Physostigmine Reverses Propofol-induced Unconsciousness and Attenuation of the Auditory Steady State Response and Bispectral Index in Human Volunteers

Meuret, Pascal; Backman, Steven B.; Bonhomme, Vincent; Plourde, Gilles; Fiset, Pierre

doi:10.1097/00000542-200009000-00020

Cited by 165 publications

(97 citation statements)

References 39 publications

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“…Physostigmine, widely used in the treatment of the central anticholinergic syndrome, is also effective in preventing and treating behavioural disturbances following propofol anaesthesia [28,29]. Physostigmine is effective in treating cerebellar ataxia [30] and reduced centrally mediated muscular hyperactivity, perhaps inhibiting the fraction of postanaesthetic shivering that resembles clonus [16].…”

Section: Discussionmentioning

confidence: 99%

THIS ARTICLE HAS BEEN RETRACTED Physostigmine for the prevention of postanaesthetic shivering following general anaesthesia – a placebo‐controlled comparison with nefopam

Röhm¹,

Riechmann²,

Boldt³

et al. 2005

Anaesthesia

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SummaryPhysostigmine was studied for its efficacy in the prevention of postanaesthetic shivering compared to nefopam and placebo. We studied 89 patients undergoing abdominal and urological surgery. The study was randomised and double-blind, the patients received physostigmine 2 mg (n = 31), nefopam 10 mg (n = 30) or saline (n = 28). Haemodynamic parameters and temperature were measured at induction of anaesthesia (T0), and 5 min (T1), 15 min (T2), 30 min (T3) and 60 min (T4) after reaching the postanaesthetic care unit (PACU). Significantly less shivering occurred following administration of physostigmine and nefopam (9.7 and 3.3%) compared to placebo (53.6%). The degree of shivering was also significantly reduced following physostigmine and nefopam (p < 0.01). Extubation time, haemodynamic parameters and tympanic temperature were found to be similar in all groups. Aldrete score, duration of PACU stay and postoperative analgesic requirements did not differ between the groups. Only nefopam significantly (p < 0.01) reduced postoperative nausea and vomiting. Physostigmine is a safe alternative to nefopam, significantly reducing the incidence and severity of postanaesthetic shivering without affecting postanaesthetic recovery.

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Section: Discussionmentioning

confidence: 99%

THIS ARTICLE HAS BEEN RETRACTED Physostigmine for the prevention of postanaesthetic shivering following general anaesthesia – a placebo‐controlled comparison with nefopam

Röhm¹,

Riechmann²,

Boldt³

et al. 2005

Anaesthesia

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“…VTA projections to the cortex induce superficial layer cortical postsynaptic depolarizations (41), which is consistent with the loss of coherence we observed in superficial layers of cortex at preROM. A number of other investigations have reported cholinergic (42)(43)(44) and dopaminergic (45,46) influences on arousal that provoke recovery of consciousness after anesthesia-induced unconsciousness. Our work, alongside this evidence from previous studies, suggests that the "hysteresis" during emergence from anesthesiainduced unconsciousness (29) could be explained by active enhancement of arousal from the basal forebrain and VTA.…”

Section: Discussionmentioning

confidence: 98%

Thalamocortical synchronization during induction and emergence from propofol-induced unconsciousness

Flores

Hartnack

Fath

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

156

130

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General anesthesia (GA) is a reversible drug-induced state of altered arousal required for more than 60,000 surgical procedures each day in the United States alone. Sedation and unconsciousness under GA are associated with stereotyped electrophysiological oscillations that are thought to reflect profound disruptions of activity in neuronal circuits that mediate awareness and cognition. Computational models make specific predictions about the role of the cortex and thalamus in these oscillations. In this paper, we provide in vivo evidence in rats that alpha oscillations (10-15 Hz) induced by the commonly used anesthetic drug propofol are synchronized between the thalamus and the medial prefrontal cortex. We also show that at deep levels of unconsciousness where movement ceases, coherent thalamocortical delta oscillations (1-5 Hz) develop, distinct from concurrent slow oscillations (0.1-1 Hz). The structure of these oscillations in both cortex and thalamus closely parallel those observed in the human electroencephalogram during propofol-induced unconsciousness. During emergence from GA, this synchronized activity dissipates in a sequence different from that observed during loss of consciousness. A possible explanation is that recovery from anesthesiainduced unconsciousness follows a "boot-up" sequence actively driven by ascending arousal centers. The involvement of medial prefrontal cortex suggests that when these oscillations (alpha, delta, slow) are observed in humans, self-awareness and internal consciousness would be impaired if not abolished. These studies advance our understanding of anesthesia-induced unconsciousness and altered arousal and further establish principled neurophysiological markers of these states.anesthesia | prefrontal cortex | thalamus | coherence | propofol G eneral anesthesia (GA) is a reversible drug-induced state consisting of unconsciousness, analgesia, amnesia, akinesia, and physiological stability (1). In the United States nearly 60,000 surgical procedures are conducted under GA every day, making GA one of the most common manipulations of the brain and central nervous system in medicine (1). The molecular mechanisms by which anesthetic drugs alter brain function have been well characterized (2, 3). Detailed analyses of neural circuitand systems-level mechanisms of GA are more recent (1, 4, 5). Understanding the system-wide effects of anesthetic drugs is necessary in order to understand how these drugs produce states of altered arousal and unconsciousness.One of the most commonly used anesthetic drugs is 2,6-diisopropylphenol (propofol), a GABA-A receptor agonist (6). Electroencephalogram (EEG) recordings in humans during gradual induction of unconsciousness with propofol show the appearance of frontal β oscillations (15-30 Hz) at the onset of sedation, followed by the appearance of coherent frontal α (8-12 Hz) oscillations (7-10) and widespread slow (0.1-1 Hz) and δ (1-4 Hz) oscillations (7, 11, 12) when subjects no longer respond to sensory stimuli. Biophysical models of neuronal dy...

