Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Uncovering the neurobiological basis of general anesthesia

30.12.2010
Review article delineates similarities with and differences from sleep and coma

The use of general anesthesia is a routine part of surgical operations at hospitals and medical facilities around the world, but the precise biological mechanisms that underlie anesthetic drugs' effects on the brain and the body are only beginning to be understood.

A review article in the December 30 New England Journal of Medicine brings together for the first time information from a range of disciplines, including neuroscience and sleep medicine, to lay the groundwork for more comprehensive investigations of processes underlying general anesthesia.

"A key point of this article is to lay out a conceptual framework for understanding general anesthesia by discussing its relation to sleep and coma, something that has not been done in this way before," says Emery Brown, MD, PhD, of the Massachusetts General Hospital (MGH) Department of Anesthesia, Critical Care and Pain Medicine, lead author of the NEJM paper. "We started by stating the specific physiological states that comprise general anesthesia – unconsciousness, amnesia, lack of pain perception and lack of movement while stable cardiovascular, respiratory and thermoregulatory systems are maintained – another thing that has never been agreed upon in the literature; and then we looked at how it is similar to and different from the states that are most similar – sleep and coma."

After laying out their definition, Brown and his co-authors – Ralph Lydic, PhD, a sleep expert from the University of Michigan, and Nicholas Schiff, MD, an expert in coma from Weill Cornell Medical College – compare the physical signs and electroencephalogram (EEG) patterns of general anesthesia to those of sleep. While it is common to describe general anesthesia as going to sleep, there actually are significant differences between the states, with only the deepest stages of sleep being similar to the lightest phases of anesthesia induced by some types of agents.

While natural sleep normally cycles through a predictable series of phases, general anesthesia involves the patient being taken to and maintained at the phase most appropriate for the procedure, and the phases of general anesthesia at which surgery is performed are most similar to states of coma. "People have hesitated to compare general anesthesia to coma because the term sounds so harsh, but it really has to be that profound or how could you operate on someone?" Brown explains. "The key difference is this is a coma that is controlled by the anesthesiologist and from which patients will quickly and safely recover."

In detailing how different anesthetic agents act on different brain circuits, the authors point out some apparently contradictory information – some drugs like ketamine actually activate rather than suppress neural activity, an action that can cause hallucinations at lower doses. Ketamine blocks receptors for the excitatory transmitter glutamate, but since it has a preference for receptors on certain inhibitory neurons, it actually stimulates activity when it blocks those inhibitors. This excess brain activity generates unconsciousness through a process similar to what happens when disorganized data travels through an electronic communication line and blocks any coherent signal. A similar mechanism underlies seizure-induced unconsciousness.

Brown also notes that recent reports suggest an unexpected use for ketamine – to treat depression. Very low doses of the drug have rapidly reduced symptoms in chronically depressed patients who had not responded to traditional antidepressants. Ketamine is currently being studied to help bridge the first days after a patient begins a new antidepressant – a time when many may be at risk of suicide – and the drug's activating effects may be akin to those of electroconvulsive therapy.

Another unusual situation the authors describe is the case of a brain-injured patient in a minimally conscious state who actually recovered some functions through administration of the sleep-inducing drug zolpidem (Ambien). That patient's case, analyzed previously by Schiff, mirrors a common occurrence called paradoxical excitation, in which patients in the first stage of general anesthesia may move around or vocalize. The authors describe how zolpidem's suppression of the activity of a brain structure called the globus pallidus – which usually inhibits the thalamus – stimulates activity in the thalamus, which is a key neural control center. They hypothesize that a similar mechanism may underlie paradoxical excitation.

"Anesthesiologists know how to safely maintain their patients in the states of general anesthesia, but most are not familiar with the neural circuit mechanisms that allow them to carry out their life-sustaining work," Brown says. "The information we are presenting in this article – which includes new diagrams and tables that don't appear in any anesthesiology textbook – is essential to our ability to further understanding of general anesthesia, and this is the first of several major reports that we anticipate publishing in the coming year."

Schiff adds, "We think this is, conceptually, a very fresh look at phenomena we and others have noticed and studied in sleep, coma and use of general anesthesia. By reframing these phenomena in the context of common circuit mechanisms, we can make each of these states understandable and predictable."

Brown is the Warren M. Zapol Professor of Anaesthesia at Harvard Medical School and also professor in the Department of Brain and Cognitive Sciences at Massachusetts Institute of Technology and in the Harvard-MIT Division of Health Sciences and Technology. Support for the authors’ report includes a National Institutes of Health Director’s Pioneer Award to Brown, other NIH grants, and support from the MGH and University of Michigan Departments of Anesthesia and the James S. McDonnell Foundation.

Celebrating the 200th anniversary of its founding in 1811, Massachusetts General Hospital is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $600 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine.

Jennifer Gundersen Harris | EurekAlert!
Further information:
http://www.mgh.harvard.edu

More articles from Health and Medicine:

nachricht Biofilm discovery suggests new way to prevent dangerous infections
23.05.2017 | University of Texas at Austin

nachricht Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina Health Care

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

How herpesviruses win the footrace against the immune system

26.05.2017 | Life Sciences

Water forms 'spine of hydration' around DNA, group finds

26.05.2017 | Life Sciences

First Juno science results supported by University of Leicester's Jupiter 'forecast'

26.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>