Effects of ulinastatin on renal perfusion evaluated by Doppler ultrasonography in a porcine model of septic shock.
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SUBMITTER: Hang CC
PROVIDER: S-EPMC8495549 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundSepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Mortality of patients with sepsis is high and largely unchanged throughout the past decades. Animal models have been widely used for the study of sepsis and septic shock, but translation into effective treatment regimes in the clinic have mostly failed. Pigs are considered as suitable research models for human diseases due to their high comparability and similarity to human anatomy, genetics, and the immune system. We here evaluated the previously reported models of septic shock in pigs and established a novel model of polymicrobial sepsis that meets the clinical criteria of septic shock in pigs.Materials and methodsThe literature search was performed using the keywords "pig", "sepsis" and "septic shock". For the establishment of septic shock in n = 10 German landrace pigs, mechanical ventilation was initiated, central venous and arterial lines and invasive hemodynamic monitoring via pulse contour cardiac output measurement (PiCCO) established. Peritoneal polymicrobial faecal sepsis was induced by application of 3 g/kg body weight faeces into the abdominal cavity. Septic shock was defined according to the third international consensus definitions (Sepsis-3). Upon shock, pigs underwent the 1-h bundle for the treatment of human sepsis. Cytokine levels were measured by ELISA.ResultsPublished porcine sepsis models exhibited high methodological variability and did not meet the clinical criteria of septic shock. In our model, septic shock developed after an average of 4.8 ± 0.29 h and was associated with a reproducible drop in blood pressure (mean arterial pressure 54 ± 1 mmHg) and significant hyperlactatemia (3.76 ± 0.65 mmol/L). Septic shock was associated with elevated levels of interleukin-6 (IL6) and initial cardiac depression followed by a hyperdynamic phase with significant loss of systemic vascular resistance index after initial resuscitation. In addition, organ dysfunction (acute kidney injury) occurred.ConclusionsWe here established a model of septic shock in pigs that meets the clinical criteria of septic shock utilized in human patients. Our model may thus serve as a reference for clinically relevant sepsis research in pigs.
| S-EPMC10235002 | biostudies-literature
Project description:Acute kidney injury (AKI) following transcatheter aortic valve replacement (TAVR) is associated with a dismal prognosis. Elevated renal resistive index (RRI), through renal Doppler ultrasound (RDU) evaluation, has been associated with AKI development and increased systemic arterial stiffness. Our pilot study aimed to investigate the performance of Doppler based RRI to predict AKI and outcomes in TAVR patients. From May 2018 to May 2019, 100 patients with severe aortic stenosis were prospectively enrolled for TAVR and concomitant RDU evaluation at our institution (Nouvel Hôpital Civil, Strasbourg University, France). AKI by serum Creatinine (sCr-AKI) was defined according to the VARC-2 definition and AKI by serum Cystatin C (sCyC-AKI) was defined as an sCyC increase of greater than 15% with baseline value. Concomitant RRI measurements as well as renal and systemic hemodynamic parameters were recorded before, one day, and three days after TAVR. It was found that 10% of patients presented with AKIsCr and AKIsCyC. The whole cohort showed higher baseline RRI values (0.76 ± 0.7) compared to normal known and accepted values. AKIsCyC had significant higher post-procedural RRI one day (Day 1) after TAVR (0.83 ± 0.1 vs. 0.77 ± 0.6, CI 95%, p = 0.005). AUC for AKIsCyC was 0.766 and a RRI cut-off value of ≥ 0.795 had the most optimal sensitivity/specificity (80/62%) combination. By univariate Cox analysis, Mehran Risk Score, higher baseline right atrial pressure at baseline > 0.8 RRI values one day after TAVR (HR 6.5 (95% CI 1.3-32.9; p = 0.021) but not RRI at baseline were significant predictors of AKIsCyC. Importantly, no significant impact of baseline biological parameters, renal or systemic parameters could be demonstrated. Doppler-based RRI can be helpful for the non-invasive assessment of AKI development after TAVR.
