Evaluation of microglia in a rodent model of Parkinson's disease primed with L-DOPA after sub-anesthetic ketamine treatment.

Parkinson's disease (PD) is a neurodegenerative disease caused by the death of dopaminergic neurons in the substantia nigra pars compacta (SNpc), characterized by motor dysfunction. While PD symptoms are well treated with L-DOPA, continuous use can cause L-DOPA-induced dyskinesia (LID). We have previously demonstrated that sub-anesthetic ketamine attenuated LID development in rodents, measured by abnormal involuntary movements (AIMs), and reduced the density of maladaptive striatal dendritic mushroom spines. Microglia may play a role by phagocytosing maladaptive neuronal spines. In this exploratory study, we hypothesized that ketamine would prevent AIMs and change microglia ramified morphology - an indicator of a microglia response. Unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats were primed with daily injections of L-DOPA for 14 days, treated on days 0 and 7 for 10-hours with sub-anesthetic ketamine (i.p.), and we replicated that this attenuated LID development. We further extended our prior work by showing that while ketamine treatment did lead to an increase of striatal interleukin-6 in dyskinetic rats, indicating a modulation of an inflammatory response, it did not change microglia number or morphology in the dyskinetic striatum. Yet an increase of CD68 in the SNpc of 6-OHDA-lesioned hemispheres post-ketamine indicates increased microglia phagocytosis suggestive of a lingering microglial response to 6-OHDA injury in the SNpc pointing to possible anti-inflammatory action in the PD model in addition to anti-dyskinetic action. In conclusion, we provide further support for sub-anesthetic ketamine treatment of LID. The mechanisms of action for ketamine, specifically related to inflammation and microglia phagocytic functions, are emerging, and require further examination.

Topical ketamine as a local anesthetic agent in reducing venipuncture pain: A randomized controlled trial.

AIM: Pain control is an important aspect of ED patient management, and there are many different protocols used around the world influenced by both availability of local resources as well as staff competency and experience. This study aims to evaluate the use of topical ketamine in acute pain reduction by directly comparing it to lidocaine-prilocaine (EMLA) cream. MATERIALS AND METHODS: In this randomized clinical trial, 300 adult patients classified as level 4 or 5 by ESI triage system were enrolled. These patients were divided randomly into three groups. The site of venipuncture was covered with 2 g of topical ketamine cream 10% in group one, 2 g of 5% EMLA cream in group two, and finally, in group 3 (control group), was covered with placebo (2 g of cold cream). The primary end point of the study was reported pain severity with secondary end points being onset of local anesthesia as well as any side effects noted. RESULTS: The data gathered showed pain score during venipuncture in both intervention groups were significantly lower when compared to the control group (P < 0.05). However, pain score did not differ between the 2 intervention groups (P = 0.395). There was no statistically significant difference between the ketamine or EMLA in onset of local anesthesia (P = 0.419). We noted itching and irritation was significantly higher in the EMLA group when compared to ketamine(P < 0.05). CONCLUSION: This study showed that local cutaneous ketamine is as effective as EMLA in relieving pain during venipuncture.

Outcomes for 298 breastfed neonates whose mothers received ketamine and diazepam for postpartum tubal ligation in a resource-limited setting.

BACKGROUND: Anesthesia in lactating women is frequently indicated for time-sensitive procedures such as postpartum tubal ligation. Ketamine and diazepam are two of the most commonly used anesthetic agents in low resource settings, but their safety profile in lactating women has not been established. METHODS: Medical records of post-partum tubal ligations between 2013 and 2018 at clinics of the Shoklo Malaria Research Unit were reviewed for completeness of key outcome variables. Logistic regression identified presence or absence of associations between drug doses and adverse neonatal outcomes: clinically significant weight loss (≥95th percentile) and neonatal hyperbilirubinemia requiring phototherapy. RESULTS: Of 358 records reviewed, 298 were lactating women with singleton, term neonates. There were no severe outcomes in mothers or neonates. On the first postoperative day 98.0% (290/296) of neonates were reported to be breastfeeding well and 6.4% (19/298) had clinically significant weight loss. Phototherapy was required for 13.8% (41/298) of neonates. There was no association between either of the outcomes and increasing ketamine doses (up to 3.8 mg/kg), preoperative oral diazepam (5 mg), or increasing lidocaine doses (up to 200 mg). Preoperative oral diazepam resulted in lower doses of intraoperative anesthetics. Doses of intravenous diazepam above 0.1 mg/kg were associated with increased risk (adjusted odds ratio per 0.1 mg/kg increase, 95%CI) of weight loss (1.95, 95%CI 1.13-3.35, p = 0.016) and jaundice requiring phototherapy (1.87, 95%CI 1.11-3.13, p = 0.017). CONCLUSIONS: In resource-limited settings ketamine use appears safe in lactating women and uninterrupted breastfeeding should be encouraged and supported. Preoperative oral diazepam may help reduce intraoperative anesthetic doses, but intravenous diazepam should be used with caution and avoided in high doses in lactating women.

