Dinalbuphine Sebacate在微創胸腔腫瘤切除術術後疼痛控制於真實世界效果：回溯性世代研究

Abstract

研究背景： 隨著低劑量電腦斷層(low-dose computed tomography, LDCT)篩檢普及與微創胸腔手術技術進步，接受肺部腫瘤切除手術之病人逐年增加。雖然胸腔鏡手術(video-assisted thoracic surgery, VATS)及機器手臂輔助手術(robot-assisted thoracic surgery, RATS)已顯著降低手術侵襲性，但術後疼痛仍為影響病人恢復的重要因素。現今術後疼痛管理多採用多模式止痛(multimodal analgesia, MMA)策略，然而中重度疼痛病人仍常需額外使用類鴉片類類藥物作為救援性止痛。Dinalbuphine sebacate(Naldebain®)為一種長效型nalbuphine前驅藥物，具有提供穩定止痛效果及降低類鴉片類藥物使用之潛力。然而，目前相關研究多集中於特定手術族群或小型研究，其於真實世界臨床環境中的效果仍有待進一步驗證。 研究目的： 本研究旨在評估於微創胸腔腫瘤切除手術病人在多模式止痛策略中加入 dinalbuphine sebacate，是否能改善術後疼痛控制、降低中度以上疼痛發生風險，以及減少術後救援性嗎啡使用。 研究方法： 本研究為單一醫學中心回溯性世代研究，收集中國醫藥大學附設醫院胸腔外科於2023年11月至2025年3月接受微創胸腔腫瘤切除手術之成人病人共542人。依是否接受dinalbuphine sebacate分為dinalbuphine sebacate組(313人)及對照組(229 人)。為降低兩組基線差異所造成之干擾，採用傾向分數配對(propensity score matching, PSM)之最近鄰匹配法並允許重複配對(matching with replacement)進行分析。主要研究終點為手術當天至術後第3天(POD0–POD3)疼痛分數變化；次要研究終點包括中度以上疼痛(Numeric Rating Scale, NRS ≥ 4)發生風險、救援性嗎啡使用率及嗎啡總使用劑量。術後疼痛評分(NRS)之重複測量資料採混合效應模型(mixed-effects model)分析，中度以上疼痛及嗎啡使用則採邏輯斯迴歸分析。 研究結果： 經傾向分數配對後，採dinalbuphine sebacate組313人及對照組137人進行配對後分析。配對後各項基線變數之標準化差異(standardized mean difference, SMD)均顯著改善，顯示兩組具有良好可比性。術後疼痛趨勢分析顯示，兩組疼痛分數皆隨時間下降，但dinalbuphine sebacate組於術後早期(POD0–POD1)呈現較低的疼痛分數。混合效應模型結果顯示，dinalbuphine sebacate與較低術後疼痛分數顯著相關(β = - 0.34，95% CI [−0.66, −0.03], p = 0.031)。在中度以上疼痛方面，dinalbuphine sebacate組的發生風險顯著較低(OR = 0.61, 95% CI [0.40, 0.93], p = 0.020)。此外，接受dinalbuphine sebacate的病人其術後救援性嗎啡使用率明顯下降(25.6% vs. 42.3%; OR = 0.46, 95% CI [0.30, 0.70], p < 0.05)。然而，在實際使用嗎啡的病人中，總嗎啡使用劑量並無顯著差異(40 mg vs. 31 mg, p = 0.52)。 結論： 於微創胸腔腫瘤切除手術病人之多模式止痛策略中加入dinalbuphine sebacate，與較低術後疼痛分數、較低中度以上疼痛風險及較低救援性嗎啡使用率具有顯著相關性。雖然其對於已需使用嗎啡病人之嗎啡總劑量未顯示顯著影響，但研究結果支持dinalbuphine sebacate作為多模式止痛策略中具有潛力之長效止痛藥物，可提供額外且穩定之止痛效益，並降低術後對救援性類鴉片類藥物的需求。未來仍需透過多中心前瞻性研究及隨機對照試驗進一步驗證其臨床效益及長期影響。

Background With the increasing use of low-dose computed tomography (LDCT) screening and advances in minimally invasive thoracic surgery, more patients undergo pulmonary tumor resection. Despite reduced surgical invasiveness, postoperative pain remains a major challenge. Dinalbuphine sebacate (Naldebain®), a long-acting nalbuphine prodrug, may provide sustained analgesia and reduce opioid requirements; however, evidence from real-world thoracic surgical practice remains limited. Objective To evaluate the effectiveness of dinalbuphine sebacate in improving postoperative pain control and reducing rescue morphine use following minimally invasive thoracic tumor resection. Methods This single-center retrospective cohort study included 542 adult patients who underwent minimally invasive thoracic tumor resection at China Medical University Hospital between November 2023 and March 2025. Patients were divided into a dinalbuphine sebacate group (n = 313) and a control group (n = 229) according to whether they received dinalbuphine sebacate. To minimize baseline differences between groups, propensity score matching (PSM) using nearest-neighbor matching with replacement was performed. The primary endpoint was the change in pain scores from operative day to postoperative day 3 (POD0–POD3). Secondary endpoints included the risk of moderate-to-severe pain (Numeric Rating Scale [NRS] ≥ 4), the rate of rescue morphine use, and total morphine consumption. Pain trajectories were analyzed using mixed-effects models, while moderate-to-severe pain and morphine use were evaluated using logistic regression analyses. Results After propensity score matching, 313 patients in the dinalbuphine sebacate group and 137 patients in the control group were included in the matched analysis. Standardized mean differences (SMDs) of baseline variables were substantially reduced after matching, indicating good comparability between groups. Postoperative pain scores decreased over time in both groups; however, patients receiving dinalbuphine sebacate exhibited lower pain scores during the early postoperative period (POD0–POD1). Mixed-effects model analysis demonstrated that dinalbuphine sebacate was significantly associated with lower postoperative pain scores (β = −0.34, 95% CI [−0.66, −0.03], p = 0.031). Furthermore, the risk of moderate-to-severe pain was significantly reduced in the dinalbuphine sebacate group (OR = 0.61, 95% CI [0.40, 0.93], p = 0.020). The rate of rescue morphine use was also significantly lower among patients receiving dinalbuphine sebacate (25.6% vs. 42.3%; OR = 0.46, 95% CI [0.30, 0.70], p < 0.05). However, among patients who required morphine, there was no significant difference in total morphine consumption between the two groups (40 mg vs. 31 mg, p = 0.52). Conclusions The addition of dinalbuphine sebacate to a multimodal analgesia regimen in patients undergoing minimally invasive thoracic tumor resection was associated with lower postoperative pain scores, a reduced risk of moderate-to-severe pain, and a lower rate of rescue morphine use. Although no significant reduction in total morphine consumption was observed among patients who required morphine, the findings support dinalbuphine sebacate as a promising long-acting analgesic within multimodal pain management strategies. Its clinical value may lie in providing additional and sustained analgesic benefits while reducing the need for rescue opioid medications after surgery. Further multicenter prospective studies and randomized controlled trials are warranted to validate its clinical efficacy and long-term outcomes.