Esketamine use for primary intelligent analgesia in adults with severe burns: A double-blind randomized trial with effects on analgesic efficacy, gastrointestinal function and mental state.

BACKGROUND: Opioid consumption for analgesia in burn patients is enormous. Non-opioid analgesics for burn pain management may result in opioid sparing, reducing opioid-related adverse reactions and drug tolerance or addiction. METHODS: A dual-center, randomized controlled trial assessed Esketamine for the perioperative period in patients with severe [20-50 % total body surface area (TBSA)] and extensive (≥ 50 % TBSA) burns, comparing analgesia with standard anesthesia. Sixty patients were randomly allocated (1:1 ratio) to two arms. In the Treatment Arm, patients received intra-operative Esketamine and postoperative intravenous primary intelligent analgesia pump with Esketamine. Patients in the Control Arm received the same intervention as Treatment Arm without Esketamine. The primary endpoint was subjective analgesic efficacy (SAE) evaluated on Day 28 or the day before hospital discharge. Secondary outcomes included the postoperative Numeric Pain Rating (NPR) Scale at rest (NPRr) and during movement (NPRm) and opioid consumption. Gastrointestinal dysfunction Scores (GIDS) and serum markers of intestinal injury [intestinal fatty acid-binding protein 2 (iFabp2) and apolipoproteinA2 (ApoA2)] were measured in the 1st and 4th post-injury weeks. Depression and sleep quality were assessed by relevant questionnaires. RESULTS: Fifty-five patients were included in the analysis. Esketamine-treated Arm recorded a better analgesic efficacy than the Control Arm (proportion of patients with Grade 1 or 2 SAE scores, 67.9 % vs. 40.7 %, p = 0.022). Esketamine-treated patients had lower NPRm values (p = 0.033) and lower daily opioid consumption (p = 0.033) when compared with Controls. Esketamine-treated patients showed comparable gastrointestinal recovery to those in the Control Arm. The overall sleep quality might be improved in the Treatment Arm. CONCLUSIONS: Esketamine use is safe for perioperative primary intelligent analgesia of severe burns, resulting in improved resting pain control and lower opioid requirements. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn/) (ChiCTR2000034069).

Ventilatory pressure parameters impact the association between acute gastrointestinal injury and all-cause mortality in mechanically ventilated patients.

Acute gastrointestinal injury (AGI) is common in mechanically ventilated (MV) patients, but the potential association between ventilatory pressure parameters and AGI grade and their impact on mortality remains unclear. This study aimed to explore the association between ventilatory pressure parameters and AGI grade, and their interaction on all-cause mortality in MV patients. This study was a secondary analysis of a multicenter, prospective, observational study that enrolled adult patients with an expected duration of mechanical ventilation ≥ 48 h from 14 general intensive care units in Zhejiang Province between March and August 2014. The AGI grade was assessed daily on the basis of gastrointestinal symptoms, intra-abdominal pressures, and feeding intolerance in the first week of admission to the ICU. This study included 331 patients (69.2% men; mean age, 64.6 ± 18.9 years). Multivariate regression analysis showed that plateau pressure (Pplat) (OR 1.044, 95% CI 1.009-1.081, P = 0.013), serum creatinine (OR 1.003, 95% CI 1.001-1.006, P = 0.042) and APACHE II score (OR 1.035, 95% CI 1.021-1.072, P = 0.045) were independently associated with global AGI grade III/IV within 7 days of ICU admission. Moreover, global AGI grade (HR 2.228, 95% CI 1.561-3.182, P < 0.001), serum creatinine (HR 1.002, 95% CI 1.001-1.003, P = 0.012) and APACHE II score (HR 1.039, 95% CI 1.015-1.063, P = 0.001) were independently associated with 60-day mortality. In addition, there were significant (Pint ≤ 0.028) interactions of Pplat and DP with AGI grade in relation to 60-days mortality, whereas no interaction (Pint = 0.061) between PEEP and AGI grade on 60-days mortality was observed. In the presence of Pplat ≥ 19 cmH2O, the patients with AGI grade III/IV had 60-day mortality rate of 72.2%, significantly higher than those with AGI grade I/II (48.7%, P = 0.018), whereas there were no significant differences (27.9% vs. 33.7%, P = 0.39) in 60-days mortality between AGI grade I/II and III/IV among the patients with Pplat < 19 cmH2O. In comparison with Pplat, DP had a similar interaction (Pint = 0.028) with AGI grade on 60-day mortality. Ventilatory pressure parameters (Pplat and DP) are independent risk factors of AGI grade III/IV. Pplat and DP interact with AGI grade on 60-days mortality, highlighting the importance of optimizing ventilatory pressure parameters to improve gastrointestinal function and survival outcomes of MV patients.Trial registration: ChiCTR-OCS-13003824.

