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      Comparison of the effects of caffeine, aminophylline, and saline on the recovery from total intravenous anesthesia in laparoscopic surgeries: A randomized controlled trial

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          Abstract

          Background and Aims:

          The return of consciousness (ROC) after general anesthesia (GA) is by stopping the administration of anesthetic agents. At present, no drug is given to reverse the loss of consciousness produced by general anesthetic agents. This study is conducted to find whether caffeine and aminophylline hasten the ROC.

          Material and Methods:

          This study was conducted on 75 American Society of Anesthesiologists (ASA) I and II female patients undergoing laparoscopic hysterectomy, aged between 18 and 60 years. The patients were divided into three equal groups (Group C: caffeine citrate, Group A: aminophylline, and Group S: saline) of 25 each by a computer-generated random number table. GA was induced with propofol, fentanyl, and maintained with propofol infusion. On completion of the surgery, the neuromuscular blocking agent was reversed and then the infusion of propofol was stopped. The study drug was administered intravenously when the BIS 60 was achieved. Time to achieve BIS 90, return of first gag reflex, eye-opening on verbal command, and extubation after study drug administration were noted. Hemodynamic parameters and SpO2 were also monitored.

          Results:

          The time for BIS 60 to 90 was 10 (4.25) min in the caffeine group, 13 (4.25) min in the aminophylline group, and 26 (9.0) min in the saline group. The time to return of gag reflex and time to extubation were shorter in the caffeine and aminophylline group compared to the saline group. The time to eye-opening on verbal command was shorter in the aminophylline group compared to the saline group. Hemodynamic parameters after infusion of the study drug were comparable in all three groups.

          Conclusion:

          Caffeine hastens the recovery from total intravenous anesthesia with propofol and fentanyl in laparoscopic hysterectomy as effectively as aminophylline.

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          Most cited references20

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          Propofol in anesthesia. Mechanism of action, structure-activity relationships, and drug delivery.

          Propofol (2,6-diisopropylphenol) is becoming the intravenous anesthetic of choice for ambulatory surgery in outpatients. It is extensively metabolized, with most of the administered dose appearing in the urine as glucuronide conjugates. Favorable operating conditions and rapid recovery are claimed as the main advantages in using propofol, whereas disadvantages include a relatively high incidence of apnea, and blood pressure reductions. Besides a literature summary of the pharmacodynamics, pharmacokinetics, toxicology, and clinical use, this review provides a deeper discussion on the current understanding of mechanism of action and structure-activity relationships, and recent findings on drug delivery technologies as applied to the improvement of propofol formulations. The action of propofol involves a positive modulation of the inhibitory function of the neurotransmitter gama-aminobutyric acid (GABA) through GABAA receptors. Recent results from recombinant human GABAA receptor experiments and findings from the work exploring the effects at other receptors (e.g., glycine, nicotinic, and M1 muscarinic receptors) are reviewed. Studies showing its antiepileptic and anxiolytic properties are also discussed. The structure-activity relationships (SAR) of series of alkylphenols and p-X-substituted congeners have been reinvestigated. Interestingly, unlike the other congeners tested sofar, p-iodo-2,6-diisopropylphenol displayed anticonvulsant and anticonflict effects, but not sedative-hypnotic and anesthetic properties. Due to its high lipid-solubility, propofol was initially formulated as a solution with the surfactant Cremophor EL, but the occurrence of pain on injection and anaphylactoid reactions prompted to search for alternative formulations. Results from using cyclodextrins, water-soluble prodrugs, and adopting Bodor's approach to the site-specific chemical delivery system (CDS), as well as the advantages provided by computer-controlled infusion systems, are examined in some detail.
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            Methylphenidate actively induces emergence from general anesthesia.

