Several general anesthetics produce their sedative effect by activating endogenous sleep pathways. We propose that general anesthesia is a two‐step process targeting sleep circuits at low doses, and synaptic release mechanisms across the entire brain at the higher doses required for surgery. Our hypothesis synthesizes data from a variety of model systems, some which require sleep (e.g. rodents and adult flies) and others that probably do not sleep (e.g. adult nematodes and cultured cell lines). Non‐sleeping systems can (...) be made insensitive (or hypersensitive) to some anesthetics by modifying a single pre‐synaptic protein, syntaxin1A. This suggests that the synaptic release machinery, centered on the highly conserved SNARE complex, is an important target of general anesthetics in all animals. A careful consideration of SNARE architecture uncovers a potential mechanism for general anesthesia, which may be the primary target in animals that do not sleep, but a secondary target in animals that sleep. (shrink)

Evidence coming from several studies into memory and awareness during general anesthesia suggests that in surgical patients who seem to be adequately anesthetized , some form of cognitive functioning is preserved. This finding has important implications both for clinical practice and for memory research. In order to give the methodological background of the present situation in this field of research, this article deals, on the basis of recent experiments, with important methodological aspects of studies into perception and memory (...) during general anesthesia. (shrink)

In 2018, the remarkable rescue of twelve young boys and their football coach trapped in a flooded cave in Thailand captured worldwide attention. The rescue required the boys to be dived out of the cave system while fully anaesthetized which presented unique practical and ethical challenges for the rescue team. Major departures from normal anaesthetic practice were required. Taking anaesthetized children underwater was unprecedented, complex, and dangerous. To do this underground in a flooded cave meant the risks were extreme. Using (...) a principlist approach, this essay will outline the rescue plan highlighting the ethical dilemmas faced by the rescue team. Informed consent and full disclosure of information are justifiably waived in emergency disaster scenarios. Beneficence as a guiding principle becomes a major challenge when all rescue options appear destined to cause likely fatalities of healthy young boys. Importantly, virtues and virtue ethics also have a vital role to play when confronting and dealing with ethical challenges in disaster scenarios—this will be discussed with particular reference to the cave rescue. (shrink)

IntroductionPreoperative neurocognitive disorder is a common condition affecting 14–51. 7% of the elderly population. General anesthesia has already been associated with the one-year post-operative neurocognitive disorder, specifically, a deficit in executive function, measured by the Trail Making Test B, but its long-term effects on cognitive function have not been investigated. We aimed to detect preO-NCD prevalence in patients scheduled for cardiac surgery and further investigate the possible role of previous general anesthesia in general preoperative cognitive (...) status [measured via the Montreal Cognitive Assessment ] and/or in executive functioning.MethodsIn this observational, prospective study, 151 adult patients scheduled for elective cardiac surgery underwent MoCA and TMT-B. Data on age, education, pGA, comorbidities, and laboratory results were collected.ResultsWe discovered a general cognitive function impairment of 79.5% and an executive function impairment of 22%. Aging is associated with an increased likelihood and education with a decreased likelihood of general cognitive impairment, but only education was significantly associated with a decreased likelihood of executive function impairment. While pGA did not significantly affect preO-NCD, a noteworthy interaction between aging and pGA was found, resulting in a synergistic effect, increasing the likelihood of executive function impairment.ConclusionWe found a high prevalence of preO-NCD in patients scheduled for cardiac surgery. General cognitive function impairment is highly associated with advancing age. However, older patients with at least one pGA appeared to be at an increased risk of preO-NCD, especially executive function impairment, suggesting that TMT-B should be associated with MoCA in the preoperative cognitive evaluation in this population. (shrink)

The cognitive unbinding paradigm suggests that the synthesis of neural information is attenuated by general anesthesia. Here, we analyzed the functional organization of brain activities in the conscious and anesthetized states, based on functional segregation and integration. Electroencephalography recordings were obtained from 14 subjects undergoing induction of general anesthesia with propofol. We quantified changes in mean information integration capacity in each band of the EEG. After induction with propofol, mean information integration capacity was reduced most prominently (...) in the γ band of the EEG . Furthermore, we demonstrate that loss of consciousness is reflected by the breakdown of the spatiotemporal organization of γ waves. We conclude that induction of general anesthesia with propofol reduces the capacity for information integration in the brain. These data directly support the information integration theory of consciousness and the cognitive unbinding paradigm of general anesthesia. (shrink)

