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Intensive Care Medicine Experimental

Christopher John Joyce, Kiran Shekar, David Andrew Cook
BACKGROUND: Venovenous extracorporeal membrane oxygenation (vv-ECMO) is an effective treatment for severe respiratory failure. The interaction between the cardiorespiratory system and the oxygenator can be explored with mathematical models. Understanding the physiology will help the clinician optimise therapy. As others have examined O2 exchange, the main focus of this study was on CO2 exchange. METHODS: A model of the cardiorespiratory system during vv-ECMO was developed, incorporating O2 , CO2 and N2 exchange in both the lung and the oxygenator...
August 9, 2018: Intensive Care Medicine Experimental
Caroline Laroye, Jérémie Lemarié, Amir Boufenzer, Pierre Labroca, Lisiane Cunat, Corentine Alauzet, Frédérique Groubatch, Clémence Cailac, Lucie Jolly, Danièle Bensoussan, Loïc Reppel, Sébastien Gibot
BACKGROUND: Septic shock is the leading cause of death in intensive care units. The pathophysiological complexity of this syndrome contributes to an absence of specific treatment. Several preclinical studies in murine models of septic shock have shown improvements to organ injury and survival after administration of mesenchymal stem cells (MSCs). To better mimic a clinical approach in humans, we investigated the impact of randomized controlled double-blind administration of clinical-grade umbilical cord-derived MSCs to a relevant pig model of septic shock...
August 8, 2018: Intensive Care Medicine Experimental
Lauge Vammen, Søren Rahbek, Niels Secher, Jonas Agerlund Povlsen, Niels Jessen, Bo Løfgren, Asger Granfeldt
BACKGROUND: Cardiac arrest carries a poor prognosis. The typical cardiac arrest patient is comorbid, and studies have shown that diabetes mellitus is an independent risk factor for increased mortality after cardiac arrest. Despite this, animal studies lack to investigate cardiac arrest in the setting of diabetes mellitus. We hypothesize that type 2 diabetes mellitus in a rat model of cardiac arrest is associated with increased organ dysfunction when compared with non-diabetic rats. METHODS: Zucker diabetic fatty (ZDF) rats (n = 13), non-diabetic Zucker lean control (ZLC) rats (n = 15), and non-diabetic Sprague Dawley (SprD) rats (n = 8), underwent asphyxia-induced cardiac arrest...
August 7, 2018: Intensive Care Medicine Experimental
Sarah Piel, Johannes K Ehinger, Imen Chamkha, Eleonor Åsander Frostner, Fredrik Sjövall, Eskil Elmér, Magnus J Hansson
BACKGROUND: Metformin is the most common pharmacological treatment for type 2 diabetes. It is considered safe but has been associated with the development of lactic acidosis under circumstances where plasma concentrations exceed therapeutic levels. Metformin-induced lactic acidosis has been linked to the drug's toxic effect on mitochondrial function. Current treatment strategies aim to remove the drug and correct for the acidosis. With a mortality of 20%, complementary treatment strategies are needed...
August 1, 2018: Intensive Care Medicine Experimental
María C Arango-Granados, Virginia Zarama Córdoba, Andrés M Castro Llanos, Luis A Bustamante Cristancho
BACKGROUND: Methods to guide fluid therapy in spontaneously breathing patients are scarce. No studies have reported the accuracy of end-tidal CO2 (ET-CO2 ) to predict volume responsiveness in these patients. We sought to evaluate the ET-CO2 gradient (ΔET-CO2 ) after a passive leg rise (PLR) maneuver to predict volume responsiveness in spontaneously breathing healthy adults. METHODS: We conducted a prospective study in healthy adult human volunteers. A PLR maneuver was performed and cardiac output (CO) was measured by transthoracic echocardiography...
July 30, 2018: Intensive Care Medicine Experimental
Ellen Broberg, Martiné Wlosinska, Lars Algotsson, Anna-Carin Olin, Darcy Wagner, Leif Pierre, Sandra Lindstedt
BACKGROUND: Different mechanical ventilation settings are known to affect lung preservation for lung transplantation. Measurement of particle flow in exhaled air may allow online assessment of the impact of ventilation before changes in the tissue can be observed. We hypothesized that by analyzing the particle flow, we could understand the impact of different ventilation parameters. METHODS: Particle flow was monitored in vivo, post mortem, and in ex vivo lung perfusion (EVLP) in six porcines with the Pexa (particles in exhaled air) instrument...
July 27, 2018: Intensive Care Medicine Experimental
Carola Venturini, Andrew N Ginn, Brooke E Wilson, Guy Tsafnat, Ian Paulsen, Sally R Partridge, Jonathan R Iredell
This study examines the impact of cefepime and APP-β (antipseudomonal penicillin/ β-lactamase inhibitor combinations) on Gram-negative bacterial colonization and resistance in two Australian ICUs. While resistance did not cumulatively increase, cefepime (but not APP-β treatment) was associated with acquisition of antibiotic resistant Enterobacteriaceae, consistent with an ecological effect. Analysis of the resident gut E. coli population in a subset of patients showed an increase in markers of horizontal gene transfer after cefepime exposure that helps explain the increase in APP-β resistance and reminds us that unmeasured impacts on the microbiome are key outcome determinants that need to be fully explored...
