Of the first five US states with food waste bans, Massachusetts alone has reduced landfill waste.

Diverting food waste from landfills is crucial to reduce emissions and meet Paris Agreement targets. Between 2014 and 2024, nine US states banned commercial waste generators-such as grocery chains-from landfilling food waste, expecting a 10 to 15% waste reduction. However, no evaluation of these bans exists. We compile a comprehensive waste dataset covering 36 US states between 1996 and 2019 to evaluate the first five implemented state-level bans. Contrary to policy-makers' expectations, we can reject aggregate waste reductions higher than 3.2%, and we cannot reject a zero-null aggregate effect. Moreover, we cannot reject a zero-null effect for any other state except Massachusetts, which gradually achieved a 13.2% reduction. Our findings reveal the need to reassess food waste bans using Massachusetts as a benchmark for success.

Association between surgical admissions, cognition, and neurodegeneration in older people: a population-based study from the UK Biobank.

BACKGROUND: Previous studies have shown that major surgical and medical hospital admissions are associated with cognitive decline in older people (aged 40-69 years at recruitment), which is concerning for patients and caregivers. We aimed to validate these findings in a large cohort and investigate associations with neurodegeneration using MRI. METHODS: For this population-based study, we analysed data from the UK Biobank collected from March 13, 2006, to July 16, 2023, linked to the National Health Service Hospital Episode Statistics database, excluding participants with dementia diagnoses. We constructed fully adjusted models that included age, time, sex, Lancet Commission dementia risk factors, stroke, and hospital admissions with a participant random effect. Primary outcomes were hippocampal volume and white matter hyperintensities, both of which are established markers of neurodegeneration, and exploratory analyses investigated the cortical thickness of Desikan-Killiany-Tourville atlas regions. The main cognitive outcomes were reaction time, fluid intelligence, and prospective and numeric memory. Surgeries were calculated cumulatively starting from 8 years before the baseline evaluation. FINDINGS: Of 502 412 participants in the UK Biobank study, 492 802 participants were eligible for inclusion in this study, of whom 46 706 underwent MRI. Small adverse associations with cognition were found per surgery: reaction time increased by 0·273 ms, fluid intelligence score decreased by 0·057 correct responses, prospective memory (scored as correct at first attempt) decreased (odds ratio 0·96 [95% CI 0·95 to 0·97]), and numeric memory maximum correct matches decreased by 0·025 in fully adjusted models. Surgeries were associated with smaller hippocampal volume (ß=-5·76 mm³ [-7·89 to -3·64]) and greater white matter hyperintensities volume (ß=100·02 mm³ [66·17 to 133·87]) in fully adjusted models. Surgeries were also associated with neurodegeneration of the insula and superior temporal cortex. INTERPRETATION: This population-based study corroborates that surgeries are generally safe but cumulatively are associated with cognitive decline and neurodegeneration. Perioperative brain health should be prioritised for older and vulnerable patients, particularly those who have multiple surgical procedures. FUNDING: The Australian and New Zealand College of Anaesthetists (ANZCA) Foundation and the University of Sydney.

International Delirium Pathophysiology & Electrophysiology Network for Data sharing (iDEPEND).

In an era of 'big data', we propose that a collaborative network approach will drive a better understanding of the mechanisms of delirium, and more rapid development of therapies. We have formed the International Delirium Pathophysiology & Electrophysiology Network for Data sharing (iDEPEND) group with a key aim to 'facilitate the study of delirium pathogenesis with electrophysiology, imaging, and biomarkers including data acquisition, analysis, and interpretation'. Our initial focus is on studies of electrophysiology as we anticipate this methodology has great potential to enhance our understanding of delirium. Our article describes this principle and is used to highlight the endeavour to the wider community as we establish key stakeholders and partnerships.

Effect of body position on transesophageal atrial pacing in dogs.

