Effect of Intranasal Ketamine on Pain Intensity after Cesarean Section: A Single-Center, Double Blind, Randomized Controlled Trial.

Background: Although intravenous or intramuscular opioids are widely used for managing postoperative pain after cesarean section (CS), their side effects are bothering and limit their use. The aim of this study was to determine the effect of intranasal ketamine on pain intensity after CS. Methods: In a single-center, double-blind, parallel-group, randomized controlled trial, a total of 120 patients who were scheduled for elective CS were randomly assigned into two groups. After birth, 1 mg of midazolam was administered to all patients. In addition, 1 mg/kg intranasal ketamine was administered to patients in the intervention group. For patients in control group, normal saline was administered intranasally as a placebo. The severity of pain and nausea in the two groups was evaluated after 15, 30 and 60 minutes, as well as 2, 6 and 12 hours after the initial administration of the medications. Results: The trend of changes in pain intensity was decreasing and these changes were statistically significant (time effect; P<0.001). The pain intensity in the placebo group was higher than the intervention and the observed difference was statistically significant, regardless of the time studied (group effect; P<0.001). In addition, it was shown that regardless of the study group, the trend of changes in nausea severity was decreasing and these changes were statistically significant (time effect; P<0.001). Regardless of the time studied, the severity of nausea in the placebo group was higher than the intervention group (group effect; P<0.001). Conclusions: According to the results of this study, it seems that the using of intranasal ketamine (1 mg/kg), can be considered as an effective, well tolerated and safe method in reducing pain intensity as well as the need for postoperative opioid consumption after CS.

Models of Affective Illness: Chronic Mild Stress in the Rat.

This article describes a chronic mild stress (CMS) model for predicting antidepressant response and investigating mechanisms of antidepressant action in rats. Following exposure to a variety of mild stressors for several weeks, the rats' behavior is modified in several ways that parallel symptoms of depression. Among these is a substantial reduction in consumption of a 1% sucrose solution, which models the cardinal symptom of major depression, anhedonia. Our standard procedure employs a battery of behavioral tests, comprising weekly assessment of sucrose intake and, at the end of treatment, the elevated plus-maze and novel object recognition tests to assess the anxiogenic and dyscognitive effects of CMS. Chronic administration of antidepressant drugs reverses the decreased sucrose intake and other behavioral changes in these subjects. Also effective are second-generation antipsychotics. The CMS model can be employed in discovery programs to identify anti-anhedonic drugs (e.g., antidepressants and antipsychotics) that act more quickly than existing agents. While most antidepressants require 3 to 5 weeks to normalize behavior, some treatments provide a faster onset of action. For example, the CMS-induced deficits can be reversed by acute or sub-chronic application of treatments that act rapidly in depressed patients, such as deep brain stimulation (DBS), ketamine, and scopolamine, as well as several compounds that have yet to be tested in humans but have fast-onset antidepressant-like effects in animals, such as the 5-HT-1A biased agonists NLX-101 and GLYX-13. Application of the CMS model in Wistar-Kyoto (WKY) rats causes similar behavioral changes to those seen in Wistars, but these are not reversed by antidepressant treatment. However, WKY rats respond to DBS and ketamine, which are effective in patients who are antidepressant non-responders, establishing CMS in WKY rats as a model of treatment-resistant depression. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Induction of chronic mild stress in rats as a model of depression and treatment-resistant depression.

Ketamine reduces electrophysiological network activity in cortical neuron cultures already at sub-micromolar concentrations - Impact on TrkB-ERK1/2 signaling.

