Newly Published
Perioperative Medicine  |   July 2018
Caffeine Accelerates Emergence from Isoflurane Anesthesia in Humans: A Randomized, Double-blind, Crossover Study
Author Notes
  • From the Departments of Anesthesia and Critical Care (R.F., L.W., J.P.Z., S.K., J.L.A., Z.X.) and Neurobiology (A.P.F.), University of Chicago, Chicago, Illinois; the Department of Anesthesia, Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China (L.W.); and the Cancer Center (J.P.Z.) and the College of Medicine (S.K.), University of Illinois at Chicago, College of Medicine, Chicago, Illinois.
  • Presented in abstract form at the Association of University Anesthesiologists annual meeting in Chicago, Illinois, on April 27, 2018.
    Presented in abstract form at the Association of University Anesthesiologists annual meeting in Chicago, Illinois, on April 27, 2018.×
  • Submitted for publication February 23, 2018. Accepted for publication June 13, 2018.
    Submitted for publication February 23, 2018. Accepted for publication June 13, 2018.×
  • Acknowledgments: The authors thank Kristen Wroblewski, M.S., Department of Public Health Sciences, University of Chicago, Chicago, Illinois, for help with the statistics; the nursing and support staff in the Anesthesia Preoperative Clinic and preoperative unit in the University of Chicago Medical Center, especially the perioperative nursing leadership, for providing space for preanesthesia evaluation and processing of urine samples; and the Department of Anesthesia and Critical Care, University of Chicago Medical Center, especially the anesthesia technologists (for providing space for the trial and setup of the anesthesia machine and ancillary equipment for each anesthesia session) and Dennis Coalson, M.D., Department of Anesthesia and Critical Care, University of Chicago (for providing advice for the institutional review board application).
    Acknowledgments: The authors thank Kristen Wroblewski, M.S., Department of Public Health Sciences, University of Chicago, Chicago, Illinois, for help with the statistics; the nursing and support staff in the Anesthesia Preoperative Clinic and preoperative unit in the University of Chicago Medical Center, especially the perioperative nursing leadership, for providing space for preanesthesia evaluation and processing of urine samples; and the Department of Anesthesia and Critical Care, University of Chicago Medical Center, especially the anesthesia technologists (for providing space for the trial and setup of the anesthesia machine and ancillary equipment for each anesthesia session) and Dennis Coalson, M.D., Department of Anesthesia and Critical Care, University of Chicago (for providing advice for the institutional review board application).×
  • Research Support: Supported by National Institutes of Health (Bethesda, Maryland) grant No. RO-1GM-116119 (to Drs. Fox and Xie) and by a Medical Student Anesthesia Research Fellowship (to Mr. Khokhar).
    Research Support: Supported by National Institutes of Health (Bethesda, Maryland) grant No. RO-1GM-116119 (to Drs. Fox and Xie) and by a Medical Student Anesthesia Research Fellowship (to Mr. Khokhar).×
  • Competing Interests: The authors declare no competing interests.
    Competing Interests: The authors declare no competing interests.×
  • Reproducible Science: Full protocol available at: jxie@dacc.uchicago.edu. Raw data available at: jxie@dacc.uchicago.edu.
    Reproducible Science: Full protocol available at: jxie@dacc.uchicago.edu. Raw data available at: jxie@dacc.uchicago.edu.×
  • Correspondence: Address correspondence to Dr. Xie: University of Chicago, 5841 S. Maryland Avenue, Chicago, Illinois 60637. jxie@dacc.uchicago.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 / Pharmacology
Perioperative Medicine   |   July 2018
Caffeine Accelerates Emergence from Isoflurane Anesthesia in Humans: A Randomized, Double-blind, Crossover Study
Anesthesiology Newly Published on July 23, 2018. doi:10.1097/ALN.0000000000002367
Anesthesiology Newly Published on July 23, 2018. doi:10.1097/ALN.0000000000002367
Abstract

What We Already Know about This Topic:

  • Caffeine may speed anesthetic emergence

What This Article Tells Us That Is New:

  • The authors tested the hypothesis that caffeine speeds anesthetic emergence

  • Volunteers anesthetized with isoflurane were given caffeine (equivalent to 7.5 mg base) or placebo in a blinded crossover trial

  • When given caffeine, the volunteers emerged more quickly and at a higher isoflurane concentration

Background: There are currently no drugs clinically available to reverse general anesthesia. We previously reported that caffeine is able to accelerate emergence from anesthesia in rodents. This study was carried out to test the hypothesis that caffeine accelerates emergence from anesthesia in humans.

Methods: We conducted a single-center, randomized, double-blind crossover study with eight healthy males. Each subject was anesthetized twice with 1.2% isoflurane for 1 h. During the final 10 min of each session, participants received an IV infusion of either caffeine citrate (15 mg/kg, equivalent to 7.5 mg/kg of caffeine base) or saline placebo. The primary outcome was the average difference in time to emergence after isoflurane discontinuation between caffeine and saline sessions. Secondary outcomes included the end-tidal isoflurane concentration at emergence, vital signs, and Bispectral Index values measured throughout anesthesia and emergence. Additional endpoints related to data gathered from postanesthesia psychomotor testing.

Results: All randomized participants were included in the analysis. The mean time to emergence with saline was 16.5 ± 3.9 (SD) min compared to 9.6 ± 5.1 (SD) min with caffeine (P = 0.002), a difference of 6.9 min (99% CI, 1.8 to 12), a 42% reduction. Participants emerged at a higher expired isoflurane concentration, manifested more rapid return to baseline Bispectral Index values, and were able to participate in psychomotor testing sooner when receiving caffeine. There were no statistically significant differences in vital signs with caffeine administration and caffeine-related adverse events.

Conclusions: Intravenous caffeine is able to accelerate emergence from isoflurane anesthesia in healthy males without any apparent adverse effects.