Nederlof Rianne, Weber Nina C, Juffermans Nicole P, de Mol Bas A M J, Hollmann Markus W, Preckel Benedikt, Zuurbier Coert J
Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Department of Anesthesiology, Academic Medical Center, Amsterdam, The Netherlands.
Laboratory of Experimental Intensive Care and Anesthesiology (L.E.I.C.A.), Department of Intensive Care Medicine, Academic Medical Center, Amsterdam, The Netherlands.
BMC Anesthesiol. 2017 Mar 29;17(1):51. doi: 10.1186/s12871-017-0330-6.
Remote ischemic preconditioning (RIPC) efficacy is debated. Possibly, because propofol, which has a RIPC-inhibiting action, is used in most RIPC trials. It has been suggested that clinical efficacy is, however, present with volatile anesthesia in the absence of propofol, although this is based on one phase 1 trial only. Therefore, in the present study we further explore the relation between RIPC and cardioprotection with perioperative anesthesia restricted to sevoflurane and fentanyl, in CABG patients without concomitant procedures.
In a single-center study, we aimed to randomize 46 patients to either RIPC (3x5 min inflation of a blood pressure cuff around the arm) or control treatment (deflated cuff around the arm). Blood samples were obtained before and after RIPC to evaluate potential RIPC-induced mediators (Interleukin (IL)-6, IL-10, Tumor Necrosis Factor-α, Macrophage Inhibitory Factor). An atrial tissue sample was obtained at cannulation of the appendix of the right atrium for determination of mitochondrial bound hexokinase II (mtHKII) and other survival proteins (Akt and AMP-activated protein kinase α). In blood samples taken before and 6, 12 and 24 h after surgery cardiac troponin T (cTnT) and C-reactive protein (CRP) were determined. Surgery was strictly performed under sevoflurane anesthesia (no propofol).
We actually randomized 16 patients to control treatment and 13 patients to RIPC. The mean 24 h area under the curve (AUC) cTnT was 11.44 (standard deviation 4.66) in the control group and 10.90 (standard deviation 4.73) in the RIPC group (mean difference 0.54, 95% CI -3.06 to 4.13; p = 0.76). The mean 24 h AUC CRP was 1319 (standard deviation 92) in the control group and 1273 (standard deviation 141) in the RIPC group (mean difference 46.2, 95% CI -288 to 380; p = 0.78). RIPC was without effect on survival proteins in atrial tissue samples obtained before surgery (mitochondrial hexokinase, Akt and AMPK) and inflammatory mediators obtained before and immediately after RIPC (IL-6, IL-10, TNF-α, macrophage migration inhibitory factor).
Many factors can interfere with the outcome of RIPC. Trying to correct for this led to strict inclusion criteria, which, in combination with a decreased institutional frequency of CABG without concomitant procedures and a change in institutional anesthetic regimen away from volatile anesthetics towards total intravenous anesthesia, caused slow inclusion and halting of this trial after 3 years, before target inclusion could be reached. Therefore this study is underpowered to prove its primary goal that RIPC reduced AUC cTnT by < 25%. Nevertheless, we have shown that the effect of RIPC on 24 h AUC cTnT, in cardiac surgery with anesthesia during surgery restricted to sevoflurane/fentanyl (no propofol), was between a decrease of 27% and an increase of 36%. These findings are not in line with previous studies in this field.
The Netherlands Trial Register: NTR2915 ; Registered 25 Mei 2011.
远程缺血预处理（RIPC）的疗效存在争议。可能是因为在大多数RIPC试验中使用了具有RIPC抑制作用的丙泊酚。然而，有人提出，在没有丙泊酚的情况下使用挥发性麻醉时临床疗效是存在的，尽管这仅基于一项1期试验。因此，在本研究中，我们进一步探讨了在不进行同期手术的冠状动脉旁路移植术（CABG）患者中，将围手术期麻醉限制于七氟醚和芬太尼时RIPC与心脏保护之间的关系。
在一项单中心研究中，我们旨在将46例患者随机分为RIPC组（用血压袖带在手臂上充气3次，每次5分钟）或对照组（手臂上的袖带放气）。在RIPC前后采集血样，以评估潜在的RIPC诱导介质（白细胞介素（IL）-6、IL-10、肿瘤坏死因子-α、巨噬细胞抑制因子）。在右心耳插管时获取心房组织样本，以测定线粒体结合己糖激酶II（mtHKII）和其他存活蛋白（Akt和AMP激活的蛋白激酶α）。在手术前以及手术后6、12和24小时采集的血样中测定心肌肌钙蛋白T（cTnT）和C反应蛋白（CRP）。手术严格在七氟醚麻醉下进行（不使用丙泊酚）。
我们实际上将16例患者随机分为对照组，13例患者随机分为RIPC组。对照组24小时曲线下面积（AUC）cTnT的平均值为11.44（标准差4.66），RIPC组为10.90（标准差4.73）（平均差异0.54，95%CI -3.06至4.13；p = 0.76）。对照组24小时AUC CRP的平均值为1319（标准差92），RIPC组为1273（标准差141）（平均差异46.2，95%CI -288至380；p = 0.78）。RIPC对手术前获取的心房组织样本中的存活蛋白（线粒体己糖激酶、Akt和AMPK）以及RIPC前后即刻获取的炎症介质（IL-6、IL-10、TNF-α和巨噬细胞迁移抑制因子）没有影响。
许多因素可能会干扰RIPC的结果。试图对此进行纠正导致了严格的纳入标准，这与不进行同期手术的CABG机构发生率降低以及机构麻醉方案从挥发性麻醉转向全静脉麻醉相结合，导致入组缓慢，并在3年后在达到目标入组人数之前停止了该试验。因此，本研究的效能不足以证明其主要目标，即RIPC使AUC cTnT降低<25%。尽管如此，我们已经表明，在手术麻醉仅限于七氟醚/芬太尼（不使用丙泊酚）的心脏手术中，RIPC对24小时AUC cTnT的影响在降低27%至增加36%之间。这些发现与该领域以前的研究不一致。
荷兰试验注册库：NTR2915；2011年5月25日注册。