The dissociative anesthetic ketamine regulates cortical activity in a dose-dependent manner. Subanesthetic-dose ketamine has paradoxical excitatory effects which is proposed to facilitate brain-derived neurotrophic factor (BDNF) (a ligand of tropomyosin receptor kinase B, TrkB) signaling, and activation of extracellular signal-regulated kinase 1/2 (ERK1/2). Previous data suggests that ketamine, at sub-micromolar concentrations, induces glutamatergic activity, BDNF release, and activation of ERK1/2 also on primary cortical neurons. We combined western blot analysis with multiwell-microelectrode array (mw-MEA) measurements to examine ketamine's concentration-dependent effects on network-level electrophysiological responses and TrkB-ERK1/2 phosphorylation in rat cortical cultures at 14 days in vitro. Ketamine did not cause an increase in neuronal network activity at sub-micromolar concentrations, but instead a decrease in spiking that was evident already at 500 nM concentration. TrkB phosphorylation was unaffected by the low concentrations, although BDNF elicited prominent phosphorylation response. High concentration of ketamine (10 µM) strongly reduced spiking, bursting and burst duration, which was accompanied with decreased phosphorylation of ERK1/2 but not TrkB. Notably, robust increases in spiking and bursting activity could be produced with carbachol, while it did not affect phosphorylation of TrkB or ERK1/2. Diazepam abolished neuronal activity, which was accompanied by reduced ERK1/2 phosphorylation without change on TrkB. In conclusion, sub-micromolar ketamine concentrations did not cause an increase in neuronal network activity or TrkB-ERK1/2 phosphorylation in cortical neuron cultures that readily respond to exogenously applied BDNF. Instead, pharmacological inhibition of network activity can be readily observed with high concentration of ketamine and it is associated with reduced ERK1/2 phosphorylation.

The Glutamatergic System in Treatment-Resistant Depression and Comparative Effectiveness of Ketamine and Esketamine: Role of Inflammation?

The glutamatergic system is the primary excitatory pathway within the CNS and is responsible for cognition, memory, learning, emotion, and mood. Because of its significant importance in widespread nervous system function, it is tightly regulated through multiple mechanisms, such as glutamate recycling, microglial interactions, and inflammatory pathways. Imbalance within the glutamatergic system has been implicated in a wide range of pathological conditions including neurodegenerative conditions, neuromuscular conditions, and mood disorders including depression. Major depressive disorder (MDD) is the most common mood disorder worldwide, has a high prevalence rate, and afflicts approximately 280 million people. While there are numerous treatments for the disease, 30-40% of patients are unresponsive to treatment and deemed treatment resistant; approximately another third experience only partial improvement (World Health Organization, Depression fact sheet [Internet], 2020). Esketamine, the S-enantiomer of ketamine, was approved by the Food and Drug Administration for treatment-resistant depression (TRD) in 2019 and has offered new hope to patients. It is the first treatment targeting the glutamatergic system through a complex mechanism. Numerous studies have implicated imbalance in the glutamatergic system in depression and treatment resistance. Esketamine and ketamine principally work through inhibition of the NMDA receptor, though more recent studies have implicated numerous other mechanisms mediating the antidepressant efficacy of these agents. These mechanisms include increase in brain-derived neurotrophic factor (BDNF), activation of mammalian target of the rapamycin complex (mTORC), and reduction in inflammation. Esketamine and ketamine have been shown to decrease inflammation in numerous ways principally through reducing pro-inflammatory cytokines (e.g., TNF-α, IL-6) (Loix et al., Acta Anaesthesiol Belg 62(1):47-58, 2011; Chen et al., Psychiatry Res 269:207-11, 2018; Kopra et al., J Psychopharmacol 35(8):934-45, 2021). This anti-inflammatory effect has also been shown to be involved in the antidepressive properties of both ketamine and esketamine (Chen et al., Psychiatry Res 269:207-11, 2018; Kopra et al., J Psychopharmacol 35(8):934-45, 2021).

Trial protocol for a multicenter randomized controlled trial to assess the efficacy and safety of intravenous ketamine for chronic daily headaches: the "KetHead" trial.

