scholarly journals Is Mitochondrial Oxidative Stress the Key Contributor to Diaphragm Atrophy and Dysfunction in Critically Ill Patients?

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Hongjie Duan ◽  
Hailiang Bai
Keyword(s):  
Oxidative Stress ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Diaphragmatic Dysfunction ◽  
Respiratory Dysfunction ◽  
Mitochondrial Oxidative Stress ◽  
Diaphragm Dysfunction ◽  
Metabolic Hormones ◽  
Diaphragm Atrophy ◽  
Functional Alteration

Diaphragm dysfunction is prevalent in the progress of respiratory dysfunction in various critical illnesses. Respiratory muscle weakness may result in insufficient ventilation, coughing reflection suppression, pulmonary infection, and difficulty in weaning off respirators. All of these further induce respiratory dysfunction and even threaten the patients’ survival. The potential mechanisms of diaphragm atrophy and dysfunction include impairment of myofiber protein anabolism, enhancement of myofiber protein degradation, release of inflammatory mediators, imbalance of metabolic hormones, myonuclear apoptosis, autophagy, and oxidative stress. Among these contributors, mitochondrial oxidative stress is strongly implicated to play a key role in the process as it modulates diaphragm protein synthesis and degradation, induces protein oxidation and functional alteration, enhances apoptosis and autophagy, reduces mitochondrial energy supply, and is regulated by inflammatory cytokines via related signaling molecules. This review aims to provide a concise overview of pathological mechanisms of diaphragmatic dysfunction in critically ill patients, with special emphasis on the role and modulating mechanisms of mitochondrial oxidative stress.

Sedation Using Propofol Induces Similar Diaphragm Dysfunction and Atrophy during Spontaneous Breathing and Mechanical Ventilation in Rats

2014 ◽  
Vol 120 (3) ◽  
pp. 665-672 ◽  
Author(s):  
Christian S. Bruells ◽  
Karen Maes ◽  
Rolf Rossaint ◽  
Debby Thomas ◽  
Nele Cielen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mechanical Ventilation ◽  
Internal Control ◽  
Spontaneous Breathing ◽  
Antioxidant Properties ◽  
Diaphragmatic Dysfunction ◽  
Cross Sectional ◽  
Diaphragm Dysfunction ◽  
Propofol Sedation ◽  
Diaphragm Atrophy

Abstract Background: Mechanical ventilation is crucial for patients with respiratory failure. The mechanical takeover of diaphragm function leads to diaphragm dysfunction and atrophy (ventilator-induced diaphragmatic dysfunction), with an increase in oxidative stress as a major contributor. In most patients, a sedative regimen has to be initiated to allow tube tolerance and ventilator synchrony. Clinical data imply a correlation between cumulative propofol dosage and diaphragm dysfunction, whereas laboratory investigations have revealed that propofol has some antioxidant properties. The authors hypothesized that propofol reduces markers of oxidative stress, atrophy, and contractile dysfunction in the diaphragm. Methods: Male Wistar rats (n = 8 per group) were subjected to either 24 h of mechanical ventilation or were undergone breathing spontaneously for 24 h under propofol sedation to test for drug effects. Another acutely sacrificed group served as controls. After sacrifice, diaphragm tissue was removed, and contractile properties, cross-sectional areas, oxidative stress, and proteolysis were examined. The gastrocnemius served as internal control. Results: Propofol did not protect against diaphragm atrophy, oxidative stress, and protease activation. The decrease in tetanic force compared with controls was similar in the spontaneous breathing group (31%) and in the ventilated group (34%), and both groups showed the same amount of muscle atrophy. The gastrocnemius muscle fibers did not show atrophy. Conclusions: Propofol does not protect against ventilator-induced diaphragmatic dysfunction or oxidative injury. Notably, spontaneous breathing under propofol sedation resulted in the same amount of diaphragm atrophy and dysfunction although diaphragm activation per se protects against ventilator-induced diaphragmatic dysfunction. This makes a drug effect of propofol likely.

scholarly journals Ultrasound diaphragm excursion and noninvasive ventilation in critically ill patients: a horse to bet on?