[Psychiatry]. / Psychiatrie.

The Covid-19 pandemic has a major impact on psychiatry by its social consequences and possible direct effect of certain forms of Covid-19 on mental health. During this crisis, the accessibility of technology meets a state of necessity, which has propelled telepsychiatry from the shadows into the light. The contribution of several technologies (i.e. virtual reality, actigraphy, computational psychiatry) combining clinical data and neuroscience underlines the great neurobehavioural variability even within the same diagnostic category, calling for greater precision in therapeutic offers as suggested e.g. by developments in neurofeedback. The place of intranasal esketamin in the panoply of antidepressent drug treatments for resistant depression has not yet been defined.

La pandémie de Covid-19 bouleverse la psychiatrie par ses conséquences sociales et par de possibles séquelles psychiatriques. La crise actuelle révèle l'accessibilité de technologies digitales telles que la télépsychiatrie. Des technologies comme la réalité virtuelle, l'actigraphie, la psychiatrie computationnelle combinées aux données cliniques et aux neurosciences révèlent une importante variabilité neurocomportementale même au sein d'une catégorie diagnostique donnée, invitant à une plus grande précision des traitements comme suggéré par les recherches en neurofeedback. La place de l'eskétamine intranasale dans la panoplie thérapeutique médicamenteuse de la dépression résistante doit encore être définie.

[Hydatid cyst in the cervical spinal cord complicated by potentially life-threatening difficult airway: a case report]. / Cisto hidático na medula cervical complicada por via aérea difícil com potencial risco de vida: relato de caso.

Hydatid cyst in the cervical region is an extremely rare condition that can create challenges for anesthesiologists. Timely recognition of difficult airway and preparing the management plan is crucial to avoid life-threatening complications such as hypoxic brain damage. We describe a case of difficult airway management in a patient with massive cervical hydatid cyst. We used a low-dose ketamine-propofol sedation and lidocaine spray for local oropharyngeal anesthesia. Muscular relaxants were not used, and spontaneous breathing was maintained during intubation. Recognition, assessment, and perioperative planning are essential for difficult airway management in patients with cervical hydatid cyst.

Hydatid cyst in the cervical spinal cord complicated by potentially life-threatening difficult airway: a case report / Cisto hidático na medula cervical complicada por via aérea difícil com potencial risco de vida: relato de caso

Abstract Hydatid cyst in the cervical region is an extremely rare condition that can create challenges for anesthesiologists. Timely recognition of difficult airway and preparing the management plan is crucial to avoid life-threatening complications such as hypoxic brain damage. We describe a case of difficult airway management in a patient with massive cervical hydatid cyst. We used a low-dose ketamine-propofol sedation and lidocaine spray for local oropharyngeal anesthesia. Muscular relaxants were not used, and spontaneous breathing was maintained during intubation. Recognition, assessment, and perioperative planning are essential for difficult airway management in patients with cervical hydatid cyst.

Resumo O cisto hidático na região cervical é uma condição extremamente rara que pode criar desafios para os anestesiologistas. O reconhecimento oportuno das vias aéreas difíceis e a preparação do plano de manejo são cruciais para evitar complicações com risco de vida, como danos cerebrais hipóxicos. Descrevemos um caso de difícil controle das vias aéreas em um paciente com cisto hidático cervical maciço. Utilizamos sedação com cetamina-propofol em baixa dose e spray de lidocaína para anestesia local orofaríngea. Relaxantes musculares não foram utilizados e a respiração espontânea foi mantida durante a intubação. O reconhecimento, a avaliação e o planejamento perioperatório são essenciais para o manejo difícil das vias aéreas em pacientes com cisto hidático cervical.

