient populations, to broaden the applicability of these findings.

CONCLUSION

This study demonstrates that nalbuphine provides effective postoperative pain control with superior safety profile compared to sufentanil following radical gastrectomy, characterized by better pain scores, reduced inflammatory response, and fewer adverse events, particularly in terms of respiratory depression and postoperative nausea and vomiting. These findings support nalbuphine as a valuable alternative in multimodal analgesic protocols, especially within ERAS pathways, though further research is needed to optimize its clinical application.