Daniels Stephen E, Gan Tong J Tj, Hamilton Douglas A, Singla Neil, Lacouture Peter G, Johnson Olufunmibi, Min Lauren H, Reyes Christian R D, Carr Daniel B
*Premier Research, Austin, Texas.
Department of Anesthesiology, Stony Brook University, Stony Brook, New York.
Pain Med. 2016 Dec;17(12):2378-2388. doi: 10.1093/pm/pnw146. Epub 2016 Jul 17.
While injectable nonsteroidal anti-inflammatory drugs (NSAIDs) are a key component of postoperative multimodal analgesia, renal safety concerns may limit use in some patients. This study examined the renal safety of injectable HPβCD-diclofenac when given for ≤ 5 days following orthopedic or abdominal/pelvic surgery. METHODS : Pooled analysis of data from two randomized, placebo- and active comparator-controlled phase III trials in 608 total patients was conducted. Renal safety was assessed by examining treatment-emergent adverse events (AEs) and postoperative blood urea nitrogen (BUN) and serum creatinine shifts. RESULTS : There were three renal AEs each in the HPβCD-diclofenac (n = 318 patients) and placebo (n = 148 patients) groups, and two renal AEs in the ketorolac group (n = 142 patients). No significant difference in renal AE risk was detected for patients receiving HPβCD-diclofenac (RR: 1.40 [0.15,13.3]; P = 0.75) or ketorolac (RR: 2.08 [0.19,22.7]; P = 0.56) versus placebo. All renal AEs were mild or moderate in severity, and a single renal AE (acute renal failure in a patient receiving HPβCD-diclofenac) was treatment-related. One incidence of postoperative shift to high (> upper limit of normal) serum creatinine occurred in the HPβCD-diclofenac group (n = 2 in the ketorolac group). Mean changes in serum creatinine or BUN did not differ significantly between patients receiving HPβCD-diclofenac and placebo. CONCLUSIONS : While this analysis examined relatively brief exposure typical for parenterally administered analgesics in the postoperative setting in patients with largely normal renal function, the results suggest that HPβCD-diclofenac use for acute postoperative pain may not be associated with added renal safety risks over placebo in this patient population.
虽然注射用非甾体抗炎药（NSAIDs）是术后多模式镇痛的关键组成部分，但肾脏安全性问题可能会限制其在某些患者中的使用。本研究探讨了在骨科或腹部/盆腔手术后≤5天给予注射用HPβCD - 双氯芬酸时的肾脏安全性。方法：对两项随机、安慰剂和活性对照药对照的III期试验数据进行汇总分析，共纳入608例患者。通过检查治疗期间出现的不良事件（AE）以及术后血尿素氮（BUN）和血清肌酐变化来评估肾脏安全性。结果：HPβCD - 双氯芬酸组（n = 318例患者）和安慰剂组（n = 148例患者）各有3例肾脏AE，酮咯酸组（n = 142例患者）有2例肾脏AE。接受HPβCD - 双氯芬酸（RR：1.40 [0.15, 13.3]；P = 0.75）或酮咯酸（RR：2.08 [0.19, 22.7]；P = 0.56）的患者与接受安慰剂的患者相比，未检测到肾脏AE风险有显著差异。所有肾脏AE的严重程度均为轻度或中度，且有一例肾脏AE（接受HPβCD - 双氯芬酸的患者发生急性肾衰竭）与治疗相关。HPβCD - 双氯芬酸组有1例术后血清肌酐升高至高于正常上限（酮咯酸组为2例）。接受HPβCD - 双氯芬酸和安慰剂的患者之间，血清肌酐或BUN的平均变化无显著差异。结论：虽然本分析研究了肾功能基本正常的患者在术后使用胃肠外给予镇痛药时相对较短的用药时间，但结果表明，在该患者群体中，使用HPβCD - 双氯芬酸治疗急性术后疼痛与安慰剂相比，可能不会增加肾脏安全性风险。
