scholarly journals Biomarkers of Cholestasis and Liver Injury in the Early Phase of Acute Respiratory Distress Syndrome and Their Pathophysiological Value

Diagnostics ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 2356
Author(s):  
Lars-Olav Harnisch ◽  
Sophie Baumann ◽  
Diana Mihaylov ◽  
Michael Kiehntopf ◽  
Michael Bauer ◽  
...  
Keyword(s):  
Liver Injury ◽  
Bile Acids ◽  
Prone Position ◽  
Early Phase ◽  
Peep Level ◽  
High Peep ◽  
Prone Positioning ◽  
Total Bile Acids ◽  
Hypoxic Liver Injury ◽  
Ecmo Treatment

Background: Impaired liver function and cholestasis are frequent findings in critically ill patients and are associated with poor outcomes. We tested the hypothesis that hypoxic liver injury and hypoxic cholangiocyte injury are detectable very early in patients with ARDS, may depend on the severity of hypoxemia, and may be aggravated by the use of rescue therapies (high PEEP level and prone positioning) but could be attenuated by extracorporeal membrane oxygenation (ECMO). Methods: In 70 patients with ARDS, aspartate-aminotransferase (AST), alanin-aminotransferase (ALT) and gamma glutamyltransferase (GGT) were measured on the day of the diagnosis of ARDS and three more consecutive days (day 3, day 5, day 10), total bile acids were measured on day 0, 3, and 5. Results: AST levels increased on day 0 and remained constant until day 5, then dropped to normal on day 10 (day 0: 66.5 U/l; day 3: 60.5 U/l; day 5: 63.5 U/l, day 10: 32.1 U/l), ALT levels showed the exact opposite kinetic. GGT was already elevated on day 0 (91.5 U/l) and increased further throughout (day 3: 163.5 U/l, day 5: 213 U/l, day 10: 307 U/l), total bile acids levels increased significantly from day 0 to day 3 (p = 0.019) and day 0 to day 5 (p < 0.001), but not between day 3 and day 5 (p = 0.217). Total bile acids levels were significantly correlated to GGT on day 0 (p < 0.001), day 3 (p = 0.02), and in a trend on day 5 (p = 0.055). PEEP levels were significantly correlated with plasma levels of AST (day 3), ALT (day 5) and GGT (day 10). Biomarker levels were not associated with the use of ECMO, prone position, the cause of ARDS, and paO2. Conclusions: We found no evidence of hypoxic liver injury or hypoxic damage to cholangiocytes being caused by the severity of hypoxemia in ARDS patients during the very early phase of the disease. Additionally, mean PEEP level, prone positioning, and ECMO treatment did not have an impact in this regard. Nevertheless, GGT levels were elevated from day zero and rising, this increase was not related to paO2, prone position, ECMO treatment, or mean PEEP, but correlated to total bile acid levels.

scholarly journals Lung Recruitment, Individualized PEEP, and Prone Position Ventilation for COVID-19-Associated Severe ARDS: A Single Center Observational Study

2021 ◽  
Vol 7 ◽  
Author(s):  
Ling Sang ◽  
Xia Zheng ◽  
Zhanqi Zhao ◽  
Min Zhong ◽  
Li Jiang ◽  
...  
Keyword(s):  
Prone Position ◽  
Distress Syndrome ◽  
Lung Mechanics ◽  
High Peep ◽  
Prone Positioning ◽  
Inclusion Criteria ◽  
Predicted Body Weight ◽  
Average Value ◽  
Volume Controlled ◽  
Single Center Observational Study