2020 ◽  
Author(s):  
Federico Barbariol ◽  
Giovanni Maria Guadagnin ◽  
Cristian Deana
Keyword(s):  
Respiratory Failure ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Area Under The Curve ◽  
Bedside Ultrasound ◽  
Medical Patients ◽  
Diaphragmatic Dysfunction ◽  
Diaphragm Dysfunction ◽  
Ultrasound Evaluation ◽  
Different Response

Abstract BACKGROUND Diaphragmatic dysfunction is seen in up to 60% of critically ill patients with respiratory failure, and it is associated with worse outcomes. The functionality of the diaphragm can be studied with simple and codified bedside ultrasound evaluation. Diaphragm excursion (echographic measurement of the inspiratory displacement of the hemidiaphragm) is one of the most studied parameters. The aim of this study was to assess the prevalence of diaphragmatic dysfunction in critically ill non-intubated patients admitted to a general intensive care unit with acute respiratory failure. Response to non-invasive ventilation (NIV) was evaluated in patients with diaphragm dysfunction, as was whether the ultrasound assessment of the diaphragm excursion may be employed as a predictor of NIV failure. METHODS We collected data, including ultrasound diaphragm excursion, at 2 time points: at T0 (at the time of recruitment, just before starting NIV) and at T1 (after one hour of NIV). RESULTS A total of 47 patients were enrolled. Prevalence of diaphragm dysfunction was 42.5% (95% CI 28, 3 - 57,8). Surgical patients showed a higher incidence (relative risk of 1.97) than medical patients. Mean DE was not significantly different between NIV responders (1,35 ± 0.78 cm) and non-responders (1.21 ± 0.85 cm, p 0,6). Patients with diaphragmatic dysfunction responded positively to NIV in 60% (95% CI 36.0 - 80.9%) of cases, while patients without diaphragmatic dysfunction responded positively to the NIV trial in 70.4% (95% CI 49.8 - 86.2%) of cases (p = 0.54). Taking the use of ultrasound diaphragm excursion as a potential predictor of NIV response, the corresponding ROC curve had an area under the curve of 0.53; the best balance between sensitivity (58.1%) and specificity (62.5%) was obtained with a cut-off diaphragm excursion of 1.37 cm. CONCLUSIONS Diaphragm dysfunction is particularly frequent in critically ill patients with respiratory failure. The functionality of the diaphragm can be effectively and easily tested by bedside ultrasound examination, and its measurement should be considered in every patient with respiratory failure. Overall, our results point towards tentative evidence of a trend of a different response to NIV in patients with vs without diaphragmatic dysfunction.

scholarly journals Real‐Time Energy Exposure Is Associated With Increased Oxidative Stress Among Feeding‐Tolerant Critically Ill Patients: Results From the FEDOX Trial

2020 ◽  
Vol 44 (8) ◽  
pp. 1484-1491 ◽  
Author(s):  
Liam McKeever ◽  
Sarah J. Peterson ◽  
Sofia Cienfuegos ◽  
Jaime Rizzie ◽  
Omar Lateef ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Real Time ◽  
Critically Ill ◽  
Critically Ill Patients

Oxidative Stress in Critically Ill Patients

2002 ◽  
Vol 11 (6) ◽  
pp. 543-551 ◽  
Author(s):  
Caryl Goodyear-Bruch ◽  
Janet D. Pierce
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Superoxide Dismutase ◽  
Free Radicals ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Oxygen Free Radicals ◽  
Oxygen Species ◽  
Defense System ◽  
Oxygen Derived Free Radicals

Oxygen-derived free radicals play an important role in the development of disease in critically ill patients. Normally, oxygen free radicals are neutralized by antioxidants such as vitamin E or enzymes such as superoxide dismutase. However, in patients who require intensive care, oxygen free radicals become a problem when either a decrease in the removal or an overproduction of the radicals occurs. This oxidative stress and the damage due to it have been implicated in many diseases in critically ill patients. Many drugs and treatments now being investigated are directed toward preventing the damage from oxidative stress. The formation of reactive oxygen species, the damage caused by them, and the body’s defense system against them are reviewed. New interventions are described that may be used in critically ill patients to prevent or treat oxidative damage.