BACKGROUND: Chronic daily headaches (CDH) are common and associated with significant morbidity, poor quality of life, and substantial burden on the healthcare system. CDH tends to be refractory to conventional medical management and/or patients cannot afford expensive treatments. It is stipulated that CDH share a mechanism of central sensitization in the trigeminocervical complex, mediated by activation of the N-methyl-D-aspartate (NMDA) receptors. Ketamine, a non-competitive NMDA antagonist, has been used in the treatment of chronic pain, but its role in CDH has not been completely established. This trial aims to evaluate the effect of high-dose IV ketamine infusions (compared to placebo) on the number of headache days at 28 days post-infusion. METHODS: A multicenter, placebo-controlled, randomized controlled trial will be conducted with two parallel groups and blinding of participants and outcome assessors. The study will include 56 adults with a CDH diagnosis as per ICHD-3 criteria. Participants will be randomized (1:1) to either ketamine (1 mg. kg-1 bolus followed by infusion of 1 mg. kg-1. h-1 for 6 h) or placebo (0.9% saline in the same volume and infusion rate as the trial medication) bolus and infusion for 6 h. The impact on the number of monthly headache days, headache intensity, physical activity, mood, sleep, quality of life, analgesic consumption, and adverse effects will be recorded at baseline, immediately post-infusion, and from 1 to 28 days, 29 to 56 days, and 57 to 84 days after the infusion DISCUSSION: Despite advancements in treatment, many patients continue to suffer from CDH. This trial investigates whether high-dose IV ketamine infusions can effectively and safely improve the CDH burden as compared to a placebo infusion. This treatment could become a safe, affordable, and widely available option for patients living with refractory headache. TRIAL REGISTRATION: ClinicalTrials.gov NCT05306899. Registered on April 1, 2022.

Effects of recurrent ketamine exposure on brain histopathology in juvenile rats.

BACKGROUND: Ketamine (KET) is a commonly used anesthetic agent. However, several previous studies reported that KET leads to neuronal damage in neurodevelopmental stages and has neuroprotective effects. The present experimental study aimed to determine the undesirable histopathological effects of KET in the cerebral cortex, striatum, and hippocampus after recurrent KET administration in juvenile rats. METHODS: After ethical approval was obtained, 32 juvenile male Wistar Albino rats were randomized into four groups: 1 mg/kg serum saline intraperitoneally (i.p.), 5 mg/kg KET i.p., 20 mg/kg KET i.p., and 50 mg/kg KET i.p. KET was administered for three consecutive days at three-h intervals in three doses. Ten days after the last KET dose, the rats were sacrificed. Cerebral hemispheres were fixed. Hematoxylin and eosin stain was used for morphometric analysis. Hippocampi were evaluated by immunohistochemistry with anticleaved caspase-3 antibodies. Statistical analysis was conducted with SPSS 21 software using the ANOVA test and Bonferroni post hoc analysis method. RESULTS: The experimental study findings revealed no difference between the groups' cell counts or sizes in cortical morphometry. No degenerative changes were observed in pyramidal and granular cells in the striatum. Mild gliosis was observed in the 20 mg/kg and 50 mg/kg KET administration groups. Immuno-histo-chemical analysis was conducted to determine apoptosis in the CA1 region of the hippocampus and revealed that caspase-3 positivity increased with the KET dose. However, there was no statistical difference between the groups. While it was lower than the control group in the 5 mg/kg KET group, it was similar to the control group in the 20 mg/kg KET group and higher in the 50 mg/kg KET group (p > 0.05). DISCUSSION: : Repetitive KET exposure did not significantly affect juvenile cerebral morphology and apoptosis in hippocampal cells.

Ketamine use for management of vaso-occlusive pain in pediatric sickle cell disease.

BACKGROUND: Typical sickle cell disease (SCD) vaso-occlusive pain episode (VOE) management includes opioids, which are often inadequate and can be associated with significant side effects. Ketamine, a dissociative anesthetic, is a potentially effective adjunct to VOE management. OBJECTIVES: This study aimed to characterize ketamine use for VOE management in pediatric SCD. METHOD: This retrospective case series summarizes a single-center experience regarding the use of ketamine for inpatient management of pediatric VOE in 156 admissions from 2014 to 2020. RESULTS: Continuous low-dose ketamine infusion was most commonly prescribed to adolescents and young adults as an adjunct to opioids (median starting dose 2.0 µg/kg/min; median maximum dose 3.0 µg/kg/min). Ketamine was started a median of 13.7 hours after admission. Median ketamine infusion duration was 3 days. In most encounters, ketamine infusion was discontinued prior to opioid patient-controlled analgesia (PCA) discontinuation. The majority of encounters (79.3%) had a reduction in either PCA dose, continuous opioid infusion, or both while receiving ketamine. Low-dose ketamine infusion was associated with side effects noted in 21.8% (n = 34) of encounters. The most common side effects included dizziness (5.6%), hallucinations (5.1%), dissociation (2.6%), and sedation (1.9%). There were no reports of ketamine withdrawal. Most patients who received ketamine went on to receive it again during a subsequent admission. CONCLUSION: Further study is needed to determine the optimal timing of ketamine initiation and dosing. The variability of ketamine administration highlights the need for standardized protocols for ketamine use in VOE management.