Background: Patients with coronavirus disease 2019 (COVID-19) may develop severe acute respiratory distress syndrome (ARDS). The aim of the study was to explore the lung recruitability, individualized positive end-expiratory pressure (PEEP), and prone position in COVID-19-associated severe ARDS.Methods: Twenty patients who met the inclusion criteria were studied retrospectively (PaO2/FiO2 68.0 ± 10.3 mmHg). The patients were ventilated under volume-controlled mode with tidal volume of 6 mL/kg predicted body weight. The lung recruitability was assessed via the improvement of PaO2, PaCO2, and static respiratory system compliance (Cstat) from low to high PEEP (5–15 cmH2O). Patients were considered recruitable if two out of three parameters improved. Subsequently, PEEP was titrated according to the best Cstat. The patients were turned to prone position for further 18–20 h.Results: For recruitability assessment, average value of PaO2 was slightly improved at PEEP 15 cmH2O (68.0 ± 10.3 vs. 69.7 ± 7.9 mmHg, baseline vs. PEEP 15 cmH2O; p = 0.31). However, both PaCO2 and Cstat worsened (PaCO2: 72.5 ± 7.1 vs. 75.1 ± 9.0 mmHg; p &lt; 0.01. Cstat: 17.5 ± 3.5 vs. 16.6 ± 3.9 ml/cmH2O; p = 0.05). Only four patients (20%) were considered lung recruitable. Individually titrated PEEP was higher than the baseline PEEP (8.0 ± 2.1 cmH2O vs. 5 cmH2O, p &lt; 0.001). After 18–20 h of prone positioning, investigated parameters were significantly improved compared to the baseline (PaO2: 82.4 ± 15.5 mmHg. PaCO2: 67.2 ± 6.4 mmHg. Cstat: 20.6 ± 4.4 ml/cmH2O. All p &lt; 0.001 vs. baseline).Conclusions: Lung recruitability was very low in COVID-19-associated severe ARDS. Individually titrated PEEP and prone positioning might improve lung mechanics and blood gasses.

scholarly journals Standard Care Versus Awake Prone Position in Adult Nonintubated Patients With Acute Hypoxemic Respiratory Failure Secondary to COVID-19 Infection—A Multicenter Feasibility Randomized Controlled Trial

2021 ◽  
pp. 088506662110144
Author(s):  
Devachandran Jayakumar ◽  
Pratheema Ramachandran, DNB ◽  
Ebenezer Rabindrarajan, DNB ◽  
Bharath Kumar Tirupakuzhi Vijayaraghavan, MD ◽  
Nagarajan Ramakrishnan, AB ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Prone Position ◽  
Feasibility Study ◽  
Standard Care ◽  
Controlled Trial ◽  
Prone Positioning ◽  
Hypoxemic Respiratory Failure ◽  
Randomized Controlled ◽  
Significant Difference ◽  
Hypoxic Respiratory Failure

Rationale: The feasibility and safety of awake prone positioning and its impact on outcomes in non-intubated patients with acute respiratory distress syndrome secondary to COVID-19 is unknown. Results of the observational studies published during this pandemic have been conflicting. In this context, we conducted a multi-center, parallel group, randomized controlled feasibility study on awake prone positioning in non-intubated patients with COVID-19 pneumonia requiring supplemental oxygen. Methods: 60 patients with acute hypoxic respiratory failure secondary to COVID-19 pneumonia requiring 4 or more liters of oxygen to maintain a saturation of ≥92% were recruited in this study. Thirty patients each were randomized to either standard care or awake prone group. Patients randomized to the prone group were encouraged to self-prone for at least 6 hours a day. The primary outcome was the proportion of patients adhering to the protocol in each group. Results: In the prone group, 43% (13 out of 30) of patients were able to self-prone for 6 or more hours a day. In the supine group, 47% (14 out of 30) were completely supine and 53% spent some hours in the prone position, but none exceeded 6 hours. There was no significant difference in any of the secondary outcomes between the 2 groups and there were no adverse events. Conclusions: Awake prone positioning in non-intubated patients with acute hypoxic respiratory failure is feasible and safe under clinical trial conditions. The results of our feasibility study will potentially help in the design of larger definitive trials to address this key knowledge gap.

Prevention of hypoxic liver injury by in vivo transfection of the human bcl-2 gene

1997 ◽  
Vol 29 (1-2) ◽  
pp. 384-385 ◽  
Author(s):  
K. Yamabe] ◽  
W. Kamiike ◽  
S. Shimizu ◽  
S. Waguri ◽  
J. Hasegawa ◽  
...  
Keyword(s):  
Liver Injury ◽  
In Vivo Transfection ◽  
Hypoxic Liver Injury

scholarly journals High-Flow Nasal Cannula and Prone Positioning in Awake Patients with COVID-19 Related Respiratory Failure: An Observational Study.

