喷他佐辛与曲马多减少儿童全身麻醉后苏醒期躁动疗效的比较：一项回顾性队列研究

文献信息

中文摘要

背景： 苏醒期躁动（EA）是儿科麻醉中常见的术后并发症，可能导致严重安全事件并增加医疗负担。喷他佐辛和曲马多均常用于儿童术后镇痛，但二者预防EA的比较有效性仍不清楚。本研究旨在比较单次静脉注射曲马多与喷他佐辛在减少接受扁桃体切除术和腺样体切除术儿童EA方面的疗效。
方法： 这项单中心回顾性队列研究纳入240例2-12岁在瑞马唑仑诱导全身麻醉下接受择期扁桃体切除术和腺样体切除术的儿童。患者在手术后立即静脉接受喷他佐辛0.4 mg/kg或曲马多1 mg/kg。主要结局为EA发生率，定义为在麻醉后监护室（PACU）停留期间任何时间儿童麻醉苏醒期谵妄（PAED）量表评分≥10。次要结局包括PAED评分随时间的变化轨迹、PACU停留时间、术后疼痛（FLACC量表）和不良事件（恶心/呕吐、呼吸抑制）。统计分析主要采用多变量logistic回归；次要和敏感性分析（线性混合模型、广义估计方程、基于样条的模型和Cox回归）用于评估稳健性，详见补充材料。
结果： 曲马多组EA的未调整发生率为0.8%（1/120），喷他佐辛组为14.2%（17/120）（相对危险度17.00，95% CI：2.30-125.73，p < 0.001）。调整潜在混杂因素后的多变量logistic回归显示，喷他佐辛组发生EA的比值更高（OR = 12.61，95% CI：2.33-234.43，p = 0.017），尽管较宽的置信区间反映了较低的事件率。线性混合模型提示存在显著的组别×时间交互作用（p < 0.001），喷他佐辛组在5分钟和10分钟时PAED评分更高，但到20分钟时趋于一致。探索性时间-事件分析（Kaplan-Meier和Cox回归）提示，与曲马多组相比，喷他佐辛组的躁动缓解速度更慢（HR = 0.73，95% CI：0.56-0.96，p = 0.025），这与曲马多组缓解更快一致。然而，由于采用固定时间评估，这些结果应谨慎解读。曲马多组PACU停留时间更短（中位数32 vs. 34分钟，p < 0.001）。两组不良事件发生率均较低且相当。扩展分析（GEE、基于样条的模型）一致支持主要发现（见补充材料）。
结论： 在这项回顾性队列中，与喷他佐辛相比，曲马多与较低的EA发生率和更快的恢复相关，且未观察到短期不良事件增加。调整后的比值比12.61具有极宽的95% CI，反映统计不稳定性；该估计值不应被解释为精确的效应量。由于事件率极低（曲马多组仅1例事件）及其他局限性（回顾性设计、潜在残余混杂），这些发现应被视为产生假设和提示性而非确定性。需要进一步的前瞻性研究来确认曲马多在该人群中是否较喷他佐辛具有临床有意义的优势。

英文摘要

BACKGROUND: Emergence agitation (EA) is a common postoperative complication in pediatric anesthesia that can lead to serious safety events and increased healthcare burden. Both pentazocine and tramadol are frequently used for postoperative analgesia in children, but their comparative effectiveness in preventing EA remains unknown. This study aimed to compare the efficacy of a single intravenous dose of tramadol versus pentazocine for reducing EA in children undergoing tonsillectomy and adenoidectomy.
METHODS: This single-center retrospective cohort study included 240 children aged 2-12 years who underwent elective tonsillectomy and adenoidectomy under general anesthesia with remimazolam induction. Patients received either pentazocine 0.4 mg/kg or tramadol 1 mg/kg intravenously immediately after surgery. The primary outcome was the incidence of EA, defined as a Pediatric Anesthesia Emergence Delirium (PAED) scale score ≥ 10 at any time during the post-anesthesia care unit (PACU) stay. Secondary outcomes included PAED score trajectories over time, PACU stay duration, postoperative pain (FLACC scale), and adverse events (nausea/vomiting, respiratory depression). Statistical analyses primarily used multivariable logistic regression; secondary and sensitivity analyses (linear mixed models, generalized estimating equations, spline-based models, and Cox regression) were performed to assess robustness and are detailed in the Supplementary Material.
RESULTS: The unadjusted incidence of EA was 0.8% (1/120) in the tramadol group and 14.2% (17/120) in the pentazocine group (relative risk 17.00, 95% CI: 2.30-125.73, p < 0.001). Multivariable logistic regression, adjusting for potential confounders, showed that the pentazocine group had higher odds of EA (OR = 12.61, 95% CI: 2.33-234.43, p = 0.017), although the wide confidence intervals reflect the low event rate. Linear mixed models suggested a significant group-by-time interaction (p < 0.001), with higher PAED scores in the pentazocine group at 5 and 10 min but convergence by 20 min. Exploratory time-to-event analyses (Kaplan-Meier and Cox regression) suggested that the pentazocine group had a slower agitation resolution rate compared with the tramadol group (HR = 0.73, 95% CI: 0.56-0.96, p = 0.025), consistent with faster resolution in the tramadol group. However, these results should be interpreted cautiously due to fixed-time assessments. PACU stay was shorter in the tramadol group (median 32 vs. 34 min, p < 0.001). Adverse event rates were low and comparable between groups. Extended analyses (GEE, spline-based models) consistently supported the primary findings (see Supplementary Material).
CONCLUSION: In this retrospective cohort, tramadol was associated with a lower incidence of EA and faster recovery compared with pentazocine, without an observed increase in short-term adverse events. The adjusted odds ratio of 12.61 has an extremely wide 95% CI, reflecting statistical instability; this estimate should not be interpreted as a precise effect size. Due to the very low event rate (one event in the tramadol group) and other limitations (retrospective design, potential residual confounding), these findings should be considered hypothesis-generating and suggestive rather than definitive. Further prospective studies are needed to confirm whether tramadol offers a clinically meaningful advantage over pentazocine in this population.