In the present article we consider general anesthesia as a means of exploring questions regarding unconscious influence. The primary questions addressed in the research are whether surgical patients who are under adequate general anesthesia unconsciously perceive auditory information and whether they can benefit from such information. In addition, we consider the relevance of individual hypnotic ability for perceptual processing in this context. Ninety-six adult patients, undergoing elective abdominal hysterectomy, were randomly allocated to one of four tape-recorded (...) conditions: therapeutic suggestions, melodies, suggestions-plus-melodies, or silence. Double-blind conditions were satisfied in every respect. Patients received a standardized, but typical, "balanced" anesthetic, and level of anesthesia was adequately monitored. Following surgery, all patients received their analgesic medication from a patient-controlled device. Patients who were played therapeutic suggestions used a significantly smaller dose of morphine than patients who were not played suggestions. Although hypnotic ability was not significantly associated with therapeutic outcome, high but not low hypnotizable patients accurately guessed whether they were played suggestions. No compelling evidence for memory of melodies was obtained. (shrink)

Consciousness, Awareness, and Anesthesia is a multidisciplinary approach to both the scientific problem of consciousness and the clinical problem of awareness during general anesthesia.

Automatic control of physiological variables is one of the most active areas in biomedical engineering. This paper is centered in the prediction of the analgesic variables evolution in patients undergoing surgery. The proposal is based on the use of hybrid intelligent modelling methods. The study considers the Analgesia Nociception Index to assess the pain in the patient and remifentanil as intravenous analgesic. The model proposed is able to make a one-step-ahead prediction of the remifentanil dose corresponding to the current state (...) of the patient. The input information is the previous remifentanil dose, the ANI variable and the electromyogram signal. Modelling techniques used are Artificial Neural Networks and Support Vector machines for Regression combined with clustering methods. Both training and validation were done with a real dataset from different patients. Results obtained show the potential of this methodology to calculate the drug dose corresponding to a given analgesic state of the patient. (shrink)

General anesthesia provides an alternative to typical laboratory paradigms for investigating implicit learning. We assess the evidence that a simple type of learning—priming—can occur without consciousness. Although priming has been shown to be a small but persistent phenomenon in surgical patients there is reason to question whether it occurs implicitly due to problems in detecting awareness using typical clinical signs. This paper reviews the published studies on priming during anesthesia that have included a measure of awareness or (...) of anesthetic depth. We conclude that perceptual priming, but not conceptual priming, takes place in the absence of conscious awareness. (shrink)

In general anesthesia, a “cocktail” of drugs renders a patient unconscious, in what has been called a “controlled coma”. Various measures of patient awareness involve overt behavior, autonomic nervous system activity, processed EEG, and event‐related potentials. The incidence of intraoperative awareness is very low, but anecdotal reports suggest that patients might process surgical events unconsciously, leading to unconscious postoperative memories. Careful experimental studies show that priming effects, similar to those observed in implicit memory, can be spared even in (...) the absence of conscious recollection, an outcome which indicates that unconscious perception can occur even in clinically adequate general anesthesia. Deeper planes of amnesia, however, appear to abolish both explicit and implicit perception. (shrink)

Possible systemic effects of general anesthetic agents on neural information processing are discussed in the context of the thalamocortical suppression hypothesis presented by Drs. Alkire, Haier, and Fallon (this issue) in their PET study of the anesthetized state. Accounts of the neural requisites of consciousness fall into two broad categories. Neuronal-specificity theories postulate that activity in particular neural populations is sufficient for conscious awareness, while process-coherence theories postulate that particular organizations of neural activity are sufficient. Accounts of anesthetic narcosis, (...) on the other hand, explain losses of consciousness in terms of neural signal-suppressions, transmission blocks, and the disruptions of signal interpretation. While signal-suppression may account for the actions of some anesthetic agents, the existence of anesthetics, such as choralose, that cause both loss of consciousness and elevated discharge rates, is problematic for a general theory of narcosis that is based purely on signal suppression and transmission-block. However, anesthetic agents also alter relative firing rates and temporal discharge patterns that may disrupt the coherence of neural signals and the functioning of the neural networks that interpret them. It is difficult at present, solely on the basis of regional brain metabolic rates, to test process-coherence hypotheses regarding organizational requisites for conscious awareness. While these pioneering PET studies have great merit as panoramic windows of mind-brain correlates, wider ranges of theory and empirical evidence need to be brought into the formulation of truly comprehensive theories of consciousness and anesthesia. (shrink)

