Chapter III: Critical Care Hemodynamics and Critical Heart Disease

Section I: New Indices for Evaluating Vasoactive Drug Responsiveness

Vasoactive drugs are the cornerstone of shock management. Historically, shock management has primarily revolved around target mean arterial pressure (MAP). However, at the same MAP level, the required doses of vasoactive drugs vary significantly among patients, reflecting distinct pathophysiological states and prognoses. This indicates that relying solely on whether blood pressure targets are met is insufficient to truly reflect circulatory responsiveness to vasoactive drugs—i.e., the hemodynamic improvement efficiency per unit of vasoactive drug administered. In recent years, novel indices such as the Blood Pressure Response Index (BPRI), Vasopressor Norepinephrine Responsiveness Index (VNERi), and Average Initial Mean Arterial Pressure Response Index to Angiotensin II (AIMRITE) have integrated multidimensional factors (hemodynamic effects, drug intensity, and compensatory capacity) into a unified evaluation system, quantifying the relationship between vasoconstrictive capacity and vasoactive drug efficacy. Based on this, this article discusses the potential application value of different indices in reflecting vascular responsiveness.

1. Blood Pressure Response Index (BPRI)
In traditional hemodynamic assessment, blood pressure and vasoactive drug doses are often interpreted separately: the former indicates whether circulatory pressure targets are met, while the latter reflects drug intensity. For example, diastolic arterial pressure (DAP) and the DAP/heart rate (HR) ratio partially reflect vascular tone, while the Vasoactive-Inotropic Score (VIS) reflects overall drug intensity. However, this separated assessment is notably insufficient when high-dose vasoactive drugs are used. Even when MAP targets are achieved, inter-patient variability in drug requirements remains high, indicating that blood pressure targets alone cannot reflect true circulatory stability.
BPRI (BPRI = MAP/VIS) bridges this gap by quantifying vasoactive drug responsiveness. Studies show BPRI is significantly associated with 28-day mortality in septic shock patients. After adjusting for disease severity, comorbidities, and treatment-related confounders, low BPRI remains an independent predictor of poor prognosis. Further analysis reveals an “L-shaped” relationship between BPRI and mortality risk: when BPRI < 7.1, mortality risk rises sharply. Low BPRI is also associated with prolonged vasoactive drug dependence and circulatory instability. A 2025 cohort study based on the MIMIC-IV database demonstrated that BPRI correlates with short-term mortality risk in septic shock, outperforming isolated blood pressure or drug dose metrics, with consistent predictive value across subgroups. Similar correlations have been validated in non-infectious shock populations. A multicenter retrospective study by You et al. on cardiogenic shock patients found BPRI correlates with in-hospital mortality, with consistent predictive value across subgroups, suggesting the BPRI-reflective blood pressure-dose relationship is a common feature across different etiologies of circulatory failure. Notably, the BPRI-mortality relationship is distinctly non-linear: when BPRI ≥ 2.4, mortality risk changes gradually; when BPRI < 2.4, mortality risk rises rapidly. These findings further indicate that under high-intensity vasoactive support, a lower BPRI reflects a significant decline in circulatory responsiveness.
However, BPRI does not replace traditional blood pressure metrics; rather, it supplements the assessment of the body’s responsiveness to vasoactive drugs. When MAP is target-achieved but BPRI continues to decline, it suggests further drug escalation may enter a low-efficacy zone. Although current evidence is primarily retrospective and VIS components vary, consistent results across different shock types suggest BPRI is valuable for assessing vasoactive drug responsiveness.

2. Vasopressor Norepinephrine Responsiveness Index (VNERi)
In assessing vasoactive drug responsiveness, ratios of blood pressure to vasoconstrictor dose can describe overall dose-effect relationships but fail to distinguish the impacts of peripheral vascular tone and sympathetic compensatory activation (“sympathetic compensation”) on blood pressure. Traditional DAP partially reflects peripheral vascular resistance, but under conditions of nitric oxide pathway activation and reduced catecholamine responsiveness, vascular functional states can differ significantly even at the same DAP, limiting its prognostic value. Introducing HR-adjusted DAP/HR partially corrects for cardiac output compensation effects on blood pressure. However, DAP/HR still struggles to distinguish true vascular responsiveness across different drug intensities. VNERi further incorporates HR correction into the blood pressure-dose assessment framework, calculated as: DAP/(NE×HR), integrating blood pressure effects, drug intensity, and HR compensation into a unified system to describe vascular response states under varying norepinephrine (NE) doses. Studies show VNERi correlates more strongly with mortality than DAP, DAP/HR, or MAP/NE, with better model fit. VNERi maintains strong correlations with mortality, vasoactive drug weaning failure, and duration of circulatory instability, outperforming DAP, DAP/HR, and MAP/NE. Notably, the VNERi-prognosis relationship follows an “inverted U-shaped” non-linear pattern: low VNERi (<2.6) indicates a hyporesponsive state where effective vascular tone cannot be established despite high NE doses and strong sympathetic compensation; excessively high VNERi (>10.8) may reflect dominant sympathetic or cardiac compensation.
VNERi does not merely reflect hemodynamic outcomes; it represents a hyporesponsive phenotype in distributive shock characterized by high NE doses, sympathetic compensation, and inadequate vasoconstrictive effects. Its clinical value lies in providing a quantitative phenotyping tool for vasoactive drug responsiveness, describing vascular responsiveness as an intermediate functional phenotype, thereby offering a functional perspective for assessment.

