A qualitative and quantitative account of patient's experiences of ketamine and its antidepressant properties.

BACKGROUND: Ketamine is central to one of the most rapidly growing areas of neuroscientific research into novel treatments for depression. Limited research has indicated that the psychedelic properties of ketamine may play a role in its antidepressant effects. AIM: The aim of the current study was to explore the psychedelic experiences and sustained impact of ketamine in major depressive disorder. METHODS: In the current study, ketamine (0.44 mg/kg) was administered to 32 volunteers with major depressive disorder in a crossover design with the active-placebo remifentanil, in a magnetic resonance imaging (MRI) environment. The 11-dimension altered states of consciousness questionnaire and individual qualitative interviews were used to capture the acute psychedelic experience. The Montgomery-Asberg Depression Rating Scale and further interviewing explored lasting effects. The second qualitative interview took place ⩾3 weeks post-ketamine. RESULTS: Greater antidepressant response (reduction in Montgomery-Asberg Depression Rating Scale at 24 h) correlated with the 11-dimension altered states of consciousness dimensions: spirituality, experience of unity, and insight. The first qualitative interview revealed that all participants experienced perceptual changes. Additional themes emerged including loss of control and emotional and mood changes. The final interview showed evidence of a psychedelic afterglow, and changes to perspective on life, people, and problems, as well as changes to how participants felt about their depression and treatments. CONCLUSIONS: The current study provides preliminary evidence for a role of the psychedelic experience and afterglow in ketamine's antidepressant properties. Reflexive thematic analysis provided a wealth of information on participants' experience of the study and demonstrated the psychedelic properties of ketamine are not fully captured by commonly used questionnaires.

Ketamine improves short-term plasticity in depression by enhancing sensitivity to prediction errors.

Major depressive disorder negatively impacts the sensitivity and adaptability of the brain's predictive coding framework. The current electroencephalography study into the antidepressant properties of ketamine investigated the downstream effects of ketamine on predictive coding and short-term plasticity in thirty patients with depression using the auditory roving mismatch negativity (rMMN). The rMMN paradigm was run 3-4 h after a single 0.44 mg/kg intravenous dose of ketamine or active placebo (remifentanil infused to a target plasma concentration of 1.7 ng/mL) in order to measure the neural effects of ketamine in the period when an improvement in depressive symptoms emerges. Depression symptomatology was measured using the Montgomery-Asberg Depression Rating Scale (MADRS); 70% of patients demonstrated at least a 50% reduction their MADRS global score. Ketamine significantly increased the MMN and P3a event related potentials, directly contrasting literature demonstrating ketamine's acute attenuation of the MMN. This effect was only reliable when all repetitions of the post-deviant tone were used. Dynamic causal modelling showed greater modulation of forward connectivity in response to a deviant tone between right primary auditory cortex and right inferior temporal cortex, which significantly correlated with antidepressant response to ketamine at 24 h. This is consistent with the hypothesis that ketamine increases sensitivity to unexpected sensory input and restores deficits in sensitivity to prediction error that are hypothesised to underlie depression. However, the lack of repetition suppression evident in the MMN evoked data compared to studies of healthy adults suggests that, at least within the short term, ketamine does not improve deficits in adaptive internal model calibration.

The videoscopic view may not be significantly superior to the directly sighted peroral view during Macintosh-style videolaryngoscopy: a randomized equivalence cadaver trial.

PURPOSE: Videolaryngoscopy is widely believed to give a superior view to that obtained by direct laryngoscopy. Published literature suggests this benefit extends to both hyper-angulated and Macintosh-style videolaryngoscopes. Notwithstanding, our clinical experience shows that the videoscopic view with a Macintosh-style videolaryngoscope is often no different or only marginally better than the directly sighted peroral view. METHODS: A human cadaver equivalence study was performed in which four experienced laryngoscopists obtained pre-assigned laryngeal views by direct sighting using the single-use Macintosh blades of the GlideScope® Spectrum™ (GS) DirectView Macintosh (DVM) and C-MAC®S videolaryngoscopes. Blinded to the laryngoscopist's view, two independent observers rated the videoscopic view presented on the proximal video monitor at the same time. Directly sighted and videoscopic views obtained by the laryngoscopist and video scorers were recorded on a visual analogue scale (VAS) for each device as the primary outcome measures and compared. RESULTS: On the VAS, the C-MAC®S videoscopic view revealed only approximately 0.9% more (99% confidence interval [CI], -2.5% to 4.3%) of the laryngeal inlet than the directly sighted view. Using GS DVM, the videoscopic view revealed 6.7% (99% CI, 2.3% to 11.0%) more of the laryngeal inlet than the directly sighted view. Although results for the GS DVM achieved statistical significance, neither device gave a clinically significantly improved videoscopic view compared with the directly sighted peroral view. CONCLUSION: This study failed to corroborate previously published findings of a clinically significantly improved videoscopic view compared with direct peroral sighting using Macintosh-style videolaryngoscopes. Further study of this class of device is warranted in human subjects.