Acute Gastrointestinal Injury in Polytrauma: Special Attention to Elderly Patients.

Background: Acute gastrointestinal injury (AGI) has been documented in critically ill patients, yet there remains a dearth of knowledge regarding its occurrence, predisposing factors, and outcomes in elderly polytrauma patients, a significant but overlooked population. This study aims to examine the frequency, risk factors, and clinical implications of AGI in elderly polytrauma patients. Methods: A retrospective, observational, multicenter study was carried out in two Level I trauma centers, encompassing a cohort of 1054 polytrauma patients from July 2020 to April 2022. Results: A total of 965 consecutive polytrauma patients were recruited who were divided into youth group (n=746) and elderly group (n=219). 73.5% of elderly patients after polytrauma were accompanied by AGI. An increasing ISS (OR=2.957, 95%CI: 1.285-7.714), SI (OR=2.861, 95%CI: 1.372-5.823), serum lactate (OR=2.547, 95%CI: 1.254-5.028), IL-6 (OR=1.771, 95%CI: 1.145-8.768), APTT (OR=1.462, 95%CI: 1.364-4.254) and a decreasing GCS (OR=0.325, 95%CI: 0.116-0.906) were each associated with an increasing risk of AGI in elderly polytrauma patients. Elderly polytrauma patients with AGI were presented relatively high 28-day mortality (40.4%) and super high 60-day mortality (61.2%) compared with elderly group without AGI and youth group with AGI. The area under the curve for predicting 28-day mortality in elderly polytrauma patients with AGI was 0.93 for AGI-III,IV with 96% sensitivity and 87% specificity. Conclusion: Elderly patients have a higher incidence and a worse prognosis of AGI after polytrauma. ISS, GCS, SI, serum lactate, IL-6, and APTT are identified as reliable prognostic markers to distinguish the AGI and N-AGI in elderly polytrauma patients. AGI-III,IV was the independent predictor of mortality in elderly polytrauma patients with AGI.

Synergizing Survival: Uniting Acute Gastrointestinal Injury Grade and Disease Severity Scores in Critical Care Prognostication.

How to cite this article: Patnaik RK, Karan N. Synergizing Survival: Uniting Acute Gastrointestinal Injury Grade and Disease Severity Scores in Critical Care Prognostication. Indian J Crit Care Med 2024;28(6):529-530.

Is reoperation required for patients presenting with hepatic portal venous gas after gastrointestinal surgery: a review of the literature.

