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Background <p>Clinical outcomes of hemoadsorption (HA) in sepsis remain uncertain despite demonstrated biological efficacy in in vivo models. Persistent knowledge gaps concern both patient selection—now increasingly interpreted through biological phenotypes—and optimal device application. In recent years, this latter aspect has been conceptualized as “dose,” yet HA dosing remains poorly defined and inconsistently applied across age groups. Interestingly, pediatric studies have reported more favorable outcomes than adult cohorts. We therefore investigated the concept of dose in pediatric septic shock to elucidate mechanistic determinants of treatment efficacy.</p> Methods <p>We retrospectively analyzed 25 children with septic shock treated with CytoSorb<sup>®</sup> combined with continuous renal replacement therapy. HA dose was expressed as Amount of Blood Purified (ABP, L/kg). Kinetic simulations incorporating staged extraction fractions were performed to model progressive cartridge saturation. Cytokine removal was modeled using log-transformed IL-6. Multivariable linear regression models assessed the relationship between ABP, baseline cytokine concentration, and cytokine reduction.</p> Results <p>Median ABP was 14.4 (9.7–21.6) L/kg, substantially exceeding previously reported adult thresholds. No linear association was observed between ABP and vasopressor reduction. IL-6 reduction was strongly associated with baseline cytokine concentration (R² = 0.79, 95%CI= [-1.08; -0.62], <i>p</i> &lt; 0.001), while ABP was not independently predictive.</p> Conclusions <p>In this exploratory pediatric cohort, hemoadsorption during CRRT was associated with high blood-purified-per-kilogram exposure and marked cytokine reduction. These findings suggest that, beyond a certain exposure level, mediator removal may become predominantly concentration-driven rather than dose-limited, supporting further investigation of dosing strategies based on inflammatory burden.</p>

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Exploratory dose modeling of hemoadsorption in pediatric septic shock

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月22日

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  • Gabriella Bottari

摘要

Background

Clinical outcomes of hemoadsorption (HA) in sepsis remain uncertain despite demonstrated biological efficacy in in vivo models. Persistent knowledge gaps concern both patient selection—now increasingly interpreted through biological phenotypes—and optimal device application. In recent years, this latter aspect has been conceptualized as “dose,” yet HA dosing remains poorly defined and inconsistently applied across age groups. Interestingly, pediatric studies have reported more favorable outcomes than adult cohorts. We therefore investigated the concept of dose in pediatric septic shock to elucidate mechanistic determinants of treatment efficacy.

Methods

We retrospectively analyzed 25 children with septic shock treated with CytoSorb® combined with continuous renal replacement therapy. HA dose was expressed as Amount of Blood Purified (ABP, L/kg). Kinetic simulations incorporating staged extraction fractions were performed to model progressive cartridge saturation. Cytokine removal was modeled using log-transformed IL-6. Multivariable linear regression models assessed the relationship between ABP, baseline cytokine concentration, and cytokine reduction.

Results

Median ABP was 14.4 (9.7–21.6) L/kg, substantially exceeding previously reported adult thresholds. No linear association was observed between ABP and vasopressor reduction. IL-6 reduction was strongly associated with baseline cytokine concentration (R² = 0.79, 95%CI= [-1.08; -0.62], p < 0.001), while ABP was not independently predictive.

Conclusions

In this exploratory pediatric cohort, hemoadsorption during CRRT was associated with high blood-purified-per-kilogram exposure and marked cytokine reduction. These findings suggest that, beyond a certain exposure level, mediator removal may become predominantly concentration-driven rather than dose-limited, supporting further investigation of dosing strategies based on inflammatory burden.