OBJECTIVE: To evaluate the effect of body position on transesophageal atrial pacing (TEAP) in dogs. STUDY DESIGN: Prospective, experimental trial. ANIMALS: A total of eight mixed-breed dogs, median body mass 25 kg (range 11-31 kg). METHODS: TEAP was performed using a 6 Fr (2 mm) pacing catheter introduced transorally and positioned in the lower esophagus in left lateral recumbency. The catheter was withdrawn in 5 mm increments until successful TEAP. The minimum pacing threshold (MPT) was determined at each 5 mm increment until atrial capture could not be achieved at a maximal pulse amplitude of 40 mA. The zone of capture (ZOC) was the total distance over which TEAP was achieved. The same process was repeated in right lateral, ventral and dorsal recumbency. A linear mixed model was used to assess the impact of body position on TEAP and ZOC. RESULTS: TEAP was achieved in all body positions. There was significant random effect of individual dogs on ZOC (p = 0.048) but not on MPT (p = 0.109). MPT was 11.56 ± 8.65 mA (mean ± SD), 8.43 ± 2.29 mA, 10.63 ± 6.91 mA and 10 ± 7.44 mA for dorsal, left and right lateral, and ventral recumbency, respectively. ZOC was 5.12 ± 2.08 cm, 6.35 ± 2.41 cm, 5.94 ± 3.23 cm and 5.31 ± 2.2 cm for dorsal, left lateral and right lateral, and ventral recumbency, respectively. Neither ZOC (p = 0.363) nor MPT (p = 0.716) varied significantly between body positions. CONCLUSIONS AND CLINICAL RELEVANCE: TEAP can be performed successfully in all body positions in dogs. Body position did not significantly influence MPT or ZOC values for TEAP. Further studies are needed to compare the efficacy of TEAP with the efficacy of standard pharmacological therapy for management of bradycardia during general anesthesia in dogs.

Mental illness comorbidity significantly impacts surgical outcomes for emergency surgical patients.

BACKGROUND: Whilst both mental illness comorbidity and the delivery of emergency surgery are commonplace in Australia, there is little evidence investigating any link between them. As such, this study examines the emergency surgical outcomes for patients with mental illness compared to other surgical patients within the Australian public surgical system. METHODS: Retrospective cohort study involving adult emergency and elective surgical patients treated at three public hospitals in Sydney, Australia between 2018 and 2019. Patients were identified using ICD-10 diagnosis codes, and grouped by those with decompensated mental illness, chronic depression, or those without mental illness. Outcome measures included those within the emergency department (ED), along with in-hospital mortality and surgical outcomes. RESULTS: Of 48 338 total patients, 31 890 (66.0%) had elective and 16 448 (34.0%) had emergency surgery. For patients with decompensated mental illness, only 228 (0.7%) had elective whilst 425 (2.6%) had emergency surgery. Their outcomes for this surgery type included being triaged significantly higher (Cat 1 or 2, 34% vs. 15%) and longer ED stays (8.3 vs. 6.6 h). They also had significantly more post-operative complications (26% vs. 8%) and total days in hospital (33.8 vs. 8.5 days). There was no significant difference for in-hospital mortality. CONCLUSION: Patients with mental illness are significantly more likely to have emergency surgery including presenting to the ED with more acute physical illness and to experience worse surgical outcomes compared to other surgical patients for every measure analyzed except mortality. There is considerable opportunity to further investigate how these differences might be improved.

The Delphi Delirium Management Algorithms. A practical tool for clinicians, the result of a modified Delphi expert consensus approach.

Delirium is common in hospitalised patients, and there is currently no specific treatment. Identifying and treating underlying somatic causes of delirium is the first priority once delirium is diagnosed. Several international guidelines provide clinicians with an evidence-based approach to screening, diagnosis and symptomatic treatment. However, current guidelines do not offer a structured approach to identification of underlying causes. A panel of 37 internationally recognised delirium experts from diverse medical backgrounds worked together in a modified Delphi approach via an online platform. Consensus was reached after five voting rounds. The final product of this project is a set of three delirium management algorithms (the Delirium Delphi Algorithms), one for ward patients, one for patients after cardiac surgery and one for patients in the intensive care unit.

