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Ultrasonography 41(2), 403-415 (2022). doi:10.14366/usg.21044, Published by Seoul

BMJ Open 11(11), e053148 (2021). doi:10.1136/bmjopen-2021-053148, Published by BMJ Publishing Group, London

Mechanical ventilation (MV) is a life-saving intervention, yet with prolonged MV (i.e., ≥6 h) there are time-dependent reductions in diaphragm blood flow and an impaired hyperemic response of unknown origin. Female Sprague-Dawley rats (4–8 mo, n = 118) were randomized into two groups; spontaneous breathing (SB) and 6-h (prolonged) MV. After MV or SB, vasodilation (flow-induced, endothelium-dependent and -independent agonists) and constriction (myogenic and α-adrenergic) responses were measured in first-order (1A) diaphragm resistance arterioles in vitro, and endothelial nitric oxide synthase (eNOS) mRNA expression was quantified. Following prolonged MV, there was a significant reduction in diaphragm arteriolar flow-induced (SB, 34.7 ± 3.8% vs. MV, 22.6 ± 2.0%; P ≤ 0.05), endothelium-dependent (via acetylcholine; SB, 64.3 ± 2.1% vs. MV, 36.4 ± 2.3%; P ≤ 0.05) and -independent (via sodium nitroprusside; SB, 65.0 ± 3.1% vs. MV, 46.0 ± 4.6%; P ≤ 0.05) vasodilation. Compared with SB, there was reduced eNOS mRNA expression ( P ≤ 0.05). Prolonged MV diminished phenylephrine-induced vasoconstriction (SB, 37.3 ± 6.7% vs. MV, 19.0 ± 1.9%; P ≤ 0.05) but did not alter myogenic or passive pressure responses. The severe reductions in diaphragmatic blood flow at rest and during contractions, with prolonged MV, are associated with diaphragm vascular dysfunction which occurs through both endothelium-dependent and endothelium-independent mechanisms. NEW & NOTEWORTHY Following prolonged mechanical ventilation, vascular alterations occur through both endothelium-dependent and -independent pathways. This is the first study, to our knowledge, demonstrating that diaphragm arteriolar dysfunction occurs consequent to prolonged mechanical ventilation and likely contributes to the severe reductions in diaphragmatic blood flow and weaning difficulties.

Scientific reports 11(1), 6302 (2021). doi:10.1038/s41598-021-85859-2, Published by Macmillan Publishers Limited, part of Springer Nature, [London]

Background Postoperative pain remains a common problem in gynecologic laparoscopy, especially in head zone-related regions, triggered by intra-abdominal pressure during capnoperitoneum. Humidified and prewarmed insufflation gas may ameliorate pain and be beneficial. Methods This prospective randomized controlled parallel group multi-arm single-center study investigated the effects of temperature and humidity of insufflation gas on postoperative pain during gynecologic laparoscopy with a duration ≥ 60 min. Female participants (18—70 years) were blinded and randomly assigned—computer generated—to either insufflation with dry cold CO2 with forced air warming blanket (“AIR”), humidified warm gas without forced air warming blanket (“HUMI”), or humidified warm gas with forced air warming blanket (“HUMI +”). We hypothesized that using humidified warm gas resulted in lower pain scores and less analgesic consumption. The primary endpoint postoperative pain was assessed for different pain localizations every 12 h during 7 days after surgery. Secondary endpoints were demand for painkillers and epidural anesthetics, length of stay in recovery room, and hospital stay. (Registration: ClinicalTrials.gov NCT02781194—completed). Results 150 participants were randomized. Compared to group “AIR” (n = 48), there was significantly less pain in group “HUMI +” (n = 48) in the recovery room (− 1.068; 95% CI − 2.08 to − 0.061), as well as significantly less ibuprofen use at day two (− 0.5871 g ± 0.258; p-value = 0.0471). Other variables did not change significantly. Stratification for presence of endometriosis or non-previous abdominal surgery in patient history revealed significantly less pain in both groups “HUMI” (n = 50) and “HUMI +” versus group “AIR.” Related side effects were not noted. Conclusion In the overall population, the use of warm, humidified insufflation gas did not yield clinically relevant effects; however, in predisposed patients with endometriosis and who could otherwise expect high pain levels, warm and humidified gas may be beneficial.

