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托珠单抗对降低血液系统和非血液系统疾病患儿难治性感染性休克死亡率的临床价值

Clinical Value of Tocilizumab in Reducing Mortality in Refractory Septic Shock in Children with Hematologic and Non-Hematologic Diseases.

作者信息

Lee En-Pei, Lin Jainn-Jim, Chen Shih-Hsiang, Chan Oi-Wa, Su Ya-Ting, Hsiao Man-Ru, Hsia Shao-Hsuan, Wu Han-Ping

机构信息

Division of Pediatric Critical Care Medicine, Department of Pediatrics, Chang Gung Memorial Hospital at Linko, Kweishan, Taoyuan 33305, Taiwan.

College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan.

出版信息

Cells. 2025 Mar 16;14(6):441. doi: 10.3390/cells14060441.

Abstract

BACKGROUND

Pediatric sepsis remains the main cause of morbidity and mortality among children. Interleukin (IL)-6 is usually produced after infection, and elevated IL-6 levels may cause multisystemic damage. This study aimed to evaluate the effect of tocilizumab, an IL-6 receptor antibody, on children with septic shock.

METHODS

We conducted a retrospective cohort study of children diagnosed with septic shock and admitted to the pediatric intensive care unit (PICU) between 2018 and 2024. Tocilizumab was administered within 24 h to patients with high IL-6 levels who developed refractory septic shock. Outcomes, including 28-day mortality, morbidity, length of PICU stay, and shock duration, were analyzed between septic children with different etiologies and differed treatments.

RESULTS

Fifty-four children with refractory septic shock were included. Patients treated with tocilizumab (n = 21) showed improved outcomes compared to those without tocilizumab (n = 33), including shorter PICU stays and lower mortality rates (14.2% vs. 54.5%, = 0.03). Subgroup analysis revealed that in the non-hematologic group, tocilizumab-treated patients had a 0% mortality rate compared to 50% in untreated patients ( = 0.006). In the hematologic group, tocilizumab-treated patients exhibited a 27.2% mortality rate compared to 61.5% in untreated patients ( = 0.09). Trends in IL-6 levels (D1 to D7) were significantly higher in non-survivors compared to survivors and in patients with hematological malignancies compared to those without. No adverse events, including secondary infections or long-term liver impairment, were observed.

CONCLUSIONS

Tocilizumab appears to mitigate systemic inflammation and improve outcomes in children with refractory septic shock and elevated IL-6 levels. Further prospective studies are warranted to confirm these findings and establish treatment guidelines.

摘要

背景

小儿脓毒症仍然是儿童发病和死亡的主要原因。白细胞介素(IL)-6通常在感染后产生,IL-6水平升高可能导致多系统损害。本研究旨在评估IL-6受体抗体托珠单抗对感染性休克患儿的疗效。

方法

我们对2018年至2024年期间诊断为感染性休克并入住儿科重症监护病房(PICU)的儿童进行了一项回顾性队列研究。对于发生难治性感染性休克且IL-6水平高的患者,在24小时内给予托珠单抗。分析了不同病因和不同治疗方法的脓毒症患儿的结局,包括28天死亡率、发病率、PICU住院时间和休克持续时间。

结果

纳入54例难治性感染性休克患儿。与未使用托珠单抗的患儿(n = 33)相比,使用托珠单抗治疗的患儿(n = 21)结局有所改善,包括PICU住院时间更短和死亡率更低(14.2%对54.5%,P = 0.03)。亚组分析显示,在非血液学组中,接受托珠单抗治疗的患者死亡率为0%,而未治疗患者为50%(P = 0.006)。在血液学组中,接受托珠单抗治疗的患者死亡率为27.2%,而未治疗患者为61.5%(P = 0.09)。与幸存者相比,非幸存者的IL-6水平(第1天至第7天)趋势显著更高,与无血液系统恶性肿瘤的患者相比,有血液系统恶性肿瘤的患者趋势显著更高。未观察到不良事件,包括继发感染或长期肝功能损害。

结论

托珠单抗似乎可以减轻全身炎症反应,并改善难治性感染性休克且IL-6水平升高患儿的结局。有必要进行进一步的前瞻性研究以证实这些发现并制定治疗指南。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/13d1/11941062/3799546413fb/cells-14-00441-g001.jpg

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