BACKGROUND AND OBJECTIVE: Hepatic portal venous gas(HPVG) represents a rare radiographic phenomenon frequently linked to intestinal necrosis, historically deemed to need immediate surgical intervention. The pivotal query arises about the imperative of urgent surgery when a patient manifests HPVG after gastrointestinal surgery. This inquiry seeks to elucidate whether emergent surgical measures remain a requisite in such cases. METHODS: The investigation into 14 cases of HPVG after gastrointestinal procedures was conducted through a comprehensive review of relevant literature. This methodological approach contributes to a nuanced understanding of HPVG occurrences following gastrointestinal surgery, informing clinical considerations and potential therapeutic strategies. RESULTS: Among the 14 patients, 12 recovered and 2 died. 6 patients underwent surgical exploration, 4 with negative findings and recovered. 8 cases received conservative treatment, resulting in improvement for 5, and 1 initially treated conservatively, revealed perforation during later surgical exploration, leading to improvement, 1 case ended in mortality. CONCLUSION: After gastrointestinal surgery, in Computed Tomography (CT) imaging, the coexistence of HPVG and gastrointestinal dilatation, without signs of peritoneal irritation on abdominal examination, may suggest HPVG due to acute gastrointestinal injury, intestinal gas, and displacement of gas-producing bacteria. These patients can be managed conservatively under close supervision. In cases where HPVG coexists with gastrointestinal dilatation and Pneumatosis intestinalis (PI) without signs of peritoneal irritation, conservative treatment may be continued under close supervision. However, if progressive exacerbation occurs despite close monitoring and the aforementioned treatments, timely surgical exploration is deemed necessary. When HPVG is combined with signs of peritoneal irritation, prompt laparotomy and exploration are preferred.

Prognostic Value of Acute Gastrointestinal Injury Combined with Disease Severity Scores in Critically Ill Patients.

Background: Critically ill patients are at high risk of multiple organ failure syndrome (MODS) and gastrointestinal (GI) injury and dysfunction, which are associated with increased mortality rates. The acute gastrointestinal injury (AGI) scale has shown promise in assessing GI dysfunction. However, the combined utility of AGI with established disease severity scores remains unclear. This study aimed to investigate the performance of AGI in conjunction with modified nutritional risk in critically ill (mNUTRIC), sequential organ failure assessment (SOFA), and acute physiology and chronic health evaluation II (APACHE II) scores for predicting mortality in critically ill patients. Materials and methods: A retrospective cross-sectional study was conducted in the intensive care unit (ICU) from May 2021 to December 2021. Demographic and clinical data were collected, including AGI grade, mNUTRIC score, SOFA score, APACHE II score, and mortality. Results: Among 93 critically ill patients, AGI was observed in 47.3% of cases, and the in-hospital mortality rate was 30.1%. The area under the curve (AUC) for AGI in predicting in-hospital mortality was 0.67 [95% confidence interval (CI), 0.56, 0.79; p = 0.008], similar to the AUCs of SOFA, APACHE II, and mNUTRIC scores. The combination of AGI with mNUTRIC, APACHE II, or SOFA scores improved the predictive performance compared with AGI alone. Conclusion: The AGI grade, in conjunction with disease severity scores, such as mNUTRIC, SOFA, and APACHE II scores, shows promise in predicting mortality in critically ill patients. Integrating AGI into evaluating critically ill patients can enhance prognostic accuracy. How to cite this article: Hai PD, Tot NH, Thao LT, Khoa Q, Thien DH. Prognostic Value of Acute Gastrointestinal Injury Combined with Disease Severity Scores in Critically Ill Patients. Indian J Crit Care Med 2024;28(6):575-580.

Trajectories of acute gastrointestinal injury grade in critically Ill children.

OBJECTIVE: To investigate the characteristics of different Acute Gastrointestinal Injury (AGI) grading trajectories and examine their impact on prognosis in the Pediatric Intensive Care Unit (PICU). METHODS: This retrospective cohort study was conducted at a large children's hospital in China. The children admitted to the PICU were included. AGI grade was assessed every other day during the initial nine days following PICU admission. RESULTS: A total of 642 children were included, of which 364 children (56.7%) exhibited varying degrees of gastrointestinal dysfunction (AGI grade ≥ 2). Based on the patterns of AGI grading over time, six groups were identified: low-stable group, low-fluctuating group, medium-decreasing group, medium-increasing group, high-decreasing group, high-persistent group. The high-persistent group accounted for approximately 90% of all recorded deaths. Compared to low-stable group, both the medium-increasing and high-persistent groups exhibited positive correlations with length of stay in PICU (PICU LOS) and length of stay (LOS). Compared to low-stable group, the five groups exhibited a negative correlation with the percentage of energy received by enteral nutrition (EN), as well as the protein received by EN. CONCLUSION: This study identified six distinct trajectory groups of AGI grade in critically ill children. The pattern of AGI grade trajectories over time were associated with EN delivery proportions and clinical outcomes.