Although mechanical ventilation (MV) is a life-saving intervention, prolonged MV can lead to deleterious effects on diaphragm function, including vascular incompetence and weaning failure. During MV, positive end-expiratory pressure (PEEP) is used to maintain small airway patency and mitigate alveolar damage. We tested the hypothesis that increased intrathoracic pressure with high levels of PEEP would increase diaphragm vascular resistance and decrease perfusion. Female Sprague-Dawley rats (~6 mo) were randomly divided into two groups receiving low PEEP (1 cmH2O; n = 10) or high PEEP (9 cmH2O; n = 9) during MV. Blood flow, via fluorescent microspheres, was determined during spontaneous breathing (SB), low-PEEP MV, high-PEEP MV, low-PEEP MV + surgical laparotomy (LAP), and high-PEEP MV + pneumothorax (PTX). Compared with SB, both low-PEEP MV and high-PEEP MV increased total diaphragm and medial costal vascular resistance (P ≤ 0.05) and reduced total and medial costal diaphragm blood flow (P ≤ 0.05). Also, during MV medial costal diaphragm vascular resistance was greater and blood flow lower with high-PEEP MV vs. low-PEEP MV (P ≤ 0.05). Diaphragm perfusion with high-PEEP MV+PTX and low-PEEP MV were not different (P > 0.05). The reduced total and medial costal diaphragmatic blood flow with low-PEEP MV appears to be independent of intrathoracic pressure changes and is attributed to increased vascular resistance and diaphragm quiescence. Mechanical compression of the diaphragm vasculature may play a role in the lower diaphragmatic blood flow at higher levels of PEEP. These reductions in blood flow to the quiescent diaphragm during MV could predispose critically ill patients to weaning complications. NEW & NOTEWORTHY This is the first study, to our knowledge, demonstrating that mechanical ventilation, with low and high positive-end expiratory pressure (PEEP), increases vascular resistance and reduces total and regional diaphragm perfusion. The rapid reduction in diaphragm perfusion and increased vascular resistance may initiate a cascade of events that predispose the diaphragm to vascular and thus contractile dysfunction with prolonged mechanical ventilation.

Der Einsatz von Muskelrelaxanzien in der Anasthesie ist aus der heutigen Praxis aufgrund des hohen Nutzens nicht wegzudenken. Lange Zeit galt die Anwendung von Succinylcholin als State of the Art fur die „rapid sequence induction“ (RSI) bei aspirationsgefahrdeten Patienten. Die gunstigen Eigenschaften sind jedoch von einer Vielzahl, teilweise gravierender, Nebenwirkungen begleitet. Die Entwicklung nichtdepolarisierender Muskelrelaxanzien, insbesondere des Rocuroniums in Kombination mit Sugammadex, ermoglichte es, ein succinylcholinahnliches und dabei nebenwirkungsarmeres Wirkprofil zu erreichen. Nach der Markteinfuhrung von Sugammadex wurden weitere Substanzen konzipiert, die eine vollstandige Aufnahme der Muskelrelaxanzien moglich machen. In der Antagonisierung von Muskelrelaxanzien ist Calabadion eine vielversprechende neue Substanz, da sie sowohl die Wirkung des Steroid- als auch des Benzylisochinolintyps antagonisieren kann. In den USA werden aktuell neue Muskelrelaxanzien erprobt, die eine schnelle Anschlagzeit besitzen und deren Wirkung durch L‑Cystein aufgehoben wird. Eine der vielversprechenden Substanzen ist Gantacurium, das sich in den USA in der Phase-III-Testung befindet. Es bleibt abzuwarten, ob diese noch nicht im Markt eingefuhrten Muskelrelaxanzien und Medikamente zur Reversierung der neuromuskularen Blockade das Potenzial besitzen, eine echte Alternative zur Kombination von Rocuronium und Sugammadex zu werden.