| S-EPMC7230258 | biostudies-literature
Project description:PurposeTerlipressin improves renal function in patients with septic shock. However, the mechanism remains unclear. Here, we aimed to evaluate the effects of terlipressin on renal perfusion in patients with septic shock.Materials and methodsThis pilot study enrolled patients with septic shock in the intensive care unit of the tertiary hospital from September 2019 to May 2020. We randomly assigned patients to terlipressin and usual care groups using a 1:1 ratio. Terlipressin was intravenously pumped at a rate of 1.3 μg/kg/hour for 24 h. We monitored renal perfusion using renal contrast-enhanced ultrasound (CEUS). The primary outcome was peak sonographic signal intensity (a renal perfusion parameter monitored by CEUS) at 24 h after enrollment.Results22 patients were enrolled in this study with 10 in the terlipressin group and 12 in the usual care group. The baseline characteristics of patients between the two groups were comparable. The peak sonographic signal intensity at 24 h after enrollment in the terlipressin group (60.5 ± 8.6 dB) was significantly higher than that in the usual care group (52.4 ± 7.0 dB; mean difference, 7.1 dB; 95% CI, 0.4-13.9; adjusted p = .04). Patients in the terlipressin group had a lower time to peak, heart rates, norepinephrine dose, and a higher stroke volume at 24 h after enrollment. No significant difference in the urine output within 24 h and incidence of acute kidney injury within 28 days was found between the two groups.ConclusionsTerlipressin improves renal perfusion, increases stroke volume, and decreases norepinephrine dose and heart rates in patients with septic shock.
| S-EPMC9307113 | biostudies-literature
Project description:Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to an infection; it carries a risk for mortality, considerably exceeding that of a mere infection. Sepsis is the leading cause for acute kidney injury (AKI) and the requirement for renal replacement therapy (RRT) in intensive care unit (ICU) patients. Almost every second critically ill patient with sepsis will develop AKI. In septic shock, the dysregulated host response to infectious pathogens leads to a cytokine storm with uncontrolled production and release of humoral proinflammatory mediators that evoke cellular toxicity and promote the development of organ dysfunction and increased mortality. In addition to treating AKI, RRT techniques can be employed for extracorporeal adsorption of inflammatory mediators using specifically developed adsorption membranes, hemoperfusion sorbent cartridges or columns; these techniques are intended to decrease the level and early deleterious effects of circulating proinflammatory cytokines and endotoxins during the first hours and days of septic shock treatment, in order to improve patient outcomes. Several methods and devices, such as high cut-off membranes, the Oxiris®-AN69 membrane, CytoSorb® and HA380 cytokine hemoadsorption, polymyxin B endotoxin adsorption, and plasmapheresis have been examined in small study series or are under evaluation as ways of improving patient outcomes in septic shock. However, to date, the data on actual outcome benefits have remained controversial, as discussed in this review.
| S-EPMC8508758 | biostudies-literature
Project description:Intrarenal Doppler ultrasonography is a non-invasive method to evaluate the renal blood flow in patients with renal arterial stenosis as well as chronic kidney diseases (CKD). Until recently, the relationship between ultrasonography findings and CKD stage has not been fully understood. Overall, 162 patients with CKD without apparent renal arterial stenosis were included in this study, and the pulsed-wave Doppler ultrasonography findings were evaluated in terms of the following parameters: peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI) at the renal arterial trunk, hilum, segmental, and interlobar regions. Age showed a significant negative correlation with the estimated glomerular filtration rate (eGFR), kidney size, and aortic PSV. Additionally, age showed a significant positive correlation with RI in all 4 regions. The eGFR showed a positive correlation with the aortic PSV and kidney size, but a negative correlation with RI. Both age and eGFR were found to be independently associated with aortic blood flow. On the intrarenal ultrasound, EDV and RI showed stronger correlations with eGFR than PSV, suggesting that the former indices would be better markers of renal function. In particular, the interlobar EDV was found to be the best index that reflects renal function. Although the RI is also a good marker of renal function, it is confounded by age; thus, its utility would be weaker than that of the EDV. In conclusion, intrarenal pulsed-wave Doppler ultrasonography is a useful tool to estimate and evaluate the renal function; the interlobar EDV may be the best index to estimate the effective perfusion and filtration of the kidneys.
