The significance of joint evaluation of gastrointestinal ultrasound results and renal artery resistance index for assessing intestinal-renal syndrome in sepsis patients: a retrospective study

Introduction

In recent years, sepsis has remained a leading cause of mortality among patients in the intensive care unit (ICU). Global data indicate that the incidence of sepsis ranges from 270 to 670 cases per 100,000 person-years, with mortality rates as high as 30–50% (1). In China, the incidence of sepsis is reported to be 236 cases per 100,000 person-years, with a mortality rate of approximately 20.6% (2). Intra-abdominal infections (IAI) are the second most common source of sepsis, accounting for 20–25% of ICU infections (3).

Intestinal-renal syndrome was first proposed by Professor Ritz in renal dialysis patients and described in related pathophysiology; it refers to the pathophysiological process of mutual influence between intestinal and renal functions. Patients with renal insufficiency, especially during renal dialysis, often have circulatory instability, which leads to inflammation, ischemia, and necrosis of the intestinal mucosa, which reduces the normal intestinal acid excretion and detoxification, reduces the secretion of immunoglobulin A (IgA), slows down peristalsis, increases the mucosal permeability and even the disorder and displacement of intestinal flora, releases endotoxin, and spreads to multiple organs and systems. Meanwhile, impaired intestinal function can also stimulate the body to produce interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α), reduce the calcium influx of cardiomyocytes, leading to myocardial ischemia, affecting cardiovascular function and circulatory stability, and aggravating the loss of renal function. In sepsis patients, the incidence of intestinal-renal syndrome can be as high as 30–40%, significantly increasing patient mortality (4). Ultrasound examination, as a non-invasive and portable bedside method, has significant value in assessing intestinal and renal blood perfusion. The superior mesenteric artery resistance index (SMARI) and renal artery resistance index (RRI) are sensitive indicators reflecting organ blood perfusion. Studies have shown that SMARI >0.85 and RRI >0.70 are closely associated with poor prognosis in sepsis patients (5,6).

Currently, there is limited research on the joint application of SMARI and RRI in assessing intestinal-renal syndrome in sepsis patients. Some researchers argue that a single indicator may not comprehensively reflect organ function status, and the combined application of multiple indicators might improve assessment accuracy. However, other studies question the clinical practicality of joint evaluation, suggesting it may increase medical costs (7). Therefore, the application value of SMARI and RRI in evaluating sepsis-related intestinal-renal syndrome remains controversial.

This retrospective cohort study aimed to evaluate the progression of intestinal-renal syndrome in sepsis patients with IAI using a combined application of SMARI and RRI. We hypothesize that the joint application of SMARI and RRI may more accurately reflect organ function status than single indicators, providing an objective basis for clinical decision-making. The innovation of this study lies in its systematic evaluation of the combined application value of SMARI and RRI in sepsis-related intestinal-renal syndrome, potentially offering new insights and methods for improving the prognosis of sepsis patients. We present this article in accordance with the STROBE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-2024-2905/rc).

Methods

Study design and participants

This retrospective observational study was conducted in the ICU of Zhangzhou Affiliated Hospital of Fujian Medical University from January 2024 to December 2024. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study protocol was approved by the Ethics Committee of Zhangzhou Affiliated Hospital of Fujian Medical University (No. 2024KYZ033). Informed consent was waived by the Ethics Committee of Zhangzhou Affiliated Hospital of Fujian Medical University, as this research did not involve commercial interests and the data were analyzed anonymously.

Patients aged ≥18 years admitted to the ICU with sepsis or septic shock induced by IAI were eligible for inclusion. Sepsis and septic shock were defined according to the Sepsis-3 criteria. The exclusion criteria were as follows: (I) open abdominal injury; (II) abdominal masses and/or profuse fluid in the abdominal cavity; (III) end-stage renal disease; (IV) unclear ultrasound images; and (V) length of ICU stay <72 hours.

A total of 74 patients meeting the inclusion criteria were enrolled. Sample size was determined based on a power analysis with α=0.05 and β=0.2, assuming a 30% difference in the primary outcome between groups.

Data collection and variables

Demographic and clinical data were collected from electronic medical records, including age, sex, Acute Physiology and Chronic Health Evaluation version II (APACHE II) score, length of ICU stay, and first medical contact (FMC) time. The primary exposure variables were gastrointestinal ultrasound parameters and RRI. The primary outcome was 28-day all-cause mortality, defined as death occurring within 28 days of ICU admission. Mortality status was ascertained through hospital electronic medical records. For patients discharged alive before day 28, survival status was confirmed via telephone follow-up. Patients with unknown survival status (if any) were censored at the date of last confirmed contact.