INTRODUCTION: Mechanical ventilation is known to activate oxidative stress and proteolytic pathways in the diaphragm. Trauma by inducing inflammation and activating proteolytic pathways may potentiate the effects of mechanical ventilation on the diaphragm. In a blunt chest trauma with concomitant injuries we tested the hypothesis that trauma via inflammation further activates the proteolytic pathways and worsens atrophy in the diaphragm. MATERIAL AND METHODS: Piglets were separated into two groups and underwent 72 h of mechanical ventilation. One group received a polytrauma (PT) by unilateral femur fracture, blunt chest trauma with lung contusion, laparotomy with standardized liver incision, and a predefined hemorrhagic shock. The second mechanically ventilated group (MV) did not receive any trauma. A non-ventilated group (Con) served as control.Diaphragmatic fiber dimensions, Western Blot analyses of proteolytic pathways, and lipid peroxidation and messenger ribonucleic acid (mRNA) levels of cytokines and nuclear factor kappa b subunit p65 were measured. RESULTS: Active Caspase-3 was significantly increased in MV (P = 0.019), and in PT (P = 0.02) compared with Con. Nuclear factor kappa b subunit p65, was upregulated in PT (P = 0.010) compared with Con. IL-6 mRNA increased significantly in PT compared with Con (P = 0.0024) but did not differ between Con and MV. CONCLUSION: Trauma and mechanical ventilation induced proteolysis and atrophy in the diaphragm, but only polytrauma induced an inflammatory response in the diaphragm. The additional traumatic inflammatory stimulus did not increase the levels of the prementioned variables. These data underline that inflammation is not a major contributor to ventilator-induced diaphragmatic dysfunction. TRIAL REGISTRY NUMBER: AZ 84-02.04.2014.A265 (Landesamt für Natur-, Umwelt- und Verbraucherschutz, LANUV NRW, Germany). ispartof: SHOCK vol:52 issue:4 pages:443-448 ispartof: location:United States status: published

Background Anesthetics in ventilated patients are critical as any cofactor hampering diaphragmatic function may have a negative impact on the weaning progress and therefore on patients’ mortality. Dexmedetomidine may display antioxidant and antiproteolytic properties, but it also reduced glucose uptake by the muscle, which may impair diaphragm force production. This study tested the hypothesis that dexmedetomidine could inhibit ventilator-induced diaphragmatic dysfunction. Methods Twenty-four rats were separated into three groups (n = 8/group). Two groups were mechanically ventilated during either dexmedetomidine or pentobarbital exposure for 24 h, referred to as interventional groups. A third group of directly euthanized rats served as control. Force generation, fiber dimensions, proteolysis markers, protein oxidation and lipid peroxidation, calcium homeostasis markers, and glucose transporter–4 (Glut-4) translocation were measured in the diaphragm. Results Diaphragm force, corrected for cross-sectional area, was significantly decreased in both interventional groups compared to controls and was significantly lower with dexmedetomidine compared to pentobarbital (e.g., 100 Hz: –18%, P < 0.0001). In contrast to pentobarbital, dexmedetomidine did not lead to diaphragmatic atrophy, but it induced more protein oxidation (200% vs. 73% in pentobarbital, P = 0.0015), induced less upregulation of muscle atrophy F-box (149% vs. 374% in pentobarbital, P < 0.001) and impaired Glut-4 translocation (–73%, P < 0.0005). It activated autophagy, the calcium-dependent proteases, and caused lipid peroxidation similarly to pentobarbital. Conclusions Twenty-four hours of mechanical ventilation during dexmedetomidine sedation led to a worsening of ventilation-induced diaphragm dysfunction, possibly through impaired Glut-4 translocation. Although dexmedetomidine prevented diaphragmatic fiber atrophy, it did not inhibit oxidative stress and activation of the proteolytic pathways.