Acute Gastrointestinal Injury in Critically Ill Patients in a South Indian Intensive Care Unit: A Prospective, Observational, Preliminary Study.

Introduction The acute gastrointestinal injury (AGI) score was proposed by the Working Group on Abdominal Problems of the European Society of Intensive Care Medicine (ESICM) as a tool to define and grade gut dysfunction. There have not been any studies in India to validate this tool. The objective of this preliminary study was primarily to study the frequency of AGI in the first week of ICU stay in critically ill patients in our intensive care unit (ICU). We also sought to determine the risk factors predisposing to the development of AGI and to determine the prognostic implication of gastrointestinal (GI) injury in critically ill patients. Materials and methods A prospective, observational, preliminary, single-center study was conducted on critically ill patients (APACHE II > 8) who were on enteral tube feeds and admitted to a mixed ICU of a tertiary care hospital. Anthropometric data, admission diagnosis, APACHE II score, and comorbidities were recorded. Data of daily heart rate, mean arterial pressure, dose of vasopressors, intra-abdominal pressure, fluid balance, feeding intolerance, mechanical ventilation, and laboratory tests were noted for the first seven days of ICU stay or till ICU discharge, whichever was earlier. The occurrence of AGI score (1-4) during the first seven days of critical illness was the primary outcome of interest. Patient outcome at 28 days was recorded and the impact of the occurrence of AGI on patient outcome was analyzed using the Chi-square test. The patient characteristics associated with AGI were characterized as risk factors and analyzed using a multivariate model. Results Data were collected from 33 patients over 201 patient days. The frequency of acute GI dysfunction in the first seven days of ICU stay in our group of patients was 45.45% (15/33). APACHE II, fluid balance, creatinine, and lactate were identified as possible predictors of GI injury based on existing literature. These four variables were entered into an ordinal logistic regression model to assess their ability to predict the occurrence of GI Injury. When fitted into a predictive model, only fluid balance and creatinine were predictive of the final model (p-value < 0.05). A greater fluid balance was predictive in the final model of the development of GI injury; however, it showed negligible clinical significance (OR: 1.00033, 95% CI: 1.000051-1.00061). Lower creatinine levels were predictive in the final model of the development of AGI Injury, as demonstrated by the negative coefficient. Creatinine also had a greater clinical significance (OR: 0.63, 95% CI: 0.44-0.90) in the development of AGI. The impact of the AGI scores on mortality was analyzed. The number of patient days with higher AGI scores was significantly associated with increased mortality at 28 days (p-value < 0.001). Conclusion The study showed that nearly half of the critically ill patients included in the study developed acute GI dysfunction. We could not identify any predictors of GI injury based on our results. The result suggested an association between the severity of GI dysfunction and mortality at 28 days.

The Predictive Value of Serum DAO, HDC, and MMP8 for the Gastrointestinal Injury in the Early Stage of Acute Pancreatitis in an Animal Model and a Clinical Study.

