British Journal of Anaesthesia
April 13, 2018
Phillip E. Vlisides, Tarik Bel‐bahar, Amanda Nelson et al.
117 citations
Subanaesthetic doses of ketamine produce altered states of consciousness dominated by dissociative experiences such as disembodiment and ego transcendence, along with sensory disturbances. These subjective effects occur alongside a broad decrease in low-frequency brain electrical activity, with the largest reductions in alpha power (8–12 Hz) in parietal and occipital regions. Specific decreases in alpha power were identified in the precuneus and temporal-parietal junction, brain areas involved in multisensory integration, body representation, and consciousness. The findings suggest that modulation of these temporal-parietal loci may be a candidate mechanism for ketamine's psychoactive effects.
British Journal of Anaesthesia
February 4, 2018
Jamie Sleigh, Catherine E. Warnaby, Irene Tracey
35 citations
Selfhood depends on brain processes that allow a person to experience being a distinct, capable agent. It includes a hierarchy of components: core self (awareness of existence), embodied self (sentience), executive self (agency), and higher-order cognition. Consciousness and selfhood are related but not identical; understanding selfhood helps explain partial consciousness during anesthesia. Brain-imaging and EEG studies show that anesthetic drugs selectively impair self-related networks, especially the anterior insula and salience network, causing depersonalization at moderate doses while preserving disembodied self-awareness. Unlike natural sleep, where loss of agency and sentience tracks with decreasing self-awareness, anesthesia maintains posterior brain connectivity even at high concentrations, possibly marking a core self involved in reduced energy homeostasis.
British Journal of Anaesthesia
March 1, 2025
Nicholas D Richards, Simon J Howell, Mark C Bellamy et al.
20 citations
Ketamine, discovered in 1962, acts as an NMDA receptor antagonist and provides dose-dependent anaesthetic, sedative, and analgesic effects. It also influences other cellular targets, yielding potential benefits including cardiovascular stability during sedation, analgesia for acute and chronic pain, bronchodilation in severe refractory asthma, anti-inflammatory properties especially in sepsis, tumour inhibition, and antidepressant effects that can reverse suicidal ideation. Reluctance to use ketamine clinically stems from stigma around its side-effects and abuse potential. This review surveys ketamine's diverse therapeutic potentials across fields and identifies areas for future research, such as perioperative medicine, pain management, ICU sedation, and tumour suppression during cancer surgery.
British Journal of Anaesthesia
February 1, 2025
Simone C Jansen, Monique van Velzen, Elise Sarton et al.
11 citations
Intravenous esketamine up to a total dose of 1 mg per kg does not impair the ventilatory response to hypoxia in healthy adults. In an open-label study of 18 subjects, esketamine increased resting ventilation by about 3.1 L per minute and raised mean arterial pressure by 10 mm Hg and heart rate by 10 beats per minute, but it did not alter the increase in breathing triggered by acute or sustained low oxygen. The drug also increased anxiety and alertness and altered external perception, which may contribute to the sustained hypoxic ventilatory response observed during infusion. These findings indicate that low-dose esketamine is safe with respect to the hypoxic chemoreflex but has cardiovascular and psychoactive effects.
British Journal of Anaesthesia
March 1, 2024
Zhenhu Liang, Yu Chang, Xiaoge Liu et al.
10 citations
Information integration and brain network measures derived from EEG can distinguish conscious from unconscious states induced by three different anaesthetics. In 72 participants given propofol, dexmedetomidine, or ketamine until they lost responsiveness, permutation cross mutual information (PCMI) within frontal, parietal, and occipital regions decreased during unresponsiveness—for example, frontal within-area PCMI fell from 0.54 to 0.46. Alpha-band PCMI in the frontal region and gamma-band PCMI in posterior areas also dropped. Network analyses showed reduced clustering coefficients and nodal efficiency in frontal, parietal, and occipital areas, while normalized path length increased in delta, theta, and gamma bands, indicating impaired global integration. The three drugs produced similar changes, suggesting a common EEG signature of anaesthesia-induced unconsciousness.
British Journal of Anaesthesia
July 7, 2025
Connor T A Brenna, Xuan W He, Daheng Liu et al.
8 citations
Postoperative delirium and other cognitive problems are common in older surgical patients. Ketamine, given before or during anesthesia, might protect cognition by reducing inflammation or allowing lower doses of other drugs, but its effectiveness is debated. This review of 58 studies involving 6830 patients found that ketamine provided no cognitive benefit in 60% of studies, while 40% reported reduced incidence or duration of cognitive disorders. No clear patterns emerged for dose, formulation, or timing. Studies assessing cognition only early after surgery were more likely to show no benefit. Most trials were too small and methods too varied for meta-analysis. The inconsistent results support the need for larger, well-designed trials to identify which patient subgroups might benefit.
British Journal of Anaesthesia
May 28, 2025
Jia Huo, Huiming Li, Dan Wang et al.