Background Perioperative temperature management is fundamental to ensure normothermia in patients. Fluid warmers, which have become smaller in size over the past few years, can help to maintain a stable body temperature. Potentially, the reduction of the size may influence the heating performance. Methods Therefore, we tested the effectiveness of enFlow®, Fluido compact® and Thermosens® fluid warmers by measuring the inlet and outlet temperature for room-tempered and ice-cooled saline at flow rates of 25, 50, 75 and 100 ml/min. Results At all examined flow rates, the tested heating devices warmed up room-tempered saline effectively. The enFlow® provided the significantly (p 38 °C at all tested flow rates. The Fluido compact® ensured this only at flow rates of 25 and 50 ml/min, while the Thermosens® provided these conditions at flow rates of 25, 50 and 75 ml/min. Conclusions The heating capability for room-tempered saline was effective in all tested devices, but with ice-cooled saline enFlow® is superior at high flow rates. At low flow rates the heating capabilities of enFlow®, Fluido compact® and Thermosens® are comparable.

Purpose: Noninvasive pressure support ventilation is intended to relieve the load on respiratory muscles and to prevent exhaustion. This includes continuous positive airway pressure (CPAP) as well as pressure support ventilation (PSV). Speckle tracking echocardiography (STE) allows quantification of tissue deformation by tracing characteristic grayscale patterns, independent of the acquisition angle. The aim of the present study was to assess the applicability of using STE as a way to investigate diaphragm movement using deformation analysis as a parameter for respiratory workload. Materials and Methods: Healthy male subjects (n = 13, 27 ± 7 years) were treated while in a seated supine position with the following respirator settings: regular breathing, 5 mbar CPAP, CPAP + 5 / + 10 / + 15 mbar PSV. A 2 – 4 MhZ M5S phased array sector transducer was used on a Vivid E 9 (GE, Horton, Norway) to visualize the diaphragm. The inspiratory peak transverse strain was measured as a parameter of maximal inspiratory muscle workload and compared to the M-mode-based fractional thickening (FT). Results: Both the FT and the transverse strain increased significantly under CPAP and PSV. The transverse strain correlated well with the FT (r = 0.753; p Conclusion: The results measured by STE were comparable to the M-mode-based measurements. The capturing of a larger diaphragmatic sample area and movement tracking possibly lead to higher precision compared to one-dimensional M-mode. The use of STE in patients might provide a reproducible, bedside method to analyze the respiratory workload. Due to the larger sampling area, it might prove superior to mere M-mode acquisition.

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.

Die mechanische Beatmung ist fur Patienten mit respiratorischem Versagen oder im Rahmen der tiefen Sedierung lebensrettend. Wahrend kontinuierlicher mandatorischer Beatmung ist das Diaphragma inaktiviert und unterliegt einer pathophysiologischen Kaskade, die zum Kraftverlust und zur Verringerung der Muskelfasermasse fuhrt. Diese Prozesse sind im Gegensatz zur peripheren Skelettmuskulatur bereits nach 12 h nachweisbar und haben Einfluss auf die Beatmungsentwohnung von Intensivpatienten – und damit auf Letalitat sowie Morbiditat. Studien der letzten Jahre haben tierexperimentell die pathophysiologischen Zusammenhange untersucht und sind durch klinische Untersuchungen bestatigt worden. Diese Ubersicht beschreibt die biochemischen Zusammenhange, Einflusse von Pharmaka und Interventionen zur Prophylaxe.

Mechanische Beatmung ist lebensrettend fur Patienten mit respiratorischer Insuffizienz oder der Notwendigkeit fur eine tiefe Sedierung. Die resultierende Inaktivierung des Diaphragmas geht mit einer profunden Veranderung der muskularen Homoostase einher, die zu einer Muskelatrophie und Kraftreduktion des Diaphragmas fuhrt. Der wichtigste Pathomechanismus ist die Generierung von oxidativem Stress, der letztendlich in einer Aktivierung der Apoptose resultiert. Die Geschwindigkeit unterscheidet sich deutlich von der peripherer Muskeln, sodass im Diaphragma bereits nach 18-stundiger Beatmung eine Atrophie um 30 % und ein 50 %iger Verlust der Kontraktionskraft nachweisbar ist. Dieser Beitrag gibt einen Uberblick uber die Pathomechanismen, die Besonderheiten des kardiochirurgischen Patientenguts und mogliche Therapieansatze geben.