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“…The results are generally consistent with previous studies. Increasing central Ach levels is known to reduce the depth of anesthesia (Meuret et al, 2000;Hudetz et al, 2003). Laalou et al (2008) reported that NBM lesion with 192IgG-saporin increased the anesthetic, but not the subanesthetic, effects of cumulative doses of propofol (i.p.).…”

Section: Correlation Of Averagementioning

confidence: 99%

“…An anticholinesterase that increased central Ach levels was shown to reduce the depth of anesthesia induced by propofol or isoflurane (Meuret et al, 2000;Hudetz et al, 2003). Pain et al (2000) reported that central Ach depletion by intracerebroventricular (icv) administration of 192IgG-saporin reduced the sedative potency of low-dose (30 mg/kg i.p.)…”

Section: Introductionmentioning

confidence: 99%

Lesion of cholinergic neurons in nucleus basalis enhances response to general anesthetics

Leung

Petropoulos

Shen

et al. 2011

Experimental Neurology

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"Lesion of cholinergic neurons in nucleus basalis enhances response to general anesthetics" (2011). Physiology and Pharmacology Publications. 72. https://ir.lib.uwo.ca/physpharmpub/72 This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. Acetylcholine in the brain has been associated with consciousness and general anesthesia effects. We tested the hypothesis that the integrity of the nucleus basalis magnocellularis (NBM) affects the response to general anesthetics. Cholinergic neurons in NBM were selectively lesioned by bilateral infusion of 192IgG-saporin in adult, male Long-Evans rats, and control rats were infused with saline. Depletion of choline-acetyltransferase (ChAT)-immunoreactive cells in the NBM and decrease in optical density of acetylcholinesterase (AChE) staining in the frontal and visual cortices confirmed a significant decrease in NBM cholinergic neurons in lesioned as compared to control rats. AChE staining in the hippocampus and ChAT-positive neurons in the medial septum-vertical limb of the diagonal band were not different between lesioned and control rats. When a general anesthetic was administered, lesioned compared to control rats showed significantly longer duration of loss of righting reflex (LORR) after propofol (5 or 10 mg/kg i.v.), pentobarbital (20 or 40 mg/kg i.p.) but not halothane (2%). However, the behavioral excitation, as indicated by horizontal movements, induced by halothane was reduced in lesioned as compared to control rats. Reversible inactivation of NBM with GABA A receptor agonist muscimol increased slow waves in the neocortex during awake immobility, and prolonged the duration of LORR and loss of tail-pinch response after propofol, pentobarbital and halothane. In summary, lesion of NBM cholinergic neurons or inactivation of the NBM prolonged the LORR response to general anesthetic drugs.

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Physostigmine Reverses Propofol-induced Unconsciousness and Attenuation of the Auditory Steady State Response and Bispectral Index in Human Volunteers

Abstract: These findings suggest that the unconsciousness produced by propofol is mediated at least in part via interruption of central cholinergic muscarinic transmission.

Cited by 165 publications

References 39 publications

THIS ARTICLE HAS BEEN RETRACTED Physostigmine for the prevention of postanaesthetic shivering following general anaesthesia – a placebo‐controlled comparison with nefopam

THIS ARTICLE HAS BEEN RETRACTED Physostigmine for the prevention of postanaesthetic shivering following general anaesthesia – a placebo‐controlled comparison with nefopam

Thalamocortical synchronization during induction and emergence from propofol-induced unconsciousness

Lesion of cholinergic neurons in nucleus basalis enhances response to general anesthetics

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