2021 ◽  
Author(s):  
Fekri Abroug ◽  
Zeineb Hammouda ◽  
Manel Lahmar ◽  
Wiem Nouira ◽  
Syrine Maatouk ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Observational Study ◽  
Prone Position ◽  
Supine Position ◽  
Early Response ◽  
High Flow ◽  
Nasal Cannula ◽  
Youden Index ◽  
Prone Positioning ◽  
High Flow Nasal Cannula

Abstract Background: We report an observational study on the use of High-flow nasal cannula (HFNC) and awake prone position in patients with Covid-19 related severe ARF.Methods: chart analysis of consecutive patients with confirmed Covid-19 and severe ARF (PaO2/FiO2 ratio <150) who received HFNC. Patients were systematically encouraged to lie in the prone position if tolerated. We calculated initial ROX index (the ratio of SpO2/FIO2 to respiratory rate) while in supine position and at the end of the first HFNC session whether in prone or supine position, and their difference (delta ROX). The success/failure of HFNC (need for intubation) was recorded. Predictors of HFNC failure were identified using ROC curve and logistic regression.Results: HFNC was administered to 213 out of 360 patients with COVID-19 related severe ARF (71% male, median age:59 years (IQR:50-68), median PaO2/FIO2: 104(73-143). At the start of HFNC, median ROX index was 4(3.4-5). Among included patients, 178 (83.5%) could tolerate prone position and had a median of 4.4(2-6) prone sessions during a median of 10(4-16) hours/day each, for a median of 4(2-7) days. Overall, HFNC failure occurred in 61 patients (28.1%) with similar proportions in patients who had HFNC in prone position and in patients who did not tolerate prone position (29% and 26%, respectively; relative risk:1.14. 95%CI:0.62-2.1). In the prediction of HFNC outcome, AUC was highest for delta ROX (AUC=0.83); AUC for baseline ROX (0.71), PaO2/FiO2 (0.73), and SpO2 (0.67), were significantly lower. The delta ROX cut-off ≤1.8 had the best Youden index indicating the best combination of sensitivity (0.89) and specificity (0.61) with a PLR (2.33) and a NLR (0.17) to predict HFNC failure. Logistic regression disclosed the following predictors of HFNC failure: delta ROX: RR=0.44, 95%CI=0.32-0.62; p-0.0001); baseline ROX index: RR=0.58, 95% CI:0.39-0.85, p=0.005); SOFA score (RR=1.6 for each point; 95%CI: 1.1-2.2, p=0.007); and PaO2/FiO2 at admission: RR=0.96, 95%CI=0.94-0.99). Prone position was not related to HFNC success.CONCLUSION: Awake HFNC in prone position is feasible in most patients with severe hypoxemic COVID-19. Indicators of ARF severity and the early response to HFNC, rather than prone position are independently associated with HFNC outcome.

scholarly journals Awake Prone Position in Hypoxemic Patients with Coronavirus Disease 19 (COVI-PRONE): A Study protocol and Statistical Analysis Plan for Randomized Clinical Trial

2021 ◽  
Author(s):  
Zainab Al Duhailib ◽  
Yaseen Arabi ◽  
Sarah Culgin ◽  
Jason Weatherald ◽  
Ken Kuljit S. Parhar ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Prone Position ◽  
Controlled Trial ◽  
Invasive Mechanical Ventilation ◽  
Target Population ◽  
Altered Mental Status ◽  
Hemodynamic Instability ◽  
Hospital Length Of Stay ◽  
Prone Positioning ◽  
Serious Adverse Events