The Effects of Exergaming on Executive and Physical Functions in Older Adults With Dementia: Randomized Controlled Trial.

BACKGROUND: Despite increasing interest in the effects of exergaming on cognitive function, little is known about its effects on older adults with dementia. OBJECTIVE: The purpose of this is to investigate the effects of exergaming on executive and physical functions in older adults with dementia compared to regular aerobic exercise. METHODS: In total, 24 older adults with moderate dementia participated in the study. Participants were randomized into either the exergame group (EXG, n=13, 54%) or the aerobic exercise group (AEG, n=11, 46%). For 12 weeks, EXG engaged in a running-based exergame and AEG performed a cycling exercise. At baseline and postintervention, participants underwent the Ericksen flanker test (accuracy % and response time [RT]) while recording event-related potentials (ERPs) that included the N2 and P3b potentials. Participants also underwent the senior fitness test (SFT) and the body composition test pre- and postintervention. Repeated-measures ANOVA was performed to assess the effects of time (pre- vs postintervention), group (EXG vs AEG), and group×time interactions. RESULTS: Compared to AEG, EXG demonstrated greater improvements in the SFT (F1.22=7.434, P=.01), reduction in body fat (F1.22=6.476, P=.02), and increase in skeletal mass (F1.22=4.525, P=.05), fat-free mass (F1.22=6.103, P=.02), and muscle mass (F1.22=6.636, P=.02). Although there was a significantly shorter RT in EXG postintervention (congruent P=.03, 95% CI 13.581-260.419, incongruent P=.04, 95% CI 14.621-408.917), no changes occurred in AEG. EXG also yielded a shorter N2 latency for central (Cz) cortices during both congruent conditions compared to AEG (F1.22=4.281, P=.05). Lastly, EXG presented a significantly increased P3b amplitude compared to AEG during the Ericksen flanker test (congruent: frontal [Fz] F1.22=6.546, P=.02; Cz F1.22=5.963, P=.23; parietal [Pz] F1.22=4.302, P=.05; incongruent: Fz F1.22=8.302, P=.01; Cz F1.22=15.199, P=.001; Pz F1.22=13.774, P=.001). CONCLUSIONS: Our results suggest that exergaming may be associated with greater improvements in brain neuronal activity and enhanced executive function task performance than regular aerobic exercise. Exergaming characterized by both aerobic exercise and cognitive stimulation can be used as an effective intervention to improve cognitive and physical functions in older adults with dementia. TRIAL REGISTRATION: Clinical Research Information Service KCT0008238; https://cris.nih.go.kr/cris/search/detailSearch.do/24170.

NMDA receptor-mediated modulation on glutamine synthetase and glial glutamate transporter GLT-1 is involved in the antidepressant-like and neuroprotective effects of guanosine.