scholarly journals REducing Deaths due to OXidative Stress (The REDOXS© Study): rationale and study design for a randomized trial of glutamine and antioxidant supplementation in critically-ill patients

2006 ◽  
Vol 65 (3) ◽  
pp. 250-263 ◽  
Author(s):  
Daren K. Heyland ◽  
Rupinder Dhaliwal ◽  
Andrew G. Day ◽  
John Muscedere ◽  
John Drover ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Randomized Trial ◽  
Critically Ill ◽  
Organ Dysfunction ◽  
Critically Ill Patients ◽  
Tertiary Care ◽  
Antioxidant Therapy ◽  
Favourable Effect ◽  
High Dose ◽  
Antioxidant Supplementation

Critically-ill patients experience an extent of hyperinflammation, cellular immune dysfunction, oxidative stress and mitochondrial dysfunction. Supplementation with key nutrients, such as glutamine and antioxidants, is most likely to have a favourable effect on these physiological derangements, leading to an improvement in clinical outcomes. The results of two meta-analyses suggest that glutamine and antioxidants may be associated with improved survival. The purpose of the present paper is to report the background rationale and study protocol for the evaluation of the effect of high-dose glutamine and antioxidant supplementation on mortality in a large-scale randomized trial in 1200 mechanically-ventilated, critically-ill patients. Patients admitted to an intensive care unit (ICU) with clinical evidence of severe organ dysfunction will be randomized to one of four treatments in a 2×2 factorial design: (1) glutamine; (2) antioxidant therapy; (3) glutamine and antioxidant therapy; (4) placebo. The primary outcome for this study is 28 d mortality. The secondary outcomes are duration of stay in ICU, adjudicated diagnosis of infection, multiple organ dysfunction, duration of mechanical ventilation, length of stay in hospital and health-related quality of life at 3 and 6 months. A novel design feature is the combined use of parenteral and enteral study nutrients dissociated from the nutrition support. The therapeutic strategies tested in the randomized trial may lead to less morbidity and improved survival in critically-ill patients. The trial will be conducted in approximately twenty tertiary-care ICU in Canada and the first results are expected in 2009.

scholarly journals Redox Changes Induced by General Anesthesia in Critically Ill Patients with Multiple Traumas

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Marius Papurica ◽  
Alexandru Florin Rogobete ◽  
Dorel Sandesc ◽  
Raluca Dumache ◽  
Radu Nartita ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
General Anesthesia ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Trauma Team ◽  
Multiple Organ ◽  
Cellular Mechanisms ◽  
Surgical Interventions ◽  
Polytrauma Patient ◽  
Multiple Traumas

The critically ill polytrauma patient is a constant challenge for the trauma team due to the complexity of the complications presented. Intense inflammatory response and infections, as well as multiple organ dysfunctions, significantly increase the rate of morbidity and mortality in these patients. Moreover, due to the physiological and biochemical imbalances present in this type of patients, the bioproduction of free radicals is significantly accelerated, thus installing the oxidative stress. In the therapeutic management of such patients, multiple surgical interventions are required and therefore they are being subjected to repeated general anesthesia. In this paper, we want to present the pathophysiological implications of oxidative stress in critically ill patients with multiple traumas and the implications of general anesthesia on the redox mechanisms of the cell. We also want to summarize the antioxidant treatments able to reduce the intensity of oxidative stress by modulating the biochemical activity of some cellular mechanisms.

scholarly journals Reliability of diaphragmatic ultrasonography to detect diaphragm dysfunction in critically ill patients

2015 ◽  
Vol 3 (S1) ◽  
Author(s):  
M Dres ◽  
B-P Dubé ◽  
J Mayaux ◽  
J Delemazure ◽  
H Prodanovic ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Diaphragm Dysfunction
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