COVID-19 recovery: potential treatments for post-intensive care syndrome.
COVID-19 recovery: potential treatments for post-intensive care syndrome.
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DOI：
10.1016/s2213-2600(20)30457-4
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发表时间：
2020-11
期刊：
影响因子：
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通讯作者：
Parekh D
中科院分区：
文献类型：
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作者：
Bangash MN;Owen A;Alderman JE;Chotalia M;Patel JM;Parekh D
评论1072 www.柳叶刀。 com/respiratory Vol 8 十一月 2020 和评估器官功能障碍和组织损伤的剂量反应（疾病剂量与发病反应）的研究表明，在这种危重疾病期间可能会发生多个器官系统的不利的长期重新编程。 1 幸存下来的人体重减轻，身体虚弱，通常还伴有认知障碍。不同组织区室的体重恢复会出现滞后现象，代谢控制常常受到干扰，受影响的个体通常会出现 2 型糖尿病和脂肪增加的情况。器官在急性炎症时会遭受微观损伤，并且修复不完善，急性肾损伤和心血管功能障碍会转变为慢性肾脏疾病和重症监护病房后的主要不良心脏事件。 1 这些过程发生在低度炎症和功能性免疫抑制的背景下，这使得进入 ICU 后幸存的个体，尤其是 PICS 患者，容易发生继发感染。 2 虽然体力活动可以对抗久坐的促炎作用，但针对残余炎症的强化恢复计划并未转化为益处，这表明药物干预具有潜在作用。 3 如果长期危重疾病（包括与 COVID-19 相关的疾病）导致患者出现慢性炎症、血栓形成和纤维化，这些过程的拮抗剂可能对幸存者有益。 CANTOS 试验表明，在使用白细胞介素 1β (IL-1β) 单克隆抗体卡那单抗进行二级预防治疗时，有低度炎症证据的群体中主要不良心脏事件、肺癌和贫血的发生率有所降低。 4 然而，我们认为重症监护专业尚不具备在 ICU 幸存者中进行此类强效抗炎药物的大规模试验。 CANTOS 和 COLCOT 试验表明，减少 IL-1β 相关炎症会增加感染风险，这是功能性免疫抑制的 PICS 人群中的一个重要考虑因素。 2 然而，其他具有良好临床原理和出色安全性的成熟心脏代谢疗法已经存在，并且为 ICU 幸存者带来了巨大希望。这些药物处于最佳位置，可以立即在大量与 COVID-19 相关的 PICS 患者中进行试验，此类研究可能有助于更好地了解谁（如果有的话）可能受益于 IL-1β 靶向治疗。非随5 SSCILL 试验旨在测试是否可以在这组 PICS 患者中使用具有疑似抗炎和已知抗纤维化作用的 RAAS 调节剂，以减少主要不良心脏事件。 6 然而，在积累 PICS 生物学数据的同时，也应该试验其他药物，包括 RAAS 调节剂。在高敏 C 反应蛋白 (CRP) 升高的健康患者和无动脉粥样硬化的老年患者（> 75 岁）中进行的他汀类药物试验表明，低风险药物如何降低心血管风险、高敏 C 反应蛋白以及肺炎和深静脉血栓形成的发生率，这些药物除其他外还可以增加
Comment1072 www. thelancet. com/respiratory Vol 8 November 2020 and studies assessing dose–responses (dose of illness vs response of morbidity) of organ dysfunction and tissue injury, suggest that an adverse long-term reprogramming of multiple organ systems can occur during such critical illness. 1 People who survive lose weight and are debilitated, often with cognitive impairments. A hysteresis of body-mass recovery in different tissue compartments occurs and metabolic control is often disrupted, with the development of type 2 diabetes and adipose gain commonly reported in affected individuals. Organs undergo microscopic damage at the time of acute inflammation and display imperfect repair, with acute kidney injury and cardiovascular dysfunction transitioning to chronic kidney disease and post-ICU major adverse cardiac events. 1 These processes occur in the context of low-grade inflammation and functional immunosuppression, which predisposes individuals who survive admission to ICU, and particularly those with PICS, to secondary infections. 2 Although physical activity counters the proinflammatory effects of sedentarism, enhanced recovery programmes against a backdrop of residual inflammation have not translated to benefit, suggesting a potential role for pharmacological intervention. 3 If prolonged critical illness, including that associated with COVID-19, causes patients to develop chronic inflammation, thrombosis, and fibrosis, antagonists of these processes might be beneficial for survivors. The CANTOS trial showed that major adverse cardiac events, lung cancer, and anaemia rates were reduced in groups with evidence of low-grade inflammation when treated for secondary prevention with the interleukin-1β (IL-1β) monoclonal antibody canakinumab. 4 However, our opinion is that the critical care specialty is not yet in a position to conduct large-scale trials of such powerful anti-inflammatory drugs in ICU survivors. The CANTOS and COLCOT trials showed that reducing IL-1β-related inflammation increases infection risk, an important consideration in the functionally immuno suppressed PICS population. 2 However, other established cardiometabolic therapeutics with good clinical rationale and excellent safety profiles already exist and hold great promise for ICU survivors. These drugs are in a prime position to be trialled immediately in large numbers of patients with COVID-19-associated PICS, and such studies might provide a better understanding of who, if anyone, might benefit from IL-1β targeting. Non-randomised studies suggest that renin–angiotensin–aldosterone system (RAAS) inhibitors reduce mortality after discharge from the ICU in people who had critical illness with acute kidney injury, whereas preclinical studies suggest a potentially beneficial modulation of frailty in models of ageassociated frailty. 5 The SSCILL trial aims to test whether a RAAS modulator with suspected anti-inflammatory and known antifibrotic effects could be used in this group of patients with PICS to reduce major adverse cardiac events. 6 However, other drugs, including RAAS modulators, should also be trialled while data for PICS biology accumulates. Statin trials in healthy patients with elevated high-sensitivity C-reactive protein (CRP) and older patients (> 75 years) without atherosclerosis show how reductions in cardiovascular risk, highsensitivity CRP, and rates of pneumonia and deep vein thrombosis can be achieved with low-risk drugs that, among other things, increase concentrations of