Perioperative Medicine  |   August 2016
A Novel Strategy to Reverse General Anesthesia by Scavenging with the Acyclic Cucurbit[n]uril-type Molecular Container Calabadion 2
Author Notes
  • From the Anesthesia, Critical Care and Pain Medicine (D.D.-G., F.H., J.C.P.S., S.D.G., I.M.D., J.F.C., M.E.), Radiology (K.E.-H.), and Biostatistics (H.D.), Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts; Cell Biology and Molecular Genetics (S.F., G.K.H., V.B.) and Chemistry and Biochemistry (S.G., B.Z., L.I.), University of Maryland, College Park, Maryland; Neurology, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, Massachusetts (N.L.C.); and Anesthesia and Critical Care Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany (M.E.).
  • Submitted for publication September 17, 2015. Accepted for publication May 9, 2016.
    Submitted for publication September 17, 2015. Accepted for publication May 9, 2016.×
  • This article is featured in “This Month in Anesthesiology,” page 1A.
    This article is featured in “This Month in Anesthesiology,” page 1A.×
  • 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).
    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).×
  • This study was selected for presentation in the Best Abstracts, Basic Science Session of the Anesthesiology 2014 Annual Meeting on October 13, 2014, New Orleans, Louisiana, and has been invited for submission to Anesthesiology. D.D.-G. and F.H. made equal contributions to this article.
    This study was selected for presentation in the Best Abstracts, Basic Science Session of the Anesthesiology 2014 Annual Meeting on October 13, 2014, New Orleans, Louisiana, and has been invited for submission to Anesthesiology. D.D.-G. and F.H. made equal contributions to this article.×
  • Address correspondence to Dr. Eikermann: Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts. meikermann@partners.org. 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 / Pharmacology
Perioperative Medicine   |   August 2016
A Novel Strategy to Reverse General Anesthesia by Scavenging with the Acyclic Cucurbit[n]uril-type Molecular Container Calabadion 2
Anesthesiology 8 2016, Vol.125, 333-345. doi:10.1097/ALN.0000000000001199
Anesthesiology 8 2016, Vol.125, 333-345. doi:10.1097/ALN.0000000000001199
Abstract

Background: Calabadion 2 is a new drug-encapsulating agent. In this study, the authors aim to assess its utility as an agent to reverse general anesthesia with etomidate and ketamine and facilitate recovery.

Methods: To evaluate the effect of calabadion 2 on anesthesia recovery, the authors studied the response of rats to calabadion 2 after continuous and bolus intravenous etomidate or ketamine and bolus intramuscular ketamine administration. The authors measured electroencephalographic predictors of depth of anesthesia (burst suppression ratio and total electroencephalographic power), functional mobility impairment, blood pressure, and toxicity.

Results: Calabadion 2 dose-dependently reverses the effects of ketamine and etomidate on electroencephalographic predictors of depth of anesthesia, as well as drug-induced hypotension, and shortens the time to recovery of righting reflex and functional mobility. Calabadion 2 displayed low cytotoxicity in MTS-3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium–based cell viability and adenylate kinase release cell necrosis assays, did not inhibit the human ether-à-go-go-related channel, and was not mutagenic (Ames test). On the basis of maximum tolerable dose and acceleration of righting reflex recovery, the authors calculated the therapeutic index of calabadion 2 in recovery as 16:1 (95% CI, 10 to 26:1) for the reversal of ketamine and 3:1 (95% CI, 2 to 5:1) for the reversal of etomidate.

Conclusions: Calabadion 2 reverses etomidate and ketamine anesthesia in rats by chemical encapsulation at nontoxic concentrations.