Perioperative Medicine  |   March 2017
Paradoxical Emergence: Administration of Subanesthetic Ketamine during Isoflurane Anesthesia Induces Burst Suppression but Accelerates Recovery
Author Notes
  • From the Department of Anesthesiology (V.S.H.-W., D.L., G.A.M.), Center of Consciousness Science (V.S.H.-W., D.L., G.A.M.), and Neuroscience Graduate Program (G.A.M.), University of Michigan, Ann Arbor, Michigan.
  • This article is featured in “This Month in Anesthesiology,” page 1A.
    This article is featured in “This Month in Anesthesiology,” page 1A.×
  • Corresponding article on page 371.
    Corresponding article on page 371.×
  • Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org). The abstract was originally selected for the Best Abstract Session at the 2016 American Society of Anesthesiology Meeting.
    Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are available in both the HTML and PDF versions of this article. Links to the digital files are provided in the HTML text of this article on the Journal’s Web site (www.anesthesiology.org). The abstract was originally selected for the Best Abstract Session at the 2016 American Society of Anesthesiology Meeting.×
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  • Submitted for publication June 7, 2016. Accepted for publication December 1, 2016.
    Submitted for publication June 7, 2016. Accepted for publication December 1, 2016.×
  • Address correspondence to Dr. Mashour: Department of Anesthesiology, Center for Consciousness Science, University of Michigan, 1500 E. Medical Center Dr., 1H247 UH, SPC 5048, Ann Arbor, Michigan 48109. gmashour@umich.edu. Information on purchasing reprints may be found at www.anesthesiology.org or on the masthead page at the beginning of this issue. Anesthesiology’s articles are made freely accessible to all readers, for personal use only, 6 months from the cover date of the issue.
Article Information
Perioperative Medicine / Basic Science / Central and Peripheral Nervous Systems / Pharmacology
Perioperative Medicine   |   March 2017
Paradoxical Emergence: Administration of Subanesthetic Ketamine during Isoflurane Anesthesia Induces Burst Suppression but Accelerates Recovery
Anesthesiology 3 2017, Vol.126, 482-494. doi:10.1097/ALN.0000000000001512
Anesthesiology 3 2017, Vol.126, 482-494. doi:10.1097/ALN.0000000000001512
Abstract

Background: Promoting arousal by manipulating certain brain regions and/or neurotransmitters has been a recent research focus, with the goal of trying to improve recovery from general anesthesia. The current study tested the hypothesis that a single subanesthetic dose of ketamine during isoflurane anesthesia would increase cholinergic tone in the prefrontal cortex and accelerate recovery.

Methods: Adult male rats were implanted with electroencephalography electrodes (frontal, parietal, and occipital cortex) and a microdialysis guide cannula targeted for the prefrontal cortex. After establishing general anesthesia with isoflurane, animals were randomly assigned to receive a saline control or ketamine injection. When isoflurane was discontinued nearly 90 min after drug or saline administration, recovery from anesthesia was measured by experimenters and blinded observers. During the entire experiment, electrophysiologic signals were recorded and acetylcholine was quantified by high-performance liquid chromatography with electrochemical detection.

Results: A single dose of subanesthetic ketamine caused an initial 125% increase in burst suppression ratio (last isoflurane sample: 37.48 ± 24.11% vs. isoflurane after ketamine injection: 84.36 ± 8.95%; P < 0.0001), but also a significant 44% reduction in emergence time (saline: 877 ± 335 s vs. ketamine: 494 ± 108 s; P = 0.0005; n = 10 per treatment). Furthermore, ketamine caused a significant 317% increase in cortical acetylcholine release (mean after ketamine injection: 0.18 ± 0.16 pmol vs. ketamine recovery: 0.75 ± 0.41 pmol; P = 0.0002) after isoflurane anesthesia was discontinued.

Conclusions: Administration of subanesthetic doses of ketamine during isoflurane anesthesia increases anesthetic depth but—paradoxically—accelerates the recovery of consciousness, possibly through cholinergic mechanisms.