Study protocol: Cerebral characterization of sensory gating in disconnected dreaming states during propofol anesthesia using fMRI.

Background: Disconnected consciousness describes a state in which subjective experience (i.e., consciousness) becomes isolated from the external world. It appears frequently during sleep or sedation, when subjective experiences remain vivid but are unaffected by external stimuli. Traditional methods of differentiating connected and disconnected consciousness, such as relying on behavioral responsiveness or on post-anesthesia reports, have demonstrated limited accuracy: unresponsiveness has been shown to not necessarily equate to unconsciousness and amnesic effects of anesthesia and sleep can impair explicit recollection of events occurred during sleep/sedation. Due to these methodological challenges, our understanding of the neural mechanisms underlying sensory disconnection remains limited. Methods: To overcome these methodological challenges, we employ a distinctive strategy by combining a serial awakening paradigm with auditory stimulation during mild propofol sedation. While under sedation, participants are systematically exposed to auditory stimuli and questioned about their subjective experience (to assess consciousness) and their awareness of the sounds (to evaluate connectedness/disconnectedness from the environment). The data collected through interviews are used to categorize participants into connected and disconnected consciousness states. This method circumvents the requirement for responsiveness in assessing consciousness and mitigates amnesic effects of anesthesia as participants are questioned while still under sedation. Functional MRI data are concurrently collected to investigate cerebral activity patterns during connected and disconnected states, to elucidate sensory disconnection neural gating mechanisms. We examine whether this gating mechanism resides at the thalamic level or results from disruptions in information propagation to higher cortices. Furthermore, we explore the potential role of slow-wave activity (SWA) in inducing disconnected consciousness by quantifying high-frequency BOLD oscillations, a known correlate of slow-wave activity. Discussion: This study represents a notable advancement in the investigation of sensory disconnection. The serial awakening paradigm effectively mitigates amnesic effects by collecting reports immediately after regaining responsiveness, while still under sedation. Ultimately, this research holds the potential to understand how sensory gating is achieved at the neural level. These biomarkers might be relevant for the development of sensitive anesthesia monitoring to avoid intraoperative connected consciousness and for the assessment of patients suffering from pathologically reduced consciousness. Clinical trial registration: European Union Drug Regulating Authorities Clinical Trials Database (EudraCT), identifier 2020-003524-17.

Update of the European Society of Anaesthesiology and Intensive Care Medicine evidence-based and consensus-based guideline on postoperative delirium in adult patients

Postoperative delirium (POD) remains a common, dangerous and resource-consuming adverse event but is often preventable. The whole peri-operative team can play a key role in its management. This update to the 2017 ESAIC Guideline on the prevention of POD is evidence-based and consensus-based and considers the literature between 01 April 2015, and 28 February 2022. The search terms of the broad literature search were identical to those used in the first version of the guideline published in 2017. POD was defined in accordance with the DSM-5 criteria. POD had to be measured with a validated POD screening tool, at least once per day for at least 3 days starting in the recovery room or postanaesthesia care unit on the day of surgery or, at latest, on postoperative day 1. Recent literature confirmed the pathogenic role of surgery-induced inflammation, and this concept reinforces the positive role of multicomponent strategies aimed to reduce the surgical stress response. Although some putative precipitating risk factors are not modifiable (length of surgery, surgical site), others (such as depth of anaesthesia, appropriate analgesia and haemodynamic stability) are under the control of the anaesthesiologists. Multicomponent preoperative, intra-operative and postoperative preventive measures showed potential to reduce the incidence and duration of POD, confirming the pivotal role of a comprehensive and team-based approach to improve patients' clinical and functional status.

Changes in Intrinsic Connectivity Networks Topology Across Levels of Dexmedetomidine-Induced Alteration of Consciousness.

