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Identifying a Refractory Shock Phenotype in Pediatric Sepsis Using a Vasoactive-Adjusted Shock Index
Cheolmin Matthew Lee1,2, Mihir R Atreya3,4, Tellen D Bennett5
1Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Insights
A new cardiovascular index, VASI, helps identify pediatric septic shock patients early. This index aids in understanding treatment effects and improving outcomes for refractory septic shock (RSS).
Area of Science:
- Pediatric critical care medicine
- Cardiovascular physiology
- Sepsis research
Background:
- Refractory septic shock (RSS) in children is a severe condition with high mortality.
- Existing hemodynamic indices may not fully capture the complexity of pediatric septic shock.
- The role of vasoactive medications complicates the assessment of hemodynamic status.
Purpose of the Study:
- To develop a novel cardiovascular index (VASI) incorporating hemodynamic status and vasoactive medication use.
- To identify pediatric patients with refractory septic shock (RSS) using early VASI trends.
- To evaluate treatment effect heterogeneity in RSS versus non-RSS patients.
Main Methods:
- Developed the Vasoactive-Adjusted Shock Index (VASI) using heart rate and systolic pressure, adjusted for vasoactive drugs.
- Applied group-based trajectory modeling and K-means with dynamic time warping to VASI trends.
- Analyzed heterogeneity of treatment effect using inverse-probability weighted logistic regression.
Main Results:
- The VASI index effectively predicted poor outcomes in pediatric sepsis patients.
- Trajectory analysis identified a distinct RSS phenotype characterized by persistently high VASI.
- Hydrocortisone use on day one was linked to reduced mortality in RSS patients, unlike fluid or albumin.
Conclusions:
- The early VASI trajectory is a valuable tool for identifying pediatric RSS phenotypes.
- This index has prognostic relevance and aids in understanding treatment responses.
- Integrating VASI into early risk assessment can improve management of high-risk pediatric sepsis.
Objectives:
This study aimed to: 1) develop a cardiovascular index that includes hemodynamic status and adjusts for vasoactive medication use; 2) identify pediatric patients with refractory septic shock (RSS) using early trends of the adjusted index, and 3) assess the heterogeneity of treatment effect (HTE) to common adjuvant therapies in RSS versus non-RSS patients.
Methods:
Children with sepsis across 13 US pediatric intensive care units between 2012 and 2018 were included. The vasoactive-adjusted shock index (VASI) was derived using the shock index (heart rate/systolic pressure) and adjusted for vasoactive use. Group-based trajectory modeling was applied to 8-hour VASI trends following pediatric intensive care unit admission to stratify patients and replicated using K-means with dynamic time warping. HTE between RSS and non-RSS patients was analyzed using inverse-probability weighted logistic regression.
Results:
17,216 patients were included (8.6% mortality). VASI demonstrated a robust progressive increase in clinical risk, outperforming other hemodynamic metrics at discriminating poor outcomes. Trajectory analysis identified four clusters, including a trajectory with persistently high VASI consistent with an RSS clinical phenotype. Unlike fluid balance and albumin use, hydrocortisone use on the first day was associated with lower mortality among RSS patients than among non-RSS patients (interaction, P = 0.002).
Conclusion:
The early trajectory of VASI identifies an RSS clinical phenotype associated with poor outcomes and HTE to adjuvant therapies. Integrating hemodynamic status and vasoactive use into early risk assessment in pediatric sepsis can help identify a high-risk RSS group, with both prognostic and therapeutic relevance.