Background Coronavirus disease 2019 (COVID-19), may progress to respiratory failure requiring invasive mechanical ventilation. Due to ventilator shortage and healthcare systems strain, affordable interventions such as awake prone positioning has been used to improve oxygenation, however, the effect of this intervention on patient-important outcomes is uncertain. The COVI-PRONE trial aims to determine if awake prone positioning in hypoxemic COVID-19 patients reduces the need for invasive mechanical ventilation. Study design A pragmatic, multicenter, international, parallel-group, and stratified randomized controlled trial, aiming to enrol 400 hospitalized adults with COVID-19. Participants The target population is hospitalized adults with confirmed or suspected COVID-19, hypoxemia that requires ≥40% oxygen or ≥ 5 L/min by nasal cannula, and abnormal chest x-ray. We will exclude patients with any of the following: immediate need for intubation; altered mental status; contraindication to prone positioning; hemodynamic instability; body mass index > 40 kg/m2; third trimester pregnancy; do not intubate status; previous enrolment or intubation within the same hospital admission; and prone positioning for more than one day prior to randomization. Study intervention and control Following informed a priori or deferred consent, eligible patients will be centrally randomized to either the intervention arm (prone positioning) or standard of care (no prone positioning). Patients randomized to the prone position will be required to either self-prone or assist-prone for a total of eight to ten hours per day until they meet pre-specified stopping criteria. Study outcomes The primary outcome is invasive mechanical ventilation at 30-days of randomization. Other outcomes include mortality at 60 days, invasive and non-invasive mechanical ventilation free days at 30 days, hospital length of stay at 60 days, days alive and outside of the hospital at 60 days, complications of proning, and serious adverse events.

scholarly journals The comparison of total bile acid concentration and alcohol dehydrogenase activity as markers of intrahepatic cholestasis of pregnancy

2021 ◽  
Author(s):  
Wojciech Jelski ◽  
Joanna Piechota ◽  
Karolina Orywal ◽  
Barbara Mroczko
Keyword(s):  
Bile Acid ◽  
Alcohol Dehydrogenase ◽  
Bile Acids ◽  
Intrahepatic Cholestasis ◽  
Total Bile Acid ◽  
Intrahepatic Cholestasis Of Pregnancy ◽  
Third Trimester ◽  
Total Bile Acids ◽  
Adh Activity ◽  
Cholestasis Of Pregnancy

Introduction: Intrahepatic cholestasis of pregnancy (ICP) is the liver disorder in the second or early third trimester of pregnancy. It is characterized by pruritus with increased serum bile acids concentration and other liver function tests. ICP  is connected with increased risk of fetal mortality, but is unfortunately detected quite late. Therefore, it is important to recognize the disease in its early stages. We aimed to investigate the serum alcohol dehydrogenase (ADH) activity and compare it with the concentration of total bile acid (TBA) in women with ICP. Methods: Serum samples were taken for routine investigation from 80 pregnancies with ICP in the second or third trimester of pregnancy and from 80 healthy pregnant women in the same time of pregnancy. For measurement of class I activity we used the spectrofluorometric methods. The total ADH activitiy was measured by the photometric method. Results: The analysis of results shows a statistically significant increase in the activity of ADH I and ADH total (about 60% and 41.3%, respectively). Activity of ADH I well correlated with aminotransferases (alanine ALT and aspartate AST) and total bile acids (TBA) concentration. The total ADH activity was also positively correlated with ALT, AST and total bile acids. Conclusion: We can state that the activity of class I alcohol dehydrogenase isoenzyme in the sera of patients with ICP is increased and seems to be a good indicator of liver cell destruction during this disease and is comparable with the value of other markers.

scholarly journals Arbutin Alleviates the Liver Injury of α-Naphthylisothiocyanate-induced Cholestasis Through Farnesoid X Receptor Activation

2021 ◽  
Vol 9 ◽  
Author(s):  
Peijie Wu ◽  
Ling Qiao ◽  
Han Yu ◽  
Hui Ming ◽  
Chao Liu ◽  
...  
Keyword(s):  
Bile Acid ◽  
Liver Injury ◽  
Protective Effect ◽  
Bile Acids ◽  
Liver Toxicity ◽  
Enterohepatic Circulation ◽  
Receptor Activation ◽  
Farnesoid X Receptor ◽  
Bile Acid Metabolism ◽  
Cholestatic Diseases