Summary Maintenance of normothermia is crucial to avoid patient morbidity. Newly released fluid warming devices have become smaller in size, but this change might impair efficacy. We performed an evaluation of the buddy lite™ and enFlow™ fluid warmers. We measured inflow and outlet temperatures of the devices at flow rates between 25 and 100 ml.min−1 using saline at room temperature or cooled to 10 °C. At a flow rate of 25 ml.min−1, the outlet temperature of the buddy lite was significantly higher than that of the enFlow (p

Background: Mechanical ventilation is a life-saving intervention for patients with respiratory failure. Unfortunately, a major complication associated with prolonged mechanical ventilation is ventilator-induced diaphragmatic atrophy and contractile dysfunction, termed ventilator-induced diaphragmatic dysfunction (VIDD). Emerging evidence suggests that positive pressure ventilation (PPV) promotes lung damage (ventilator-induced lung injury [VILI]), resulting in the release of signaling molecules that foster atrophic signaling in the diaphragm and the resultant VIDD. Although a recent report suggests that negative pressure ventilation (NPV) results in less VILI than PPV, it is unknown whether NPV can protect against VIDD. Therefore, the authors tested the hypothesis that compared with PPV, NPV will result in a lower level of VIDD. Methods: Adult rats were randomly assigned to one of three experimental groups (n = 8 each): (1) acutely anesthetized control (CON), (2) 12 h of PPV, and (3) 12 h of NPV. Dependent measures included indices of VILI, diaphragmatic muscle fiber cross-sectional area, diaphragm contractile properties, and the activity of key proteases in the diaphragm. Results: Our results reveal that no differences existed in the degree of VILI between PPV and NPV animals as evidenced by VILI histological scores (CON = 0.082 ± 0.001; PPV = 0.22 ± 0.04; NPV = 0.25 ± 0.02; mean ± SEM). Both PPV and NPV resulted in VIDD. Importantly, no differences existed between PPV and NPV animals in diaphragmatic fiber cross-sectional area, contractile properties, and the activation of proteases. Conclusion: These results demonstrate that NPV and PPV result in similar levels of VILI and that NPV and PPV promote comparable levels of VIDD in rats.

Assessment of diaphragmatic effort is challenging, especially in critically ill patients in the phase of weaning. Fractional thickening during inspiration assessed by ultrasound has been used to estimate diaphragm effort. It is unknown whether more sophisticated ultrasound techniques such as speckle tracking are superior in the quantification of inspiratory effort. This study evaluates the validity of speckle tracking ultrasound to quantify diaphragm contractility. Thirteen healthy volunteers underwent a randomized stepwise threshold loading protocol of 0–50% of the maximal inspiratory pressure. Electric activity of the diaphragm and transdiaphragmatic pressures were recorded. Speckle tracking ultrasound was used to assess strain and strain rate as measures of diaphragm tissue deformation and deformation velocity, respectively. Fractional thickening was assessed by measurement of diaphragm thickness at end-inspiration and end-expiration. Strain and strain rate increased with progressive loading of the diaphragm. Both strain and strain rate were highly correlated to transdiaphragmatic pressure (strain r2 = 0.72; strain rate r2 = 0.80) and diaphragm electric activity (strain r2 = 0.60; strain rate r2 = 0.66). We conclude that speckle tracking ultrasound is superior to conventional ultrasound techniques to estimate diaphragm contractility under inspiratory threshold loading. NEW & NOTEWORTHY Transdiaphragmatic pressure using esophageal and gastric balloons is the gold standard to assess diaphragm effort. However, this technique is invasive and requires expertise, and the interpretation may be complex. We report that speckle tracking ultrasound can be used to detect stepwise increases in diaphragmatic effort. Strain and strain rate were highly correlated with transdiaphragmatic pressure, and therefore, diaphragm electric activity and speckle tracking might serve as reliable tools to quantify diaphragm effort in the future.

