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 Investigators may unlock mystery of how staph cells dodge the body's immune system
22.09.2017 | Cedars-Sinai Medical Center

nachricht Monitoring the heart's mitochondria to predict cardiac arrest?
21.09.2017 | Boston Children's Hospital

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: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>