Gases for the Brain!

Saturday 3 June, 17h00-18h30, Room X

A fascinating session on gases will explore five gases commonly encountered by the anaesthesiologist: carbon dioxide, xenon, argon, nitric oxide and oxygen.

Carbon dioxide

The first talk on carbon dioxide will be given by Dr Markus Skrifvars, Helsinki University Hospital, Finland. “Carbon dioxide is an important regulator of blood flow of the brain and therefore highly important in various forms of brain injury,” says Dr Skrifvars, who is currently doing a one-year research fellowship at the Australian and New Zealand Intensive Care Society Clinical Trials Group, based in Monash University, Melbourne, Australia.

Elevated carbon dioxide or hypercapnia increases blood flow and blood volume and may therefore increase intracerebral pressure (ICP). Hypocapnia, on the other hand decreases blood flow and ICP, but may also cause local tissue hypoxia. Novel data suggest that moderate hypercapnia may be beneficial especially in the setting of brain injury related to cardiac arrest. The mechanism includes alleviating central nervous system alkalosis and decreased epileptic activity.

Dr Skrifvars concludes: “My talk reviews current evidence on the control of carbon dioxide in the setting of anoxic brain injury, with a special emphasis placed on patients undergoing treatment with targeted temperature management.”


In the second talk, xenon will be discussed by Professor Marianne Thoresen, University of Bristol, UK and Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Norway.  “Xenon is a known anaesthetic gas since 1939. However, this inert gas is difficult and expensive to extract from air, and research and clinical use has been limited for these reasons,” she says.

In 1998 xenon was shown to be an NMDA antagonist as well as being neuroprotective in cell culture and later in whole animal models.  This presentation will summarise the research of Prof Thoresen’s team on xenon gas by inhalation with and without therapeutic hypothermia (TH) in brain injury animal models, leading to the ongoing randomised clinical study on newborn infants receiving TH or TH with 50% xenon.

In the animal models, adding xenon to TH doubled the neuroprotective effect. Examination of minimum alveolar concentration values, neurotoxicity, safety, effects on cardio- and cerebrovascular and autonomic control will be reviewed. Prof Thoresen will also discuss the high costs of xenon delivery and the use of recycling delivery systems to reduce consumption.


Argon will be covered by Nikki Robertson, Professor of Perinatal Neuroscience UCL and Consultant Neonatologist UCLH, and Institute for Women’s Health, University College London, UK. Prof Robertson will discuss findings from her study: Inhaled 45–50% argon augments hypothermic brain protection in a piglet model of perinatal asphyxia.

“Neonatal encephalopathy (NE) is a huge global burden; cooling to 33.5 °C for 72h in NE significantly reduces death and disability, however additional therapies are needed to maximise brain protection,” says Prof Robertson. “We used an established piglet mode to assess whether inhaled 45–50% Argon from 2–26 h after hypoxia-ischaemia augmented hypothermic neuroprotection, using magnetic resonance spectroscopy and aEEG, which predict outcome in babies with NE, and immunohistochemistry.”

Her talk will summarise the findings of her study, including exploring cell death in seven different brain regions and comparing cooling plus argon with cooling alone at both 24 and 48 hours. She will discuss the potential use of argon as a cheap and practical therapy to augment cooling for neonatal encephalopathy.

Nitric oxide

In his talk, Dr Michael Fries of St Vincenz Hospital, Limburg, Germany, will discuss how use of inhaled nitric oxide (iNO) has become routine in large intensive care units for the treatment of severe cases of neonatal and adult respiratory distress as well as for the mitigation of right heart failure. Recently, several investigators demonstrated beneficial effects of iNO on neurological outcomes in animal models of stroke and traumatic brain injury. Notably, clinical data had earlier suggested that neonates who had been treated with iNO due to severe respiratory failure had favourable neurodevelopmental outcomes several years later in comparison to children who had not received the gas.

He will discuss some of his team’s research in this area, including showing that in rats 20 ppm iNO resulted in significantly greater resuscitability — probably by increasing diastolic arterial pressure which is a surrogate of coronary perfusion. In addition, animals surviving 7 days after the arrest had better functional outcomes and less cerebral and cardiac injuries. In a second set of experiments pigs were resuscitated using an Impella pump. Here, use of iNO resulted in significant improvements in transpulmonary blood flow and coronary perfusion pressure. Metabolic changes such as hyperlactataemia and hyperglycaemia were less pronounced in iNO treated animals. Finally, these animals had also better neurological outcomes.

Dr Fries concludes: “These results prompted others to start a clinical phase II clinical trial in the US. Post cardiac arrest patients are randomised to be treated with 20 ppm iNO and we are anxious to see the results.”


Perhaps that most important gas of all (at least for life!) will be discussed by Sharon Einav, Professor of Anaesthesia and Critical Care Medicine and Director of Surgical Intensive Care at the Shaare Zedek Medical Centre and Hebrew University Faculty of Medicine, Jerusalem, Israel.

Prof Einav proposes the following hypothetical situation: imagine you were a member of the Pharmacology Committee of your hospital and you were required to approve a new medication for patients with traumatic brain injury and stroke. Although people are exposed to the molecule comprising this medication on a daily basis, the normal level of exposure is very low. The medication in question requires that your patients receive several times the physiological dose. The molecule has known damaging effects yet the manufacturer insert recommends that it be administered during the stage of the disease that it may cause the greatest degree of harm. The manufacturer claims that the drug could provide benefit to your patients. The medication in question is oxygen.

Prof Einav says: “In order to make a learned decision one must put aside all the preconceptions one has gathered over the years regarding the need for oxygen in various neurological crises, and study the question from the viewpoint presented above. Phase I, II and III trials which have used oxygen in traumatic brain injury and stroke will be presented and the audience will be asked whether they would approve the drug based on the existing data or request that additional data be collected prior to approval.”