RéSUMé: OBJECTIF: La vidéolaryngoscopie est considérée par beaucoup comme une modalité offrant une visualisation supérieure à celle obtenue par laryngoscopie directe. Selon la littérature publiée, cet avantage s'étendrait tant aux vidéolaryngoscopes hyper-angulés qu'aux vidéolaryngoscopes de style Macintosh. Ceci dit, notre expérience clinique montre que la visualisation par vidéoscopie obtenue à l'aide d'un vidéolaryngoscope de style Macintosh est souvent similaire ou seulement légèrement meilleure à une visualisation per-orale directe. MéTHODE: Une étude d'équivalence sur cadavre humain a été réalisée dans laquelle quatre opérateursexpérimentés en laryngoscopies ont obtenu des vues laryngées pré-assignées par visualisation directe à l'aide de lames de Macintosh à usage unique avec unDirectView Macintosh (DVM) GlideScope® Spectrum™ (GS) et un vidéolaryngoscope C-MAC®S. Sans avoir accès à la visualisation de l'opérateur, deux observateurs indépendants ont simultanémentévalué la visualisation vidéoscopique présentée sur le moniteur vidéo proximal. Les visualisations directes et vidéoscopiques obtenues par l'opérateur et les évaluateurs des vidéos ont été enregistrées sur une échelle visuelle analogique (EVA) pour chaque dispositif en tant que critère d'évaluation principal, puis comparées. RéSULTATS: Sur l'EVA, la visualisation vidéoscopique obtenue avec le C-MAC®S n'a montré qu'approximativement 0,9 % de plus (intervalle de confiance [IC] 99 %, -2,5 % à 4,3 %) de l'orifice laryngé que la visualisation directe. Avec le GS DVM, la visualisation vidéoscopique a révélé 6,7 % (IC 99 %, 2,3 % à 11,0 %) de plus de l'orifice laryngé que la visualisation directe. Bien que les résultats obtenus avec le GS DVM aient atteint une signification statistique, aucun dispositif n'a permis d'obtenir une visualisation vidéoscopique significativement améliorée d'un point de vue clinique par rapport à la visualisation per-orale directe. CONCLUSION: Cette étude n'est pas parvenue à corroborer les résultats précédemment publiés d'une visualisation vidéoscopique améliorée et cliniquement significative avec les vidéolaryngoscopes de style Macintosh par rapport à une visualisation per-orale directe. Des recherches supplémentaires sur cette classe de dispositifs sont nécessaires chez des sujets humains.

Ketamine Enhances Visual Sensory Evoked Potential Long-term Potentiation in Patients With Major Depressive Disorder.

BACKGROUND: The rapid-acting clinical effects of ketamine as a novel treatment for depression along with its complex pharmacology have made it a growing research area. One of the key mechanistic hypotheses for how ketamine works to alleviate depression is by enhancing long-term potentiation (LTP)-mediated neural plasticity. METHODS: The objective of this study was to investigate the plasticity hypothesis in 30 patients with depression noninvasively using visual LTP as an index of neural plasticity. In a double-blind, active placebo-controlled crossover trial, electroencephalography-based LTP was recorded approximately 3 to 4 hours following a single 0.44-mg/kg intravenous dose of ketamine or active placebo (1.7 ng/mL remifentanil) in 30 patients. Montgomery-Åsberg Depression Rating Scale scores were used to measure clinical symptoms. Visual LTP was measured as a change in the visually evoked potential following high-frequency visual stimulation. Dynamic causal modeling investigated the underlying neural architecture of visual LTP and the contribution of ketamine. RESULTS: Montgomery-Åsberg Depression Rating Scale scores revealed that 70% of participants experienced 50% or greater reduction in their depression symptoms within 1 day of receiving ketamine. LTP was demonstrated in the N1 (p = .00002) and P2 (p = 2.31 × 10-11) visually evoked components. Ketamine specifically enhanced P2 potentiation compared with placebo (p = .017). Dynamic causal modeling replicated the recruitment of forward and intrinsic connections for visual LTP and showed complementary effects of ketamine indicative of downstream and proplasticity modulation. CONCLUSIONS: This study provides evidence that LTP-based neural plasticity increases within the time frame of the antidepressant effects of ketamine in humans and supports the hypothesis that changes to neural plasticity may be key to the antidepressant properties of ketamine.

Modulation of simultaneously collected hemodynamic and electrophysiological functional connectivity by ketamine and midazolam.