            Although accumulating evidence suggests that arousal pathways in the brain play important roles in emergence from general anesthesia, the roles of monoaminergic arousal circuits are unclear. In this study, the authors tested the hypothesis that methylphenidate (an inhibitor of dopamine and norepinephrine transporters) induces emergence from isoflurane general anesthesia. Using adult rats, the authors tested the effect of intravenous methylphenidate on time to emergence from isoflurane general anesthesia. They then performed experiments to test separately for methylphenidate-induced changes in arousal and changes in minute ventilation. A dose-response study was performed to test for methylphenidate-induced restoration of righting during continuous isoflurane general anesthesia. Surface electroencephalogram recordings were performed to observe neurophysiological changes. Plethysmography recordings and arterial blood gas analysis were performed to assess methylphenidate-induced changes in respiratory function. Intravenous droperidol was administered to test for inhibition of methylphenidate's actions. Methylphenidate decreased median time to emergence from 280 to 91 s. The median difference in time to emergence without methylphenidate compared with administration of methylphenidate was 200 [155-331] s (median, [95% CI]). During continuous inhalation of isoflurane, methylphenidate induced return of righting in a dose-dependent manner, induced a shift in electroencephalogram power from delta (less than 4 Hz) to theta (4-8 Hz), and induced an increase in minute ventilation. Administration of intravenous droperidol (0.5 mg/kg) before intravenous methylphenidate (5 mg/kg) largely inhibited methylphenidate-induced emergence behavior, electroencephalogram changes, and changes in minute ventilation. Methylphenidate actively induces emergence from isoflurane general anesthesia by increasing arousal and respiratory drive, possibly through activation of dopaminergic and adrenergic arousal circuits. The authors' findings suggest that methylphenidate may be useful clinically as an agent to reverse general anesthetic-induced unconsciousness and respiratory depression at the end of surgery.
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              Arousal effect of caffeine depends on adenosine A2A receptors in the shell of the nucleus accumbens.

              Caffeine, the most widely used psychoactive compound, is an adenosine receptor antagonist. It promotes wakefulness by blocking adenosine A(2A) receptors (A(2A)Rs) in the brain, but the specific neurons on which caffeine acts to produce arousal have not been identified. Using selective gene deletion strategies based on the Cre/loxP technology in mice and focal RNA interference to silence the expression of A(2A)Rs in rats by local infection with adeno-associated virus carrying short-hairpin RNA, we report that the A(2A)Rs in the shell region of the nucleus accumbens (NAc) are responsible for the effect of caffeine on wakefulness. Caffeine-induced arousal was not affected in rats when A(2A)Rs were focally removed from the NAc core or other A(2A)R-positive areas of the basal ganglia. Our observations suggest that caffeine promotes arousal by activating pathways that traditionally have been associated with motivational and motor responses in the brain.
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                Author and article information

                Journal
                J Anaesthesiol Clin Pharmacol
                J Anaesthesiol Clin Pharmacol
                JOACP
                J Anaesthesiol Clin Pharmacol
                Journal of Anaesthesiology, Clinical Pharmacology
                Wolters Kluwer - Medknow (India )
                0970-9185
                2231-2730
                Jul-Sep 2023
                02 September 2022
                : 39
                : 3
                : 404-410
                Affiliations
                [1]Department of Anesthesiology and Critical Care, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
                Author notes
                Address for correspondence: Dr. Bharat Paliwal, Associate Professor, Department of Anaesthesiology and Critical Care, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India. E-mail: docbpali@ 123456gmail.com
                Article
                JOACP-39-404
                10.4103/joacp.joacp_528_21
                10661620
                7f94f3ed-6e14-4e3a-b135-e276e06693f3
                Copyright: © 2022 Journal of Anaesthesiology Clinical Pharmacology

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

                History
                : 06 December 2021
                : 28 January 2022
                : 31 January 2022
                Categories
                Original Article

                Anesthesiology & Pain management
                aminophylline,bis,caffeine,propofol,recovery,reversal of loss of consciousness,and total intravenous anesthesia

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