Concerns regarding the definition of fluid responsiveness incorporating mean arterial pressure in mechanically ventilated shock patients

We read with interest the study by Tongyoo et al. comparing mitral E/e′ with the inferior vena cava variability index (IVCVI) for predicting fluid responsiveness in mechanically ventilated adults with shock [1]. The study addresses an important clinical question in a real-world intensive care unit population. We would like to raise a methodological concern regarding the composite definition of fluid responsiveness used in the analysis, because this choice may influence the reported diagnostic performance of the evaluated variables.

Tongyoo et al. defined fluid responsiveness as either an increase in cardiac index (CI) of > 15% or an increase in mean arterial pressure (MAP) of > 5 mmHg after a 300-mL fluid bolus [1]. Of the 51 patients classified as responders, 27 fulfilled the MAP criterion alone, without a concomitant increase in CI. Thus, more than half of the responder group was defined by a pressure response rather than by an increase in flow. The authors suggest that these patients would have been misclassified without the MAP criterion. We believe this interpretation deserves caution, because it departs from the conventional hemodynamic definition of fluid responsiveness.

Fluid responsiveness is generally understood as an increase in cardiac output (CO), cardiac index, or stroke volume after a fluid challenge. The recent CODEFIRE consensus from the European Society of Intensive Care Medicine (ESICM) reported strong agreement that CO or CI should be the reference variable for defining fluid responsiveness in ICU studies [2]. The 2025 ESICM guidelines on circulatory shock similarly emphasize assessment of fluid responsiveness before further fluid administration and recommend dynamic variables, with CO and/or stroke volume monitoring in patients who do not respond to initial therapy [3]. These recommendations do not support MAP as a standalone reference endpoint for fluid responsiveness.

There are also physiological reasons for this distinction. MAP depends on both cardiac output and systemic vascular resistance; therefore, an isolated MAP increase after fluid administration does not necessarily indicate improved forward flow. In the study by Monnet et al., changes in MAP after volume expansion were only moderately correlated with changes in CO, and their ability to detect a fluid-induced CI increase of > 15% was significantly lower than that of pulse pressure [4]. In a larger cohort, Ait-Hamou et al. likewise found only a weak correlation between fluid-induced changes in MAP and CO, with poorer discrimination than pulse pressure [5]. These data suggest that a MAP response may reflect changes in vascular tone as much as, or more than, changes in preload-dependent flow.

This issue is particularly relevant to the cohort studied by Tongyoo et al., in which septic shock accounted for 75 of 80 patients [1]. In septic shock, vascular tone is labile and may be affected by endogenous catecholamines, sedatives, vasopressors, and baroreflex responses during or after the fluid bolus. Tongyoo et al. did not report systemic vascular resistance before and after the fluid challenge, nor did they provide detailed information on concurrent vasoactive medication changes. Without these data, it is difficult to determine whether the 27 MAP-only responders experienced true preload-dependent improvement or pressure changes driven predominantly by altered vasomotor tone.

The composite endpoint may therefore have reclassified a substantial proportion of patients and could have affected the area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity of IVCVI, mitral E/e′, central venous pressure, and pulse pressure variation. We respectfully suggest that the authors perform a sensitivity analysis and, where feasible, report concomitant changes in noninvasive surrogates of cardiac output, such as end-tidal carbon dioxide, to help determine whether MAP-only responses are accompanied by an increase in forward flow. Such an analysis would clarify whether the diagnostic performance of the investigated variables remains robust when fluid responsiveness is defined by the conventional flow-based endpoint and would improve comparability with the broader fluid-responsiveness literature.

We thank the authors for their valuable contribution to hemodynamic monitoring in shock and hope that this comment helps further contextualize their findings.

Abbreviations

AUROC

Area under the receiver operating characteristic curve

CI

Cardiac index

CO

Cardiac output

ESICM

European Society of Intensive Care Medicine

IVCVI

Inferior vena cava variability index

MAP

Mean arterial pressure

Author contributions

All authors contributed equally to the conception and drafting of this letter. YL and YW conducted the literature review and drafted the initial manuscript. YZ critically revised the manuscript for important intellectual content and approved the final version for submission. All authors agree to be accountable for all aspects of the work.

Funding

This work was supported by the Construction Fund of Key Medical Disciplines of Hangzhou (Grant No. 2025HZZD04).

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

Not applicable. This manuscript is a commentary based on previously published data. No original human participant data were collected or analyzed.

Consent for publication

Not applicable. No individual patient data, images, or personal details are included in this manuscript.

Competing interests

The authors declare no competing interests.