Purpose: This study was aimed at exploring the use of the acute gastrointestinal injury (AGI) grade and sensitive biomarkers to investigate gastrointestinal (GI) injury in early stage of acute pancreatitis (AP). Patients and Methods: The AGI grade was used to evaluate intestinal function. Any GI injury above grade I (grades II-IV) was considered as severe. An AP rat model was created by retrograde injection of 4% sodium taurocholate. The pancreatic and intestinal histopathology scores were calculated by hematoxylin-eosin staining. Human and rat sera were assessed using ELISA. Tight junction (TJ) proteins were detected by Western blotting. Results: In clinical study, the GI injury rate in mild acute pancreatitis (MAP), moderate severe acute pancreatitis (MSAP), and severe acute pancreatitis (SAP) groups was 26.8%, 78.4%, and 94.8%, respectively (P < 0.05). Diamine oxidase (DAO), histidine decarboxylase (HDC), and matrix metalloproteinase 8 (MMP8) serum levels were higher in AP patients than in healthy people (P < 0.05). Patients with GI injury had higher serum levels of DAO, HDC, and MMP8 than those without GI injury (P < 0.05). In animal experiments, the serum levels of DAO, HDC, and MMP8 were higher in the AP group than in normal and sham-operated (SO) groups (P < 0.05). The expressions of tricellulin, claudin-1, ZO-1, and occludin were significantly lower in the AP group than in normal and SO groups (P < 0.05). Conclusion: The serum levels of DAO, HDC, and MMP8 are novel biomarkers of GI injury in the early stage of AP; their elevation indicates the development of GI injury in AP. The intestinal TJ disruption may be a primary mechanism of GI injury and requires more in-depth research.

Restraint Stress-Induced Neutrophil Inflammation Contributes to Concurrent Gastrointestinal Injury in Mice.

Psychological stress increases risk of gastrointestinal tract diseases. However, the mechanism behind stress-induced gastrointestinal injury is not well understood. The objective of our study is to elucidate the putative mechanism of stress-induced gastrointestinal injury and develop an intervention strategy. To achieve this, we employed the restraint stress mouse model, a well-established method to study the pathophysiological changes associated with psychological stress in mice. By orally administering gut-nonabsorbable Evans blue dye and monitoring its plasma levels, we were able to track the progression of gastrointestinal injury in live mice. Additionally, flow cytometry was utilized to assess the viability, death, and inflammatory status of splenic leukocytes, providing insights into the stress-induced impact on the innate immune system associated with stress-induced gastrointestinal injury. Our findings reveal that neutrophils represent the primary innate immune leukocyte lineage responsible for stress-induced inflammation. Splenic neutrophils exhibited elevated expression levels of the pro-inflammatory cytokine IL-1, cellular reactive oxygen species, mitochondrial burden, and cell death following stress challenge compared to other innate immune cells such as macrophages, monocytes, and dendritic cells. Regulated cell death analysis indicated that NETosis is the predominant stress-induced cell death response among other analyzed regulated cell death pathways. NETosis culminates in the formation and release of neutrophil extracellular traps, which play a crucial role in modulating inflammation by binding to pathogens. Treatment with the NETosis inhibitor GSK484 rescued stress-induced neutrophil extracellular trap release and gastrointestinal injury, highlighting the involvement of neutrophil extracellular traps in stress-induced gastrointestinal inflammation. Our results suggest that neutrophil NETosis could serve as a promising drug target for managing psychological stress-induced gastrointestinal injuries.

Ferroptosis, Inflammation, and Microbiome Alterations in the Intestine in the Göttingen Minipig Model of Hematopoietic-Acute Radiation Syndrome.

Hematopoietic acute radiation syndrome (H-ARS) involves injury to multiple organ systems following total body irradiation (TBI). Our laboratory demonstrated that captopril, an angiotensin-converting enzyme inhibitor, mitigates H-ARS in Göttingen minipigs, with improved survival and hematopoietic recovery, as well as the suppression of acute inflammation. However, the effects of captopril on the gastrointestinal (GI) system after TBI are not well known. We used a Göttingen minipig H-ARS model to investigate captopril's effects on the GI following TBI (60Co 1.79 or 1.80 Gy, 0.42-0.48 Gy/min), with endpoints at 6 or 35 days. The vehicle or captopril (0.96 mg/kg) was administered orally twice daily for 12 days, starting 4 h post-irradiation. Ilea were harvested for histological, protein, and RNA analyses. TBI increased congestion and mucosa erosion and hemorrhage, which were modulated by captopril. GPX-4 and SLC7A11 were downregulated post-irradiation, consistent with ferroptosis at 6 and 35 days post-irradiation in all groups. Interestingly, p21/waf1 increased at 6 days in vehicle-treated but not captopril-treated animals. An RT-qPCR analysis showed that radiation increased the gene expression of inflammatory cytokines IL1B, TNFA, CCL2, IL18, and CXCL8, and the inflammasome component NLRP3. Captopril suppressed radiation-induced IL1B and TNFA. Rectal microbiome analysis showed that 1 day of captopril treatment with radiation decreased overall diversity, with increased Proteobacteria phyla and Escherichia genera. By 6 days, captopril increased the relative abundance of Enterococcus, previously associated with improved H-ARS survival in mice. Our data suggest that captopril mitigates senescence, some inflammation, and microbiome alterations, but not ferroptosis markers in the intestine following TBI.

