Tuesday, April 29, 2014

Reducing Risk in Pediatric General Anesthesia

Patrick L. Purdon, PhD,
Associate Bioengineer, Massachusetts General Hospital, Assistant Professor of Anaesthesia, Harvard Medical School

One immediate strategy would be to develop novel monitoring technologies to precisely indicate the required anesthetic dose in each child, to avoid over-exposure and toxicity.  Unfortunately, present-day depth-of-anesthesia monitors are unable to provide an accurate measure of brain activity during GA, and simply do not work in children.  As a result, anesthesiologists are unable to accurately monitor the brain states of their child patients. 

General anesthetic and sedative drugs induce stereotyped changes in the electroencephalogram (EEG) that were first observed in the 1930’s, providing the basis for present day anesthetic brain monitors. The most popular approach to EEG-based anesthesia monitoring has been to use empirically-derived indices that reduce the EEG to a single number between 0 an 100.  Existing EEG-based depth-of-anesthesia monitors fail to accurately characterize brain function and level of consciousness for three fundamental reasons. First, they attempt to reduce all of the information in the EEG down to a single number between 0 and 100, which vastly over-simplifies the problem. Second, they try to do so uniformly across different anesthetic drugs, failing to account for the fact that different anesthetic drugs work through different mechanisms, which result in different EEG dynamics that cannot be placed on a single 0 to 100 scale.  Finally, these existing monitors fail to account for differences in how individual patients respond to anesthetic drugs. These monitors were developed using adult EEG data, but children’s brains are wired differently than adults. It is no surprise that these depth-of-anesthesia monitors do not work for children.

Over the past several years, my laboratory has made fundamental advances in understanding the neurophysiology of anesthesia-induced unconsciousness, characterizing multiple levels of brain activity, from EEG down to the single-neuron activity, during general anesthesia.  Our work suggests that anesthestic drugs produce different states of altered consciousness and unconsciousness by inducing large, stereotyped brain oscillations that disrupt normal brain function.  These oscillations are easy to observe in the EEG, and have distinct forms associated with different drugs and states of consciousness. This knowledge is paving the way for a transformative new approach to anesthetic brain monitoring.

Based on this work, we have developed novel technologies to characterize the EEG under general anesthesia and are teaching anesthesiologists how to use the EEG to precisely monitor their patients’ brain states under general anesthesia.  We are currently working to characterize the EEG during general anesthesia in children. Our group was recently awarded a Partners Healthcare Innovation Development Grant to develop an advanced EEG sensor specifically to monitor children during general anesthesia. Our team includes anesthesiologist and computational neuroscientist Emery N. Brown, M.D., Ph.D., pediatric anesthesiologists Paul Firth, M.D. and Erik Shank, M.D., anesthesiologist and medical innovator Nathaniel Sims, M.D., and electrical engineer Matt Hickcox.

Want to learn more?  Take an audio tour of anesthesia, neuroscience, and the operating room with Drs. Purdon, Brown, and NPR’s Radiolab!

Selected Publications:

  1. Lewis LD, Weiner VS, Mukamel EA, Donoghue JA, Eskandar EN, Madsen JR, Anderson WS, Hochberg LR, Cash SS, Brown EN, Purdon PL. Rapid fragmentation of neuronal networks at the onset of propofol-induced unconsciousness. Proceedings of the National Academy of Sciences, 2012 Dec 4;109(49):E3377-86. Epub 2012 Nov 5.
  2. Purdon PL, Pierce ET, Mukamel EA, Prerau MJ, Walsh JL, Wong KFK, Salazar-Gomez AF, Harrell PG, Sampson A, Cimenser A, Ching S, Kopell N, Tavares-Stoeckel CL, Habeeb K, Merhar R, Brown EN. Electroencephalogram signatures of loss and recovery of consciousness from propofol. Proceedings of the National Academy of Sciences, 2013 Mar 19;110(12):E1142-51.Epub Mar 4 2013
  3. Mukamel EA, Pirondini E, Babadi B, Wong KFK, Pierce ET, Harrell PG, Walsh JL, Salazar-Gomez AF, Cash SS, Eskandar EN, Weiner VS, Brown EN, Purdon PL. A transition in brain state during propofol induced unconsciousness. Journal of Neuroscience. 2014 Jan 15;34(3):839-45.

Patrick L. Purdon, PhD: Figure 1

(Purdon, et al., PNAS 2013) Spatially coherent alpha (8-12 Hz) oscillations at loss (LOC) and recovery (ROC) of consciousness under the anesthetic drug propofol. (A) At baseline, spatially coherent alpha oscillations are concentrated in occipital channels. (B) This occipital coherent oscillation dissipates at LOC (Left) and returns at ROC (Right). (C) In the unconscious state, spatially coherent alpha oscillations are concentrated in frontal channels. (D) This frontal activity begins after LOC and ceases at ROC.  This frontal alpha oscillation likely reflects a state of disrupted processing in frontal thalamocortical circuits that contributes to the unconscious state under propofol.

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