Scientific reports 6, 35725 (2016). doi:10.1038/srep35725, Published by Nature Publishing Group, London

Introduction: Assessment of diaphragm function should ideally be assessed using magnetic twitch pressure or esophageal and gastric balloons. Conventional sonographic techniques as thickness and fractional thickening (FT), only provide limited insight in diaphragm function. Speckle tracking echocardiography allows reliable quantification of muscle function by tracking of grey patterns and their motion; strain as parameter of muscle deformation and strain rate as deformation velocity. Aim: To investigate whether speckle tracking can quantify loading of the diaphragm, superior to FT. Methods: 13 healthy volunteers underwent an inspiratory loading protocol with recording of transdiaphragmatic pressure (Pdi) and diaphragm electromyography (EMGdi). Inspiratory loading of 0 to 30% of maximal inspiratory pressure was applied in random order for 5 minutes per applied load. Diaphragmatic sonography was performed using a 2-4 MHz linear phased array transducer positioned at the right-lateral thoracic wall in the anterior axillary line longitudinal to the body axis. Ultrasound recordings of the diaphragm were made at the marked location during 10 seconds. Results: Increased inspiratory loading increased Pdi and EMGdi. Sonographic markers of contractility increased with incremental loading. Pdi correlated with strain (r=0.75; p=0.000) and strain rate (r=0.77; p=0.000). Contrarily, FT was not correlated with Pdi. Conclusion: Speckle tracking of the diaphragm can detect changes in diaphragmatic loading up to 30% of maximal inspiratory pressure. It might be a valuable tool to detect changes in loading in specific patient categories, including patients with acute respiratory failure and ventilated ICU patients.

Background Mechanical ventilation (MV) is associated with diaphragm weakness, a phenomenon termed ventilator-induced diaphragmatic dysfunction. Weaning should balance diaphragmatic loading as well as prevention of overload after MV. The weaning methods pressure support ventilation (PSV) and spontaneous breathing trials (SBT) lead to gradual or intermittent reloading of a weak diaphragm, respectively. This study investigated which weaning method allows more efficient restoration of diaphragm homeostasis. Methods Rats (n = 8 per group) received 12 h of MV followed by either 12 h of pressure support ventilation (PSV) or intermittent spontaneous breathing trials (SBT) and were compared to rats euthanized after 12 h MV (CMV) and to acutely euthanized rats (CON). Force generation, activity of calpain-1 and caspase-3, oxidative stress, and markers of protein synthesis (phosphorylated AKT to total AKT) were measured in the diaphragm. Results Reduction of diaphragmatic force caused by CMV compared to CON was worsened with PSV and SBT (both p

Previous workers have demonstrated that controlled mechanical ventilation results in diaphragm inactivity and elicits a rapid development of diaphragm weakness as a result of both contractile dysfunction and fiber atrophy. Limited data exist regarding the impact of pressure support ventilation, a commonly used mode of mechanical ventilation-that permits partial mechanical activity of the diaphragm-on diaphragm structure and function. We carried out the present study to test the hypothesis that high-level pressure support ventilation decreases the diaphragm pathology associated with CMV.Sprague-Dawley rats were randomly assigned to one of the following five groups:1) control (no mechanical ventilation); 2) 12 hrs of controlled mechanical ventilation (12CMV); 3) 18 hrs of controlled mechanical ventilation (18CMV); 4) 12 hrs of pressure support ventilation (12PSV); or 5) 18 hrs of pressure support ventilation (18PSV).We carried out the following measurements on diaphragm specimens: 4-hydroxynonenal-a marker of oxidative stress, active caspase-3 (casp-3), active calpain-1 (calp-1), fiber type cross-sectional area, and specific force (sp F). Compared with the control, both 12PSV and 18PSV promoted a significant decrement in diaphragmatic specific force production, but to a lesser degree than 12CMV and 18CMV. Furthermore, 12CMV, 18PSV, and 18CMV resulted in significant atrophy in all diaphragm fiber types as well as significant increases in a biomarker of oxidative stress (4-hydroxynonenal) and increased proteolytic activity (20S proteasome, calpain-1, and caspase-3). Furthermore, although no inspiratory effort occurs during controlled mechanical ventilation, it was observed that pressure support ventilation resulted in large decrement, approximately 96%, in inspiratory effort compared with spontaneously breathing animals.High levels of prolonged pressure support ventilation promote diaphragmatic atrophy and contractile dysfunction. Furthermore, similar to controlled mechanical ventilation, pressure support ventilation-induced diaphragmatic atrophy and weakness are associated with both diaphragmatic oxidative stress and protease activation.

