Septic shock is a life-threatening condition that challenges immune cells to reprogram their mitochondrial metabolism towards to increase ATP synthesis for building an appropriate immunity. This could print metabolic signatures in mitochondria whose association with disease progression and clinical outcomes remain elusive. This is a single-center prospective cohort study performed in the ICU of one tertiary referral hospital in Brazil. Between November 2017 and July 2018, 90 consecutive patients, aged 18 years or older, admitted to the ICU with septic shock were enrolled. Seventy-five patients had Simplified Acute Physiology Score (SAPS 3) assessed at admission, and Sequential Organ Failure Assessment (SOFA) assessed on the first (D1) and third (D3) days after admission. Mitochondrial respiration linked to complexes I, II, V, and biochemical coupling efficiency (BCE) were assessed at D1 and D3 and Δ (D3–D1) in isolated lymphocytes. Clinical and mitochondrial endpoints were used to dichotomize the survival and death outcomes. Our primary outcome was 6-month mortality, and secondary outcomes were ICU and hospital ward mortality. The mean SAPS 3 and SOFA scores at septic shock diagnosis were 75.8 (± 12.9) and 8 (± 3) points, respectively. The cumulative ICU, hospital ward, and 6-month mortality were 32 (45%), 43 (57%), and 50 (66%), respectively. At the ICU, non-surviving patients presented elevated arterial lactate (2.8 mmol/L, IQR, 2–4), C-reactive protein (220 mg/L, IQR, 119–284), and capillary refill time (5.5 s, IQR, 3–8). Respiratory rates linked to CII at D1 and D3, and ΔCII were decreased in non-surviving patients. Also, the BCE at D1 and D3 and the ΔBCE discriminated patients who would evolve to death in the ICU, hospital ward, and 6 months after admission. After adjusting for possible confounders, the ΔBCE value but not SOFA scores was independently associated with 6-month mortality (RR 0.38, CI 95% 0.18–0.78; P = 0.009). At a cut-off of − 0.002, ΔBCE displayed 100% sensitivity and 73% specificity for predicting 6-month mortality The ΔBCE signature in lymphocytes provided an earlier recognition of septic shock patients in the ICU at risk of long-term deterioration of health status.

中文翻译：

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感染性休克患者的死亡率与淋巴细胞线粒体氧化偶联效率受损有关：一项前瞻性队列研究

感染性休克是一种危及生命的疾病，它挑战免疫细胞重新编程其线粒体代谢，以增加 ATP 合成以建立适当的免疫力。这可以在线粒体中打印代谢特征，其与疾病进展和临床结果的关联仍然难以捉摸。这是在巴西一家三级转诊医院的 ICU 中进行的单中心前瞻性队列研究。2017 年 11 月至 2018 年 7 月期间，连续招募了 90 名年龄在 18 岁或以上、因感染性休克入住 ICU 的患者。75 名患者在入院时进行了简化急性生理学评分 (SAPS 3) 评估，并在入院后第一天 (D1) 和第三天 (D3) 评估了顺序器官衰竭评估 (SOFA)。线粒体呼吸与复合物 I、II、V、在分离的淋巴细胞中在 D1 和 D3 和 Δ（D3-D1）评估和生化偶联效率（BCE）。临床和线粒体终点用于区分生存和死亡结果。我们的主要结果是 6 个月死亡率，次要结果是 ICU 和医院病房死亡率。感染性休克诊断时的平均 SAPS 3 和 SOFA 评分分别为 75.8 (± 12.9) 和 8 (± 3) 分。ICU、医院病房和 6 个月的累计死亡率分别为 32 (45%)、43 (57%) 和 50 (66%)。在 ICU，未存活的患者出现动脉乳酸升高（2.8 mmol/L，IQR，2–4）、C 反应蛋白（220 mg/L，IQR，119–284）和毛细血管再充盈时间（5.5 秒， IQR，3-8）。在第 1 天和第 3 天，与 CII 相关的呼吸频率和未存活患者的 ΔCII 降低。还，D1 和 D3 的 BCE 和 ΔBCE 区分了在 ICU、医院病房和入院 6 个月后将演变为死亡的患者。调整可能的混杂因素后，ΔBCE 值而非 SOFA 评分与 6 个月死亡率独立相关（RR 0.38，CI 95% 0.18–0.78；P = 0.009）。在 - 0.002 的临界值下，ΔBCE 在预测 6 个月死亡率方面表现出 100% 的敏感性和 73% 的特异性淋巴细胞中的 ΔBCE 特征提供了对 ICU 中存在健康状况长期恶化风险的感染性休克患者的早期识别.