Ultrasound measurements were performed at three time points: upon ICU admission (T0), 24 hours (T24), and 72 hours (T72) after admission. The following parameters were assessed: SMARI, the ultrasonographic transverse area of gastric antrum (CSA), colonic diameter (Diam), and RRI, and serum creatinine (SCR) was measured as an additional indicator of renal function. Total fluid injection volumes at 24 and 72 hours were also recorded.

Ultrasound examination protocol

All ultrasound examinations were performed by two experienced sonographers (each with >5 years of critical care ultrasound experience) using a Sonosite EDGE device (FUJIFILM Sonosite, Bothell, WA, USA) with a 2–5 MHz convex array probe. The sonographers were blinded to the patients’ clinical data and outcomes. Examinations were conducted in accordance with the Technical Specification for Clinical Application of Critical Ultrasound in China (8). It is routine practice to regularly check the SMARI/RRI of each ICU patient at a fixed time point. Three patients with a body mass index of 35 kg/m² or higher and five patients with severe abdominal gas disturbances were removed from the trial group because we could not obtain a clear picture or reliable data, but all these patients were treated according to the standard of care.

For SMARI measurement (9), patients were placed in a supine position (7). The probe was positioned along the longitudinal section of the abdominal aorta to visualize the long axis of the superior mesenteric artery. Measurements were taken 1.0–2.0 cm distal to the origin of the artery. The pulsed wave Doppler was used to obtain the blood flow velocity spectrum, with an angle of 25°–45° between the bloodstream and the sound beam. The waveform was recorded for three cardiac cycles, and the mean value was calculated (Figure 1).

Figure 1 Measurement of SMARI. AT, acceleration time; MDV, maximum diastolic velocity; PI, pulsatility index; RI, resistance index; S/D, systolic/diastolic velocity ratio; SMARI, superior mesenteric artery resistance index; TAM, time-averaged mean velocity; TAP, time-average peak velocity; Vmax, maximum velocity.

CSA was measured with the patient in a right lateral recumbent position and the head of the bed elevated 30°–45°. The gastric antrum was imaged on the right side of the midsagittal axis below the xiphoid process. The area was computed graphically to estimate gastric content volume (10).

The Diam in this experiment refers to the diameter of the colon, including the right ascending colon and the left descending colon, and the clearest picture obtained was recorded as the experimental data. The colonic pocket was used as a definitive mark to distinguish the colon from the small intestine. For left hemicolon examination, the ultrasound probe was placed in the left abdomen, between the left midclavicular line and the anterior axillary line, along the descending colon, from the top to the bottom, and the probe could be rotated 90° if necessary to increase the transverse sliding scanning. For right hemicolon examination, the ultrasound probe was placed in the right abdomen, between the right midclavicular line and the anterior axillary line, along the descending intestine, from top to bottom, and rotated 90° to increase the lateral slide scan if necessary.

For RRI measurement (11), intrarenal vessels were located on the coronal plane of the kidney. Blood flow velocity was measured for two to three arteries of each kidney, with three continuous velocity waveforms obtained for each artery. The median value was taken as the resistance index of each artery, and the median resistance index of multiple arteries was considered the resistance index of each kidney (Figure 2).

Figure 2 Measurement of RRI. A, peak systolic velocity; A/B, systolic/diastolic velocity ratio; B, end diastolic velocity; ET, ejection time; RI, resistance index; RRI, renal artery resistance index.

Statistical analysis

Data were analyzed using the software SPSS 25.0 (IBM Corp., Armonk, NY, USA). The Shapiro-Wilk test was used to assess the normality of continuous variables. Normally distributed variables were presented as mean ± standard deviation and compared using Student’s t-test. Non-normally distributed variables were presented as median (interquartile range) and compared using the Mann-Whitney U test. Categorical variables were presented as frequencies (percentages) and compared using the Chi-squared test or Fisher’s exact test.

Repeated measures analysis of variance (ANOVA) with Bonferroni correction was used for pairwise comparisons of ultrasound parameters at different time points within each group. Receiver operating characteristic (ROC) curves were constructed to evaluate the predictive value of ultrasound parameters for 28-day mortality. The area under the curve (AUC) was calculated, and optimal cut-off values were determined using the Youden index.

A two-sided P value <0.05 was considered statistically significant. To address potential confounders, multivariate logistic regression analysis was performed, adjusting for age, APACHE II, and FMC.

Results

Patient characteristics

A total of 74 patients were included in this study, comprising 46 males and 28 females. Based on 28-day survival, patients were divided into two groups: a survival group (n=51) and a death group (n=23). Baseline characteristics, including age, APACHE II score, length of hospital stay, total fluid injection at 24 and 72 hours, and FMC time were compared between the two groups. A statistically significant difference was observed in FMC time between the survival and death groups (P<0.05) (Table 1).

Comparison of ultrasound parameters and SCR

Upon admission, 24 hours, and 72 hours after hospitalization, the following parameters were measured and compared between the survival and death groups: RRI, SMARI, CSA, Diam, SCR.