Pre-emptive low-dose ketamine with local anesthesia reduces postoperative morbidity after third molar surgery: a systematic review and meta-analysis / Ketamina en dosis bajas con anestesia local reduce la morbilidad postoperatoria de la cirugía del tercer molar: revisión sistemática y metanálisis

Objective: This review addresses a clinical research question related to lower third molar surgery (L3MS): does the combination of pre-emptive low-dose ketamine with local anesthesia (KLA) reduce postoperative complications compared with local anesthesia (LA) alone? Material and methods: A systematic literature search was performed to identify eligible articles by electronic searches of PubMed, Cochrane Central Register of Controlled Trials, EBSCO Library, Web of Science and grey literature through June 2019 without data or language restrictions. We analyzed all randomized controlled clinical studies (RCTs) comparing use of KLA with use of LA in L3MS regarding pain, swelling, and trismus outcomes. The quality of evidence was rated according to Cochrane's tool for assessing risk of bias. Results: Five RCTs encompassing 230 extraction sites (KLA = 115, LA = 115) were included in this study. The standardized mean difference (SMD) with the 95% confidence interval (CI) was used to synthesize the results. The data show that there were significant differences between the two groups in post-operative pain (SMD -1.464, 95% CI -1.683 to -0.949, p= 0.001) and swelling (SMD -0.450, 95% CI -0.758 to -0.142, p= 0.004, all low quality evidence). However, there was no significant difference in the trismus (SMD -0.754, CI -1.487 to -0.022, p = 0.043, very low quality evidence). Conclusion: The combination of pre-emptive low-dose ketamine with LA significantly decreased pain and swelling within the first 24 hours after L3MS compared with the control group.

Objetivo: Esta revisión aborda una pregunta de investigación clínica relacionada con la cirugía del tercer molar inferior (L3MS): ¿la combinación de ketamina preventiva en dosis bajas con anestesia local (KLA) reduce las complicaciones postoperatorias en comparación con la anestesia local (AL) sola? Material y Métodos: Se realizó una búsqueda bibliográfica sistemática para identificar artículos elegibles mediante búsquedas electrónicas en PubMed, Registro Cochrane Central de Ensayos Controlados, Biblioteca EBSCO, Web of Science y literatura gris hasta junio de 2019 sin restricciones de datos ni de idioma. Se analizaron todos los estudios clínicos controlados aleatorios (ECA) que compararon el uso de KLA con el uso de LA en L3MS con respecto a los resultados de dolor, hinchazón y trismo. La calidad de la evidencia se clasificó de acuerdo con la herramienta Cochrane para evaluar el riesgo de sesgo. Resultados: Se incluyeron en este estudio cinco ECA que abarcan 230 sitios de extracción (KLA = 115, LA = 115). La diferencia de medias estandarizada (DME) con el intervalo de confianza (IC) del 95% se utilizó para sintetizar los resultados. Los datos muestran que hubo diferencias significativas entre los dos grupos en el dolor posoperatorio (DME -1,464; IC del 95%: -1,683 a -0,949; p= 0,001) e hinchazón (DME -0,450; IC del 95%: -0,758 a -0,142, p= 0,004, todas las pruebas de baja calidad). Sin embargo, no hubo diferencias significativas en el trismo (DME -0,754; IC: -1,487 a -0,022; p= 0,043, evidencia de muy baja calidad). Conclusión: La combinación de ketamina preventiva en dosis bajas con LA disminuyó significativamente el dolor y la hinchazón dentro de las primeras 24 horas después de la L3MS en comparación con el grupo de control.

Ketamine Affects Prediction Errors about Statistical Regularities: A Computational Single-Trial Analysis of the Mismatch Negativity.

The auditory mismatch negativity (MMN) is significantly reduced in schizophrenia. Notably, a similar MMN reduction can be achieved with NMDA receptor (NMDAR) antagonists. Both phenomena have been interpreted as reflecting an impairment of predictive coding or, more generally, the "Bayesian brain" notion that the brain continuously updates a hierarchical model to infer the causes of its sensory inputs. Specifically, neurobiological interpretations of predictive coding view perceptual inference as an NMDAR-dependent process of minimizing hierarchical precision-weighted prediction errors (PEs), and disturbances of this putative process play a key role in hierarchical Bayesian theories of schizophrenia. Here, we provide empirical evidence for this theory, demonstrating the existence of multiple, hierarchically related PEs in a "roving MMN" paradigm. We applied a hierarchical Bayesian model to single-trial EEG data from healthy human volunteers of either sex who received the NMDAR antagonist S-ketamine in a placebo-controlled, double-blind, within-subject fashion. Using an unrestricted analysis of the entire time-sensor space, our trial-by-trial analysis indicated that low-level PEs (about stimulus transitions) are expressed early (102-207 ms poststimulus), while high-level PEs (about transition probability) are reflected by later components (152-199 and 215-277 ms) of single-trial responses. Furthermore, we find that ketamine significantly diminished the expression of high-level PE responses, implying that NMDAR antagonism disrupts the inference on abstract statistical regularities. Our findings suggest that NMDAR dysfunction impairs hierarchical Bayesian inference about the world's statistical structure. Beyond the relevance of this finding for schizophrenia, our results illustrate the potential of computational single-trial analyses for assessing potential pathophysiological mechanisms.

