Tocilizumab in treating children with refractory septic shock

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

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.