Philosophical (p-) zombies are constructs that possess all of the behavioral features and responses of a sentient human being, yet are not conscious. P-zombies are intimately linked to the hard problem of consciousness and have been invoked as arguments against physicalist approaches. But what if we were to invert the characteristics of p-zombies? Such an inverse (i-) zombie would possess all of the behavioral features and responses of an insensate being yet would nonetheless be conscious. While p-zombies are logically possible (...) but naturally improbable, an approximation of i-zombies actually exists: individuals experiencing what is referred to as “anesthesia awareness.” Patients under general anesthesia may be intubated (preventing speech), paralyzed (preventing movement), and narcotized (minimizing response to nociceptive stimuli). Thus, they appear—and typically are—unconscious. In 1-2 cases/1000, however, patients may be aware of intraoperative events, sometimes without any objective indices. Furthermore, a much higher percentage of patients (22% in a recent study) may have the subjective experience of dreaming during general anesthesia. P-zombies confront us with the hard problem of consciousness—how do we explain the presence of qualia? I-zombies present a more practical problem—how do we detect the presence of qualia? The current investigation compares p-zombies to i-zombies and explores the “hard problem” of unconsciousness with a focus on anesthesia awareness. (shrink)

It has frequently been suggested that science and religion are innately in conflict. One example from the history of medicine is the introduction of anaesthesia into obstetrics in 1847, which is commonly said to have stimulated massive religious opposition. Historians have almost unanimously averred that such opposition arose from the belief that obstetric anaesthesia interfered with the primeval curse— ‘In sorrow thou shalt bring forth children’ . Despite considerable opposition to obstetric anaesthesia upon medical, physiological, and general moral grounds, (...) evidence of genuine religious opposition in contemporary sources has proved to be virtually non-existent. On examination, this particular ‘conflict’ appears to be an artifact of historiography based upon a contemporary defence prepared against an attack which never materialized. (shrink)

This paper explores the changes in cognitive function which occur as someone "loses consciousness" under anesthesia. Seven volunteers attempted a categorization task and a within-list recognition test while inhaling air, 0.2% isoflurane, and 0.4% isoflurane. In general, performance on these tests declined as the dose of anesthetic was increased and returned to baseline after 10 min of breathing air. A measure of auditory evoked responding termed "coherent frequency" showed parallel changes. At 0.2% isoflurane, subjects could still identify and (...) respond to category exemplars but showed impaired short-term memory function. Electrical stimulation at 0.4% isoflurane, intended to mimic the arousing effects of surgery, had a small, beneficial effect on performance. A mean of 63% of category exemplars was identified at this stage, but recognition memory for those exemplars was at chance on recovery. There was no evidence for learning of words presented at 0.8% isoflurane. (shrink)

Information processing that subserves conscious cognitive functions is thought to involve recurrent signaling through feedforward and feedback loops among hierarchically arranged functional regions of the cerebral cortex. In the current issue of Consciousness and Cognition, Lee et al. report that loss of consciousness, as produced by a bolus injection of the general anesthetic propofol to human volunteers, was accompanied by a decrease in wide-band EEG feedback connectivity from frontal cortex to parietal cortex, confirming a prediction from previous experimental studies. (...) Interestingly, frontoparietal feedback connectivity did not fully recover after the anesthetic effect wore off and the subjects first opened their eyes in response to a verbal command. Possible interpretations of the results and their implications with respect to the neural correlates of consciousness and unconsciousness are discussed. (shrink)

A theory of anaesthesia is presented. It consists of four hypotheses: (1) The occurrence of states of consciousness causally depends on the formation of transient higher-order, self-referential mental representations. The occurrence of such states is identical with the appearance of conscious phenomena. Loss of consciousness will occur, if and only if the brain's representational activity falls below a critical threshold. (2) Mental representations are instantiated by neural cell assemblies. (3) The formation of assemblies involves the activation of the NMDA receptor (...) channel complex. The activation state of this receptor determines the rate at which assemblies are generated. (4) General anaesthetics have a common operative mechanism: they directly or indirectly affect the function of the NMDA system. (shrink)

