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Frontiers of Inhalation Technologies: Xenon Anesthesia

CIMIT Summer Series 2009: Frontiers of Inhalation Technologies in Biomedical Sciences and Clinical Medicine

Week Three: ROLE OF INHALATION TECHNOLOGIES FOR ORGAN PROTECTION AND PATIENT SEDATION IN CRITICAL CARE

Moderator: Augustine Choi, MD, Chief, Pulmonary and Critical Care Medicine, Brigham and Women's Hospital; CIMIT Co-Program Leader, Inhalation Technology

Xenon Anesthesia - What Else? 

Philippe Richebé, MD, PhD, Associate Professor in Anesthesiology and Pain Medicine, University of Washington Medical Center, Department of Anesthesiology and Pain Medicine 

An inert gas, Xenon was first used for its anesthetic properties in the early 50’s. Its anesthetic effects seem to be based on an action on the NMDA glutamate receptors and not by an inhibition of GABA-receptors as most of the anesthetics usable in the clinical daily practice. It showed surprising characteristics regarding onset and recovery of anesthesia. It is not toxic and environmentally friendly.

Xenon got its market authorization in 10 European countries during the last five years. Many clinical studies have evaluated Xenon anesthesia in regards to different criteria. The most interesting results were gathered in clinical studies on hemodynamic stability under Xenon anesthesia. Hemodynamic data (heart rate and blood pressure) were more stable under Xenon anesthesia as compared to other drugs like propofol or halogenous gases, even in patients with preoperative heart failure. Therefore Xenon seems to be a promising anesthetic for patients with compromised cardiac function. As Xenon did show impressive effects in keeping hemodynamic data very stable, it was suggested that it could have also an impact on postoperative cognitive function not only because it would maintain a good level of brain perfusion during anesthesia, but also because of some neuroprotective properties of the gas. Regarding postoperative neurological dysfunction especially in elderly, only one clinical study showed a quicker emergence from anesthesia in elderly but without any change in terms of postoperative cognitive dysfunction in this population. If Xenon has these strong NMDA receptor blocker properties, it would suggest its use would lead also to some decrease of pain sensitization after the surgery as shown with other anti-NMDA drugs, but this point has never been studied yet.

Regarding the technical aspect of the use of Xenon, Xenon has to be used with a specific ventilator in totally closed circuit with micro-injections of gas as needed according to the monitoring of the inspired concentration of Xenon. This new technology in the field of anesthesiology has been developed lately, allowing anesthesiologists to use Xenon at 1 MAC (Minimum Alveolar Concentration) which is 60% (and 40% O2), without having a very high consumption of this gas.

Nevertheless, despite the use of this closed-circuit, Xenon anesthesia remains much more costly as compared to the classical anesthesia with iv propofol or halogenous gases. Moreover, Xenon production has and will have some limitations. Those are the reasons why we should have a better understanding of the real clinical benefits of such an anesthesia with Xenon in order to use it for the right and selected patients.

Clinical Challenges of Xenon Anesthesia: Pros and Cons

Thomas Marx, MD, PD, Anesthesia Pole Leader, Air Liquide 

Dr. Thomas Marx, Air Liquide, will explore the history of Xenon, from its first detecton by Ramsey and Travers in 1898 to its use in medicine in deep sea anesthesia when, in 1937, Behnke investigated causes of diver’s delirium, and years following. He will discuss experimental results of xenon anesthesia, its main medical indication in high risk patients and surgery and its use as an agent for high risk patients and surgery, trauma care, long haul transport like MEDEVAC missions and special ICU indications.

After two multicenter trials, xenon was approved for anesthesia in Germany in 2005. The approval of the BfArM; the German Medical authority included cardiovascular risk patients and patients classified to be ASA III. The European Medical Authority in 2007 regarded the number of ASA III patients in those studies to be too low and excluded those patients in 2007. Since then xenon was approved in Europe, but the patients with the highest benefit  from xenon administration are excluded.

Air Liquide’s research is concentrated to increase the number of risk patients to re-extend the xenon authorization into this group and, based on the assumption that the mechanisms described are present in the whole organ system, Air Liquide investigates organ protective properties of xenon.

