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Xenon resuscitation

Richie Robel, Peter Caroccio, Mervyn Maze
Xenon has features that make it an ideal general anesthetic agent; cost and scarcity mitigate xenon's widespread use in the operating room. Discovery of xenon's cytoprotective properties resulted in its application to thwart ongoing acute neurologic injury, an unmet clinical need. The discovery that xenon's neuroprotective effect interacts synergistically with targeted temperature management (TTM) led to its investigation in clinical settings, including in the management of the postcardiac arrest syndrome, in which TTM is indicated...
2018: Methods in Enzymology
A J Gardner, D K Menon
Despite the global burden of brain injury, neuroprotective agents remain elusive. There are no clinically effective therapies which reduce mortality or improve long-term cognitive outcome. Ventilation could be an easily modifiable variable in resuscitation; gases are relatively simple to administer. Xenon is the prototypic agent of a new generation of experimental treatments which show promise. However, use is hindered by its prohibitive cost and anaesthetic properties. Argon is an attractive option, being cheaper, easy to transport, non-sedating, and mechanistically distinct from xenon...
March 2018: British Journal of Anaesthesia
Anne Brücken, Christian Bleilevens, Philipp Föhr, Kay Nolte, Rolf Rossaint, Gernot Marx, Michael Fries, Matthias Derwall
AIM OF THE STUDY: Combining xenon and mild therapeutic hypothermia (MTH) after cardiac arrest (CA) confers a degree of protection that is greater than either of the two interventions alone. However, xenon is very costly which might preclude a widespread use. We investigated whether the inexpensive gas argon would enhance hypothermia induced neurologic recovery in a similar manner. METHODS: Following nine minutes of CA and three minutes of cardiopulmonary resuscitation 21 male Sprague-Dawley rats were randomized to receive MTH (33°C for 6h), MTH plus argon (70% for 1h), or no treatment...
August 2017: Resuscitation
Patrick Zuercher, Dirk Springe, Denis Grandgirard, Stephen L Leib, Marius Grossholz, Stephan Jakob, Jukka Takala, Matthias Haenggi
BACKGROUND: The noble gas xenon is considered as a neuroprotective agent, but availability of the gas is limited. Studies on neuroprotection with the abundant noble gases helium and argon demonstrated mixed results, and data regarding neuroprotection after cardiac arrest are scant. We tested the hypothesis that administration of 50% helium or 50% argon for 24 h after resuscitation from cardiac arrest improves clinical and histological outcome in our 8 min rat cardiac arrest model. METHODS: Forty animals had cardiac arrest induced with intravenous potassium/esmolol and were randomized to post-resuscitation ventilation with either helium/oxygen, argon/oxygen or air/oxygen for 24 h...
2016: BMC Neurology
Ruut Laitio, Marja Hynninen, Olli Arola, Sami Virtanen, Riitta Parkkola, Jani Saunavaara, Risto O Roine, Juha Grönlund, Emmi Ylikoski, Johanna Wennervirta, Minna Bäcklund, Päivi Silvasti, Eija Nukarinen, Marjaana Tiainen, Antti Saraste, Mikko Pietilä, Juhani Airaksinen, Leena Valanne, Juha Martola, Heli Silvennoinen, Harry Scheinin, Veli-Pekka Harjola, Jussi Niiranen, Kirsi Korpi, Marjut Varpula, Outi Inkinen, Klaus T Olkkola, Mervyn Maze, Tero Vahlberg, Timo Laitio
IMPORTANCE: Evidence from preclinical models indicates that xenon gas can prevent the development of cerebral damage after acute global hypoxic-ischemic brain injury but, thus far, these putative neuroprotective properties have not been reported in human studies. OBJECTIVE: To determine the effect of inhaled xenon on ischemic white matter damage assessed with magnetic resonance imaging (MRI). DESIGN, SETTING, AND PARTICIPANTS: A randomized single-blind phase 2 clinical drug trial conducted between August 2009 and March 2015 at 2 multipurpose intensive care units in Finland...
March 15, 2016: JAMA: the Journal of the American Medical Association
Denis Azzopardi, Nicola J Robertson, Alan Bainbridge, Ernest Cady, Geoffrey Charles-Edwards, Aniko Deierl, Gianlorenzo Fagiolo, Nicholas P Franks, James Griffiths, Joseph Hajnal, Edmund Juszczak, Basil Kapetanakis, Louise Linsell, Mervyn Maze, Omar Omar, Brenda Strohm, Nora Tusor, A David Edwards
BACKGROUND: Moderate cooling after birth asphyxia is associated with substantial reductions in death and disability, but additional therapies might provide further benefit. We assessed whether the addition of xenon gas, a promising novel therapy, after the initiation of hypothermia for birth asphyxia would result in further improvement. METHODS: Total Body hypothermia plus Xenon (TOBY-Xe) was a proof-of-concept, randomised, open-label, parallel-group trial done at four intensive-care neonatal units in the UK...