Effects of different dietary fiber supplement strategies on incidence of acute gastrointestinal injury in ICU patients: A prospective observational study.

OBJECTIVE: This study aimed to explore the effects of dietary fiber (DF) supplement strategies on the incidence of acute gastrointestinal injury (AGI) in critically ill patients. DESIGN: A prospective observational study. SETTING: The study was conducted in the First Affiliated Hospital of Soochow University from April 2021 to March 2023. METHODS: Using a five-day dietary log counted the amount of DF supplement. The best fitting trajectories of DF supplement were determined based on the latent class trajectory modelling (LCTM). The data of AGI were evaluated on the day 5 (D5) and day 7 (D7) after intensive care unit admission. RESULTS: A total of 179 patients were included in the study. The LCTM yielded a four-trajectories of models, named; Sustained Low - Group, Slowly Rising - Group, Early Supplement & Slowly Rising - Group and Rapidly Rising - Group, respectively. The incidences of AGI on D5 and D7 were 51.4 % and 40.0 %, respectively. There was an increased risk in the grade of AGI in the Sustained Low - Group compared with the Rapidly Rising - Group on D5 [odds ratio (OR), 4.8; 95 % confidence interval (CI), 1.9-12.1] and D7 (OR, 12.0; 95 % CI, 3.9-37.0); and an increased risk in the Slowly Rising - Group on D5 (OR, 3.6; 95 % CI, 1.3-9.9). CONCLUSION: The supplement of DF in critically ill patients may be insufficient and the incidence of AGI is high. Sustained low and slow rising DF supplement may be associated with an increased risk in the AGI. IMPLICATIONS FOR CLINICAL PRACTICE: The clinical staff could focus on the supplementation of not only the three macronutrients, but also DF in critically ill patients.

Safety and efficacy of a probiotic cocktail containing P. acidilactici and L. plantarum for gastrointestinal discomfort in endurance runners: randomized double-blinded crossover clinical trial.

Probiotics are increasingly used to treat conditions associated with gastrointestinal injury and permeability, including exercise-induced gastrointestinal discomfort. This study assessed safety and efficacy of a probiotic in altering the intestinal milieu and mitigating gastrointestinal symptoms (GIS) in endurance runners. In a double blind, crossover study, 16 runners were randomized to 4 weeks of daily supplementation with a probiotic cocktail containing Pediococcus acidilactici bacteria and Lactobacillus plantarum or placebo. Fasting blood and stool samples were collected for measurement of gut permeability markers, immune parameters, and microbiome analyses. Treadmill run tests were performed before and after treatment; participants ran at 65%-70% of VO2max at 27 °C for a maximum of 90 min or until fatigue/GIS developed. A blood sample was collected after the treadmill run test. In healthy individuals, 4 weeks of probiotic supplementation did not alter health parameters, although a marginal reduction in aspartate aminotransferase levels was observed with probiotic treatment only (p = 0.05). GIS, gut permeability-associated parameters (intestinal fatty acid binding protein, lipopolysaccharide binding protein, zonulin, and cytokines), and intestinal microbial content were not altered by the probiotic supplementation. Post-run measurements of GIS and gut-associated parameters did not differ between groups; however, the observed lack of differences is confounded by an absence of measurable functional outcome as GIS was not sufficiently induced during the run. Under the current study conditions, the probiotic was safe to use, and did not affect gut- or immune-associated parameters, or intestinal symptoms in a healthy population. The probiotic might reduce tissue damage, but more studies are warranted.