According to Marx, though, problems need to be resolved. For instance, in applying xenon in emergency care, ICU and transports, small and lightweight ventilator devices in “closed system” design are required. Secondly, availability of xenon needs to be increased and missing xenon” needs to be recovered

CIMIT blog is part of the Center for Integration of Medicine and Innovative Technology (CIMIT.org)

Frontiers of Inhalation Technologies: Treatment

CIMIT Summer Series 2009: Frontiers of Inhalation Technologies in Biomedical Sciences and Clinical Medicine

Week Two: TREATMENT OF RESPIRATORY DISEASES

Moderator: Dean Hess, PhD, Assistant Director of Respiratory Care, Massachusetts General Hospital; Associate Professor of Anesthesia, Harvard Medical School

Inhalation Technology for Obstructive Lung Disease 

Sabine Häussermann, PhD, Chief of Medical Device Development, Air Liquide

While helium/oxygen (He/O2) mixtures have been described in clinical use since 1934, consensus over their range of clinical applications has been slow to emerge. The physical properties of He/O2 mixtures appear to be valuable in a variety of respiratory care applications. Inhaling He/O2 reduces the resistance to gas flow and hence reduces the work of breathing. In addition, breathing these mixtures alters the distribution of ventilation within the lung and could potentially improve aerosol delivery.

With increasing interest in He/O2 for severely ill patients, He/O2 delivery methods have evolved from spontaneous mask breathing up to latest-generation mechanical ventilators. Until recently, administering He/O2 has required modifications by doctors, respiratory therapists and their technicians on devices which were not designed for the use with He/O2, but for air and oxygen. This caused problems, especially with regard to flow measurement, and therefore led to uncertainty in the volumes delivered to the patients. Sabine Häussermann will review the use of He/O2 in practice and described current devices which are available to deliver the gas.

Aerosolized Drugs in Medicine: Where are They? 

Gerald C. Smaldone, MD, PhD, Professor of Medicine, Physiology and Biophysics at the State University of New York at Stony Brook

Aerosols have significant potential as new medical therapeutics both targeted to the lungs or for systemic drug delivery. This belief has stimulated the formation of new companies, many new innovations in technology and potential therapies. However, no aerosol drug  has been successful in impacting medical practice since aerosolized pentamidine was approved 20 years ago. Beyond the usual therapies in asthma and COPD, physicians do not recognize aerosols as viable treatments for any other diseases. In twenty years of observation and research, a model of aerosol development has emerged at Stony Brook that might lead to new therapies. This model comprises three key components: (1) perceived need by practicing physicians, (2) local expertise in aerosol technology and medicine (3) recognition of the business needs in bringing a drug to medical practice. According to Dr. Gerald Smaldone, failure of any one of these components may prevent the emergence of new therapeutics.

CIMIT blog is part of the Center for Integration of Medicine and Innovative Technology (CIMIT.org)

Frontiers of Inhalation Technologies: Fundamentals

CIMIT Summer Series 2009: Frontiers of Inhalation Technologies in Biomedical Sciences and Clinical Medicine

Week One: INHALATION TECHNOLOGY FUNDAMENTALS

Moderator: Jose Venegas, PHD, Associate Professor of Anesthesia (Bioengineering), Harvard Medical School; Massachusetts General Hospital, Department of Anesthesia and Critical Care

Systemic Delivery of Proteins via the Lungs: Setbacks and Advances

Joseph Brain, SD, Cecil K. and Philip Drinker Professor of Environmental Physiology, Harvard School of Public Health

A variety of formulations and technologies have been developed focusing on the delivery of proteins to and through the lungs. Billions of dollars have been invested, and hundreds, perhaps thousands, of patents relate to this topic. The anatomy and physiology of the lungs seem well suited for transport of proteins from alveolar and airway surfaces to the blood. Bioavailability following pulmonary delivery of proteins such as insulin is far more favorable than for oral or dermal delivery. Yet, challenges remain. Less than 2 years after Pfizer's inhaled insulin was approved by the FDA and the EU, the program was cancelled. This talk will review these past efforts and highlight new possibilities.  

Design Factors Influencing Aerosol Delivery by Pharmaceutical Inhalers

Anthony J. Hickey, PhD, DSc, Professor of Molecular Pharmaceutics of the School of Pharmacy, and Biomedical Engineering of the School of Medicine, University of North Carolina at Chapel Hill

Inhalers consist of three major components: drug formulation, dose metering system and aerosol dispersion mechanism. The design and integration of these components in each of the major aerosol delivery systems: propellant driven metered dose inhalers, dry powder inhalers and; nebulizers, defines their performance and ultimately their efficacy and reliability in treating specific diseases. Reviewing the performance advantages and limitations of components and devices offers insight into their therapeutic application.

CIMIT blog is part of the Center for Integration of Medicine and Innovative Technology (CIMIT.org)