Meyer Talón, Marlet¹,²; Morales Acero, Jaime Adulfo¹,³; Esponda Prado, Juan Gerardo¹,⁴

Language: English/Spanish [Versión en español]
References: 14
Page: 87-92
PDF size: 484.10 Kb.

ABSTRACT

Introduction: hemodynamic management in critically ill patients focuses on maintaining optimal cardiac output and blood pressure. In the context of septic shock, vasopressors are used to achieve this. Renal perfusion is evaluated as a success parameter through diuresis and creatinine clearance, as variations in blood pressure directly impact perfusion once the autoregulation threshold is reached. The VeXus protocol uses Doppler ultrasound to classify venous congestion and predict acute kidney injury. Objective: to compare the baseline renal resistance index measured by ultrasonography upon admission to the intensive care unit (ICU) in patients diagnosed with sepsis and to assess changes in this index with the use of Norepinephrine. Material and methods: descriptive, longitudinal, prospective, single-center study evaluating variations in the renal resistance index using Norepinephrine. Results: in a sample of 42 patients, no significant changes were observed in the index of the dose of norepinephrine, with a correlation of 0.2369033. Conclusions: no changes were observed in the renal resistance index in patients requiring Norepinephrine during their ICU stay.

ABBREVIATIONS:

• DO₂ = oxygen delivery
• AKI = acute kidney injury
• RRI = renal resistance index
• ICU = intensive care unit
• VO₂ = oxygen consumption

INTRODUCTION

In critically ill patients, sepsis and acute kidney injury are very frequent conditions and are associated with increased hospitalizations and high mortality rates in the intensive care unit (ICU). This occurs as a consequence of an increase in renal vascular resistance associated with a reduction in renal blood change and, therefore, renal ischemia.^1,2 Consequently, rapid circulatory resuscitation and optimal perfusion pressure are the primary therapies for critically ill patients.³ In septic shock, when fluid administration fails to restore blood pressure and adequate organ perfusion, vasopressor therapy must be initiated.⁴ To determine the optimal blood pressure for renal perfusion in patients with septic shock, the variables used are typically diuresis, renal blood flow index, and creatinine clearance. Arterial blood pressure is the driving force of blood flow through tissues; according to the principle of blood flow autoregulation, if cardiac output is constant, blood flow to tissues does not change until arterial pressure falls below a critical value. When this autoregulation reaches its threshold, any further decrease in blood pressure levels will compromise organ blood flow.⁵ Acute kidney injury (AKI) is a dynamic process that evolves from an early reversible condition to an established disease, leading to sustained renal failure, cell death, and delayed renal recovery.

Consequently, rapid circulatory resuscitation and optimal perfusion pressure are the primary therapies for critically ill patients with AKI. These methods are mainly based on the proper management of intravenous fluid replenishment and the administration of vasopressors under strict hemodynamic monitoring.⁶

Septic shock is characterized by severe vasodilation and hypotension refractory to aggressive fluid resuscitation. Despite the normalization of cardiac output, there is frequently evidence of tissue hypoperfusion. As a consequence, organ dysfunctions generally develop despite normal or elevated levels of oxygen delivery (DO₂). Microcirculatory alterations could be an underlying explanation for these findings. Experimental models of resuscitated septic shock show that microvascular perfusion is altered despite the normalization of systemic and regional hemodynamics.⁶ In patients with septic shock, the increase in mean arterial pressure (MAP) induced by norepinephrine from 65 to 75 mmHg is associated with significant decreases in renal vascular resistance and the renal resistance index.⁴ Conversely, some authors reported that the resistance index was not influenced by vasoactive drug therapy.^7,8 However, intravascular thrombosis and vasoconstrictor mediators, along with regional deficiencies in nitric oxide production, could alter vascular reactivity and shift the autoregulation threshold to higher values.⁶ Normally, oxygen consumption (VO₂) is independent of DO₂ until tissues can meet metabolic demands by increasing oxygen extraction when DO₂ decreases. This mechanism has an intrinsic limit; beyond the critical DO₂, the compensatory increase in O₂ extraction is exhausted and VO₂ becomes dependent on DO₂.⁹

