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围手术期静脉ω-3 脂肪酸对结肠癌患者的影响:一项随机、双盲、安慰剂对照的临床试验。

Effects of perioperative intravenous ω-3 fatty acids in colon cancer patients: a randomized, double-blind, placebo-controlled clinical trial.

机构信息

Northwest Clinics Alkmaar, Alkmaar, Netherlands.

Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, Netherlands.

出版信息

Am J Clin Nutr. 2020 Feb 1;111(2):385-395. doi: 10.1093/ajcn/nqz281.

DOI:10.1093/ajcn/nqz281
PMID:31826232
Abstract

BACKGROUND

The postoperative inflammatory response contributes to tissue healing and recovery but overwhelming inflammation is associated with postoperative complications. n-3 (ω-3) PUFAs modulate inflammatory responses and may help to prevent a proinflammatory cascade.

OBJECTIVES

We aimed to investigate the effects of perioperative intravenous n-3 PUFAs on inflammatory cytokines in colon cancer surgery.

METHODS

This study is a randomized, double-blind, placebo-controlled clinical trial. Forty-four patients undergoing elective colon resection for nonmetastasized cancer were randomly assigned to 2 intravenous n-3 PUFA or saline control infusions the night before and the morning after surgery. Blood was sampled at 6 perioperative time points for changes in cytokines in serum and in LPS-stimulated whole blood samples and leukocyte membrane fatty acid profiles.

RESULTS

Twenty-three patients received saline and 21 patients received n-3 PUFAs. Patient and operation characteristics were equal between groups, except for open resection (saline n = 5 compared with n-3 PUFA n = 0, P = 0.056). Ex-vivo IL-6 after LPS stimulation was significantly higher in the n-3 PUFA group at the first day after surgery (P = 0.014), but not different at the second day after surgery (P = 0.467). White blood cell count was higher in the n-3 PUFA group at the fourth day after surgery (P = 0.029). There were more patients with infectious complications in the n-3 PUFA group (8 compared with 3, P = 0.036). There were no overall differences in serum IL-6, IL-10, C-reactive protein, and length of stay. The administration of n-3 PUFAs resulted in rapid increases in leukocyte membrane n-3 PUFA content.

CONCLUSIONS

In the n-3 PUFA group a clear relation with serum and LPS-stimulated cytokines was not found but, unexpectedly, more infectious complications occurred. Caution is thus required with the off-label use of a perioperative intravenous n-3 PUFA emulsion as a standalone infusion in the time sequence reported in the present study in colon resections with primary anastomosis. This trial was registered at clinicaltrials.gov as NCT02231203.

摘要

背景

术后炎症反应有助于组织愈合和恢复,但过度炎症与术后并发症有关。n-3(ω-3)多不饱和脂肪酸可调节炎症反应,有助于预防促炎级联反应。

目的

本研究旨在探讨围手术期静脉内 n-3 多不饱和脂肪酸对结肠癌手术中炎症细胞因子的影响。

方法

这是一项随机、双盲、安慰剂对照的临床试验。44 例接受择期结肠癌切除术的非转移性癌症患者被随机分配至静脉内 n-3 多不饱和脂肪酸或生理盐水对照组,于术前一晚和术后次日晨输注。在 6 个围手术期时间点采集血清和脂多糖刺激全血样本中的细胞因子变化及白细胞膜脂肪酸谱。

结果

23 例患者接受生理盐水,21 例患者接受 n-3 多不饱和脂肪酸。两组患者和手术特点相同,除开腹手术(生理盐水组 n=5,n-3 多不饱和脂肪酸组 n=0,P=0.056)。术后第一天,n-3 多不饱和脂肪酸组经脂多糖刺激后的白细胞介素-6(IL-6)明显升高(P=0.014),但术后第二天差异无统计学意义(P=0.467)。术后第四天,n-3 多不饱和脂肪酸组的白细胞计数较高(P=0.029)。n-3 多不饱和脂肪酸组感染并发症患者较多(8 例对比 3 例,P=0.036)。血清白细胞介素-6、白细胞介素-10、C 反应蛋白和住院时间无总体差异。n-3 多不饱和脂肪酸的给予导致白细胞膜 n-3 多不饱和脂肪酸含量迅速增加。

结论

在 n-3 多不饱和脂肪酸组,并未发现血清和脂多糖刺激的细胞因子之间存在明确的关系,但出乎意料的是,感染并发症更多。因此,在本研究报告的时间序列中,在结肠吻合术的原发性吻合中,不建议将围手术期静脉内 n-3 多不饱和脂肪酸乳剂作为单一药物使用。本试验在 clinicaltrials.gov 上注册,编号为 NCT02231203。

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