Bro-Jeppesen John, Kjaergaard Jesper, Wanscher Michael, Nielsen Niklas, Friberg Hans, Bjerre Mette, Hassager Christian
1Department of Cardiology, The Heart Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 2Department of Cardiology, Aarhus University Hospital, Skejby, Denmark. 3Department of Cardiothoracic Anaesthesia, The Heart Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 4Department of Anesthesia and Intensive Care, Lund University, Helsingborg Hospital, Helsingborg, Sweden. 5Department of Anesthesia and Intensive Care, Skåne University Hospital, Lund University, Lund, Sweden. 6The Medical Research Laboratory, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Crit Care Med. 2015 Jun;43(6):1223-32. doi: 10.1097/CCM.0000000000000937.
Whole-body ischemia during out-of-hospital cardiac arrest triggers immediate activation of inflammatory systems leading to a sepsis-like syndrome. The aim was to investigate the association between level of systemic inflammation and mortality in survivors after out-of-hospital cardiac arrest treated with targeted temperature management.
Post hoc analysis.
Single-center study of a prospective multicenter randomized study.
One hundred sixty-nine patients (99%) with available blood samples out of 171 patients included in the Target Temperature Management trial, randomly assigning patients to targeted temperature management at 33°C or 36°C.
None.
At baseline and 24, 48, and 72 hours after out-of-hospital cardiac arrest, blood samples were obtained and screened for a battery of inflammatory markers. Level of interleukin-1β, interleukin-2, interleukin-4, interleukin-5, interleukin-6, interleukin-9, interleukin-10, interleukin-12, interleukin-13, tumor necrosis factor-α, interferon-γ, C-reactive protein, and procalcitonin were measured. Mortality at 30 days was evaluated by Cox analysis, and the predictive capability of inflammatory markers was evaluated by area under the curve. Level of all inflammatory markers changed significantly within 72 hours after out-of-hospital cardiac arrest (all p values<0.001), but only procalcitonin levels showed overall differences between nonsurvivors and survivors (p=0.0002). At baseline, interleukin-6 was independently associated with mortality, whereas both interleukin-6 levels (hazard ratio=1.23 [1.01-1.49]; p=0.04) and procalcitonin levels (hazard ratio=1.20 [1.03-1.39]; p=0.02) 24 hours after out-of-hospital cardiac arrest were associated with 30-day mortality with no interactions between targeted temperature management group and levels of interleukin-6 (p=0.25) or procalcitonin (p=0.85). None of the other inflammatory markers were independently associated with mortality. Area under the curve for procalcitonin and interleukin-6, 24 hours after out-of-hospital cardiac arrest, were 0.74 and 0.63, respectively.
Level of inflammation, assessed by interleukin-6 and procalcitonin, was independently associated with increased mortality with the highest discriminative value obtained 24 hours after out-of-hospital cardiac arrest. Interventions aiming at decreasing level of inflammation as a way to improve outcome may be investigated in future studies.
院外心脏骤停期间的全身缺血会引发炎症系统的立即激活，导致类似脓毒症的综合征。本研究旨在探讨在接受目标温度管理治疗的院外心脏骤停幸存者中，全身炎症水平与死亡率之间的关联。
事后分析。
一项前瞻性多中心随机研究的单中心研究。
目标温度管理试验纳入的171例患者中有169例（99%）有可用血样，这些患者被随机分配至33°C或36°C的目标温度管理组。
无。
在院外心脏骤停后的基线、24、48和72小时采集血样，并检测一系列炎症标志物。检测白细胞介素-1β、白细胞介素-2、白细胞介素-4、白细胞介素-5、白细胞介素-6、白细胞介素-9、白细胞介素-10、白细胞介素-12、白细胞介素-13、肿瘤坏死因子-α、干扰素-γ、C反应蛋白和降钙素原的水平。通过Cox分析评估30天死亡率，并通过曲线下面积评估炎症标志物的预测能力。院外心脏骤停后72小时内，所有炎症标志物水平均有显著变化（所有p值<0.001），但只有降钙素原水平在非幸存者和幸存者之间存在总体差异（p = 0.0002）。基线时，白细胞介素-6与死亡率独立相关，而院外心脏骤停后24小时的白细胞介素-6水平（风险比=1.23 [1.01 - 1.49]；p = 0.04）和降钙素原水平（风险比=1.20 [1.03 - 1.39]；p = 0.02）均与30天死亡率相关，目标温度管理组与白细胞介素-6水平（p = 0.25）或降钙素原水平（p = 0.85）之间无相互作用。其他炎症标志物均与死亡率无独立相关性。院外心脏骤停后24小时，降钙素原和白细胞介素-6的曲线下面积分别为0.74和0.63。
通过白细胞介素-6和降钙素原评估的炎症水平与死亡率增加独立相关，院外心脏骤停后24小时获得的判别价值最高。未来研究可探讨旨在降低炎症水平以改善预后的干预措施。