February 2016: Lancet Neurology
Kasper J Kyng, Torjus Skajaa, Sigrid Kerrn-Jespersen, Christer S Andreassen, Kristine Bennedsgaard, Tine B Henriksen
Birth asphyxia, which causes hypoxic-ischemic encephalopathy (HIE), accounts for 0.66 million deaths worldwide each year, about a quarter of the world's 2.9 million neonatal deaths. Animal models of HIE have contributed to the understanding of the pathophysiology in HIE, and have highlighted the dynamic process that occur in brain injury due to perinatal asphyxia. Thus, animal studies have suggested a time-window for post-insult treatment strategies. Hypothermia has been tested as a treatment for HIE in pdiglet models and subsequently proven effective in clinical trials...
May 16, 2015: Journal of Visualized Experiments: JoVE
Hannah Gill, Marianne Thoresen, Elisa Smit, Jonathan Davis, Xun Liu, John Dingley, Maja Elstad
AIM: Heart rate (HR) plays an important role in the assessment of stress during therapeutic hypothermia (TH) for neonatal encephalopathy; we aimed to quantify the effect on HR of endotracheal (ET) intubation and drugs given to facilitate it. If atropine premedication independently increased HR, the main indicator of effective sedation, we hypothesised that increased sedation would have been given. METHODS: Thirty-two, term, neonates recruited into a randomised pilot study comparing TH and TH combined with 50% Xenon inhalation were studied...
October 2014: Resuscitation
Dustin B Mangus, Lei Huang, Patricia M Applegate, Jason W Gatling, John Zhang, Richard L Applegate
Neurocognitive deficits are a major source of morbidity in survivors of cardiac arrest. Treatment options that could be implemented either during cardiopulmonary resuscitation or after return of spontaneous circulation to improve these neurological deficits are limited. We conducted a literature review of treatment protocols designed to evaluate neurologic outcome and survival following cardiac arrest with associated global cerebral ischemia. The search was limited to investigational therapies that were utilized to treat global cerebral ischemia associated with cardiac arrest...
2014: Medical Gas Research
Antonio M Dell'anna, Sabino Scolletta, Katia Donadello, Fabio S Taccone
PURPOSE OF REVIEW: Many efforts have been made in the last decades to improve outcome in patients who are successfully resuscitated from sudden cardiac arrest. Despite some advances, postanoxic encephalopathy remains the most common cause of death among those patients and several investigations have focused on early neuroprotection in this setting. RECENT FINDINGS: Therapeutic hypothermia is the only strategy able to provide effective neuroprotection in clinical practice...
June 2014: Current Opinion in Critical Care
Lisa Lee Kirkland
No abstract text is available yet for this article.
September 2013: Critical Care Medicine
Olli J Arola, Ruut M Laitio, Risto O Roine, Juha Grönlund, Antti Saraste, Mikko Pietilä, Juhani Airaksinen, Juha Perttilä, Harry Scheinin, Klaus T Olkkola, Mervyn Maze, Timo T Laitio
OBJECTIVES: Preclinical studies reveal the neuroprotective properties of xenon, especially when combined with hypothermia. The purpose of this study was to investigate the feasibility and cardiac safety of inhaled xenon treatment combined with therapeutic hypothermia in out-of-hospital cardiac arrest patients. DESIGN: An open controlled and randomized single-centre clinical drug trial ( NCT00879892). SETTING: A multipurpose ICU in university hospital...
September 2013: Critical Care Medicine
A Brücken, A Cizen, C Fera, A Meinhardt, J Weis, K Nolte, R Rossaint, T Pufe, G Marx, M Fries
BACKGROUND: Xenon has profound neuroprotective effects after neurological injury and is currently undergoing phase 2 clinical trials in cardiac arrest patients. However, xenon is very costly, which might preclude its widespread use. We hypothesized argon, which is more available, might also protect central nervous tissues and allow better functional recovery in a rodent model of global cerebral ischaemia. METHODS: Fourteen male Sprague-Dawley rats were subjected to 7 min of cardiac arrest and 3 min of cardiopulmonary resuscitation (CPR)...