The Doppler-based measurement of the renal resistance index (RRI) is a rapid and non-invasive tool that can be useful for detecting tissue hypoperfusion and oxygenation, and for measuring blood flow resistance in the renal vessels of ICU patients.¹⁰

Sampling interlobar or arcuate renal arteries with pulsed Doppler ultrasound allows obtaining a "low resistance" profile characteristic of territories with high perfusion at rest. In intrarenal arteries, the classic morphology of the Doppler waveform is characterized by a pronounced systolic peak, followed by an upward movement with the so-called early systolic peak; followed by a decreasing portion of the wave that represents its diastolic component. By combining the main elements of spectral analysis, the renal resistance index can be calculated using the following formula:

RRI = (maximum systolic velocity - end-diastolic velocity) / maximum systolic velocity¹¹

Evidence of a direct correlation between RRI and cardiovascular damage is increasingly frequent; therefore, RRI has been proposed as a new tool for monitoring patients in the ICU.

Under normal conditions, renal artery blood flow occurs during both the systolic and diastolic phases. In contrast, in various pathological conditions such as shock, systemic inflammation, and obstruction, renal arterial blood flow decreases and may even reverse during the diastolic phase, causing an increase in RRI.¹¹

A large body of evidence shows that RRI is a valid index of vascular impedance resulting from the interaction between vascular pulsatility and compliance. Furthermore, a linear correlation between RRI and pulse pressure, which can be considered the most direct hemodynamic expression of systemic vascular compliance, has been well-documented in animal and clinical models. Renal perfusion, much like cerebral perfusion, is characterized by high flows maintained throughout the entire cardiac cycle, which are transmitted unchanged to the renal arterioles. Various conditions cause reductions in vessel compliance (Table 1), that is, an increase in micro- and macrovascular impedance, an increase in pulse pressure, and the consequent elevation of RRI, which heavily depend on cardiac function and, therefore, vary inversely with heart rate and directly with systolic cardiac output.¹¹

Pulse pressure is related to cardiac function and systemic arterial compliance, affecting the maximum systolic velocity value. The vascular compliance of large arteries determines arterial pressure pulsatility; consequently, under conditions of reduced systemic compliance, RRI results are strongly modified.¹²

Additionally, RRI is considered a marker of renal damage progression and an indicator of irreversible damage in chronic renal failure.⁹

A major limitation of intrarenal Doppler is its technique; since the vessels are small, the Doppler sample moves out of the plane with respiration. Other factors, besides right atrial pressure, can alter the venous waveform, such as structural abnormalities of the kidney and advanced chronic kidney disease.¹²

In the clinical context of septic shock, acute kidney injury is a common complication and its timely prediction can be challenging. Determining RRI during the first 24 hours appeared to be useful for anticipating sepsis-induced AKI, especially when combined with central venous pressure measurement. The diagnosis of the renal resistance index in predicting the short-term reversibility of acute kidney injury was confirmed in a recent systematic review.¹³

Measuring the renal resistance index via Doppler ultrasonography in subjects with signs of venous congestion is an effective tool to predict patients who will respond to diuretics, and even to predict who will require renal replacement therapy, since most cases with sepsis or those evolving into septic shock develop some degree of renal injury.⁴ It is a non-invasive method that can be performed at the patient's bedside, offering advantages over other methods.¹⁴

Therefore, it is important to perform these determinations upon admission to the intensive care unit as a baseline measurement and subsequently after vasopressor use, specifically in patients with sepsis from any source and with a diagnosis of septic shock according to the international guidelines of the Surviving Sepsis Campaign 2021, admitted to the intensive care unit of Hospital Angeles Pedregal.

The objective of the study was to compare whether the renal resistance index in cases with a diagnosis of sepsis and septic shock from any source (pulmonary, abdominal, urinary, soft tissues) upon admission to the intensive care unit undergoes modifications with the use of norepinephrine to maintain a MAP of 65 mmHg in patients without prior acute kidney injury.

