1Division of Critical Care Medicine, Department of Anesthesia and Critical Care, The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. 2Department of Emergency Medicine, Center for Resuscitation Science, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. 3Flow Cytometry Research Core, The Children's Hospital of Philadelphia Research Institute, Philadelphia, PA. 4Department of Anesthesiology and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA. 5Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA.
Pediatr Crit Care Med. 2015 Jan;16(1):e4-e12. doi: 10.1097/PCC.0000000000000277.
Mitochondrial dysfunction in peripheral blood mononuclear cells has been linked to immune dysregulation and organ failure in adult sepsis, but pediatric data are limited. We hypothesized that pediatric septic shock patients exhibit mitochondrial dysfunction within peripheral blood mononuclear cells which in turn correlates with global organ injury.
Prospective observational study.
Academic PICU.
Thirteen pediatric patients with septic shock and greater than or equal to two organ failures and 11 PICU controls without sepsis or organ failure.
Ex vivo measurements of mitochondrial oxygen consumption and membrane potential (ΔΨm) were performed in intact peripheral blood mononuclear cells on day 1-2 and day 5-7 of septic illness and in controls. The Pediatric Logistic Organ Dysfunction score, inotrope score, and organ failure-free days were determined from medical records.
Spare respiratory capacity, an index of bioenergetic reserve, was lower in septic peripheral blood mononuclear cells on day 1-2 (median, 1.81; interquartile range, 0.52-2.09 pmol O2/s/10 cells) compared with controls (5.55; 2.80-7.21; p = 0.03). Spare respiratory capacity normalized by day 5-7. Patients with sepsis on day 1-2 exhibited a higher ratio of LEAK to maximal respiration than controls (17% vs < 1%; p = 0.047) with normalization by day 5-7 (1%; p = 0.008), suggesting mitochondrial uncoupling early in sepsis. However, septic peripheral blood mononuclear cells exhibited no differences in basal or adenosine triphosphate-linked oxygen consumption or ΔΨm. Oxygen consumption did not correlate with Pediatric Logistic Organ Dysfunction score, inotrope score, or organ failure-free days (all p > 0.05). Although there was a weak overall association between ΔΨm on day 1-2 and organ failure-free days (Spearman ρ = 0.56, p = 0.06), patients with sepsis with normal organ function by day 7 exhibited higher ΔΨm on day 1-2 compared with patients with organ failure for more than 7 days (p = 0.04).
Mitochondrial dysfunction was present in peripheral blood mononuclear cells in pediatric sepsis, evidenced by decreased bioenergetic reserve and increased uncoupling. Mitochondrial membrane potential, but not respiration, was associated with duration of organ injury.
外周血单个核细胞中线粒体功能障碍与成人脓毒症的免疫失调和器官衰竭有关，但儿科数据有限。我们假设儿科脓毒性休克患者外周血单个核细胞中线粒体功能障碍，进而与全身器官损伤相关。
前瞻性观察性研究。
学术性儿科重症监护病房（PICU）。
13 名患有脓毒性休克和≥2 个器官衰竭的儿科患者，以及 11 名无脓毒症或器官衰竭的儿科 PICU 对照者。
在脓毒症发病第 1-2 天和第 5-7 天以及对照者中，对完整的外周血单个核细胞进行线粒体耗氧量和膜电位（ΔΨm）的体外测量。从病历中确定儿科逻辑器官功能障碍评分、儿茶酚胺评分和器官衰竭无天数。
与对照者（中位数 5.55；2.80-7.21；p = 0.03）相比，脓毒症外周血单个核细胞在第 1-2 天的备用呼吸能力（生物能量储备的一个指标）较低（中位数 1.81；四分位距 0.52-2.09 pmol O2/s/10 细胞）。第 5-7 天患者备用呼吸能力恢复正常。第 1-2 天患有脓毒症的患者的 LEAK 与最大呼吸的比值高于对照者（17%对<1%；p = 0.047），第 5-7 天恢复正常（p = 0.008），提示脓毒症早期线粒体解偶联。然而，脓毒症外周血单个核细胞在基础或三磷酸腺苷（adenosine triphosphate，ATP）连接的耗氧量或 ΔΨm 方面无差异。氧耗量与儿科逻辑器官功能障碍评分、儿茶酚胺评分或器官衰竭无天数无相关性（均 p > 0.05）。尽管第 1-2 天的 ΔΨm 与器官衰竭无天数之间存在总体较弱的相关性（Spearman ρ = 0.56，p = 0.06），但第 7 天器官功能正常的脓毒症患者在第 1-2 天的 ΔΨm 高于器官衰竭超过 7 天的患者（p = 0.04）。
儿科脓毒症患者外周血单个核细胞中线粒体功能障碍，表现为生物能量储备减少和解偶联增加。线粒体膜电位，而不是呼吸，与器官损伤的持续时间有关。