Cholestasis is a kind of stressful syndrome along with liver toxicity, which has been demonstrated to be related to fibrosis, cirrhosis, even cholangiocellular or hepatocellular carcinomas. Cholestasis usually caused by the dysregulated metabolism of bile acids that possess high cellular toxicity and synthesized by cholesterol in the liver to undergo enterohepatic circulation. In cholestasis, the accumulation of bile acids in the liver causes biliary and hepatocyte injury, oxidative stress, and inflammation. The farnesoid X receptor (FXR) is regarded as a bile acid–activated receptor that regulates a network of genes involved in bile acid metabolism, providing a new therapeutic target to treat cholestatic diseases. Arbutin is a glycosylated hydroquinone isolated from medicinal plants in the genus Arctostaphylos, which has a variety of potentially pharmacological properties, such as anti-inflammatory, antihyperlipidemic, antiviral, antihyperglycemic, and antioxidant activity. However, the mechanistic contributions of arbutin to alleviate liver injury of cholestasis, especially its role on bile acid homeostasis via nuclear receptors, have not been fully elucidated. In this study, we demonstrate that arbutin has a protective effect on α-naphthylisothiocyanate–induced cholestasis via upregulation of the levels of FXR and downstream enzymes associated with bile acid homeostasis such as Bsep, Ntcp, and Sult2a1, as well as Ugt1a1. Furthermore, the regulation of these functional proteins related to bile acid homeostasis by arbutin could be alleviated by FXR silencing in L-02 cells. In conclusion, a protective effect could be supported by arbutin to alleviate ANIT-induced cholestatic liver toxicity, which was partly through the FXR pathway, suggesting arbutin may be a potential chemical molecule for the cholestatic disease.

scholarly journals Bile Acid and Fibroblast Growth Factor 19 Regulation in Obese Diabetics, and Non-Alcoholic Fatty Liver Disease after Sleeve Gastrectomy

2019 ◽  
Vol 8 (6) ◽  
pp. 815 ◽  
Author(s):  
Hsien-Hao Huang ◽  
Wei-Jei Lee ◽  
Shu-Chun Chen ◽  
Tung-Fang Chen ◽  
Shou-Dong Lee ◽  
...  
Keyword(s):  
Bile Acid ◽  
Fatty Liver ◽  
Bile Acids ◽  
Fatty Liver Disease ◽  
Total Bile Acid ◽  
Alcoholic Fatty Liver ◽  
Liver Index ◽  
Fatty Liver Index ◽  
Total Bile Acids ◽  
Alcoholic Fatty Liver Disease

Background: Sleeve gastrectomy (SG) is an effective treatment for obesity and type 2 diabetes mellitus (T2DM), and non-alcoholic fatty liver disease (NAFLD); however, the mechanism is not completely understood. Bile acids and fibroblast growth factors (FGFs) are involved in the regulation of energy metabolism. Methods: We investigated the roles of total bile acid and FGF 19 in T2DM remission and NAFLD improvement in obese subjects undergoing SG. A total of 18 patients with obesity and T2DM undergoing laparoscopic SG were enrolled in this study. Serial plasma total bile acid and FGF 19 levels were measured, while the fatty liver index was calculated before and after surgery. Results: The FGF 19 level significantly increased, and the total bile acid level and fatty liver index decreased 1 year after surgery. The complete T2DM remission rate was 66.7% one year after surgery; the complete remitters had significantly lower FGF 19 levels and higher insulin levels than the non-complete remitters. The complete remitters also had significantly decreased total bile acid levels and increased FGF 19 levels 1 year after surgery compared with those before surgery. The fatty improvers had significantly decreased total bile acid levels and increased FGF 19 levels 1 year after surgery compared with those before surgery. Conclusion: The total bile acids level and fatty liver index decreased, and the FGF 19 levels increased 1 year after SG. Both T2DM complete remitters and NAFLD improvers showed significantly decreased total bile acid levels and increased FGF 19 levels 1 year after SG. Plasma total bile acids and FGF 19 might have roles in T2DM remission and NAFLD improvement. Low preoperative FGF 19 levels might be a predictor for NAFLD improvement after SG.

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