The pharmacological modulation of functional connectivity in the brain may underlie therapeutic efficacy for several neurological and psychiatric disorders. Functional magnetic resonance imaging (fMRI) provides a noninvasive method of assessing this modulation, however, the indirect nature of the blood-oxygen level dependent signal restricts the discrimination of neural from physiological contributions. Here we followed two approaches to assess the validity of fMRI functional connectivity in developing drug biomarkers, using simultaneous electroencephalography (EEG)/fMRI in a placebo-controlled, three-way crossover design with ketamine and midazolam. First, we compared seven different preprocessing pipelines to determine their impact on the connectivity of common resting-state networks. Independent components analysis (ICA)-denoising resulted in stronger reductions in connectivity after ketamine, and weaker increases after midazolam, than pipelines employing physiological noise modelling or averaged signals from cerebrospinal fluid or white matter. This suggests that pipeline decisions should reflect a drug's unique noise structure, and if this is unknown then accepting possible signal loss when choosing extensive ICA denoising pipelines could engender more confidence in the remaining results. We then compared the temporal correlation structure of fMRI to that derived from two connectivity metrics of EEG, which provides a direct measure of neural activity. While electrophysiological estimates based on the power envelope were more closely aligned to BOLD signal connectivity than those based on phase consistency, no significant relationship between the change in electrophysiological and hemodynamic correlation structures was found, implying caution should be used when making cross-modal comparisons of pharmacologically-modulated functional connectivity.

Simultaneous EEG/fMRI recorded during ketamine infusion in patients with major depressive disorder.

A single subanaesthetic dose of ketamine rapidly alleviates the symptoms of major depressive disorder (MDD). However, few studies have investigated the acute effects of ketamine on the BOLD pharmacological magnetic resonance imaging (phMRI) response and EEG spectra. In a randomised, double-blind, active placebo-controlled crossover trial, resting-state simultaneous EEG/fMRI was collected during infusion of ketamine or active placebo (remifentanil) in 30 participants with MDD. Montgomery-Asberg depression rating scale scores showed a significant antidepressant effect of ketamine compared to placebo (69% response rate). phMRI analyses showed BOLD signal increases in the anterior cingulate and medial prefrontal cortices and sensitivity of the decrease in subgenual anterior cingulate cortex (sgACC) BOLD signal to noise correction. EEG spectral analysis showed increased theta, high beta, low and high gamma power, and decreased delta, alpha, and low beta power with differing time-courses. Low beta and high gamma power time courses explained significant variance in the BOLD signal. Interestingly, the variance explained by high gamma power was significantly associated with non-response to ketamine, but significant associations were not found for other neurophysiological markers when noise correction was implemented. The results suggest that the decrease in sgACC BOLD signal is potentially noise and unrelated to ketamine's antidepressant effect, highlighting the importance of noise correction and multiple temporal regressors for phMRI analyses. The lack of effects significantly associated with antidepressant response suggests the phMRI methodology employed was unable to detect such effects, the effect sizes are relatively small, or that other processes, e.g. neural plasticity, underlie ketamine's antidepressant effect.

Temporal dynamics of the pharmacological MRI response to subanaesthetic ketamine in healthy volunteers: A simultaneous EEG/fMRI study.

BACKGROUND: Pharmacological magnetic resonance imaging has been used to investigate the neural effects of subanaesthetic ketamine in healthy volunteers. However, the effect of ketamine has been modelled with a single time course and without consideration of physiological noise. AIMS: This study aimed to investigate ketamine-induced alterations in resting neural activity using conventional pharmacological magnetic resonance imaging analysis techniques with physiological noise correction, and a novel analysis utilising simultaneously recorded electroencephalography data. METHODS: Simultaneous electroencephalography/functional magnetic resonance imaging and physiological data were collected from 30 healthy male participants before and during a subanaesthetic intravenous ketamine infusion. RESULTS: Consistent with previous literature, we show widespread cortical blood-oxygen-level dependent signal increases and decreased blood-oxygen-level dependent signals in the subgenual anterior cingulate cortex following ketamine. However, the latter effect was attenuated by the inclusion of motion regressors and physiological correction in the model. In a novel analysis, we modelled the pharmacological magnetic resonance imaging response with the power time series of seven electroencephalography frequency bands. This showed evidence for distinct temporal time courses of neural responses to ketamine. No electroencephalography power time series correlated with decreased blood-oxygen-level dependent signal in the subgenual anterior cingulate cortex. CONCLUSIONS: We suggest the decrease in blood-oxygen-level dependent signals in the subgenual anterior cingulate cortex typically seen in the literature is the result of physiological noise, in particular cardiac pulsatility. Furthermore, modelling the pharmacological magnetic resonance imaging response with a single temporal model does not completely capture the full spectrum of neuronal dynamics. The use of electroencephalography regressors to model the response can increase confidence that the pharmacological magnetic resonance imaging is directly related to underlying neural activity.

