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Caffeine Accelerates Emergence from Isoflurane Anesthesia in Humans: A Randomized, Double-blind, Crossover Study.

ABSTRACT: WHAT WE ALREADY KNOW ABOUT THIS TOPIC:WHAT THIS ARTICLE TELLS US THAT IS NEW: 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.

SUBMITTER: Fong R

PROVIDER: S-EPMC6191316 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Caffeine Accelerates Emergence from Isoflurane Anesthesia in Humans: A Randomized, Double-blind, Crossover Study.

Fong Robert R Wang Lingzhi L Zacny James P JP Khokhar Suhail S Apfelbaum Jeffrey L JL Fox Aaron P AP Xie Zheng Z

Anesthesiology 20181101 5

<h4>What we already know about this topic</h4>WHAT THIS ARTICLE TELLS US THAT IS NEW: 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.<h4>Methods</h4>We conducted a single-center, randomized, double-blind crossover study with eight healthy males ...[more]

PMID: 30044241

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Project description:Currently no drugs are employed clinically to reverse the unconsciousness induced by general anesthetics. Our previous studies showed that caffeine, when given near the end of an anesthesia session, accelerated emergence from isoflurane anesthesia, likely caused by caffeine's ability to elevate intracellular cAMP levels and to block adenosine receptors. These earlier studies showed that caffeine did not rouse either rats or humans from deep anesthesia (≥ 1 minimum alveolar concentration, MAC). In this current crossover study, we examined whether caffeine reversed the unconsciousness produced by light anesthesia (< 1 MAC) in the continued presence of isoflurane. The primary endpoint of this study was to measure isoflurane levels at the time of recovery of righting reflex, which was a proxy for consciousness. Rats were deeply anesthetized with 2% isoflurane (~1.5 MAC) for 20 minutes. Subsequently, isoflurane was reduced to 1.2% for 10 minutes, then by 0.2% every 10 min; animals were monitored until the recovery of righting reflex occurred, in the continued presence of isoflurane. Respiration rate, heart rate and electroencephalogram (EEG) were monitored. Our results show that caffeine-treated rats recovered their righting reflex at a significantly higher inspired isoflurane concentration, corresponding to light anesthesia, than the same rats treated with saline (control). Respiration rate and heart rate increased initially after caffeine injection but were then unchanged for the rest of the anesthesia session. Deep anesthesia is correlated with burst suppression in EEG recordings. Our data showed that caffeine transiently reduced the burst suppression time produced by deep anesthesia, suggesting that caffeine altered neuronal circuit function but not to a point where it caused arousal. In contrast, under light anesthesia, caffeine shifted the EEG power to high frequency beta and gamma bands. These data suggest that caffeine may represent a clinically viable drug to reverse the unconsciousness produced by light anesthesia.

Dataset Information

Caffeine Accelerates Emergence from Isoflurane Anesthesia in Humans: A Randomized, Double-blind, Crossover Study.

Publications

Caffeine Accelerates Emergence from Isoflurane Anesthesia in Humans: A Randomized, Double-blind, Crossover Study.

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