MATERIAL AND METHODS

A descriptive, longitudinal, prospective, and single-center study was conducted. Forty-two patients from the intensive care unit of Hospital Angeles Pedregal were included, in the period from February to May 2022, with a diagnosis of sepsis and septic shock from any source. A renal Doppler was performed upon admission and a subsequent measurement was taken after vasopressor use (Figures 1 and 2). Baseline renal resistance index values were obtained via renal Doppler in patients with a diagnosis of sepsis upon admission to the intensive care unit; as they progressed to septic shock and vasopressor initiation, measurements were performed to obtain the renal resistance index again and record its changes in vasopressor-dependent cases to maintain MAP above 65 mmHg. These notations and changes were recorded by the investigator and a second observer to corroborate the proper position of the transducer, as well as to locate the interlobar artery (Figures 3 and 4).

A descriptive statistical analysis was performed using measures of central tendency and dispersion, and bar graphs were used. For the comparative analysis, Pearson's correlation coefficient was used (Figura 5).

RESULTS

Forty-two patients with a diagnosis of sepsis and septic shock, mainly of abdominal, pulmonary, and urinary origin, were included. Their renal resistance index was measured after initial fluid management, recording it in a database. In patients diagnosed with septic shock, vasopressor therapy was started with norepinephrine as the first choice to maintain mean arterial pressure above 65 mmHg. Ultrasonography was used to measure RRI in both groups.

In patients diagnosed with sepsis of abdominal origin according to international Surviving Sepsis guidelines, the average renal resistance index ranged from 0.6 to 1; however, some of these patients progressed to septic shock, which led to an increase in the renal resistance index at higher vasopressor doses (RRI 1.2) in some individuals. The correlation coefficient was 0.2369033.

DISCUSSION

In the context of this study, it was observed that the administration of norepinephrine in patients with septic shock did not result in significant changes in RRI, with a low correlation (0.2369033) between the dose of norepinephrine and variations in RRI. These findings contrast with previous studies indicating that increasing mean arterial pressure via vasopressors could reduce renal vascular resistance, suggesting a more favorable perfusion response. However, other authors have reported results similar to ours, in which RRI remains unaltered by vasopressor intervention, indicating a possible lack of microvascular response in certain patients with septic shock.

The heterogeneity in responses could be due to several factors, such as the presence of microvascular thrombosis and inflammatory mediators that alter vascular reactivity, as well as variability in renal vessel compliance among individuals. Although RRI is a useful tool for evaluating renal vascular resistance, in critical situations such as septic shock, the utility of this index could be limited by intrinsic factors of the pathology and inter-individual variability.

The study highlights the relevance of continuing to explore more precise hemodynamic evaluation methods and the importance of contextualizing the interpretation of RRI within each patient's clinical environment.

CONCLUSIONS

The objective of this study was to observe whether there are changes in the renal resistance index related to the dose in patients requiring norepinephrine admitted to the intensive care unit. We conclude from the results that patients aged 50 to 60 years were the most affected, type 2 diabetes was the most common comorbidity, and diuretic therapy was the most widely used treatment (Figure 6). It was observed that there are no significant changes regarding the resistance index and its relationship with the dose of norepinephrine, with a correlation index of 0.2369033.

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AFFILIATIONS

¹ Hospital Angeles Pedregal. Ciudad de México, México.

² Unidad de Terapia Intensiva. Facultad Mexicana de Medicina, Universidad La Salle México.

³ Departamento de Urgencias.

⁴ Jefe Unidad de Terapia Intensiva y Cuidados Coronarios.

If you wish to consult the supplementary data for this article, please contact editorial.actamedica@saludangeles.mx

CORRESPONDENCE

Marlet Meyer Talón. Correo electrónico: marleth_meyer@hotmail.com

Received: 2024-10-25. Accepted: 2025-04-19.