The Role of ECMO in the "At-Risk" Tracheal Extubation: A Case Report.

Tracheal extubation requires careful planning and preparation. We present the extubation of a patient with severe ankylosing spondylitis after cervical spine surgery. We discuss the use of extracorporeal membrane oxygenation (ECMO) in this "at-risk" extubation, where our ability to oxygenate was uncertain and reintubation was predicted to be difficult. To our knowledge, ECMO has not previously been used in this context. We suggest preparing ECMO for rescue oxygenation when all other fundamental oxygenation techniques are predicted to be difficult or impossible. ECMO could be included in airway management and extubation guidelines.

Comparison of local spectral modulation, and temporal correlation, of simultaneously recorded EEG/fMRI signals during ketamine and midazolam sedation.

RATIONALE AND OBJECTIVES: The identification of biomarkers of drug action can be supported by non-invasive brain imaging techniques, such as electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), with simultaneous collection plausibly overcoming the limitations of either modality alone. Despite this, few studies have assessed the feasibility and utility of recording simultaneous EEG/fMRI in a drug study. METHODS: We used simultaneous EEG/fMRI to assess the modulation of neural activity by ketamine and midazolam, in a placebo-controlled, single-blind, three-way cross-over design. Specifically, we analysed the sensitivity and direction of the spectral effects of each modality and the temporal correlations between the modulations of power of the common EEG bands and the blood-oxygen-level-dependent (BOLD) signal. RESULTS AND CONCLUSIONS: Demonstrating feasibility, local spectral effects were similar to those found in previous non-simultaneous EEG and fMRI studies. Ketamine administration resulted in a widespread reduction of BOLD fractional amplitude of low frequency fluctuations (fALFF) and a diverse pattern of effects in the different EEG bands. Midazolam increased fALFF in occipital, parietal, and temporal areas, and frontal delta and beta EEG power. While EEG spectra were more sensitive to pharmacological modulations than the fALFF bands, there was no clear spatial relationship between the two modalities. Additionally, ketamine modulated the temporal correlation strengths between the theta EEG band and the BOLD signal, whereas midazolam altered temporal correlations with the alpha and beta bands. Taken together, these results demonstrate the utility of simultaneous recording: each modality provides unique insights, and combinatorial analyses elicit more information than separate recordings.

The use of extracorporeal membrane oxygenation in the anticipated difficult airway: a case report and systematic review.

While extracorporeal membrane oxygenation (ECMO) is an effective method of oxygenation for patients with respiratory failure, further refinement of its incorporation into airway guidelines is needed. We present a case of severe glottic stenosis from advanced thyroid carcinoma in which gas exchange was facilitated by veno-arterial ECMO prior to achieving a definitive airway. We also conducted a systematic review of the MEDLINE, EMBASE, CINAHL, and Web of Science databases, using the keywords "airway/ tracheal obstruction", "anesthesia", "extracorporeal", and "cardiopulmonary bypass" to identify reports where ECMO was initiated as the a priori method of oxygenation during difficult airway management.Thirty-six papers were retrieved discussing the use of ECMO or cardiopulmonary bypass (CPB) for the management of critical airway obstruction. Forty-five patients underwent pre-induction of anesthesia institution of CPB or ECMO for airway obstruction. The patients presenting with critical airway obstruction had a range of airway pathologies with tracheal tumours (31%), tracheal stenosis (20%), and head and neck cancers (20%) being the most common. All cases reported a favourable patient outcome with all patients surviving to hospital discharge without significant complications.While most practitioners are familiar with the fundamental airway techniques of bag-mask ventilation, supraglottic airway use, tracheal intubation, and front-of-neck airway access for oxygenation, these techniques have limitations in managing patients with pre-existing severe airway obstruction. The use of ECMO should be considered in patients with severe (or near-complete) airway obstruction secondary to anterior neck or tracheal disease. This approach can provide essential tissue oxygenation while attempts to secure a definitive airway are carried out in a controlled environment.

Transoral laser microsurgery for early laryngeal cancer.

The decision to treat patients suffering from glottic cancer with either radiotherapy or surgery is both complex and controversial. Transoral laser microsurgery is a surgical technique that offers an attractive alternative therapy for laryngeal cancer. In addition to excellent oncologic outcomes and organ preservation, the benefits of transoral laser microsurgery include low morbidity and mortality, shorter periods of hospitalization and exceptional functional results. As the evidence base for the effectiveness of laser surgery grows, transoral laser microsurgery has become established as a valid surgical option for the treatment of early laryngeal cancer. In this article we examine the surgical technique and discuss the oncologic and functional outcomes of transoral laser microsurgery. Furthermore, we offer a vision of the future of endoscopic laser surgery for the management of cancer of the larynx and the upper aerodigestive tract.