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心脏及心肺移植中类固醇的应用:时机是否恰当?

Steroid administration in heart and heart-lung transplantation: is the timing adequate?

作者信息

Wan S, DeSmet J M, Antoine M, Goldman M, Vincent J L, LeClerc J L

机构信息

Department of Cardiac Surgery, University Hospital Erasme, Free University of Brussels, Belgium, USA.

出版信息

Ann Thorac Surg. 1996 Feb;61(2):674-8. doi: 10.1016/0003-4975(95)01059-9.

DOI:10.1016/0003-4975(95)01059-9
PMID:8572786
Abstract

BACKGROUND

The release of cytokines after cardiopulmonary bypass may play an important role in postoperative morbidity. The release of proinflammatory cytokines, such as tumor necrosis factor alpha, interleukin (IL)-6 and IL-8, is even greater in patients undergoing heart transplantation (HTx) than coronary artery grafting. We tested the hypothesis that in HTx patients the earlier administration of steroids, before rather than after cardiopulmonary bypass as usual, can reduce the inflammatory response.

METHODS

In 20 consecutive patients who underwent HTx or heart-lung transplantation (HLTx), plasma levels of tumor necrosis factor alpha, IL-6, IL-8, and anti-inflammatory cytokine IL-10 were measured before heparin administration, at aortic cross-clamping and declamping, and 0.5, 1, 1.5, 2, 4, 12, and 24 hours after aortic declamping. In 10 patients (group I, 6 HTx and 4 HLTx), 500 mg of methylprednisolone was first given as usual at 1.5 hours after aortic declamping (at the end of cardiopulmonary bypass). In the next 10 patients (group II, 6 HTx and 4 HLTx), the first doses of methylprednisolone were given 1 hour before operation. In both groups, 125 mg of methylprednisolone were given every 8 hours thereafter during the first postoperative day.

RESULTS

The ischemic time and cardiopulmonary bypass time were similar in the two groups (166 +/- 16 minutes versus 157 +/- 13 minutes, and 192 +/- 21 minutes versus 186 +/- 20 minutes, respectively, mean +/- standard error of the mean). At 30 minutes after aortic declamping and throughout the next 4 hours, tumor necrosis factor alpha levels were significantly lower in group II than in group I (all p < 0.03). Interleukin-8 values 1 hour after declamping were also lower in group II than in group I (49 +/- 15 pg/mL versus 130 +/- 38 pg/mL, p < 0.02). Interleukin-10 levels were significantly higher in group II than in group I from 30 minutes after declamping through 2 hours after (all p < 0.03). Interleukin-6 levels were similar in the two groups.

CONCLUSIONS

Earlier steroid administration in the immunosuppressive protocol for HTx or HLTx may be preferable to reduce the inflammatory response to cardiopulmonary bypass, as reflected by a lower production of tumor necrosis factor alpha and IL-8, and a greater release of IL-10.

摘要

背景

体外循环后细胞因子的释放可能在术后发病中起重要作用。在心脏移植(HTx)患者中,促炎细胞因子如肿瘤坏死因子α、白细胞介素(IL)-6和IL-8的释放甚至比冠状动脉搭桥术患者更多。我们检验了这样一个假设:在HTx患者中,在体外循环前而非像往常一样在体外循环后更早给予类固醇,可以减轻炎症反应。

方法

在连续20例接受HTx或心肺移植(HLTx)的患者中,在肝素给药前、主动脉阻断和开放时以及主动脉开放后0.5、1、1.5、2、4、12和24小时测量血浆中肿瘤坏死因子α、IL-6、IL-8和抗炎细胞因子IL-10的水平。在10例患者(I组,6例HTx和4例HLTx)中,在主动脉开放后1.5小时(体外循环结束时)像往常一样首先给予500mg甲泼尼龙。在接下来的10例患者(II组,6例HTx和4例HLTx)中,在手术前1小时给予第一剂甲泼尼龙。在两组中,术后第一天期间此后每8小时给予125mg甲泼尼龙。

结果

两组的缺血时间和体外循环时间相似(分别为166±16分钟对157±13分钟,以及192±21分钟对186±20分钟,均值±均值标准误)。在主动脉开放后30分钟及接下来的4小时内,II组的肿瘤坏死因子α水平显著低于I组(所有p<0.03)。开放后1小时的白细胞介素-8值II组也低于I组(49±15pg/mL对130±38pg/mL,p<0.02)。从开放后30分钟到开放后2小时,II组的白细胞介素-10水平显著高于I组(所有p<0.03)。两组的白细胞介素-6水平相似。

结论

在HTx或HLTx的免疫抑制方案中更早给予类固醇可能更有利于减轻对体外循环的炎症反应,这表现为肿瘤坏死因子α和IL-8产生减少以及IL-10释放增加。

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