| S-EPMC6711528 | biostudies-literature
Project description:Sepsis is one of the main reasons for intensive care unit admission and is responsible for high morbidity and mortality. The usual hemodynamic targets for resuscitation of patients with septic shock use macro-hemodynamic parameters (hearth rate, mean arterial pressure, central venous pressure). However, persistent alterations of microcirculatory blood flow despite restoration of macro-hemodynamic parameters can lead to organ failure. This dissociation between macro- and microcirculatory compartments brings a need to assess end organs tissue perfusion in patients with septic shock. Traditional markers of tissue perfusion may not be readily available (lactate) or may take time to assess (urine output). The skin, an easily accessible organ, allows clinicians to quickly evaluate the peripheral tissue perfusion with noninvasive bedside parameters such as the skin temperatures gradient, the capillary refill time, the extent of mottling and the peripheral perfusion index.
| S-EPMC6419794 | biostudies-literature
Project description:BackgroundWe sought to determine the effects of alternative resuscitation strategies on microcirculatory perfusion and examine any association between microcirculatory perfusion and mortality in sepsis.MethodsThis was a prospective, formally designed substudy of participants in the Protocolized Care in Early Septic Shock (ProCESS) trial. We recruited from six sites with the equipment and training to perform these study procedures. All subjects were adults with septic shock, and each was assigned to alternative resuscitation strategies. The two main analyses assessed (1) the impact of resuscitation strategies on microcirculatory perfusion parameters and (2) the association of microcirculatory perfusion with 60-day in-hospital mortality. We measured sublingual microcirculatory perfusion using sidestream dark field in vivo video microscopy at the completion of the 6-h ProCESS resuscitation protocol and then again at 24 and 72 h.ResultsWe enrolled 207 subjects (demographics were similar to the overall ProCESS cohort) and observed 40 (19.3%) deaths. There were no differences in average perfusion characteristics between treatment arms. Analyzing the relationship between microcirculatory perfusion and mortality, we found an association between vascular density parameters and mortality. Total vascular density (beta = 0.006, p < 0.003), perfused vascular density (beta = 0.005, p < 0.04), and De Backer score (beta = 0.009, p < 0.01) were higher overall in survivors in a generalized estimating equation model, and this association was significant at the 72-h time point (p < 0.05 for each parameter).ConclusionsMicrocirculatory perfusion did not differ between three early septic shock treatment arms. We found an association between microcirculatory perfusion parameters of vascular density at 72 h and mortality.Trial registrationClinicalTrials.gov, NCT00510835 . Registered on August 2, 2007.
| S-EPMC6245723 | biostudies-literature
Project description:BackgroundAlthough many sepsis treatments have shown efficacy in acute animal models, at present only activated protein C is effective in humans. The likely reason for this discrepancy is that most of the animal models used for preclinical testing do not accurately replicate the complex pathogenesis of human sepsis. Our objective in this study was to develop a clinically applicable model of severe sepsis and gut ischemia/reperfusion (I/R) that would cause multiple organ injury over a period of 48 h.Materials and methodsAnesthetized, instrumented, and ventilated pigs were subjected to a "two-hit" injury by placement of a fecal clot through a laparotomy and by clamping the superior mesenteric artery (SMA) for 30 min. The animals were monitored for 48 h. Wide spectrum antibiotics and intravenous fluids were given to maintain hemodynamic status. FiO(2) was increased in response to oxygen desaturation. Twelve hours following injury, a drain was placed in the laparotomy wound. Extensive hemodynamic, lung, kidney, liver, and renal function measurements and serial measurements of arterial and mixed venous blood gases were made. Bladder pressure was measured as a surrogate for intra-peritoneal pressure to identify the development of the abdominal compartment syndrome (ACS). Plasma and peritoneal ascites cytokine concentration were measured at regular intervals. Tissues were harvested and fixed at necropsy for detailed morphometric analysis.ResultsPolymicrobial sepsis developed in all animals. There was a progressive deterioration of organ function over the 48 h. The lung, kidney, liver, and intestine all demonstrated clinical and histopathologic injury. Acute lung injury (ALI) and ACS developed by consensus definitions. Increases in multiple cytokines in serum and peritoneal fluid paralleled the dysfunction found in major organs.ConclusionThis animal model of Sepsis+I/R replicates the systemic inflammation and dysfunction of the major organ systems that is typically seen in human sepsis and trauma patients. The model should be useful in deciphering the complex pathophysiology of septic shock as it transitions to end-organ injury thus allowing sophisticated preclinical studies on potential treatments.