July 27, 2018: Intensive Care Medicine Experimental
Safiah H C Mai, Neha Sharma, Andrew C Kwong, Dhruva J Dwivedi, Momina Khan, Peter M Grin, Alison E Fox-Robichaud, Patricia C Liaw
BACKGROUND: Despite increasing ethical standards for conducting animal research, death is still often used as an endpoint in mouse sepsis studies. Recently, the Murine Sepsis Score (MSS), Mouse Clinical Assessment Score for Sepsis (M-CASS), and Mouse Grimace Scale (MGS) were developed as surrogate endpoint scoring systems for assessing pain and disease severity in mice. The objective of our study was to compare the effectiveness of these scoring systems and monitoring of body temperature for predicting disease progression and death in the cecal ligation and puncture (CLP) sepsis model, in order to better inform selection of surrogate endpoints for death in experimental sepsis...
July 27, 2018: Intensive Care Medicine Experimental
Jayesh A Dhanani, Jeremy Cohen, Suzanne L Parker, Hak-Kim Chan, Patricia Tang, Benjamin J Ahern, Adeel Khan, Manoj Bhatt, Steven Goodman, Sara Diab, Jivesh Chaudhary, Jeffrey Lipman, Steven C Wallis, Adrian Barnett, Michelle Chew, John F Fraser, Jason A Roberts
BACKGROUND: Nebulised antibiotics are frequently used for the prevention or treatment of ventilator-associated pneumonia. Many factors may influence pulmonary drug concentrations with inaccurate dosing schedules potentially leading to therapeutic failure and/or the emergence of antibiotic resistance. We describe a research pathway for studying the pharmacokinetics of a nebulised antibiotic during mechanical ventilation using in vitro methods and ovine models, using tobramycin as the study antibiotic...
July 11, 2018: Intensive Care Medicine Experimental
Natalia Hernandez-Pacheco, Beatriz Guillen-Guio, Marialbert Acosta-Herrera, Maria Pino-Yanes, Almudena Corrales, Alfonso Ambrós, Leonor Nogales, Arturo Muriel, Elena González-Higueras, Francisco J Diaz-Dominguez, Elizabeth Zavala, Javier Belda, Shwu-Fan Ma, Jesús Villar, Carlos Flores
BACKGROUND: The acute respiratory distress syndrome (ARDS) is one of the main causes of mortality in adults admitted to intensive care units. Previous studies have demonstrated the existence of genetic variants involved in the susceptibility and outcomes of this syndrome. We aimed to identify novel genes implicated in sepsis-induced ARDS susceptibility. METHODS: We first performed a prioritization of candidate genes by integrating our own genomic data from a transcriptomic study in an animal model of ARDS and from the only published genome-wide association study of ARDS study in humans...
July 9, 2018: Intensive Care Medicine Experimental
R M Koch, D A Diavatopoulos, G Ferwerda, P Pickkers, M I de Jonge, M Kox
BACKGROUND: Influenza infections are often complicated by secondary infections, which are associated with high morbidity and mortality, suggesting that influenza profoundly influences the immune response towards a subsequent pathogenic challenge. However, data on the immunological interplay between influenza and secondary infections are equivocal, with some studies reporting influenza-induced augmentation of the immune response, whereas others demonstrate that influenza suppresses the immune response towards a subsequent challenge...
July 5, 2018: Intensive Care Medicine Experimental
Jerome Aboab, Louis Mayaud, Veronique Sebille, Rodrigo de Oliveira, Merce Jourdain, Djillali Annane
BACKGROUND: There is an increasing interest in beta-blockade as a therapeutic approach to sepsis following consistent experimental findings of attenuation of inflammation and improved survival with beta1 selective antagonist. However, the mechanism of these beneficial effects remains very uncertain. Thus, this study is aimed at investigating the effects of a beta-1 selective blockade on sympathetic/parasympathetic activity in endotoxin-challenged pigs using heart rate variability. The hypothesis is that an adrenergic blockade could promote parasympathetic activity...
July 4, 2018: Intensive Care Medicine Experimental
John P R Moore, Chris Anstey, Lauren Murray, John F Fraser, Mervyn Singer
BACKGROUND: A dysregulated stress response has been implicated in the pathogenesis of critical illness. Sedative agents utilised in the critically unwell patient may impact upon the stress response with a downstream negative effect on multiple organ systems. This study was designed to assess the feasibility of investigating components of the stress response as a sub-study of the current SPICE-III study (NCT01728558). METHODS: This pilot observational cohort study was conducted in a single intensive care unit in Queensland, Australia...
