Section of Anaesthetics, Pain Medicine and Intensive Care Medicine, Department of Surgery and Cancer, Imperial College London and Imperial College Healthcare NHS Trust, London, UK.
Imperial Clinical Trials Unit, Imperial College London, London, UK.
Intensive Care Med. 2019 Oct;45(10):1392-1400. doi: 10.1007/s00134-019-05731-w. Epub 2019 Aug 19.
Myocardial dysfunction is common in sepsis but optimal treatment strategies are unclear. The inodilator, levosimendan was suggested as a possible therapy; however, the levosimendan to prevent acute organ dysfunction in Sepsis (LeoPARDS) trial found it to have no benefit in reducing organ dysfunction in septic shock. In this study we evaluated the effects of levosimendan in patients with and without biochemical cardiac dysfunction and examined its non-inotropic effects.
Two cardiac biomarkers, troponin I (cTnI) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and five inflammatory mediators were measured in plasma from patients recruited to the LeoPARDS trial at baseline and over the first 6 days. Mean total Sequential Organ Failure Assessment (SOFA) score and 28-day mortality were compared between patients with normal and raised cTnI and NT-proBNP values, and between patients above and below median values.
Levosimendan produced no benefit in SOFA score or 28-day mortality in patients with cardiac dysfunction. There was a statistically significant treatment by subgroup interaction (p = 0.04) in patients with NT-proBNP above or below the median value. Those with NT-proBNP values above the median receiving levosimendan had higher SOFA scores than those receiving placebo (mean daily total SOFA score 7.64 (4.41) vs 6.09 (3.88), mean difference 1.55, 95% CI 0.43-2.68). Levosimendan had no effect on the rate of decline of inflammatory biomarkers.
Adding levosimendan to standard care in septic shock was not associated with less severe organ dysfunction nor lower mortality in patients with biochemical evidence of cardiac dysfunction.
脓毒症常伴有心肌功能障碍，但最佳治疗策略仍不明确。正性肌力药物左西孟旦被认为是一种可能的治疗方法；然而，左西孟旦预防脓毒症急性器官功能障碍（LeoPARDS）试验发现，它并不能降低脓毒性休克患者器官功能障碍的发生率。在这项研究中，我们评估了左西孟旦在伴有和不伴有生化性心肌功能障碍患者中的作用，并研究了其非正性肌力作用。
在 LeoPARDS 试验中，我们在基线和前 6 天测量了招募患者的血浆中两种心脏生物标志物肌钙蛋白 I（cTnI）和脑钠肽前体 N 末端（NT-proBNP），以及五种炎症介质。比较 cTnI 和 NT-proBNP 值正常和升高患者、炎症介质高于和低于中位数患者的平均总序贯器官衰竭评估（SOFA）评分和 28 天死亡率。
在伴有心肌功能障碍的患者中，左西孟旦并未改善 SOFA 评分或 28 天死亡率。在 NT-proBNP 值高于或低于中位数的患者中，治疗与亚组之间存在显著的交互作用（p=0.04）。与接受安慰剂的患者相比，接受左西孟旦的 NT-proBNP 值高于中位数的患者 SOFA 评分更高（平均每日总 SOFA 评分 7.64（4.41）vs 6.09（3.88），平均差值 1.55，95%CI 0.43-2.68）。左西孟旦对炎症生物标志物下降速度无影响。
在伴有生化心肌功能障碍证据的脓毒性休克患者中，在标准治疗的基础上加用左西孟旦与更严重的器官功能障碍或更低的死亡率无关。