4 citations
Orexin promotes arousal from general anaesthesia, but the mechanisms are unclear. The nucleus accumbens (NAc), a target of orexin neurons, helps regulate consciousness. During isoflurane anaesthesia, orexinergic afferents in the NAc were wake-active. Optogenetic activation of these terminals prolonged induction time, shortened emergence time, and reduced the burst suppression ratio from 67.4% to 14.5% during 1.4 vol% isoflurane anaesthesia. Microinjection of orexin-A into the NAc promoted arousal. Orexin-1 receptors were expressed mainly in NAc D1 receptor-positive neurons. Activation increased D1R+ neuron firing from 0.77 to 2.53 spikes per second and restored NAc-to-frontal cortex coherence. Orexin restores communication between the NAc and frontal cortex by upregulating D1R+ neuron activity, thereby promoting arousal from isoflurane anaesthesia.
British Journal of Anaesthesia
April 1, 2025
Milan Van Maldegem, Jakub Vohryzek, Selen Atasoy et al.
3 citations
Ketamine, at anesthetic doses, produces a state where people are unresponsive yet often report vivid inner experiences, separating conscious awareness from behavioral responsiveness. Using connectome harmonic decomposition on fMRI data, researchers found that brain signals during ketamine-induced unresponsiveness show increased fine-grained spatial patterns, indicating higher neural granularity. This harmonic signature aligned with those of LSD-induced and ketamine-induced psychedelic states, but misaligned with signatures from unconscious individuals due to propofol sedation or brain injury. The method can track changes in conscious awareness even when behavior is absent, offering a tool for consciousness and anesthesia research.
British Journal of Anaesthesia
August 1, 2026
Pilleriin Sikka, Sherry Hu, Boris D. Heifets
Dreaming during anaesthesia is common and has been documented for over a century, but remains poorly understood. This review of 157 studies from 1921 to 2024 involving 87,866 participants found that dream recall rates vary widely, from 3% to 8% in large clinical trials to 40% to 80% in experimental settings. Ketamine and propofol are most consistently associated with recall. Dreams are predominantly pleasant and feature everyday autobiographical content. Dream recall is not linked to intraoperative awareness, challenging the idea that dreams indicate inadequate anaesthetic depth. Higher home dream recall, preoperative suggestion, and immediate post-emergence assessment increase recall rates. Unpleasant dreams reduce willingness to undergo the same anaesthetic again. The positive nature and suggestibility of anaesthesia dreams suggest potential therapeutic uses.
British Journal of Anaesthesia
February 1, 2024
Cameron P Casey, Sean Tanabe, Zahra Z Farahbakhsh et al.
Many EEG-based measures previously thought to indicate unconsciousness actually track sensory connectedness—awareness of the environment—rather than consciousness itself. Analyzing data from the UNderstanding Consciousness Connectedness and Intra-Operative Unresponsiveness Study, researchers tested 10 resting-state EEG markers derived from unresponsive subjects during dexmedetomidine and propofol sedation and natural sleep. While several markers correlated with reported subjective experience (consciousness), none were specific to consciousness alone; each was also linked to connectedness. Loss of normalized-symbolic transfer entropy (front to back) was associated with connectedness across all conditions, and the shift from disconnected consciousness to unconsciousness involved significant decreases in permutation entropy and spectral exponent. The findings caution against equating unresponsiveness with unconsciousness.
British Journal of Anaesthesia
August 1, 2023
Katja Valli, Linda Radek, Roosa E Kallionpää et al.
Anaesthetic-induced unresponsiveness and non-rapid eye movement (NREM) sleep share similar conscious experiences. In a within-subject study, 39 healthy males received either dexmedetomidine or propofol to induce unresponsiveness, and 37 were later awakened from NREM sleep. Most participants were rousable, with no difference between the two drugs. Lower drug concentrations were linked to being rousable but not to recall of experiences. Of interviews after anaesthesia and sleep, 69.7% and 64.4% included experiences, respectively, with no significant difference in recall. Disconnected dream-like experiences and memory incorporation of the research setting occurred equally often in both states, while awareness was rare. The findings suggest that both states involve disconnected conscious experiences with similar recall frequencies and content.
British Journal of Anaesthesia
July 1, 2018
L Radek, R E Kallionpää, M Karvonen et al.
During anaesthetic-induced unresponsiveness, most people still have experiences, primarily internally generated dreaming rather than external awareness. In a study where healthy participants received stepwise infusions of dexmedetomidine or propofol, 84% of interviews conducted during periods of unresponsiveness contained reports of experiences (90% for dexmedetomidine, 74% for propofol). Internally generated experiences (dreaming) dominated 86% of reports, while externally generated experiences (awareness) were rare and linked to brief arousals. Participants receiving dexmedetomidine reported dreaming and awareness more often than those receiving propofol and recognized emotional sounds better (42% vs 15%), though none spontaneously mentioned sounds. Anaesthetic-induced unresponsiveness does not necessarily induce unconsciousness or disconnectedness.