At 24 hours after hospitalization (Table 2), the survival group showed significant improvements in RRI, CSA, and Diam compared to the death group (P<0.001 for all). SMARI also showed improvement in the survival group, whereas SCR did not show significant improvement at this time point.

At 72 hours after hospitalization (Table 3), the survival group demonstrated significant improvements in all parameters (RRI, SMARI, CSA, Diam, and SCR) compared to the death group (P<0.001 for all).

Longitudinal analysis of parameters

Single factor pairwise comparisons using the Bonferroni method were conducted for RRI, SMARI, CSA, Diam, and SCR within the survival group at admission, 24 hours, and 72 hours after hospitalization (Table 4). In the survival group, RRI and SCR showed statistically significant differences between admission and 24 hours, and between 24 and 72 hours. SMARI, CSA, and Diam did not show significant improvement at 24 hours compared to admission, but significant improvements were observed at 72 hours compared to 24 hours. In the death group, no concurrent improvements in gastrointestinal and renal function parameters were observed over the three time points.

ROC curve analysis

ROC curve analysis was performed to evaluate the predictive value of RRI, SMARI, Diam, and SCR for 28-day mortality.

At 24 hours after hospitalization (Tables 5,6, Figure 3): RRI ≤1.03 cm/s: survival rate 87.5%, AUC 0.897. SMARI ≤0.88 cm/s: survival rate 97.6%, AUC 0.943. Diam ≤3.6 cm: survival rate 95.7%, AUC 0.928. SCR ≤3.6 mg/dL: survival rate 73.8%, AUC 0.546. The combined evaluation of these four parameters at 24 hours predicted a survival rate of 97.9% with an AUC of 0.974.

Figure 3 ROC curve of RRI, SMARI, Diam and SCR jointly evaluated at the 24th hour after hospitalization. 1, the check at the 24th hour; Diam, colonic diameter; PRE, predictive model; RRI, renal artery resistance index; ROC, receiver operating characteristic; SCR, serum creatinine; SMARI, superior mesenteric artery resistance index.

At 72 hours after hospitalization (Tables 7,8, Figure 4): RRI ≤0.93 cm/s: survival rate 93.2%, AUC 0.913. SMARI ≤0.88 cm/s: survival rate 96.2%, AUC 0.977. Diam ≤3.6 cm: survival rate 100%, AUC 0.987. SCR ≤3.2 mg/dL: survival rate 79.7%, AUC 0.812. The combined evaluation of these four parameters at 72 hours predicted a survival rate of 98% with an AUC of 0.980.

Figure 4 ROC curves of RRI 2, SMARI 2, and SCR 2 jointly evaluated at the 72nd hour after hospitalization. PRE, predictive model; ROC, receiver operating characteristic; RRI, renal artery resistance index; SCR, serum creatinine; SMARI, superior mesenteric artery resistance index.

Pairwise comparisons of ROC curves showed that the combined predictive model (PRE) had significantly higher AUC compared to individual parameters, except for SMARI, which showed no significant difference from the combined model.

These results suggest that the joint evaluation of gastrointestinal ultrasound parameters (SMARI, CSA, Diam) and renal function indicators (RRI, SCR) provides a robust predictive model for assessing the progression of intestinal-renal syndrome in sepsis patients.

Discussion

This retrospective cohort study investigated the association between gastrointestinal ultrasound parameters and RRI with the progression of intestinal-renal syndrome in sepsis patients. Over a 10-month period, we followed 74 consecutive patients admitted to the ICU with sepsis or septic shock due to IAI. The study’s strength lies in its use of multiple time point ultrasound measurements and the combination of both gastrointestinal and renal parameters. Our findings suggest that SMARI, Diam, RRI, and SCR are reliable indicators for assessing the progression of intestinal-renal syndrome. The combined evaluation of these parameters at 72 hours post-admission predicted 98% survival with high accuracy [AUC 0.980, 95% confidence interval (CI): 0.918–0.998].

Our findings on the predictive value of gastrointestinal ultrasound parameters and RRI for assessing intestinal-renal syndrome in sepsis patients are consistent with several recent studies. For instance, a prospective observational study involving 120 sepsis patients found that SMARI and RRI are significant predictors of 28-day mortality, with AUCs of 0.892 and 0.865, respectively (12). However, our study demonstrated higher predictive accuracy, particularly when combining multiple parameters. This improvement may be attributed to our more frequent measurement intervals and the inclusion of additional ultrasound parameters such as the Diam. In contrast, a retrospective study (13) with a larger sample size (n=200) reported lower predictive values for SMARI and RRI (AUCs of 0.78 and 0.72). This discrepancy could be due to differences in patient populations, as that study included a broader range of sepsis etiologies beyond IAI. Additionally, our study’s focus on early assessment (within 72 hours of ICU admission) may have captured more dynamic changes in organ perfusion. The observed slower recovery of gastrointestinal function compared to renal function in our study aligns with the findings of Kapadia et al. (14), who proposed that this difference is related to the structural complexity and extensive mucosal surface area of the gastrointestinal tract, making it more susceptible to prolonged ischemia-reperfusion injury. Our results underscore the importance of integrating multiple ultrasound parameters for a more comprehensive evaluation of organ dysfunction in sepsis, potentially guiding more targeted therapeutic interventions.