BACKGROUND: Human consciousness is generally thought to emerge from the activity of intrinsic connectivity networks (resting-state networks [RSNs]) of the brain, which have topological characteristics including, among others, graph strength and efficiency. So far, most functional brain imaging studies in anesthetized subjects have compared wakefulness and unresponsiveness, a state considered as corresponding to unconsciousness. Sedation and general anesthesia not only produce unconsciousness but also phenomenological states of preserved mental content and perception of the environment (connected consciousness), and preserved mental content but no perception of the environment (disconnected consciousness). Unresponsiveness may be seen during unconsciousness, but also during disconnectedness. Deep dexmedetomidine sedation is frequently a state of disconnected consciousness. In this study, we were interested in characterizing the RSN topology changes across 4 different and steady-state levels of dexmedetomidine-induced alteration of consciousness, namely baseline (Awake, drug-free state), Mild sedation (drowsy, still responding), Deep sedation (unresponsive), and Recovery, with a focus on changes occurring between a connected consciousness state and an unresponsiveness state. METHODS: A functional magnetic resonance imaging database acquired in 14 healthy volunteers receiving dexmedetomidine sedation was analyzed using a method combining independent component analysis and graph theory, specifically looking at changes in connectivity strength and efficiency occurring during the 4 above-mentioned dexmedetomidine-induced altered consciousness states. RESULTS: Dexmedetomidine sedation preserves RSN architecture. Unresponsiveness during dexmedetomidine sedation is mainly characterized by a between-networks graph strength alteration and within-network efficiency alteration of lower-order sensory RSNs, while graph strength and efficiency in higher-order RSNs are relatively preserved. CONCLUSIONS: The differential dexmedetomidine-induced RSN topological changes evidenced in this study may be the signature of inadequate processing of sensory information by lower-order RSNs, and of altered communication between lower-order and higher-order networks, while the latter remain functional. If replicated in an experimental paradigm distinguishing, in unresponsive subjects, disconnected consciousness from unconsciousness, such changes would sustain the hypothesis that disconnected consciousness arises from altered information handling by lower-order sensory networks and altered communication between lower-order and higher-order networks, while the preservation of higher-order networks functioning allows for an internally generated mental content (or dream).

Update of the European Society of Anaesthesiology and Intensive Care Medicine evidence-based and consensus-based guideline on postoperative delirium in adult patients.

Postoperative delirium (POD) remains a common, dangerous and resource-consuming adverse event but is often preventable. The whole peri-operative team can play a key role in its management. This update to the 2017 ESAIC Guideline on the prevention of POD is evidence-based and consensus-based and considers the literature between 01 April 2015, and 28 February 2022. The search terms of the broad literature search were identical to those used in the first version of the guideline published in 2017. POD was defined in accordance with the DSM-5 criteria. POD had to be measured with a validated POD screening tool, at least once per day for at least 3 days starting in the recovery room or postanaesthesia care unit on the day of surgery or, at latest, on postoperative day 1. Recent literature confirmed the pathogenic role of surgery-induced inflammation, and this concept reinforces the positive role of multicomponent strategies aimed to reduce the surgical stress response. Although some putative precipitating risk factors are not modifiable (length of surgery, surgical site), others (such as depth of anaesthesia, appropriate analgesia and haemodynamic stability) are under the control of the anaesthesiologists. Multicomponent preoperative, intra-operative and postoperative preventive measures showed potential to reduce the incidence and duration of POD, confirming the pivotal role of a comprehensive and team-based approach to improve patients' clinical and functional status.

Delirium is associated with loss of feedback cortical connectivity.