Measurements of I-FABP and citrulline in the postoperative period of non-cardiac surgeries with gastrointestinal complications: A prospective cohort observational study.

BACKGROUND: Acute Gastrointestinal Injury (AGI) is associated with adverse clinical outcomes, including increased mortality. We aimed to investigate the potential of citrulline and intestinal fatty acid binding protein (I-FABP) as biomarkers for early AGI diagnosis and predicting outcomes in surgical patients. METHODS: Prospective cohort study involving patients who underwent non-cardiac surgeries and were admitted to Intensive Care Units. AGI diagnosis was based on specific criteria, and severity was categorised following established guidelines. Statistical analyses were performed to assess the diagnostic accuracy of the biomarkers and their association with outcomes, P significant when <0.05. RESULTS: AGI was identified in 40.3% of patients with varying severity. Mortality rates were significantly higher in the AGI group in the ICU (19.4% vs. 0%, p = 0.001) and hospital (22.6% vs. 2.17%, p = 0.003). Urinary I-FABP levels on days 3 and 7 showed reasonable and good accuracy for AGI diagnosis (AUC 0.732 and 0.813, respectively). Urinary I-FABP levels on days 2 and 3 accurately predict sepsis. Urinary citrulline levels on day one predicted mortality (AUC 0.87) furthermore urinary I-FABP levels on day 2 showed reasonable accuracy (sensitivity 83.3%, specificity 92.4%). CONCLUSION: Urinary I-FABP and citrulline levels are promising diagnostic and prognostic markers in ICU patients following non-cardiac surgeries.

Restraint stress-associated gastrointestinal injury and implications from the Evans blue-fed restraint stress mouse model.

The association between stress and gastrointestinal (GI) tract diseases is well established, while the exact mechanism remains elusive. As a result, it is urgent to establish mouse models to investigate restraint stress-associated GI leakage, but current models have their limitations. A new Evans blue-fed restraint mouse model has recently been developed that allows researchers to study restraint stress-associated GI leakage in live animals. This review article will focus on this model, including its mechanisms, clinical implications, and applications for studying restraint stress-associated GI injury. Recent findings from studies using this model will also be highlighted, along with their potential for diagnosis and treatment. The article aims to discuss about current research and provide recommendations for further study, ultimately improving our understanding of the link between stress and GI injury and improving patient outcomes.

Serum ACTH and Cortisol Level is Associated with the Acute Gastrointestinal Injury Grade in ICU Patients.

Background: The relationship between acute gastrointestinal symptoms and cortisol or adrenocorticotropic hormone (ACTH) levels has rarely been reported. We hypothesized that the elevation of serum cortisol or ACTH levels may be correlated with the severity of the acute gastrointestinal injury grade (AGI). Methods: This study was an observational study. All patients were admitted to the ICU between 2019.1.1 and 2020.1.1.. Serum ACTH and cortisol levels and clinical data were collected from the electronic medication records. The highest AGI grade during the ICU stay was the major endpoint to observe. The patient was treated in a standard procedure in the ICU. Results: A total of 235 patients were included in our study, 132 of whom developed AGI. In univariate regression, cortisol level was found to be a risk factor for 28-day mortality. Serum cortisol and ACTH levels correlated with APACHE II, AGI grade, PCT, and CRP levels. Spearman analysis and partial correlation analysis indicated that cortisol and ACTH levels were correlated with AGI grade. Conclusion: The ACTH and cortisol levels were positively correlated with the higher severity of AGI grade. The cortisol level may be a useful way to access the GI injury.

Enteral feeding strategies in patients with acute gastrointestinal injury: From limited to progressive to open feeding.

