High-volume hemofiltration (HVHF) has been proposed as an adjunctive extracorporeal strategy for children with sepsis or septic shock requiring continuous renal replacement therapy (CRRT), based on the biological premise that enhanced convective clearance may attenuate circulating inflammatory mediator peaks. The 2026 Surviving Sepsis Campaign pediatric guidelines issued a conditional recommendation favoring HVHF over standard-volume hemofiltration in this setting, despite low-certainty evidence. This narrative review critically examines the biological rationale, available pediatric and adult evidence, and practical limitations of HVHF in pediatric septic shock. Although cytokines targeted by HVHF fall within the molecular-weight range theoretically amenable to clearance by high-flux membranes, clinical translation remains uncertain. Pediatric studies supporting HVHF are limited to small, single-center trials with heterogeneous dose definitions, variable treatment protocols, and fragile statistical estimates. In contrast, the largest observational pediatric datasets show no consistent dose–outcome relationship, while adult randomized trials and systematic reviews have failed to demonstrate survival benefit from higher-intensity or high-volume strategies. In small children, interpretation is further complicated by routine use of regional citrate anticoagulation, which may increase delivered effluent volume and blur the distinction between standard and high-volume prescriptions. Moreover, escalating CRRT dose has been potentially associated with dialytrauma, hemodynamic instability, micronutrient and amino acid losses, and clinically relevant antimicrobial underexposure.Conclusion: Current evidence supports HVHF as biologically plausible but clinically unproven, with risks that should not be overlooked.<Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry nameend="c2" namest="c1"> What is Known: • High-volume hemofiltration has a plausible biological rationale in pediatric sepsis, based on enhanced convective clearance of circulating inflammatory mediators. • The 2026 pediatric Surviving Sepsis Campaign guidelines recommended HVHF for children with sepsis or septic shock requiring renal replacement therapy. • The recommendation is labeled as “conditional” due to limited supporting evidence. </entry> </row> <row> <entry nameend="c2" namest="c1"> What is New: • This review highlights that the pediatric evidence supporting HVHF is based on small single-center trials with heterogeneous definitions and statistically fragile estimates, while larger pediatric observational data and adult trials do not show a consistent dose-related clinical benefit. • Pediatric-specific factors, including regional citrate anticoagulation, high relative effluent doses in small children, and potential dialytrauma, may blur the distinction between standard and high-volume prescriptions and should temper routine clinical adoption. </entry> </row> </tbody> </tgroup> </Table>

Continuous renal replacement therapy for septic shock: practicalities for a pediatric intensivist

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2026年7月29日

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Lara Mary Titherington,
Tommaso Bottesi,
Francesco Guzzi,
Stefano Romagnoli,
Zaccaria Ricci

摘要

High-volume hemofiltration (HVHF) has been proposed as an adjunctive extracorporeal strategy for children with sepsis or septic shock requiring continuous renal replacement therapy (CRRT), based on the biological premise that enhanced convective clearance may attenuate circulating inflammatory mediator peaks. The 2026 Surviving Sepsis Campaign pediatric guidelines issued a conditional recommendation favoring HVHF over standard-volume hemofiltration in this setting, despite low-certainty evidence. This narrative review critically examines the biological rationale, available pediatric and adult evidence, and practical limitations of HVHF in pediatric septic shock. Although cytokines targeted by HVHF fall within the molecular-weight range theoretically amenable to clearance by high-flux membranes, clinical translation remains uncertain. Pediatric studies supporting HVHF are limited to small, single-center trials with heterogeneous dose definitions, variable treatment protocols, and fragile statistical estimates. In contrast, the largest observational pediatric datasets show no consistent dose–outcome relationship, while adult randomized trials and systematic reviews have failed to demonstrate survival benefit from higher-intensity or high-volume strategies. In small children, interpretation is further complicated by routine use of regional citrate anticoagulation, which may increase delivered effluent volume and blur the distinction between standard and high-volume prescriptions. Moreover, escalating CRRT dose has been potentially associated with dialytrauma, hemodynamic instability, micronutrient and amino acid losses, and clinically relevant antimicrobial underexposure.

Conclusion: Current evidence supports HVHF as biologically plausible but clinically unproven, with risks that should not be overlooked.

What is Known:

• High-volume hemofiltration has a plausible biological rationale in pediatric sepsis, based on enhanced convective clearance of circulating inflammatory mediators.

• The 2026 pediatric Surviving Sepsis Campaign guidelines recommended HVHF for children with sepsis or septic shock requiring renal replacement therapy.

• The recommendation is labeled as “conditional” due to limited supporting evidence.

What is New:

• This review highlights that the pediatric evidence supporting HVHF is based on small single-center trials with heterogeneous definitions and statistically fragile estimates, while larger pediatric observational data and adult trials do not show a consistent dose-related clinical benefit.

• Pediatric-specific factors, including regional citrate anticoagulation, high relative effluent doses in small children, and potential dialytrauma, may blur the distinction between standard and high-volume prescriptions and should temper routine clinical adoption.