ORAL HALOPERIDOL PREMEDICATION TO REDUCE CAPTURE STRESS PRIOR TO XYLAZINE-KETAMINE ANESTHESIA IN CAPTIVE SPOTTED DEER (AXIS AXIS).

A prospective clinical trial was performed to evaluate the efficacy of haloperidol premedication prior to xylazine-ketamine anesthesia with a goal of reducing capture stress in adult male captive spotted deer (Axis axis). On the morning of the study, deer were fed a banana either containing haloperidol tablets (1 mg/kg) (haloperidol group, n = 10) or without haloperidol (placebo group, n = 10). Six hours postadministration, xylazine (3 mg/kg) and ketamine (2 mg/kg) was administered intramuscularly via a dart. Rectal temperature, heart rate, respiratory rate, and SpO2 (percent hemoglobin saturation) were recorded at 5-min intervals. Blood gas analysis was performed at time 0 (venous blood) and 10 and 20 min (arterial blood) postinduction. Serum cortisol was determined from venous blood (35 min postinduction), following which yohimbine was administered at a dose of 0.15 mg/kg intramuscular and 0.15 mg/kg intravenous. Statistical analysis of repeated measures data was performed with a two-way analysis of variance. Paired data were analyzed with a Wilcoxon rank-sum test (categorical data) or a paired t-test (continuous data). Significance was set at P ≤ 0.05, and results were expressed as mean ± SEM. There was no significant difference in induction time or recovery time between treatment groups. Rectal temperature and heart rate were significantly lower in the haloperidol group. Both groups demonstrated acidosis with venous pH being significantly lower in the placebo group when compared to the haloperidol group. Serum cortisol and arterial plasma lactate were lower in the haloperidol group indicative of reduced stress and physical exertion. Haloperidol premedication proved to be beneficial in reducing capture stress, when administered prior to xylazine-ketamine anesthesia, in spotted deer.

Ketamine Restores Thalamic-Prefrontal Cortex Functional Connectivity in a Mouse Model of Neurodevelopmental Disorder-Associated 2p16.3 Deletion.

2p16.3 deletions, involving heterozygous NEUREXIN1 (NRXN1) deletion, dramatically increase the risk of developing neurodevelopmental disorders, including autism and schizophrenia. We have little understanding of how NRXN1 heterozygosity increases the risk of developing these disorders, particularly in terms of the impact on brain and neurotransmitter system function and brain network connectivity. Thus, here we characterize cerebral metabolism and functional brain network connectivity in Nrxn1α heterozygous mice (Nrxn1α+/- mice), and assess the impact of ketamine and dextro-amphetamine on cerebral metabolism in these animals. We show that heterozygous Nrxn1α deletion alters cerebral metabolism in neural systems implicated in autism and schizophrenia including the thalamus, mesolimbic system, and select cortical regions. Nrxn1α heterozygosity also reduces the efficiency of functional brain networks, through lost thalamic "rich club" and prefrontal cortex (PFC) hub connectivity and through reduced thalamic-PFC and thalamic "rich club" regional interconnectivity. Subanesthetic ketamine administration normalizes the thalamic hypermetabolism and partially normalizes thalamic disconnectivity present in Nrxn1α+/- mice, while cerebral metabolic responses to dextro-amphetamine are unaltered. The data provide new insight into the systems-level impact of heterozygous Nrxn1α deletion and how this increases the risk of developing neurodevelopmental disorders. The data also suggest that the thalamic dysfunction induced by heterozygous Nrxn1α deletion may be NMDA receptor-dependent.

Ketofol performance to reduce postoperative emergence agitation in children undergoing adenotonsillectomy.