Acute gastrointestinal injury (AGI) is very common in critically ill patients, and its severity is positively correlated with mortality. Critically ill patients with digestive and absorption dysfunction caused by AGI face higher nutritional risks, making nutritional support particularly important. Early enteral nutrition (EN) support is extremely important because it can promote the recovery of intestinal function, protect the intestinal mucosal barrier, reduce microbiota translocation, reduce postoperative complications, shorten hospital stay, and improve clinical prognosis. In recent years, many nutritional guidelines have been proposed for critically ill patients; however, there are few recommendations for the implementation of EN in patients with AGI, and their quality of evidence is low. The use of EN feeding strategies in critically ill patients with AGI remains controversial. The aim of this review was to elaborate on how EN feeding strategies should transition from limited to progressive to open feeding and explain the time window for this transition.

Investigation of Gut Microbiota Disorders in Sepsis and Sepsis Complicated with Acute Gastrointestinal Injury Based on 16S rRNA Genes Illumina Sequencing.

Background: Sepsis is a life-threatening organ dysfunction caused by the host's dysfunctional response to infection, which can cause acute gastrointestinal injury (AGI). The gut microbiota is dynamic and plays a role in the immune and metabolic. The aim of this study was to investigate the composition and function of gut microbiota in patients with sepsis, as well as the gut microbiome that may be involved in the occurrence of AGI. Methods: A total of 23 stool samples from healthy control individuals and 41 stool samples from sepsis patients were collected. Patients with sepsis were followed up for one week to observe whether AGI has occurred. Finally, 41 patients included 21 sepsis complicated with AGI (referred to as Com-AGI) and 20 sepsis without complicated with AGI (referred to as No-AGI). The gut microbiota was analyzed by 16S rRNA gene sequencing, followed by composition analysis, difference analysis, correlation analysis, functional prediction analysis. Results: The diversity and evenness of gut microbiota were decreased in patients with sepsis. Compared with No-AGI, the gut microbiota of Com-AGI has higher community diversity, richness, and phylogenetic diversity. Escherichia-Shigella, Blautia and Enterococcus may be important indicators of sepsis. The correlation analysis showed that aspartate aminotransferase (AST) and Barnesiella have the most significant positive correlation. Moreover, Clostridium_innocuum_group, Christensenellaceae_R-7_group and Eubacterium were all significantly correlated with LAC and DAO. Clostridium_innocuum_group, Barnesiella, Christensenellaceae_R-7_group and Eubacterium may play important roles in the occurrence of AGI in sepsis. PICRUSt analysis revealed multiple functional pathways involved in the relationship between gut microbiota and sepsis, including starch degradation V, glycogen degradation I (bacterial), Lipoic acid metabolism and Valine, leucine and isoleucine biosynthesis. BugBase analysis showed that the gut microbiota with Aerobic phenotype may play an important role in sepsis. Conclusion: Dysfunction of gut microbiota was associated with sepsis and AGI in patients with sepsis.

Recovery from indomethacin-induced gastrointestinal bleeding by treatment with teprenone.

BACKGROUND: Gastrointestinal injuries caused by nonsteroidal anti-inflammatory drugs (NSAIDs) is a serious side effect in patients with rheumatoid arthritis (RA). However, effective therapeutic strategies have yet to be established. In this study, we investigated the therapeutic effects of teprenone (TEP), a gastric mucosal protective drug, on NSAID-induced gastrointestinal injuries in rats with RA (AA rats). METHODS: Gastrointestinal injury was induced by oral administration of indomethacin (IMC), a typical NSAID. TEP was orally administered after IMC-induced gastrointestinal bleeding, and the stomach, jejunum, and ileum were excised. RESULTS: On day 14 of IMC administration, lesion areas in the stomach, jejunum, and ileum were significantly larger in AA rats than in normal rats. When TEP was orally administered to AA rats, the lesion areas in the stomach, jejunum, and ileum significantly decreased compared with those in control rats (IMC-induced AA rats). Therefore, we measured NOS2 mRNA and NO levels, which were significantly decreased in rats with IMC-induced AA after treatment with TEP. CONCLUSIONS: These results suggest that the oral administration of TEP may be useful for the treatment of NSAID-induced gastrointestinal injuries in patients with RA.