Synthesis and liberation of adrenomedullin (ADM) are found in different tissues and endothelial cells and ADM is induced by hypoxia, oxidative stress, and pro-inflammatory cytokines [1]. The prognostic value of ADM is described in general patient populations, in medical patients and in particular recently in patients with suspected sepsis in the emergency department [2, 3]. In surgical patients, the obstacle is to differentiate between postoperative inflammation and sepsis and to assess the patients' prognosis.

Enkephalins are opioid peptides and enkephalin and its precursor pro-enkephalin (pro-ENK) are found to be widely distributed in organ tissues including the kidney [1]. Pro-ENK is a predictor for acute kidney injury (AKI) in patients after cardiac surgery and can detect severity of AKI in patients admitted to the emergency department with sepsis [2, 3]. In surgical ICU-patients with sepsis, information on the suitability of pro-ENK to determine kidney function is lacking.

Ventilator-induced diaphragmatic dysfunction is associated with the generation of oxidative stress, enhanced proteolysis, autophagy and reduced protein synthesis in the diaphragm. Sevoflurane is a common operating room anesthetic and can be used in the intensive care medicine as well. Besides its anesthetic properties, its use in cardiac ischemia-reperfusion models can maintain protein synthesis and inhibit generation of reactive oxygen species, if used at the beginning of heart surgery. This study has been performed on the hypothesis that sevoflurane might protect against ventilator-induced diaphragmatic dysfunction by preventing the production of oxidative stress.Four-month-old, male Sprague-Dawley rats sedated with sevoflurane (minimal alveolar concentration = 1) were either mechanically ventilated (MV) for 12 hours (n = 8) or allowed to breathe spontaneously (SB) for 12 hours (n = 8). An acutely anesthetized group was used as a control (Con) group (n = 8). After euthanization, diaphragmatic contractile properties, fiber cross-sectional areas, proteolysis (calpain-1 and caspase-3), and oxidative stress (lipid peroxidation, protein oxidation) were examined. After testing for normality, 1-way or 2-way analysis of variance with the Dunnett post hoc test was used to test for significance.The diaphragm contractile force was similarly reduced at all stimulation frequencies in the SB and MV groups compared with controls. Markers of oxidative stress and fiber cross-sectional areas were unaltered between Con and SB/MV, respectively. The calcium-dependent proteases (calpain-1 and caspase-3) were enhanced in the MV group. The p-AKT/AKT ratio and p-FoxO1/FoxO1 ratio were significantly and similarly reduced after sevoflurane exposure in the SB and MV group compared with Con group.Exposure to sevoflurane did not induce oxidative stress. It led to reduction in diaphragmatic force. In the MV group, sevoflurane led to the activation of atrophy signaling pathways. These findings are of particular importance for clinical utilization in intensive care units and question its use, especially during the phases of SB.

Critical care : the leading online forum for critical care, intensive care and emergency medicine 19, 365 (2015). doi:10.1186/s13054-015-1082-7, Published by Current Science Ltd, London

PLoS one 9(1), e87460 (2014). doi:10.1371/journal.pone.0087460, Published by PLoS [u.a.], Lawrence, Kan.

BMC neurology 13, 106 (2013). doi:10.1186/1471-2377-13-106, Published by BioMed Central [u.a.], London

Journal of cardiothoracic surgery 8(1), 159 (2013). doi:10.1186/1749-8090-8-159, Published by BioMed Central, London

PLoS one 8(8), e70524 (2013). doi:10.1371/journal.pone.0070524, Published by PLoS [u.a.], Lawrence, Kan.

