William Harvey Research Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, UK; Homerton College, University of Cambridge, Cambridge, UK; Birmingham Acute Care Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
Institute of Applied Health Research, University of Birmingham, Birmingham, UK.
Br J Anaesth. 2024 Sep;133(3):538-549. doi: 10.1016/j.bja.2024.03.038. Epub 2024 Apr 30.
Persistent inflammation, immunosuppression, and catabolism syndrome (PICS) has been proposed as an endotype of chronic critical illness (CCI). The aim of this systematic review is to synthesise the available evidence of risk factors, biomarkers, and biological mechanisms underlying PICS.
MEDLINE, CENTRAL, and EMBASE were searched on June 2, 2023. Our population of interest was adult intensive care unit survivors. The exposure group was patients with PICS and the comparator group was patients with no PICS, CCI, or rapid recovery. Mean differences were pooled for each biomarker using a random effects DerSimonian-Laird method. Risk of bias assessment was done using the Newcastle-Ottawa Scale.
Six papers were included. Five were single-centre retrospective cohort studies, and one was a prospective cohort study, with sample sizes ranging from 22 to 391 patients. Two studies showed an increased incidence of PICS with age, and two studies showed an association between PICS and Charlson Comorbidity Index scores. PICS was associated with requiring mechanical ventilation in four studies. Meta-analysis showed a 34.4 mg L higher C-reactive protein (95% confidence interval [CI] 12.7-56.2 mg L; P<0.01), a 4.4 g L lower albumin (95% CI 0.5-8.3 g L; P<0.01), and a 0.36×10 L lower lymphocyte count (95% CI 0.25-0.47×10 L; P=0.01) in the PICS compared with the non-PICS group. There are a large variety of other potential biomarkers but limited validation studies. The overall quality of evidence is limited, and these results should be interpreted accordingly.
While older patients and those with co-morbidities could be at greater risk for PICS, acquired risk factors, such as injury severity, are potentially more predictive of PICS than intrinsic patient characteristics. There are many potential biomarkers for PICS, but limited validation studies have been conducted. Persistent myeloid-derived suppressor cell expansion, the continual release of danger-associated molecular patterns and pathogen-associated molecular patterns propagating inflammation, and bioenergetic failure are all mechanisms underlying PICS that could offer potential for novel biomarkers and therapeutic interventions.
International Prospective Register of Systematic Reviews (PROSPERO; CRD42023427749).
持续性炎症、免疫抑制和分解代谢综合征（PICS）已被提出作为慢性危重病（CCI）的一种内型。本系统综述的目的是综合现有关于 PICS 风险因素、生物标志物和生物学机制的证据。
于 2023 年 6 月 2 日检索了 MEDLINE、CENTRAL 和 EMBASE。我们的研究人群为重症监护病房幸存者。暴露组为患有 PICS 的患者，对照组为无 PICS、CCI 或快速康复的患者。使用随机效应 DerSimonian-Laird 方法对每种生物标志物的平均值差异进行汇总。使用纽卡斯尔-渥太华量表进行偏倚风险评估。
纳入了 6 篇论文。其中 5 篇为单中心回顾性队列研究，1 篇为前瞻性队列研究，患者样本量从 22 例到 391 例不等。有 2 项研究表明，年龄越大，PICS 的发病率越高，有 2 项研究表明 PICS 与 Charlson 合并症指数评分之间存在关联。4 项研究表明，机械通气与 PICS 有关。Meta 分析显示，PICS 组 C 反应蛋白（CRP）升高 34.4 mg/L（95%置信区间[CI]为 12.7-56.2 mg/L；P<0.01），白蛋白降低 4.4 g/L（95%CI 为 0.5-8.3 g/L；P<0.01），淋巴细胞计数降低 0.36×10/L（95%CI 为 0.25-0.47×10/L；P=0.01）。虽然还有许多其他潜在的生物标志物，但仅有有限的验证研究。总体证据质量有限，因此应相应地解释这些结果。
尽管年龄较大的患者和合并症患者可能面临更大的 PICS 风险，但获得性风险因素（如损伤严重程度）可能比患者固有特征更能预测 PICS。有许多潜在的 PICS 生物标志物，但进行了有限的验证研究。持续性髓系来源抑制细胞扩张、持续释放危险相关分子模式和病原体相关分子模式传播炎症、以及生物能量衰竭是 PICS 的潜在机制，这些机制可能为新的生物标志物和治疗干预提供潜在的可能性。
国际前瞻性系统评价注册库（PROSPERO；CRD42023427749）。