3. Other Novel Vasoactive Drug Responsiveness Indices
Vasoactive drug responsiveness assessment has shifted from single-timepoint blood pressure or dose evaluation to decomposed assessment across different physiological levels. For instance, circulatory instability in distributive shock is not instantaneous but results from the interplay of vascular regulation, baseline vascular tone, compensatory mechanisms, and time exposure, which single indices cannot fully capture.
At the upstream vascular regulation level, AIMRITE (ΔMAP/ΔAng II dose) represents a dynamic responsiveness assessment centered on specific pharmacological pathways. Angiotensin II mediates vasoconstriction primarily via angiotensin II type 1 receptors (AT1), partially reflecting renin-angiotensin system (RAS) function in early stages. Based on the ATHOS-3 trial, in distributive shock patients receiving angiotensin II, AIMRITE significantly correlates with 28-day mortality: each 1-unit increase in AIMRITE reduces mortality risk by ~16%. Compared to hyporesponsive patients, hyperresponsive patients with high AIMRITE have significantly lower mortality risk.
Introducing the time dimension further advances responsiveness assessment from instantaneous judgment to process description. Time-weighted pressor indices, represented by Diastolic Blood Pressure Time Under Range (DBP-TUR), reflect the duration of low circulatory states by quantifying cumulative time DAP spends below a threshold. Studies show that even when MAP targets are met, prolonged low DAP duration correlates with mortality risk and organ injury severity. This index supplements traditional blood pressure target assessment from a cumulative burden perspective, offering a new analytical angle for understanding the dynamic features of circulatory instability in distributive shock.

4. Summary and Outlook
Currently, vasoactive drug responsiveness assessment is transitioning from single-parameter to multi-parameter synergistic descriptive models. Different responsiveness indices supplement traditional hemodynamic evaluation from perspectives of blood pressure-drug efficiency, vascular tone regulation, specific pathway responsiveness, and time dimensions. The core is not simple parameter stacking, but comprehensive observation across different physiological levels to determine whether macro-hemodynamic improvements induced by vasoactive drugs truly reflect synchronized recovery of vascular tone and tissue perfusion. Emphasis must be placed on the fact that among patients with similar blood pressure or drug dose responses, perfusion status, tissue oxygenation, and their consistency with blood pressure changes determine treatment efficacy. Thus, multi-parameter responsiveness assessment emphasizes response consistency over numerical targets, i.e., whether vasoconstrictive effects can stably translate into perfusion improvement over time. In practice, different responsiveness indices should not be used in isolation but integrated with pathophysiological processes. This paradigm shifts vasoactive drug responsiveness evaluation from outcome-oriented blood pressure target management to process-oriented circulatory function assessment, providing reference metrics for identifying states of superficial blood pressure stability with underlying perfusion inadequacy. Notably, as pathophysiology changes, the interpretation of vasoactive drug responsiveness also evolves. For example, in cardiogenic shock, blood pressure response to vasoactive drugs no longer primarily reflects vascular tone recovery but rather reflects afterload changes and ventricular-vascular coupling. At this stage, vasoactive drug-induced blood pressure elevation may come at the cost of reduced cardiac output, resulting in improved macro-circulation but worsened perfusion. Similarly, under mechanical circulatory support, blood pressure is no longer solely determined by cardiac function and vascular tone but is influenced by flow rates, venous return conditions, and device-heart interactions. Vascular responsiveness indices based on blood pressure changes often reflect mechanical parameter adjustments or vascular compliance changes rather than true tissue perfusion improvement.

For novel vasoactive drug responsiveness indices, current evidence remains primarily observational. Standardization across indices, threshold setting, and their definitive value in clinical decision-making are unclear and require further research. Therefore, these new indices are currently more suitable as adjuncts to traditional hemodynamic management rather than replacements.
(Hu Juntao, Zhou Kaihuan, Tang Zhanhong, First Affiliated Hospital of Guangxi Medical University)

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