June 2013: British Journal of Anaesthesia
Michael Fries, Anne Brücken, Ayşegül Çizen, Maren Westerkamp, Céline Löwer, Jan Deike-Glindemann, Nora K Schnorrenberger, Steffen Rex, Mark Coburn, Kay W Nolte, Joachim Weis, Rolf Rossaint, Matthias Derwall
OBJECTIVE: Despite the introduction of mild therapeutic hypothermia into postcardiac arrest care, cerebral and myocardial injuries represent the limiting factors for survival after cardiac arrest. Administering xenon may confer an additional neuroprotective effect after successful cardiopulmonary resuscitation due to its ability to stabilize cellular calcium homeostasis via N-methyl-D-aspartate-receptor antagonism. DESIGN: In a porcine model, we evaluated effects of xenon treatment in addition to therapeutic hypothermia on neuropathologic and functional outcomes after cardiopulmonary resuscitation...
April 2012: Critical Care Medicine
Daniela Schifilliti, Giovanni Grasso, Alfredo Conti, Vincenzo Fodale
In designing the anaesthetic plan for patients undergoing surgery, the choice of anaesthetic agent may often appear irrelevant and the best results obtained by the use of a technique or a drug with which the anaesthesia care provider is familiar. Nevertheless, in those surgical procedures (cardiopulmonary bypass, carotid surgery and cerebral aneurysm surgery) and clinical situations (subarachnoid haemorrhage, stroke, brain trauma and post-cardiac arrest resuscitation) where protecting the CNS is a priority, the choice of anaesthetic drug assumes a fundamental role...
November 2010: CNS Drugs
Matthias Derwall, Anne Timper, Kai Kottmann, Rolf Rossaint, Michael Fries
OBJECTIVE: Neurologic outcome after cardiopulmonary resuscitation from cardiac arrest carries a poor prognosis and treatment options to ameliorate brain damage are limited. DESIGN: Report of two protocols investigating the effects of xenon (Xe) and isoflurane (Iso) in a porcine model of prolonged cardiac arrest and subsequent cardiopulmonary resuscitation on functional neurologic outcomes. SETTING: Prospective, randomized, laboratory animal study...
November 2008: Critical Care Medicine
Nasser A Tawfeeq, Mohammed M Halawani, Khulood Al-Faridi, Wa'el A Aal-Shaya, Wa'el S Taha
Traumatic brain injuries remain an area of great challenge to both neurosurgeons and neuroanaesthesiologists. The management of these injuries starts at the scene of the accident. However, strategies for preventing secondary brain injury and its sequelae are continuing to evolve. These strategies include the use of pharmacological and nonpharmacological techniques. Preventing hypoxia and the use of hypertonic saline have been shown to have favourable results on the outcome of these injuries. The use of isoflurane has been shown to have a neuronprotective effect...
November 2009: Injury
Michael Fries, Mark Coburn, Kay W Nolte, Anne Timper, Kai Kottmann, Timur H Kuru, Joachim Weis, Rolf Rossaint
BACKGROUND: Xenon (Xe) is neuroprotective when given 1h after cardiopulmonary resuscitation (CPR). Here, we investigated if an earlier administration of Xe or isoflurane (Iso) would also reduce neurological dysfunction. METHODS: 10 min after CPR from 8 min of cardiac arrest 21 pigs were randomized to three groups (n=7/group) and then ventilated for 1h with gas mixtures as follows: (1) control: 30% O(2)+70% N(2); (2) Iso: 30% O(2)+69% N(2)+1% Iso; (3) Xe: 30% O(2)+70% Xe...
May 2009: Resuscitation
Michael Fries, Kay Wilhelm Nolte, Mark Coburn, Steffen Rex, Anne Timper, Kai Kottmann, Katharina Siepmann, Martin Häusler, Joachim Weis, Rolf Rossaint
OBJECTIVE: Treatment options to ameliorate brain damage following cardiopulmonary resuscitation from cardiac arrest are limited. DESIGN: In a porcine model, we evaluated the effects of xenon treatment on neuropathologic and functional outcomes after cardiopulmonary resuscitation. SETTING: Prospective, randomized laboratory animal study. SUBJECTS: Male pigs. INTERVENTIONS: Following successful resuscitation from 8 mins of cardiac arrest and 5 mins of cardiopulmonary resuscitation, 24 pigs were randomized to one of three groups receiving either 70% xenon for 1 or 5 hrs or untreated controls receiving 70% nitrogen...
August 2008: Critical Care Medicine
Michael Schmidt, Thomas Marx, Egon Glöggl, Helmut Reinelt, Uwe Schirmer
BACKGROUND: Cerebral blood flow may be compromised in a variety of anesthetic procedures, and ischemic cerebral complications represent the leading cause of morbidity after cardiac operations. With the growing importance of neuroprotective strategies, the current study was designed to determine whether xenon would attenuate cardiac arrest-induced brain injury in pigs. METHODS: Twenty-four pigs (aged 12-16 weeks) were investigated in a randomized design. General hemodynamics, intracranial pressure, brain tissue oxygenation, and cerebral microdialysis parameters were investigated...
May 2005: Anesthesiology
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