Department of Surgery, Herlev Hospital, University of Copenhagen, 2730 Herlev, Denmark.
BMJ. 2012 Sep 26;345:e6166. doi: 10.1136/bmj.e6166.
To evaluate the effect of postoperative use of non-steroidal anti-inflammatory drugs (NSAIDs) on anastomotic leakage requiring reoperation after colorectal resection.
Cohort study based on data from a prospective clinical database and electronically registered medical records.
Six major colorectal centres in eastern Denmark.
2766 patients (1441 (52%) men) undergoing elective operation for colorectal cancer with colonic or rectal resection and primary anastomosis between 1 January 2006 and 31 December 2009. Median age was 70 years (interquartile range 62-77).
Postoperative use of NSAID (defined as at least two days of NSAID treatment in the first seven days after surgery).
Frequency of clinical anastomotic leakage verified at reoperation; mortality at 30 days.
Of 2756 patients with available data and included in the final analysis, 1871 (68%) did not receive postoperative NSAID treatment (controls) and 885 (32%) did. In the NSAID group, 655 (74%) patients received ibuprofen and 226 (26%) received diclofenac. Anastomotic leakage verified at reoperation was significantly increased among patients receiving diclofenac and ibuprofen treatment, compared with controls (12.8% and 8.2% v 5.1%; P<0.001). After unadjusted analyses and when compared with controls, more patients had anastomotic leakage after treatment with diclofenac (7.8% (95% confidence interval 3.9% to 12.8%)) and ibuprofen (3.2% (1.0% to 5.7%)). But after multivariate logistic regression analysis, only diclofenac treatment was a risk factor for leakage (odds ratio 7.2 (95% confidence interval 3.8 to 13.4), P<0.001; ibuprofen 1.5 (0.8 to 2.9), P=0.18). Other risk factors for anastomotic leakage were male sex, rectal (v colonic) anastomosis, and blood transfusion. 30 day mortality was comparable in the three groups (diclofenac 1.8% v ibuprofen 4.1% v controls 3.2%; P=0.20).
Diclofenac treatment could result in an increased proportion of patients with anastomotic leakage after colorectal surgery. Cyclo-oxygenase-2 selective NSAIDs should be used with caution after colorectal resections with primary anastomosis. Large scale, randomised controlled trials are urgently needed.
评估结直肠切除术后使用非甾体抗炎药（NSAIDs）对需要再次手术的吻合口漏的影响。
基于前瞻性临床数据库和电子登记病历数据的队列研究。
丹麦东部的 6 个主要结直肠中心。
2006 年 1 月 1 日至 2009 年 12 月 31 日期间接受择期手术治疗结直肠癌、结肠或直肠切除和一级吻合的 2766 例患者（男性 1441 例（52%））。中位年龄为 70 岁（四分位距 62-77）。
术后使用 NSAID（定义为术后 7 天内至少使用 2 天 NSAID 治疗）。
再次手术时临床吻合口漏的发生率；30 天死亡率。
在 2756 例有可用数据并纳入最终分析的患者中，1871 例（68%）未接受术后 NSAID 治疗（对照组），885 例（32%）接受了治疗。在 NSAID 组中，655 例（74%）患者接受布洛芬治疗，226 例（26%）接受双氯芬酸治疗。与对照组相比，接受双氯芬酸和布洛芬治疗的患者吻合口漏的发生率显著增加（分别为 12.8%和 8.2%比 5.1%；P<0.001）。在未调整分析中，与对照组相比，接受双氯芬酸治疗的患者发生吻合口漏的比例更高（7.8%（95%置信区间 3.9%至 12.8%））和布洛芬（3.2%（1.0%至 5.7%））。但经多变量逻辑回归分析后，只有双氯芬酸治疗是漏诊的危险因素（比值比 7.2（95%置信区间 3.8 至 13.4），P<0.001；布洛芬 1.5（0.8 至 2.9），P=0.18）。吻合口漏的其他危险因素包括男性、直肠（而非结肠）吻合和输血。三组间 30 天死亡率相当（双氯芬酸 1.8%比布洛芬 4.1%比对照组 3.2%；P=0.20）。
结直肠手术后使用双氯芬酸治疗可能会导致更多的吻合口漏。结直肠切除和一级吻合后应谨慎使用环氧化酶-2 选择性 NSAIDs。急需开展大规模、随机对照试验。
