Department of Research, The Norwegian Air Ambulance Foundation, Oslo, Norway.
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Mol Med. 2021 Apr 8;27(1):35. doi: 10.1186/s10020-021-00286-3.
Complement activation is a central mechanism in systemic inflammation and remote organ dysfunction following major trauma. Data on temporal changes of complement activation early after injury is largely missing. We aimed to describe in detail the kinetics of complement activation in individual trauma patients from admission to 10 days after injury, and the association with trauma characteristics and outcome.
In a prospective cohort of 136 trauma patients, plasma samples obtained with high time resolution (admission, 2, 4, 6, 8 h, and thereafter daily) were assessed for terminal complement complex (TCC). We studied individual TCC concentration curves and calculated a summary measure to obtain the accumulated TCC response 3 to 6 h after injury (TCC-AUC). Correlation analyses and multivariable linear regression analyses were used to explore associations between individual patients' admission TCC, TCC-AUC, daily TCC during the intensive care unit stay, trauma characteristics, and predefined outcome measures.
TCC concentration curves showed great variability in temporal shapes between individuals. However, the highest values were generally seen within the first 6 h after injury, before they subsided and remained elevated throughout the intensive care unit stay. Both admission TCC and TCC-AUC correlated positively with New Injury Severity Score (Spearman's rho, p-value 0.31, 0.0003 and 0.21, 0.02) and negatively with admission Base Excess (- 0.21, 0.02 and - 0.30, 0.001). Multivariable analyses confirmed that deranged physiology was an important predictor of complement activation. For patients without major head injury, admission TCC and TCC-AUC were negatively associated with ventilator-free days. TCC-AUC outperformed admission TCC as a predictor of Sequential Organ Failure Assessment score at day 0 and 4.
Complement activation 3 to 6 h after injury was a better predictor of prolonged mechanical ventilation and multiple organ dysfunction syndrome than admission TCC. Our data suggest that the greatest surge of complement activation is found within the first 6 h after injury, and we argue that this time period should be in focus in the design of future experimental studies and clinical trials using complement inhibitors.
补体激活是全身性炎症和大创伤后远处器官功能障碍的核心机制。关于损伤后早期补体激活的时间变化的数据在很大程度上是缺失的。我们的目的是详细描述从受伤入院到受伤后 10 天的个体创伤患者的补体激活动力学，并探讨其与创伤特征和结局的关系。
在一项前瞻性队列的 136 名创伤患者中，以高时间分辨率（入院时、2、4、6、8 小时，此后每天）获得的血浆样本用于检测末端补体复合物（TCC）。我们研究了个体 TCC 浓度曲线，并计算了获得损伤后 3 至 6 小时累积 TCC 反应的综合测量值（TCC-AUC）。使用相关分析和多变量线性回归分析来探讨个体患者入院时 TCC、TCC-AUC、重症监护病房期间的每日 TCC、创伤特征和预定结局测量之间的关系。
TCC 浓度曲线显示个体之间的时间形状变化很大。然而，最高值通常出现在损伤后 6 小时内，然后下降并在重症监护病房期间保持升高。入院 TCC 和 TCC-AUC 均与新损伤严重程度评分呈正相关（Spearman's rho，p 值分别为 0.31、0.0003 和 0.21、0.02），与入院时碱缺失呈负相关（-0.21、0.02 和-0.30、0.001）。多变量分析证实，生理紊乱是补体激活的重要预测因素。对于没有严重头部损伤的患者，入院 TCC 和 TCC-AUC 与无机械通气天数呈负相关。TCC-AUC 作为序贯器官衰竭评估评分在第 0 天和第 4 天的预测因子优于入院 TCC。
与入院 TCC 相比，损伤后 3 至 6 小时的补体激活是机械通气延长和多器官功能障碍综合征的更好预测因子。我们的数据表明，补体激活的最大峰值发生在损伤后 6 小时内，我们认为这一时间窗应该是未来使用补体抑制剂的实验研究和临床试验设计的重点。