Frontoparietal connectivity has been suggested to be important in conscious processing and its interruption is thought to be one mechanism of general anesthesia. Data in animals demonstrate that feedforward processing of information may persist during the anesthetized state, while feedback processing is inhibited. We investigated the directionality and functional organization of frontoparietal connectivity in 10 human subjects anesthetized with propofol on two separate occasions. Multichannel electroencephalography and a computational method of assessing directed functional connectivity were employed. We demonstrate (...) that directed feedback connectivity is diminished with loss of consciousness and returns with responsiveness to verbal command. We also applied the Dendrogram classification method to assess the global organization of directed functional connectivity during consciousness and anesthesia. We demonstrate a state-specific hierarchy and subject-specific subhierarchy in functional organization. These data support the hypothesis that specific states of human consciousness are defined by specific states of frontoparietal connectivity. (shrink)

Recent media articles have stirred controversy over anecdotal reports of medical students practising educational pelvic examinations on women under anaesthesia without explicit consent. The understandable public outrage that followed merits a substantive response from the medical community. As medical students, we offer a unique perspective on consent for trainee involvement informed by the transitional stage we occupy between patient and physician. We start by contextualising the role of educational pelvic examinations under anaesthesia (EUAs) within general clinical skill development in (...) medical education. Then we analyse two main barriers to achieving explicit consent for educational pelvic EUAs: ambiguity within professional guidelines on how to operationalize ‘explicit consent’ and divergent patient and physician perspectives on harm which prevent physicians from understanding what a reasonable patient would want to know before a procedure. To overcome these barriers, we advocate for more research on patient perspectives to empower the reasonable patient standard. Next, we call for minimum disclosure standards informed by this research and created in conjunction with students, physicians and patients to improve the informed consent process and relieve medical student moral injury caused by performing ‘unconsented’ educational pelvic exams. (shrink)

A cross-sectional study to ascertain what the Singapore population would regard as material risk in the anaesthesia consent-taking process and identify demographic factors that predict patient preferences in medical decision-making to tailor a more patient-centered informed consent. A survey was performed involving patients 21 years old and above who attended the pre-operative evaluation clinic over a 1-month period in Singapore General Hospital. Questionnaires were administered to assess patients’ perception of material risks, by trained interviewers. Patients’ demographics were obtained. Mann–Whitney (...) U test and Kruskal-Wallis one-way analysis of variance was used. Statistical significance was taken at p < 0.05. Four hundred fourteen patients were eligible of which 26 refused to participate and 24 were excluded due to language barrier. 364 patients were recruited. A higher level of education, being employed and younger age group are factors identified in patients who wanted greater participation in medical decisions. Gender, marital status, type of surgery, and previous surgical history did not affect their level of participation. The complications most patients knew about were Nausea, Drowsiness and Surgical Wound Pain. Patients ranked Heart Attack, Death and Stroke as the most significant risks that they wanted to be informed about in greater detail. Most patients wanted to make a joint decision with the anaesthetist, instead of letting the doctor decide or deciding for themselves. Discussion with the anaesthetist is the preferred medium of communication compared to reading a pamphlet or watching a video. Age and educational level can influence medical decision-making. Despite the digital age, most patients still prefer a clinic consult instead of audio-visual multimedia for pre-operative anaesthetic counselling. The local population appears to place greater importance on rare but serious complications compared to common complications. This illustrates the need to contextualize information provided during informed consent to strengthen the doctor-patient relationship. (shrink)

For millennia self has been conjectured to be necessary for consciousness. But scant empirical evidence has been adduced to support this hypothesis. Inconsistent explications of “self” and failure to design apt experiments have impeded progress. Advocates of phenomenological psychiatry, however, have helped explicate “self,” and employed it to explain some psychopathological symptoms. In those studies, “self” is understood in a minimalist sense, sheer “for-me-ness.” Unfortunately, explication of the “minimal self” (MS) has relied on conceptual analysis, and applications to psychopathology have (...) been hermeneutic, allowing for many degrees of interpretive latitude. The result is that MS’s current scientific status is analogous to that of the “atom,” at the time when “atom” was just beginning to undergo transformation from a philosophical to a scientific concept. Fortunately, there is now an opportunity to promote a similar transformation for “MS.” Discovery of the brain’s Default Mode Network (DMN) opened the door to neuroimaging investigations of self. Taking the DMN and other forms of intrinsic activity as a starting point, an empirical foothold can be established, one that spurs experimental research and that enables extension of research into multiple phenomena. New experimental protocols that posit “MS” can help explain phenomena hitherto not thought to be related to self, thereby hastening development of a mature science of self. In particular, targeting phenomena wherein consciousness is lost and recovered, as in some cases of Unresponsive Wakefulness Syndrome (UWS), allow for design of neuroimaging probes that enable detection of MS during non-conscious states. These probes, as well as other experimental protocols applied to NREM Sleep, General Anesthesia (GA), and the waking state, provide some evidence to suggest that not only can self and consciousness dissociate, MS might be a necessary precondition for conscious experience. Finally, these findings have implications for the science of consciousness: it has been suggested that “levels of consciousness” (LoC) is not a legitimate concept for the science of consciousness. But because we have the conceptual and methodological tools with which to refine investigations of MS, we have the means to identify a possible foundation—a bifurcation point—for consciousness, as well as the means by which to measure degrees of distance from that foundation. These neuroimaging investigations of MS position us to better assess whether LoC has a role to play in a mature science of consciousness. (shrink)