| S-EPMC3061050 | biostudies-literature
Project description:BackgroundThe decision of when to stop septic shock resuscitation is a critical but yet a relatively unexplored aspect of care. This is especially relevant since the risks of over-resuscitation with fluid overload or inotropes have been highlighted in recent years. A recent guideline has proposed normalization of central venous oxygen saturation and/or lactate as therapeutic end-points, assuming that these variables are equivalent or interchangeable. However, since the physiological determinants of both are totally different, it is legitimate to challenge the rationale of this proposal. We designed this study to gain more insights into the most appropriate resuscitation goal from a dynamic point of view. Our objective was to compare the normalization rates of these and other potential perfusion-related targets in a cohort of septic shock survivors.MethodsWe designed a prospective, observational clinical study. One hundred and four septic shock patients with hyperlactatemia were included and followed until hospital discharge. The 84 hospital-survivors were kept for final analysis. A multimodal perfusion assessment was performed at baseline, 2, 6, and 24 h of ICU treatment.ResultsSome variables such as central venous oxygen saturation, central venous-arterial pCO2 gradient, and capillary refill time were already normal in more than 70% of survivors at 6 h. Lactate presented a much slower normalization rate decreasing significantly at 6 h compared to that of baseline (4.0 [3.0 to 4.9] vs. 2.7 [2.2 to 3.9] mmol/L; p?<?0.01) but with only 52% of patients achieving normality at 24 h. Sublingual microcirculatory variables exhibited the slowest recovery rate with persistent derangements still present in almost 80% of patients at 24 h.ConclusionsPerfusion-related variables exhibit very different normalization rates in septic shock survivors, most of them exhibiting a biphasic response with an initial rapid improvement, followed by a much slower trend thereafter. This fact should be taken into account to determine the most appropriate criteria to stop resuscitation opportunely and avoid the risk of over-resuscitation.
| S-EPMC4273696 | biostudies-literature
Project description:BackgroundIn un-resuscitated rodent models of septic shock, the peroxisome proliferator-activated receptor-?/? (PPAR-?/?) agonist GW0742 improved visceral organ function. Therefore, we tested the hypothesis whether GW0742 would attenuate kidney injury during long-term, resuscitated, porcine polymicrobial septic shock.MethodsSix, 12, and 18 h after the induction of fecal peritonitis by inoculation of autologous feces, anesthetized, mechanically ventilated, and instrumented male pigs with pre-existing atherosclerosis resulting from familial hypercholesteremia and atherogenic diet randomly received either vehicle (dimethyl sulfoxide, n = 12) or GW0742 (n = 10). Resuscitation comprised hydroxyethyl starch and norepinephrine infusion titrated to maintain mean arterial pressure at baseline values.ResultsDespite aggressive fluid resuscitation, fecal peritonitis was associated with arterial hypotension requiring norepinephrine infusion, ultimately resulting in progressive lactic acidosis and acute kidney injury. GW0742 did not beneficially affect any parameter of systemic and regional hemodynamics, gas exchange, metabolism, or organ function. The parameters of inflammation, oxidative and nitrosative stress, and organ injury (post-mortem analysis for histomorphology and markers of apoptosis) were not influenced either. Immunohistochemistry of pre-shock kidney biopsies from a previous study in this swine strain showed markedly lower PPAR-?/? receptor expression than in healthy animals.ConclusionsIn swine with pre-existing atherosclerosis, the PPAR-?/? agonist GW0742 failed to attenuate septic shock-induced circulatory failure and kidney dysfunction, most likely due to reduced receptor expression coinciding with cardiovascular and metabolic co-morbidity.
| S-EPMC4796150 | biostudies-literature