Background: Emergence agitation is a reformed state of mindfulness, which starts with a sudden form of anesthesia and progresses through the early repossession age. Thus, the purpose of this study is to evaluate 1:3 ketofol performance on children 3-15 years old undergoing adenotonsillectomy.Methods: A total of 60 children aged 3-15 years undergoing adenotonsillectomy were randomly allocated to receive low-dose ketamine 0.15 mg/kg followed by propofol 0.45 mg/kg i.v. ketofol (1:3) about 10 min before the end of surgery in comparison to 60 children aged 3-15 years who received only normal saline and dextrose. Anesthesia was induced and maintained with sevoflurane. Postoperative pain and EA were assessed with objective pain score (OPS) and the Pediatric Anesthesia Emergence Delirium (PAED) scale, respectively. EA was defined as a PAED 10 points. Recovery profile and postoperative complications were also recorded.Results: The incidence and severity of EA were found significantly lower in the ketofol group in comparison to the control group with a percentage of (13.33% vs 48.33%) (8% vs 15%) respectively (P < 0.05). Also, the time for interaction from anesthetic tainted to extubating in the ketofol set was significantly less than in the control group (P < 0.05). Interestingly, there are no opposing events such as nausea, laryngospasm, bronchospasm, hypotension, bradycardia, bleeding, or postoperative respiratory depression (respiratory rate: <16) were noticed in the ketofol supervision (P > 0.05). Moreover, the heart rate was meaningfully higher in the control group starting at the time of tracheal extubating in comparison to the children undergone ketofol (P < 0.05). Alert score and time from painkilling tainted till liberation from PACU showed substantial significant changes at ketofol set (P < 0.05).Conclusion: Ketofol (1:3) shows significant performance to reduce postoperative agitation in the children undergone adenotonsillectomy.

Adjuvants in clinical regional anesthesia practice: A comprehensive review.

Adjuvants are medications that work synergistically with local anesthetics to help enhance the duration and quality of analgesia in regional techniques. Regional anesthesia has become more prevalent as evidence continues to show efficacy, enhancement of patient care, increased patient satisfaction, and improved patient safety. Practitioners in the perioperative setting need to not only be familiar with regional techniques but also the medications used for them. Some examples of adjuvant medications for regional techniques include dexamethasone, alpha 2 agonists such as clonidine and dexmedetomidine, midazolam, buprenorphine, NMDA antagonists, including ketamine and magnesium, neostigmine, sodium bicarbonate, epinephrine, and non-steroidal anti-inflammatory drugs. The aim of the present investigation, therefore, is to provide a comprehensive review of the most commonly used non-opioid adjuvants in clinical practice today. Regional adjuvants can improve patient safety, increase patient satisfaction, and enhance clinical efficacy. Future studies and best practice techniques can facilitate standardization of regional anesthesia adjuvant dosing when providing nerve blocks in clinical practice.

Effects of ketamine on circadian rhythm and synaptic homeostasis in patients with treatment-resistant depression: A protocol for mechanistic studies of its rapid and sustained antidepressant actions in humans.

BACKGROUND: The breakthrough discovery has been made that a single dose of ketamine, an N-methyl-D-aspartate receptor antagonist, achieves rapid and sustained (~7 days) antidepressant activity in patients with major depressive disorder (MDD). This discovery has ushered in an exciting era of research and brought new hope for patients with MDD. However, the mechanisms underlying the specific antidepressant actions of ketamine in humans remain to be elucidated. OBJECTIVES: This study protocol was designed to test the main hypothesis that ketamine could rapidly reverse depression- and stress-associated synaptic loss and deficits in resting-state functional connectivity and that this action could be affected by circadian rhythm, in patients with treatment-resistant depression. METHODS/STUDY DESIGN: In this clinical study, adults (aged 18-65 years) with treatment-resistant depression will be randomized to intravenous administration of placebo (control group) or ketamine (0.5 mg/kg body weight) at 11 a.m. (daytime group), or 6 p.m. (nighttime group) for 24 weeks. The primary outcome will be the change from baseline to 24 weeks in the total Montgomery-Asberg Depression Rating Scale score. Brain imaging, sleep, and genetic studies, including functional magnetic resonance imaging, positron emission tomography, polysomnography, and genetic analyses, will be performed to examine whether and how ketamine can rapidly reverse deficits in synaptic function and to identify objective markers for the assessment of ketamine infusion therapy for treatment-resistant depression. CONCLUSIONS: This clinical study protocol is the first, to our knowledge, to describe the prospective testing of the hypothesis that daytime and nighttime administrations of ketamine would have different antidepressant effects. The brain imaging, sleep, and genetic findings from patients with treatment-resistant depression are expected to shed new light on the mechanisms of ketamine and its interaction with target sites in the brain, which can be used for objective evaluation of the efficacy of ketamine.