INTRODUCTION: Post-operative delirium (POD) is associated with increased morbidity and mortality but is bereft of treatments, largely due to our limited understanding of the underlying pathophysiology. We hypothesized that delirium reflects a disturbance in cortical connectivity that leads to altered predictions of the sensory environment. METHODS: High-density electroencephalogram recordings during an oddball auditory roving paradigm were collected from 131 patients. Dynamic causal modeling (DCM) analysis facilitated inference about the neuronal connectivity and inhibition-excitation dynamics underlying auditory-evoked responses. RESULTS: Mismatch negativity amplitudes were smaller in patients with POD. DCM showed that delirium was associated with decreased left-sided superior temporal gyrus (l-STG) to auditory cortex feedback connectivity. Feedback connectivity also negatively correlated with delirium severity and systemic inflammation. Increased inhibition of l-STG, with consequent decreases in feed-forward and feed-back connectivity, occurred for oddball tones during delirium. DISCUSSION: Delirium is associated with decreased feedback cortical connectivity, possibly resulting from increased intrinsic inhibitory tone. HIGHLIGHTS: Mismatch negativity amplitude was reduced in patients with delirium. Patients with postoperative delirium had increased feedforward connectivity before surgery. Feedback connectivity was diminished from left-side superior temporal gyrus to left primary auditory sensory area during delirium. Feedback connectivity inversely correlated with inflammation and delirium severity.

Evaluation of putative signatures of consciousness using specific definitions of responsiveness, connectedness, and consciousness.

BACKGROUND: Understanding the neural correlates of consciousness has important ramifications for the theoretical understanding of consciousness and for clinical anaesthesia. A major limitation of prior studies is the use of responsiveness as an index of consciousness. We identified a collection of measures derived from unresponsive subjects and more specifically their association with consciousness (any subjective experience) or connectedness (specific experience of environmental stimuli). METHODS: Using published data generated through the UNderstanding Consciousness Connectedness and Intra-Operative Unresponsiveness Study (NCT03284307), we evaluated 10 previously published resting-state EEG-based measures that were derived using unresponsiveness as a proxy for unconsciousness. Measures were tested across dexmedetomidine and propofol sedation and natural sleep. These markers represent the complexity, connectivity, cross-frequency coupling, graph theory, and power spectrum measures. RESULTS: Although many of the proposed markers were associated with consciousness per se (reported subjective experience), none were specific to consciousness alone; rather, each was also associated with connectedness (i.e. awareness of the environment). In addition, multiple markers showed no association with consciousness and were associated only with connectedness. Of the markers tested, loss of normalised-symbolic transfer entropy (front to back) was associated with connectedness across all three experimental conditions, whereas the transition from disconnected consciousness to unconsciousness was associated with significant decreases in permutation entropy and spectral exponent (P<0.05 for all conditions). CONCLUSIONS: None of the proposed EEG-based neural correlates of unresponsiveness corresponded solely to consciousness, highlighting the need for a more conservative use of the term (un)consciousness when assessing unresponsive participants. CLINICAL TRIAL REGISTRATION: NCT03284307.

Risk of Mortality Following Surgery in Patients With a Previous Cardiovascular Event.

Importance: There is a lack of consensus regarding the interval of time-dependent postoperative mortality risk following acute coronary syndrome or stroke. Objective: To determine the magnitude and duration of risk associated with the time interval between a preoperative cardiovascular event and 30-day postoperative mortality. Design, Setting, and Participants: This is a longitudinal retrospective population-based cohort study. This study linked data from the Hospital Episode Statistics for National Health Service England, Myocardial Ischaemia National Audit Project and the Office for National Statistics mortality registry. All adults undergoing a National Health Service-funded noncardiac, nonneurologic surgery in England between April 1, 2007, and March 31, 2018, registered in Hospital Episode Statistics Admitted Patient Care were included. Data were analyzed from July 2021 to July 2022. Exposure: The time interval between a previous cardiovascular event (acute coronary syndrome or stroke) and surgery. Main Outcomes and Measures: The primary outcome was 30-day all-cause mortality. Secondary outcomes were postoperative mortality at 60, 90, and 365 days. Multivariable logistic regression models with restricted cubic splines were used to estimate adjusted odds ratios. Results: There were 877 430 patients with and 20 582 717 without a prior cardiovascular event (overall mean [SD] age, 53.4 [19.4] years; 11 577 157 [54%] female). Among patients with a previous cardiovascular event, the time interval associated with increased risk of postoperative mortality was surgery within 11.3 months (95% CI, 10.8-11.7), with subgroup risks of 14.2 months before elective surgery (95% CI, 13.3-15.3) and 7.3 months for emergency surgery (95% CI, 6.8-7.8). Heterogeneity in these timings was noted across many surgical specialties. The time-dependent risk intervals following stroke and myocardial infarction were similar, but the absolute risk was greater following a stroke. Regarding surgical urgency, the risk of 30-day mortality was higher in those with a prior cardiovascular event for emergency surgery (adjusted hazard ratio, 1.35; 95% CI, 1.34-1.37) and an elective procedure (adjusted hazard ratio, 1.83; 95% CI, 1.78-1.89) than those without a prior cardiovascular event. Conclusions and Relevance: In this study, surgery within 1 year of an acute coronary syndrome or stroke was associated with increased postoperative mortality before reaching a new baseline, particularly for elective surgery. This information may help clinicians and patients balance deferring the potential benefits of the surgery against the desire to avoid increased mortality from overly expeditious surgery after a recent cardiovascular event.

