Tocilizumab in treating children with refractory septic shock

Abstract

Pediatric septic shock causes significant morbidity and mortality, contributing to over 4.5 million deaths annually worldwide [1]. It stems from a dysregulated host immune response to infection, characterized by high levels of cytokines, including interleukin-6 (IL-6). Tocilizumab, an IL-6 receptor antagonist, has shown promise in managing cytokine storms in adult sepsis and COVID-19 cases [2]. However, its efficacy in pediatric septic shock remains underexplored.

A total of 13 pediatric patients (aged 1–19 years) treated at a pediatric intensive care unit (PICU) from April 2023 to February 2024 were recorded. Participants were categorized based on underlying conditions: hematological malignancy (n = 7) or other diseases (n = 6). Following diagnosis and confirmation of elevated IL-6 levels, all patients received a single dose of tocilizumab within 24 h. Outcomes were assessed in terms of 28-day mortality, shock duration, and morbidity.

Among the 13 patients, seven had hematological malignancies, primarily presenting with bacteremia or neutropenic fever, and six had other underlying diseases (Table 1).

Table 1 Clinical characteristics of the patients with septic shock

Full size table

Tocilizumab administration resulted in significant reductions in IL-6 levels for all patients, accompanied by improved hemodynamics and survival in 12 patients (92.3%). The median shock duration was approximately 5.5 days, and the 28-day mortality rate was 7.6%. Patients with malignancies showed a reduced shock duration (median 82 h) compared to previous reports (96 h).

No complications, such as secondary infections or long-term liver impairment, were observed.

One of the main pathophysiologies of sepsis is the upregulation of both pro- and anti-inflammatory pathways. Many proinflammatory cytokines, such as IL-1, IL-6, IL-8, IL-12, IL-18, TNF-a, and IFN-r, are highly expressed, leading to cytokine storms after sepsis develops [3]. Excessive cytokine levels result in progressive tissue damage, resulting in multiorgan impairment. A previous study reported that among the various cytokines, IL-6 was the most valuable cytokine associated with sepsis severity and outcome prediction [4]. Among patients with septic shock, survivors usually show a decreasing trend of IL-6 levels and non-survivors usually show increasing IL-6 levels [4]. By targeting the IL-6 signaling pathway, tocilizumab may suppress cytokine storms and reduce the risk of multiorgan dysfunction. The observed 28-day mortality rate (7.6%) and reduced shock duration align with findings from studies in adult populations, emphasizing the potential of tocilizumab as an adjunctive therapy [5].

Tocilizumab appears to be a promising therapeutic adjunct in managing pediatric septic shock with elevated IL-6 levels. It demonstrates potential for reducing mortality, shortening shock duration, and mitigating systemic inflammation without significant adverse effects.

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

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

   En-Pei Lee

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

   En-Pei Lee, Shih-Hsiang Chen & Han-Ping Wu

3. Divisions of Hematology and Oncology, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan

   Shih-Hsiang Chen

4. Department of Pediatrics, Chiayi Chang-Gung Memorial Hospital, No. 6, W. Sec., Jiapu Rd., Puzi City, Chiayi County, 613, Taiwan

   Han-Ping Wu

Authors

1. En-Pei LeeView author publications

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2. Shih-Hsiang ChenView author publications

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Contributions

EPL: writing—review & editing, conceptualization, project administration. SHC: conceptualization, data curation. HPW: writing—review & editing. All authors reviewed drafts of the manuscript, provided feedback and approved the final draft for submission.

Corresponding author

Correspondence to Han-Ping Wu.

Ethics approval and consent to participate

The establishment of the database was approved by the Institutional Review Board of Chang Gung Memorial Hospital (IRB No. 202400310B0). All methods were performed in accordance with the relevant guidelines and regulations by the IRB of Gung Memorial Hospital. The requirement for informed consent was waived by the Institutional Review Board of Chang Gung Memorial Hospital because of the anonymized nature of the data and scientific purpose of the study.

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Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Lee, EP., Chen, SH. & Wu, HP. Tocilizumab in treating children with refractory septic shock. Crit Care 29, 87 (2025). https://doi.org/10.1186/s13054-025-05318-6

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• Received: 10 February 2025

• Accepted: 12 February 2025

• Published: 24 February 2025

• DOI: https://doi.org/10.1186/s13054-025-05318-6

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