A Single Ketamine Infusion Combined With Mindfulness-Based Behavioral Modification to Treat Cocaine Dependence: A Randomized Clinical Trial.

OBJECTIVE: Research has suggested that subanesthetic doses of ketamine may work to improve cocaine-related vulnerabilities and facilitate efforts at behavioral modification. The purpose of this trial was to test whether a single ketamine infusion improved treatment outcomes in cocaine-dependent adults engaged in mindfulness-based relapse prevention. METHODS: Fifty-five cocaine-dependent individuals were randomly assigned to receive a 40-minute intravenous infusion of ketamine (0.5 mg/kg) or midazolam (the control condition) during a 5-day inpatient stay, during which they also initiated a 5-week course of mindfulness-based relapse prevention. Cocaine use was assessed through self-report and urine toxicology. The primary outcomes were end-of-study abstinence and time to relapse (defined as first use or dropout). RESULTS: Overall, 48.2% of individuals in the ketamine group maintained abstinence over the last 2 weeks of the trial, compared with 10.7% in the midazolam group (intent-to-treat analysis). The ketamine group was 53% less likely (hazard ratio=0.47; 95% CI=0.24, 0.92) to relapse (dropout or use cocaine) compared with the midazolam group, and craving scores were 58.1% lower in the ketamine group throughout the trial (95% CI=18.6, 78.6); both differences were statistically significant. Infusions were well tolerated, and no participants were removed from the study as a result of adverse events. CONCLUSIONS: A single ketamine infusion improved a range of important treatment outcomes in cocaine-dependent adults engaged in mindfulness-based behavioral modification, including promoting abstinence, diminishing craving, and reducing risk of relapse. Further research is needed to replicate these promising results in a larger sample.

Reduced auditory evoked gamma-band response and schizophrenia-like clinical symptoms under subanesthetic ketamine.

Abnormal gamma-band oscillations (GBO) have been frequently associated with the pathophysiology of schizophrenia. GBO are modulated by glutamate, a neurotransmitter, which is continuously discussed to shape the complex symptom spectrum in schizophrenia. The current study examined the effects of ketamine, a glutamate N-methyl-D-aspartate receptor (NMDAR) antagonist, on the auditory-evoked gamma-band response (aeGBR) and psychopathological outcomes in healthy volunteers to investigate neuronal mechanisms of psychotic behavior. In a placebo-controlled, randomized crossover design, the aeGBR power, phase-locking factor (PLF) during a choice reaction task, the Positive and Negative Syndrome Scale (PANSS) and the Altered State of Consciousness (5D-ASC) Rating Scale were assessed in 25 healthy subjects. Ketamine was applied in a subanaesthetic dose. Low-resolution brain electromagnetic tomography was used for EEG source localization. Significant reductions of the aeGBR power and PLF were identified under ketamine administration compared to placebo (p < 0.01). Source-space analysis of aeGBR generators revealed significantly reduced current source density (CSD) within the anterior cingulate cortex during ketamine administration. Ketamine induced an increase in all PANSS (p < 0.001) as well as 5D-ASC scores (p < 0.01) and increased response times (p < 0.001) and error rates (p < 0.01). Only negative symptoms were significantly associated with an aeGBR power decrease (p = 0.033) as revealed by multiple linear regression. These findings argue for a substantial role of the glutamate system in the mediation of dysfunctional gamma band responses and negative symptomatology of schizophrenia and are compatible with the NMDAR hypofunction hypothesis of schizophrenia.

Selective Prefrontal Disinhibition in a Roving Auditory Oddball Paradigm Under N-Methyl-D-Aspartate Receptor Blockade.