Neuronal connected burst cascades bridge macroscale adaptive signatures across arousal states.

The human brain displays a rich repertoire of states that emerge from the microscopic interactions of cortical and subcortical neurons. Difficulties inherent within large-scale simultaneous neuronal recording limit our ability to link biophysical processes at the microscale to emergent macroscopic brain states. Here we introduce a microscale biophysical network model of layer-5 pyramidal neurons that display graded coarse-sampled dynamics matching those observed in macroscale electrophysiological recordings from macaques and humans. We invert our model to identify the neuronal spike and burst dynamics that differentiate unconscious, dreaming, and awake arousal states and provide insights into their functional signatures. We further show that neuromodulatory arousal can mediate different modes of neuronal dynamics around a low-dimensional energy landscape, which in turn changes the response of the model to external stimuli. Our results highlight the promise of multiscale modelling to bridge theories of consciousness across spatiotemporal scales.

Similarities in consciousness occurring during sleep and sedation.

The subjective experiences of sedation or anaesthesia are underexplored. A recent study by Valli and colleagues (Br J Anaesth 2023; 131: 348-59) found similar frequency and content of recalled experiences after both non-rapid eye movement sleep and target-controlled infusions of propofol or dexmedetomidine titrated to verbal unresponsiveness. The authors find that the phenomenological similarities between consciousness during sleep and sedation mirror their physiological similarities. Intriguingly, in this small sample, conscious experience did not show a dose-dependent response suggesting other factors are important in determining the propensity for consciousness under sedation.

Depth of sedation with dexmedetomidine increases transcranial magnetic stimulation-evoked potential amplitude non-linearly.

BACKGROUND: Cortical excitability is higher in unconsciousness than in wakefulness, but it is unclear how this relates to anaesthesia. We investigated cortical excitability in response to dexmedetomidine, the effects of which are not fully known. METHODS: We recorded transcranial magnetic stimulation (TMS) and EEG in frontal and parietal cortex of 20 healthy subjects undergoing dexmedetomidine sedation in four conditions (baseline, light sedation, deep sedation, recovery). We used the first component (0-30 ms) of the TMS-evoked potential (TEP) to measure cortical excitability (amplitude), slope, and positive and negative peak latencies (collectively, TEP indices). We used generalised linear mixed models to test the effect of condition, brain region, and responsiveness on TEP indices. RESULTS: Compared with baseline, amplitude in the frontal cortex increased by 6.52 µV (P<0.001) in light sedation, 4.55 µV (P=0.003) in deep sedation, and 5.03 µV (P<0.001) in recovery. Amplitude did not change in the parietal cortex. Compared with baseline, slope increased in all conditions (P<0.02) in the frontal but not parietal cortex. The frontal cortex showed 5.73 µV higher amplitude (P<0.001), 0.63 µV ms-1 higher slope (P<0.001), and 2.2 ms shorter negative peak latency (P=0.001) than parietal areas. Interactions between dexmedetomidine and region had effects over amplitude (P=0.004) and slope (P=0.009), with both being higher in light sedation, deep sedation, and recovery compared with baseline. CONCLUSIONS: Transcranial magnetic stimulation-evoked potential amplitude changes non-linearly as a function of depth of sedation by dexmedetomidine, with a region-specific paradoxical increase. Future research should investigate other anaesthetics to elucidate the link between cortical excitability and depth of sedation.