This study offers significant clinical value by providing a comprehensive, non-invasive approach to monitoring intestinal-renal syndrome progression in sepsis patients. Our findings demonstrate that the combined evaluation of SMARI, Diam, RRI, and SCR offers superior predictive accuracy for patient outcomes compared to individual parameters alone. This multi-parameter approach addresses a critical gap in current clinical practice, where the assessment of organ dysfunction in sepsis often relies on less specific or more invasive methods. The high specificity and AUC of SMARI, in particular, suggest its potential as an independent predictor of intestinal-renal syndrome progression (15). These results could significantly impact clinical decision-making, especially in guiding the timing of reverse fluid resuscitation and initiation of enteral nutrition. We propose that incorporating these ultrasound parameters into routine ICU monitoring protocols could lead to more personalized and timely interventions, potentially improving patient outcomes. However, the widespread implementation of this approach would require training clinicians in specialized ultrasound techniques (16). Future research should focus on validating these findings in larger, multi-center studies and exploring the potential of SMARI as a standalone monitoring tool. Additionally, investigating the correlation between these parameters and long-term outcomes could further enhance their clinical utility.

This study offers several notable strengths in its design and analytical approach. Firstly, we routinely used ultrasound to monitor SMARI/RRI allowed for real-time data collection at multiple time points, providing a dynamic view of disease progression. The inclusion of both gastrointestinal and renal parameters offers a comprehensive assessment of the intestinal-renal syndrome, addressing a significant gap in current clinical practice. The use of non-invasive ultrasound techniques, particularly the novel application of SMARI in this context, represents a significant advancement in bedside monitoring for critically ill patients (17). Our statistical analysis, including ROC curve analysis and pairwise comparisons, provides robust evidence for the predictive value of these parameters. The combination of multiple indicators into a single predictive model enhances the accuracy and clinical utility of our findings. Furthermore, the study’s focus on early assessment within 72 hours of ICU admission offers valuable insights into the critical initial phase of sepsis management. These methodological strengths collectively contribute to the study’s potential to inform and improve clinical decision-making in the management of sepsis-induced intestinal-renal syndrome (18).

This study has several limitations that should be considered when interpreting the results. Firstly, as a single-center study conducted in China, the generalizability of our findings to other populations or healthcare settings may be limited. Further multi-center studies are needed to validate our results across diverse patient populations. Secondly, our exclusion criteria, which included patients with open abdominal injuries, abdominal masses, profuse abdominal fluid, and end-stage renal diseases, limit the applicability of our findings to these specific patient groups. The study’s focus on sepsis induced by IAI also restricts the generalizability to sepsis from other sources. Thirdly, as an observational study, we can only detect associations between the ultrasound parameters and patient outcomes, rather than establish causal relationships. Fourthly, Patients with ICU stays <72 hours were excluded to ensure complete data collection at all three measurement time points (T0, T24, T72). However, this exclusion may have introduced selection bias by omitting patients with rapid clinical deterioration (e.g., early death) or improvement (e.g., early discharge). A sensitivity analysis including these patients (with imputation for missing data) was not performed, which limits the generalizability of our findings. Lastly, although we adjusted for measurable confounding factors, unmeasured confounders may still influence our results. The requirement for trained clinicians to perform gastrointestinal and renal ultrasound examinations may also limit the widespread applicability of this approach in resource-constrained settings.

Conclusions

SMARI, Diam, RRI, and SCR can be monitored to reflect blood perfusion and functional recovery of the gastrointestinal tract and kidneys, serving as objective indicators for assessing the progression of intestinal-renal syndrome. They can guide clinicians in determining when to initiate reverse fluid resuscitation and enteral nutrition.

Acknowledgments

We would like to thank all the patients and their families who participated in this study.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-2024-2905/rc

Data Sharing Statement: Available at https://qims.amegroups.com/article/view/10.21037/qims-2024-2905/dss

Funding: This study was supported by The Climbing Project of the Doctor’s Studio of Zhangzhou Municipal Hospital (No. PDB202201).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2024-2905/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of Zhangzhou Affiliated Hospital of Fujian Medical University (No. 2024KYZ033). Informed consent was waived by the Ethics Committee of Zhangzhou Affiliated Hospital of Fujian Medical University, as this research did not involve commercial interests and the data were analyzed anonymously.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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