BACKGROUND: Disturbances in N-methyl-D-aspartate receptors (NMDARs)-as implicated in patients with schizophrenia-can cause regionally specific electrophysiological effects. Both animal models of NMDAR blockade and clinical studies in patients with schizophrenia have suggested that behavioral phenotypes are associated with reduction in inhibition within the frontal cortex. METHODS: Here we investigate event-related potentials to a roving auditory oddball paradigm under ketamine in healthy human volunteers (N= 18; double-blind, placebo-controlled, crossover design). Using recent advances in Bayesian modeling of group effects in dynamic causal modeling, we fit biophysically plausible network models of the auditory processing hierarchy to whole-scalp event-related potential recordings. This allowed us to identify regionally specific effects of ketamine in a distributed network of interacting cortical sources. RESULTS: We show that the effect of ketamine is best explained as a selective change in intrinsic inhibition, with a pronounced ketamine-induced reduction of inhibitory interneuron connectivity in frontal sources, compared with temporal sources. Simulations of these changes in an integrated microcircuit model shows that they are associated with a reduction in superficial pyramidal cell activity that can explain drug effects observed in the event-related potential. CONCLUSIONS: These results are consistent with findings from invasive recordings in animal models exposed to NMDAR blockers, and provide evidence that inhibitory interneuron-specific NMDAR dysfunction may be sufficient to explain electrophysiological abnormalities induced by NMDAR blockade in human subjects.

Activation in the auditory pathway of the gerbil studied with 18F-FDG PET: effects of anesthesia.

Here, we present results from an 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) study in the Mongolian gerbil, a preferred animal model in auditory research. One major issue in preclinical nuclear imaging, as well as in most of the neurophysiological methods investigating auditory processing, is the need of anesthesia. We compared the usability of two types of anesthesia which are frequently employed in electrophysiology, ketamine/xylazine (KX), and fentanyl/midazolam/medetomidine (FMM), for valid measurements of auditory activation with 18F-FDG PET. Gerbils were placed in a sound-shielding box and injected with 18F-FDG. Two acoustic free-field conditions were used: (1) baseline (no stimulation, 25 dB background noise) and (2) 90 dB frequency-modulated tones (FM). After 40 min of 18F-FDG uptake, a 30 min acquisition was performed using a small animal PET/CT system. Blood glucose levels were measured after the uptake phase before scanning. Standardized uptake value ratios for relevant regions were determined after implementing image and volume of interest templates. Scans demonstrated a significantly higher uptake in the inferior colliculus with FM stimulation compared to baseline in awake subjects (+ 12%; p = 0.02) and with FMM anesthesia (+ 13%; p = 0.0012), but not with KX anesthesia. In non-auditory brain regions, no significant difference was detected. Blood glucose levels were significantly higher under KX compared to FMM anesthesia (17.29 ± 0.42 mmol/l vs. 14.30 ± 1.91 mmol/l; p = 0.024). These results suggest that valid 18F-FDG PET measurements of auditory activation comparable to electrophysiology can be obtained from gerbils during opioid-based anesthesia due to its limited effects on interfering blood glucose levels.

KETAMINE AS A POSSIBLE MODERATOR OF HYPNOTIZABILITY: A FEASIBILITY STUDY.

This pilot study explored the feasibility of using ketamine to increase hypnotizability scores. Ketamine, classified as a dissociative hallucinogen, is used clinically as an anesthetic in high doses and as a treatment for chronic pain and depression in lower doses. Low-dose ketamine can contribute to dissociation and heightened perceptions and feelings of detachment, arguably hypnotic-like states. The authors predicted that a low dose of ketamine in healthy volunteers who scored in the low hypnotizable range on the Stanford Clinical Hypnotizability Scale would (a) cause an increase in subjective ratings of dissociation and (b) lead to an increase in hypnotizability. The findings were in the predicted direction, warranting further investigation into the use of this agent to increase hypnotizability.

Ketamine as an adjunct to bupivacaine in infra-orbital nerve block analgesia after cleft lip repair / Cetamina como adjuvante de bupivacaína em bloqueio do nervo infraorbitário para analgesia após correção de lábio leporino