Subanaesthetic doses of ketamine reduce but do not eliminate predictive coding responses: implications for mechanisms of sensory disconnection.

BACKGROUND: Sensory disconnection is a key feature of sleep and anaesthesia. We have proposed that predictive coding offers a framework for understanding the mechanisms of disconnection. Low doses of ketamine that do not induce disconnection should thus diminish predictive coding, but not abolish it. METHODS: Ketamine was administered to 14 participants up to a blood concentration of 0.3 µg ml-1 Participants were played a series of tones comprising a roving oddball sequence while electroencephalography evoked response potentials were recorded. We fit a Bayesian observer model to the tone sequence, correlating neural activity with the prediction errors generated by the model using linear mixed effects models and cluster-based statistics. RESULTS: Ketamine modulated prediction errors associated with the transition of one tone to the next (transitional probability), but not how often tones changed (environmental volatility), of the system. Transitional probability was reduced when blood concentrations of ketamine were increased to 0.2-0.3 µg ml-1 (96-208 ms, P=0.003); however, correlates of prediction error were still evident in the electroencephalogram (124-168 ms, P=0.003). Prediction errors related to environmental volatility were associated with electroencephalographic activity before ketamine (224-284 ms, P=0.028) and during 0.2-0.3 µg ml-1 ketamine (108-248 ms, P=0.003). At this subanaesthetic dose, ketamine did not exert a dose-dependent modulation of prediction error. CONCLUSIONS: Subanaesthetic dosing of ketamine reduced correlates of predictive coding but did not eliminate them. Future studies should evaluate whether states of sensory disconnection, including anaesthetic doses of ketamine, are associated with a complete absence of predictive coding responses. CLINICAL TRIAL REGISTRATION: NCT03284307.

Impact of female sex on anaesthetic awareness, depth, and emergence: a systematic review and meta-analysis.

BACKGROUND: Suggested anaesthetic dose ranges do not differ by sex, likely because of limited studies comparing sexes. Our objective was to systematically synthesise studies with outcomes of unintended anaesthesia awareness under anaesthesia, intraoperative connected consciousness, time to emergence from anaesthesia, and dosing to achieve adequate depth of anaesthesia, and to compare between females and males. METHODS: Studies were identified from MEDLINE, Embase, and the Cochrane library databases until August 2, 2022. Controlled clinical trials (randomised/non-randomised) and prospective cohort studies that reported outcomes by sex were included. Results were synthesised by random effects meta-analysis where possible, or narrative form. RESULTS: Of the 19 749 studies identified, 64 (98 243 participants; 53 143 females and 45 100 males) were eligible for inclusion, and 44 citations contributed to meta-analysis. Females had a higher incidence of awareness with postoperative recall (33 studies, odds ratio 1.38, 95% confidence interval [CI] 1.09-1.75) and connected consciousness during anaesthesia (three studies, OR 2.09, 95% CI 1.04-4.23) than males. Time to emergence was faster in females, including time to eye-opening (10 studies, mean difference -2.28 min, 95% CI -3.58 to -0.98), and time to response to command (six studies, mean difference -2.84 min, 95% CI -4.07 to -1.62). Data on depth of anaesthesia were heterogenous, limiting synthesis to a qualitative review which did not identify sex differences. CONCLUSIONS: Female sex was associated with a greater incidence of awareness under general anaesthesia, and faster emergence from anaesthesia. These data suggest reappraisal of anaesthetic care, including whether similar drug dosing for females and males represents best care. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022336087.