The dual effects of dexmedetomidine on intestinal barrier and intestinal motility during sepsis.

BACKGROUND: Sepsis, characterized by dysregulated host responses to infection, remains a critical global health concern, with high morbidity and mortality rates. The gastrointestinal tract assumes a pivotal role in sepsis due to its dual functionality as a protective barrier against injurious agents and as a regulator of motility. Dexmedetomidine, an α2-adrenergic agonist commonly employed in critical care settings, exhibits promise in influencing the maintenance of intestinal barrier integrity during sepsis. However, its impact on intestinal motility, a crucial component of intestinal function, remains incompletely understood. METHODS: In this study, we investigated dexmedetomidine's multifaceted effects on intestinal barrier function and motility during sepsis using both in vitro and in vivo models. Sepsis was induced in Sprague-Dawley rats via cecal ligation and puncture. Rats were treated with dexmedetomidine post-cecal ligation and puncture, and various parameters were assessed to elucidate dexmedetomidine's impact. RESULTS: Our findings revealed a dichotomous influence of dexmedetomidine on intestinal physiology. In septic rats, dexmedetomidine administration resulted in improved intestinal barrier integrity, as evidenced by reduced mucosal hyper-permeability and morphological alterations. However, a contrasting effect was observed on intestinal motility, as dexmedetomidine treatment inhibited both the frequency and amplitude of contractions in isolated intestinal strips and decreased the distance of ink migration in vivo. Additionally, dexmedetomidine suppressed the secretion of pro-motility hormones while having no influence on hormones that inhibit intestinal peristalsis. CONCLUSION: The study revealed that during sepsis, dexmedetomidine exhibited protective effects on barrier integrity, although concurrently it hindered intestinal motility, partly attributed to its modulation of pro-motility hormone secretion. These findings underscore the necessity of a comprehensive understanding of dexmedetomidine's impact on multiple facets of gastrointestinal physiology in sepsis management, offering potential implications for therapeutic strategies and patient care.

Shear wave elastography: A noninvasive approach for assessing acute kidney injury in critically ill patients.

Traditional markers, such as serum creatinine and blood urea nitrogen, frequently show delayed elevations following acute kidney injury (AKI), limiting their utility for prompt detection and timely intervention in AKI management. Shear wave elastography (SWE) exhibits potential for AKI diagnosis by measuring tissue stiffness. Our study aimed to evaluate the diagnostic performance of SWE in detecting AKI by measuring the stiffness of kidney tissue. Between July 2022 and December 2022, a total of 103 consecutive participants who met the eligibility criteria were prospectively enrolled, underwent SWE measurements, and were classified into AKI or non-AKI groups based on the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) criteria. A receiver operating characteristic (ROC) curve was drawn to examine the feasibility of differentiating between AKI and non-AKI patients and assessing diagnostic performance. The effects of tissue anisotropy on SWE measurements were also examined. Our results revealed that patients in the AKI group exhibited significantly increased stiffness values in specific kidney regions compared with those in the non-AKI group. For the diagnosis of AKI, the optimal cut-off values were identified as 9.9 kPa, 2.9 kPa, and 4.4 kPa for the upper pole medulla, middle cortex, and middle medulla, respectively, in the longitudinal plane. Correspondingly, the areas under the ROC curves for these regions were 0.737 (95% confidence interval [CI]: 0.637, 0.822), 0.736 (95% CI: 0.637, 0.821), and 0.784 (95% CI: 0.688, 0.861). Additionally, we observed a significant variability in stiffness values due to tissue anisotropy, specifically in the segments of the upper pole cortex, and medulla across both longitudinal and transverse planes. SWE serves as a noninvasive approach for the quantification of tissue stiffness and shows promise as an adjunctive tool for the assessment of AKI.

ALTERATION IN SHEAR WAVE ELASTOGRAPHY IS ASSOCIATED WITH ACUTE KIDNEY INJURY: A PROSPECTIVE OBSERVATIONAL PILOT STUDY.

ABSTRACT: Background: Kidney stiffness could change during kidney disease. We hypothesize that acute kidney injury (AKI) would increase renal stiffness. Therefore, evaluating kidney Young's modulus (YM; a measure of tissue stiffness) using shear wave elastography (SWE) might help to diagnose AKI. Methods: This research was divided into two studies. Study A: Male C57BL/6 mice were used to observe kidney YM changes induced by sepsis-associated AKI, which was established by cecal ligation and puncture (CLP). Study B included 54 consecutive critically ill patients with or without AKI. Changes in renal YM were observed. Results: Study A: CLP mice showed a significantly higher kidney YM compared with the sham group. The YM gradually increased from CLP 0 hours to CLP 24 hours, and presented a fair relationship with the renal tubular injury score ( R2 = 0.71) and serum creatinine ( R2 = 0.73). Study B: YM was easily accessible, and the intraclass correlation coefficient ranged from 0.62 to 0.84. Kidney YM was higher in AKI patients and gradually increased from non-AKI to AKI III patients. Furthermore, the YM in the upper, middle, and lower poles of the renal cortex presented a fair relationship with kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin ( R2 ranging from 0.4 to 0.58), and the areas under the curve of the above five indicators for the diagnosis of AKI were 0.7, 0.73, 0.70, 0.74, and 0.79, respectively. Conclusion: SWE-derived estimates of renal stiffness are higher in AKI patients and sepsis-associated AKI mice. However, it has no advantage over NGAL and KIM-1. Trial Registration: Chinese Clinical Trial Registry No: ChiCTR2200061725. Retrospectively registered July 1, 2022, https://www.chictr.org.cn/showproj.aspx?proj=169359 .

[Quantitative approach for calculation of pharmacodynamic interactions and simulation of combined response].

OBJECTIVE: An approach is set up to calculate pharmacodynamic interaction and simulate the combined response. METHOD: An orthogonal design with 1-level = high dose and 2-level = low dose was adopted. An example of the compound with four components was applied to evaluate this quantitative approach. The bias was evaluated by the both scatter plots. RESULT: This approach can calculate the value of each component with different dose by its contribution to combined response, and the value is related to the importance of a compound. Drug interactions were evaluated among the combinations in each group. The prediction model performed well and simulated the combined response in the different of components in combination. CONCLUSION: The approach can be used in the similar research, and it also provides predictions of component combinations from the other studies by simulation.