Abstract Objectives: We conducted this study to investigate the safety and analgesic efficacy of the addition of Ketamine to Bupivacaine in bilateral extra-oral infra-orbital nerve block in children undergoing cleft lip surgeries. Methods: Sixty patients were randomly allocated into two groups (n = 30), Group B received infra-orbital nerve block with 2 mL of 0.25% Bupivacaine and Group BK received 0.5 mg.kg-1 Ketamine for each side added to 1 mL of 0.5% Bupivacaine solution diluted up to 2 mL solution to 0.25% Bupivacaine concentration. Assessment parameters included; hemodynamics, recovery time, time to first oral intake, postoperative Faces Legs Activity Cry Consolability (FLACC) scores, Four-point Agitation scores, analgesic consumption and adverse effects. Results: Patients in Group BK showed lower postoperative FLACC scores during all recorded time points (p < 0.0001). Two patients in Group BK versus 12 in Group B requested for postoperative rescue analgesia (p < 0.001). There were no differences between groups in time, minutes (min), to first request for rescue analgesia. Patients in Group BK reported lower analgesic consumption (366.67 ± 45.67 vs. 240.0 ± 0.0 mg, p < 0.04). The time to first oral intake was significantly reduced in Group BK (87.67 ± 15.41 vs. 27.33 ± 8.68 min, p < 0.001). Lower postoperative Agitation scores were recorded in Group BK patients that reached a statistical significance at 45 min (0.86 ± 0.11 vs. 0.46 ± 0.16, p < 0.04) and in the first hour (h) postoperatively (1.40 ± 0.17 vs. 0.67 ± 0.14, p < 0.003). Higher parent satisfaction scores were recorded in Group BK (p < 0.04) without significant adverse effects. Conclusions: The addition of Ketamine to Bupivacaine has accentuated the analgesic efficacy of infra-orbital nerve block in children undergoing cleft lip repair surgeries.

Resumo Objetivos: Realizamos este estudo para avaliar a segurança e eficácia da analgesia com a adição de cetamina à bupivacaína em bloqueio do nervo infraorbitário, bilateral e extraoral, em crianças submetidas à cirurgia de lábio leporino. Métodos: Foram randomicamente alocados 60 pacientes em dois grupos (n = 30): o Grupo B recebeu bloqueio do nervo infraorbitário com bupivacaína a 0,25% (2 mL) e o Grupo BC recebeu bloqueio com cetamina (0,5 mg.kg-1) em cada lado, mais a adição de 1 mL de solução de bupivacaína a 0,5% diluída até 2 mL da concentração a 0,25%. Os parâmetros de avaliação incluíram: hemodinâmica, tempo de recuperação, tempo até a primeira ingestão oral, escores da escala FLACC (que avalia a expressão facial [Face], os movimentos das pernas [Legs], a atividade [Activity], o choro [Cry] e a consolabilidade [Consolability]), escores de agitação em escala de quatro pontos, consumo de analgésicos e efeitos adversos no pós-operatório. Resultados: Os pacientes do Grupo BC apresentaram escores FLACC mais baixos em todos os momentos mensurados no pós-operatório (p < 0,0001). Dois pacientes do Grupo BC versus 12 do Grupo B solicitaram analgesia de resgate no pós-operatório (p < 0,001). Não houve diferenças entre os grupos em relação ao tempo até a primeira solicitação de analgesia de resgate. Os pacientes do Grupo BC relataram consumo menor de analgésicos (366,67 ± 45,67 vs. 240,0 ± 0,0 mg, p < 0,04). O tempo em minutos (min) até a primeira ingestão oral foi significativamente reduzido no Grupo BC (87,67 ± 15,41 vs. 27,33 ± 8,68 min, p < 0,001). Escores mais baixos de agitação no pós-operatório foram registrados para os pacientes do Grupo BC, com significância estatística no tempo de 45 min (0,86 ± 0,11 vs. 0,46 ± 0,16; p < 0,04) e na primeira hora de pós-operatório (1,40 ± 0,17 vs. 0,67 ± 0,14; p < 0,003). Índices mais altos de satisfação dos pais foram registrados no Grupo BC (p < 0,04), sem efeitos adversos significativos. Conclusões: A adição de cetamina à bupivacaína acentuou a eficácia analgésica do bloqueio do nervo infraorbitário em crianças submetidas à cirurgia de correção de lábio leporino.

Successful Improvement of Pain Symptomatology in a Suspected Case of Cramp-Fasciculation Syndrome via Interventional Pain Treatment.

Peripheral nerve hyperexcitability (PNH) syndromes are a rare set of neuromuscular disorders that include cramp-fasciculation syndrome (CFS) and Isaacs syndrome (IS). Successful treatment of these diseases has been achieved with antiepileptic medications; however, chronic pain symptoms can persist. We provide a case report of a 25-year-old female who has suffered from painful severe muscle spasms and fasciculations since childhood. With CFS as our working diagnosis, a treatment regimen using interventional pain techniques, including sympathetic chain blocks, ketamine infusions, and trigger point injections, resulted in a significant decrease in the patient's chronic pain symptoms. This case offers a novel application of interventional pain procedures and may help further our understanding of PNH syndromes.