Cardiac surgery is associated with release of the pleiotropic cytokine macrophage migration inhibitory factor (MIF). The trigger for MIF release has not yet been elucidated. Owing to its intrinsic antioxidative activity, MIF might reduce oxidative stress and protect from myocardial ischemia and reperfusion (I/R) injury. In the present study, patients scheduled for elective cardiac surgery (n=46) were randomized to undergo coronary artery bypass grafting either conventionally with cardiopulmonary bypass and cardioplegic arrest-induced I/R (cCABG) or in an off-pump procedure (OPCAB) with minimized I/R. We report that only patients who underwent cCABG exhibited a postoperative increase of MIF (p=0.024), while both groups showed an increase in interleukin-6. MIF release appears to be primarily mediated by I/R and to a lesser extent by inflammation. Endogenous peroxidase activity (p=0.021) and serum levels of thioredoxin (p=0.003) were significantly higher in patients who underwent cCABG after surgery. Interestingly, perioperative MIF release was associated with an enhanced antioxidant capacity and a significantly reduced postoperative incidence of atrial fibrillation (p=0.018) and acute kidney injury (p=0.048). The present study highlights the role of MIF increase during cardiac surgery in response to oxidative stress. Based on current observations, we hypothesize that intraoperative MIF secretion is due to I/R and enhances the antioxidant capacity in patients during cardiac surgery. Antioxid. Redox Signal. 19, 231–239.

Mechanical ventilation is a prerequisite for many surgical interventions. Furthermore, during states of severe gas exchange disturbance or impaired neurological conditions with the threat of aspiration or cardiovascular instability, it is a life-saving intervention on every ICU. Even the induction of anaesthesia disturbs the physiological lung function, due to changes in chest wall mechanics and diaphragm relaxation, generating atelectases, gas exchange disturbance and ventilation-perfusion mismatch. Additionally, the application of positive pressure to lung structures elicits ventilator-induced lung injury, with the severity of injury dependent on the applied volume, peak pressures and levels of positive end-expiratory pressure. Although these pathophysiological changes may be of minor importance for the majority of ventilated patients in the operating room, these mechanisms may harm patients during surgical interventions with the need for one-lung ventilation or with underlying co-morbidities such as chronic obstructive pulmonary disease (COPD) or acute respiratory distress syndrome (ARDS). This review provides an outline of the major components of the pathophysiological changes associated with general anaesthesia and describes the additional risks in patients with COPD and ARDS as common co-morbidities in every hospital.

With advancing age, there is a reduction in exercise tolerance, resulting, in part, from a perturbed ability to match O2 delivery to uptake within skeletal muscle. In the spinotrapezius muscle (which is not recruited during incline treadmill running) of aged rats, we tested the hypotheses that exercise training will 1) improve the matching of O2 delivery to O2 uptake, evidenced through improved microvascular Po2 (PmO2), at rest and throughout the contractions transient; and 2) enhance endothelium-dependent vasodilation in first-order arterioles. Young (Y, ∼6 mo) and aged (O, >24 mo) Fischer 344 rats were assigned to control sedentary (YSED; n = 16, and OSED; n = 15) or exercise-trained (YET; n = 14, and OET; n = 13) groups. Spinotrapezius blood flow (via radiolabeled microspheres) was measured at rest and during exercise. Phosphorescence quenching was used to quantify PmO2 in vivo at rest and across the rest-to-twitch contraction (1 Hz, 5 min) transition in the spinotrapezius muscle. In a follow-up study, vasomotor responses to endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside) stimuli were investigated in vitro. Blood flow to the spinotrapezius did not increase above resting values during exercise in either young or aged groups. Exercise training increased the precontraction baseline PmO2 (OET 37.5 ± 3.9 vs. OSED 24.7 ± 3.6 Torr, P < 0.05); the end-contracting PmO2 and the time-delay before PmO2 fell in the aged group but did not affect these values in the young. Exercise training improved maximal vasodilation in aged rats to acetylcholine (OET 62 ± 16 vs. OSED 27 ± 16%) and to sodium nitroprusside in both young and aged rats. Endurance training of aged rats enhances the PmO2 in a nonrecruited skeletal muscle and is associated with improved vascular smooth muscle function. These data support the notion that improvements in vascular function with exercise training are not isolated to the recruited muscle.

Medical Gas Research 3(1), 12,11 S. (2013). doi:10.1186/2045-9912-3-12, Published by BioMed Central, London