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依诺肝素与阿司匹林相比,会增加持续性伤口引流的风险吗?CRISTAL 随机试验数据的二次分析。

Is Enoxaparin Associated With a Higher Risk of Persistent Wound Drainage Than Aspirin? A Secondary Analysis of Data From the CRISTAL Randomized Trial.

机构信息

School of Clinical Medicine, UNSW Medicine and Health, South West Sydney Clinical School, Faculty of Medicine and Health, UNSW Sydney, Sydney, NSW, Australia.

Whitlam Orthopaedic Research Centre, Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia.

出版信息

Clin Orthop Relat Res. 2023 Jul 1;481(7):1351-1359. doi: 10.1097/CORR.0000000000002544. Epub 2023 Jan 17.

Abstract

BACKGROUND

Owing to its association with prosthetic joint infection, persistent wound drainage has become an important clinical entity after THA or TKA. The association between venous thromboembolism (VTE) prophylaxis and persistent wound drainage has not been extensively reported before but has potentially important clinical implications.

QUESTIONS/PURPOSES: (1) Is the type of VTE prophylaxis (enoxaparin or aspirin) used after hip arthroplasty or knee arthroplasty associated with a higher risk of persistent wound drainage? (2) In patients who experience persistent wound drainage, is the type of VTE prophylaxis associated with a longer time taken to achieve a dry wound? (3) Is type of VTE prophylaxis associated with a higher risk of joint-related reoperation within 6 months?

METHODS

This was a secondary analysis of data from an earlier cluster-randomized trial conducted through the Australian Orthopaedic Association National Joint Replacement Registry; data were drawn from two participating hospitals from that study. According to the trial's allocation sequence, the two participating hospitals were randomized to administer aspirin (100 mg daily) or enoxaparin (40 mg daily) as VTE prophylaxis to all patients undergoing hip arthroplasty for 35 days after the procedure and for all patients undergoing knee arthroplasty for 14 days afterwards. Crossover to the alternate prophylaxis group occurred after the patient enrollment target had been met for the first arm. Between April 2019 and December 2020, 1339 of 1679 eligible patients were included in this study; 82% (707 of 861) of eligible patients were allocated to the enoxaparin group and 77% (632 of 818) of eligible patients we allocated to the aspirin group. The mean age in both groups was 67 ± 10 years and the mean BMI was 32 ± 7 kg/m 2 . There was a higher proportion of male patients (43% [302 of 707] versus 36% [227 of 632]; p = 0.01), hip arthroplasties (36% [254 of 707] versus 29% [182 of 632]; p = 0.006), and patients receiving subcuticular closure (62% [441 of 707] versus 33% [208 of 631]; p < 0.001) in the enoxaparin group than in the aspirin group. Patients were monitored for wound drainage on each postoperative day until discharge, and this was recorded in the medical record once per day. Assessors were not blinded to the type of prophylaxis each patient received. Persistent wound drainage was defined as any wound drainage beyond Postoperative Day 3. For patients who experienced persistent wound drainage, the time taken to achieve a dry wound was defined as the number of days beyond Postoperative Day 3 for the wound to become dry. Logistic regression was used to determine whether the prophylaxis type was associated with persistent wound drainage. For patients with persistent wound drainage, the median time of drainage was compared between groups using the Kruskal-Wallis test. The number of patients undergoing a joint-related reoperation within 6 months was identified through data linkage to the Australian Orthopaedic Association National Joint Replacement Registry and electronic record review, and was compared using a Fisher exact test.

RESULTS

We found no difference between the enoxaparin and aspirin groups in terms of the percentage of patients who had persistent wound drainage (9% [65 of 707] versus 8% [49 of 632], odds ratio 1.2 [95% confidence interval 0.8 to 1.8]; p = 0.40). For patients receiving subcuticular closure, after controlling for other potentially confounding variables, including age, sex, BMI, preoperative anticoagulant use, and type of arthroplasty, enoxaparin was associated with a higher risk of persistent wound drainage than aspirin (OR 3.6 [95% CI 1.5 to 10.6]; p = 0.009). For patients receiving a skin staple closure, after controlling for the same variables above, we found enoxaparin was not associated with a higher risk of persistent wound drainage (OR 1.1 [95% CI 0.7 to 1.9]; p = 0.66). For patients who experienced persistent wound drainage patients (114: 65 in the enoxaparin group and 49 in the aspirin group), there was no difference in the median (interquartile range) time taken to achieve a dry wound (enoxaparin: 1 day [IQR 1 to 2 days], aspirin: 1 day [IQR 1 to 3 days]; p = 0.22). There was no difference in the risk of joint-related reoperation within 6 months between enoxaparin (2.4% [17 of 707]) and aspirin (2.2% [14 of 632], OR 1.1 [95% CI 0.5 to 2.4]; p = 0.86).