June 20, 2018: Intensive Care Medicine Experimental
Benjamin Malard, Corine Lambert, John A Kellum
BACKGROUND: Septic shock, a leading cause of acute kidney injury, induces release of pro-/anti-inflammatory mediators, leading to increased mortality and poor renal recovery. This is the first in vitro study directly comparing three single-use blood purification devices in terms of removing sepsis-associated mediators and endotoxins. METHODS: In vitro hemoperfusion was performed using oXiris® , CytoSorb® , and Toraymyxin® . Heparinized human plasma from healthy volunteers was pre-incubated with pathologic quantities of inflammatory mediators and filtered in a closed-loop circulation model for 2 h...
May 4, 2018: Intensive Care Medicine Experimental
Osamu Nagano, Tetsuya Yumoto, Atsunori Nishimatsu, Shunsuke Kanazawa, Takahisa Fujita, Sunao Asaba, Hideo Yamanouchi
BACKGROUND: Bias flow (BF) is essential to maintain mean airway pressure (MAP) and to washout carbon dioxide (CO2 ) from the oscillator circuit during high-frequency oscillatory ventilation (HFOV). If the BF rate is inadequate, substantial CO2 rebreathing could occur and ventilation efficiency could worsen. With lower ventilation efficiency, the required stroke volume (SV) would increase in order to obtain the same alveolar ventilation with constant frequency. The aim of this study was to assess the effect of BF rate on ventilation efficiency during adult HFOV...
April 19, 2018: Intensive Care Medicine Experimental
Carmen Andrea Pfortmueller, Dominik Uehlinger, Stephan von Haehling, Joerg Christian Schefold
No abstract text is available yet for this article.
April 13, 2018: Intensive Care Medicine Experimental
Gustavo A Cortes-Puentes, Kenneth E Gard, Alexander B Adams, David J Dries, Michael Quintel, Richard A Oeckler, Luciano Gattinoni, John J Marini
BACKGROUND: Body positioning affects the configuration and dynamic properties of the chest wall and therefore may influence decisions made to increase or decrease ventilating pressures and tidal volume. We hypothesized that unlike global functional residual capacity (FRC), component sector gas volumes and their corresponding regional tidal expansions would vary markedly in the setting of unilateral pleural effusion (PLEF), owing to shifting distributions of aeration and collapse as posture changed...
April 10, 2018: Intensive Care Medicine Experimental
Miguel Sánchez-García, Passio Santos, Gema Rodríguez-Trigo, Fernando Martínez-Sagasti, Tomás Fariña-González, Ángela Del Pino-Ramírez, Carlos Cardenal-Sánchez, Beatriz Busto-González, Mónica Requesens-Solera, Mercedes Nieto-Cabrera, Francisco Romero-Romero, Antonio Núñez-Reiz
BACKGROUND: Catheter suctioning of respiratory secretions in intubated subjects is limited to the proximal airway and associated with traumatic lesions to the mucosa and poor tolerance. "Mechanical insufflation-exsufflation" exerts positive pressure, followed by an abrupt drop to negative pressure. Potential advantages of this technique are aspiration of distal airway secretions, avoiding trauma, and improving tolerance. METHODS: We applied insufflation of 50 cmH2 O for 3 s and exsufflation of - 45 cmH2 O for 4 s in patients with an endotracheal tube or tracheostomy cannula requiring secretion suctioning...
April 3, 2018: Intensive Care Medicine Experimental
Yu Onodera, Ryo Akimoto, Hiroto Suzuki, Masayuki Okada, Masaki Nakane, Kaneyuki Kawamae
BACKGROUND: Although clinical studies of the high-flow nasal cannula (HFNC) and its effect on positive end-expiratory pressure (PEEP) have been done, the washout effect has not been well evaluated. Therefore, we made an experimental respiratory model to evaluate the respiratory physiological effect of HFNC. METHODS: An airway model was made by a 3D printer using the craniocervical 3D-CT data of a healthy 32-year-old male. CO2 was infused into four respiratory lung models (normal-lung, open- and closed-mouth models; restrictive- and obstructive-lung, open-mouth models) to maintain the partial pressure of end-tidal CO2 (PET CO2 ) at 40 mmHg...
March 15, 2018: Intensive Care Medicine Experimental
Taressa Bull, Amanda Corley, Danielle J Smyth, David J McMillan, Kimble R Dunster, John F Fraser
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) delivers cardiac and/or respiratory support to critically ill patients who have failed conventional medical therapies. If the large-bore cannulas used to deliver ECMO become infected or dislodged, the patient consequences can be catastrophic. ECMO cannula-related infection has been reported to be double the rate of other vascular devices (7.1 vs 3.4 episodes/1000 ECMO days respectively). The aim of this study was to assess the ability of cyanoacrylate tissue adhesive (TA) to inhibit bacterial growth at the ECMO cannulation site, and the effectiveness of TA and securement devices in securing ECMO cannulas and tubing...
March 12, 2018: Intensive Care Medicine Experimental
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