Different anesthetics are known to modulate different types of membrane-bound receptors. Their common mechanism of action is expected to alter the mechanism for consciousness. Consciousness is hypothesized as the integral of all the units of internal sensations induced by reactivation of inter-postsynaptic membrane functional LINKs during mechanisms that lead to oscillating potentials. The thermodynamics of the spontaneous lateral curvature of lipid membranes induced by lipophilic anesthetics can lead to the formation of non-specific inter-postsynaptic membrane functional LINKs by different mechanisms. These (...) include direct membrane contact by excluding the inter-membrane hydrophilic region and readily reversible partial membrane hemifusion. The constant reorganization of the lipid membranes at the lateral edges of the postsynaptic terminals (dendritic spines) resulting from AMPA receptor-subunit vesicle exocytosis and endocytosis can favor the effect of anesthetic molecules on lipid membranes at this location. Induction of a large number of non-specific LINKs can alter the conformation of the integral of the units of internal sensations that maintain consciousness. Anesthetic requirement is reduced in the presence of dopamine that causes enlargement of dendritic spines. Externally applied pressure can transduce from the middle ear through the perilymph, cerebrospinal fluid, and the recently discovered glymphatic pathway to the extracellular matrix space, and finally to the paravenular space. The pressure gradient reduce solubility and displace anesthetic molecules from the membranes into the paravenular space, explaining the pressure reversal of anesthesia. Changes in membrane composition and the conversion of membrane hemifusion to fusion due to defects in the checkpoint mechanisms can lead to cytoplasmic content mixing between neurons and cause neurodegenerative changes. The common mechanism of anesthetics presented here can operate along with the known specific actions of different anesthetics. (shrink)

The Royal College of Physicians of London published the 2013 national clinical guidelines on prolonged disorders of consciousness in vegetative and minimally conscious states. The guidelines acknowledge the rapidly advancing neuroscientific research and evolving therapeutic modalities in PDOC. However, the guidelines state that end-of-life decisions should be made for patients who do not improve with neurorehabilitation within a finite period, and they recommend withdrawal of clinically assisted nutrition and hydration . This withdrawal is deemed necessary because patients in PDOC can (...) survive for years with continuation of CANH, even when a ceiling on medical care has been imposed, i.e., withholding new treatment such as cardiopulmonary resuscitation for acute life-threatening illness. The end-of-life care pathway is centered on a staged escalation of medications, including sedatives, opioids, barbiturates, and general anesthesia, concurrent with withdrawal of CANH. Agitation and distress may last from several days to weeks because of the slow dying process from starvation and dehydration. The potential problems of this end-of-life care pathway are similar to those of the Liverpool Care Pathway. After an independent review in 2013, the Department of Health discontinued the Liverpool Care pathway in England. The guidelines assert that clinicians, supported by court decisions, have become the final authority in nonconsensual withdrawal of CANH on the basis of “best interests” rationale. We posit that these guidelines lack high-quality evidence supporting: 1) treatment futility of CANH, 2) reliability of distress assessment from starvation and dehydration, 3) efficacy of pharmacologic control of this distress, and 4) proximate causation of death. Finally, we express concerns about the utilitarian-based assessment of what constitutes a person’s best interests. We are disturbed by the level and the role of medical authoritarianism institutionalized by these national guidelines when deciding on the worthiness of life in PDOC. We conclude that these guidelines are not only harmful to patients and families, but they represent the means of nonconsensual euthanasia. The latter would constitute a gross violation of the public’s trust in the integrity of the medical profession. (shrink)