CONCLUSION

Enoxaparin was not associated with an increased risk of persistent wound drainage compared with aspirin for all patients included in this study. Enoxaparin may be associated with a higher risk of drainage for patients receiving subcuticular closure. However, this finding should be interpreted cautiously, given the small sample size in this analysis. The duration of drainage was short regardless of the prophylaxis used, and enoxaparin was not associated with an increased risk of joint-related reoperation. These findings should not deter clinicians from using enoxaparin for VTE prophylaxis after hip or knee arthroplasty.

LEVEL OF EVIDENCE

Level III, therapeutic study.

摘要

背景

由于与人工关节感染相关,全髋关节置换术(THA)或全膝关节置换术(TKA)后持续性伤口引流已成为一个重要的临床问题。静脉血栓栓塞症(VTE)预防与持续性伤口引流之间的关系尚未得到广泛报道,但具有重要的临床意义。

问题/目的:(1)髋关节置换术或膝关节置换术后使用的 VTE 预防类型(依诺肝素或阿司匹林)是否与更高的持续性伤口引流风险相关?(2)在经历持续性伤口引流的患者中,VTE 预防类型是否与伤口达到干燥所需的时间更长相关?(3)VTE 预防类型是否与 6 个月内与关节相关的再手术风险更高相关?

方法

这是对通过澳大利亚矫形协会全国关节置换登记处进行的一项早期聚类随机试验数据的二次分析;数据来自该研究的两个参与医院。根据试验的分配顺序,两个参与医院被随机分配至所有接受髋关节置换术的患者中,在术后 35 天内使用阿司匹林(每日 100 毫克)或依诺肝素(每日 40 毫克)作为 VTE 预防,在所有接受膝关节置换术的患者中,在术后 14 天内使用依诺肝素作为 VTE 预防。当第一组的入组目标达到后,就会发生从一种预防方法到另一种预防方法的交叉。在 2019 年 4 月至 2020 年 12 月期间,在符合条件的 1679 名患者中,有 1339 名(82% [707/861])被纳入本研究;707 名患者被分配至依诺肝素组,632 名患者被分配至阿司匹林组,依诺肝素组的平均年龄为 67 ± 10 岁,平均 BMI 为 32 ± 7 kg/m 2 。在依诺肝素组中,男性患者比例较高(43% [302/707]与 36% [227/632];p = 0.01),髋关节置换术比例较高(36% [254/707]与 29% [182/632];p = 0.006),接受皮内缝合的患者比例较高(62% [441/707]与 33% [208/631];p < 0.001)。在术后每天监测伤口引流,每天记录一次。评估人员未对每位患者接受的预防类型进行盲法评估。持续性伤口引流定义为术后第 3 天以后的任何伤口引流。对于经历持续性伤口引流的患者,伤口达到干燥的时间定义为术后第 3 天以后伤口达到干燥的天数。采用逻辑回归来确定预防类型是否与持续性伤口引流相关。对于经历持续性伤口引流的患者,使用 Kruskal-Wallis 检验比较两组之间的中位引流时间。通过与澳大利亚矫形协会全国关节置换登记处的数据链接和电子病历审查确定 6 个月内进行与关节相关的再手术的患者人数,并使用 Fisher 确切检验进行比较。

结果

我们发现依诺肝素组和阿司匹林组在持续性伤口引流的患者比例方面没有差异(9% [65/707]与 8% [49/632],比值比 1.2 [95%置信区间 0.8 至 1.8];p = 0.40)。对于接受皮内缝合的患者,在控制其他可能的混杂变量(包括年龄、性别、BMI、术前抗凝治疗和关节置换类型)后,依诺肝素与阿司匹林相比,持续性伤口引流的风险更高(比值比 3.6 [95%置信区间 1.5 至 10.6];p = 0.009)。对于接受皮肤钉合的患者,在控制上述所有变量后,我们发现依诺肝素与持续性伤口引流的风险无相关性(比值比 1.1 [95%置信区间 0.7 至 1.9];p = 0.66)。对于经历持续性伤口引流的患者(依诺肝素组 65 例,阿司匹林组 49 例),达到伤口干燥的中位(四分位间距)时间无差异(依诺肝素组:1 天 [四分位间距 1 至 2 天],阿司匹林组:1 天 [四分位间距 1 至 3 天];p = 0.22)。在 6 个月内与关节相关的再手术风险方面,依诺肝素组(2.4% [17/707])和阿司匹林组(2.2% [14/632])之间无差异(比值比 1.1 [95%置信区间 0.5 至 2.4];p = 0.86)。

结论

与所有纳入本研究的患者相比,依诺肝素并未增加持续性伤口引流的风险。对于接受皮内缝合的患者,依诺肝素可能与更高的引流风险相关。然而,鉴于本分析中样本量较小,这一发现应谨慎解释。无论使用何种预防措施,引流时间都很短,依诺肝素与关节相关的再手术风险增加无关。这些发现不应阻止临床医生在髋关节或膝关节置换术后使用依诺肝素进行 VTE 预防。

证据水平

III 级,治疗性研究。

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