Guanosine has been reported to elicit antidepressant-like responses in rodents, but if these actions are associated with its ability to afford neuroprotection against glutamate-induced toxicity still needs to be fully understood. Therefore, this study investigated the antidepressant-like and neuroprotective effects elicited by guanosine in mice and evaluated the possible involvement of NMDA receptors, glutamine synthetase, and GLT-1 in these responses. We found that guanosine (0.05 mg/kg, but not 0.01 mg/kg, p. o.) was effective in producing an antidepressant-like effect and protecting hippocampal and prefrontocortical slices against glutamate-induced damage. Our results also unveiled that ketamine (1 mg/kg, but not 0.1 mg/kg, i. p, an NMDA receptor antagonist) effectively elicited antidepressant-like actions and protected hippocampal and prefrontocortical slices against glutamatergic toxicity. Furthermore, the combined administration of sub-effective doses of guanosine (0.01 mg/kg, p. o.) with ketamine (0.1 mg/kg, i. p.) promoted an antidepressant-like effect and augmented glutamine synthetase activity and GLT-1 immunocontent in the hippocampus, but not in the prefrontal cortex. Our results also showed that the combination of sub-effective doses of ketamine and guanosine, at the same protocol schedule that exhibited an antidepressant-like effect, effectively abolished glutamate-induced damage in hippocampal and prefrontocortical slices. Our in vitro results reinforce that guanosine, ketamine, or sub-effective concentrations of guanosine plus ketamine protect against glutamate exposure by modulating glutamine synthetase activity and GLT-1 levels. Finally, molecular docking analysis suggests that guanosine might interact with NMDA receptors at the ketamine or glycine/d-serine co-agonist binding sites. These findings provide support for the premise that guanosine has antidepressant-like effects and should be further investigated for depression management.

[Sole abscess (Pododermatitis purulenta superficialis) in a Bactrian camel - diagnosis, treatment, and healing process]. / Sohlenabszess (Pododermatitis purulenta superficialis) bei einem Trampeltier ­ Diagnostik, Therapie und Heilungsverlauf.

An approximately 14-year-old female Bactrian camel was referred to the University Clinic for Ruminants with left hindlimb lameness of two weeks duration. All findings of the general clinical examination were within normal limits. Orthopedic examination revealed a left supporting limb lameness score of 2 with moderate weight-shifting and reluctance to bear weight on the lateral toe at walk. The camel was sedated (0.24 mg/kg BW xylazine i.m.+1.92 mg/kg BW ketamine i.m., 0.04 mg/kg BW butorphanol) and rolled in lateral recumbency for further investigations. Sonographic examination of the cushion of the left hindlimb revealed an abscess of diameters of 11×2.3 cm impinging both digits between the sole horn and lateral and medial cushions. The abscess was opened under local infiltration anesthesia after a 5×5 cm incision at the central sole area, the abscess capsule removed with a sharp curette and the abscess cavity flushed. The wound was then bandaged. Postoperative treatment consisted of bandage changes every 5-7 days. For these procedures the camel was repeatedly sedated. At the first change the xylazine dosage was the same for surgery, and sequentially the dosage could be reduced (0.20 mg/kg BW i.m.), but finally increased for the last dressing changes (0.22 mg/kg BW i.m.). Ketamine dosages were also reduced slightly throughout the hospitalization period (1.51 mg/kg BW i.m.), enabling a reduction of the recovery period duration. After 6 weeks of regular bandage changes the wound had healed completely with a new horn layer and showing no lameness the camel could be discharged.

A Postsynaptic Density Immediate Early Gene-Based Connectome Analysis of Acute NMDAR Blockade and Reversal Effect of Antipsychotic Administration.

Although antipsychotics' mechanisms of action have been thoroughly investigated, they have not been fully elucidated at the network level. We tested the hypothesis that acute pre-treatment with ketamine (KET) and administration of asenapine (ASE) would modulate the functional connectivity of brain areas relevant to the pathophysiology of schizophrenia, based on transcript levels of Homer1a, an immediate early gene encoding a key molecule of the dendritic spine. Sprague-Dawley rats (n = 20) were assigned to KET (30 mg/kg) or vehicle (VEH). Each pre-treatment group (n = 10) was randomly split into two arms, receiving ASE (0.3 mg/kg), or VEH. Homer1a mRNA levels were evaluated by in situ hybridization in 33 regions of interest (ROIs). We computed all possible pairwise Pearson correlations and generated a network for each treatment group. Acute KET challenge was associated with negative correlations between the medial portion of cingulate cortex/indusium griseum and other ROIs, not detectable in other treatment groups. KET/ASE group showed significantly higher inter-correlations between medial cingulate cortex/indusium griseum and lateral putamen, the upper lip of the primary somatosensory cortex, septal area nuclei, and claustrum, in comparison to the KET/VEH network. ASE exposure was associated with changes in subcortical-cortical connectivity and an increase in centrality measures of the cingulate cortex and lateral septal nuclei. In conclusion, ASE was found to finely regulate brain connectivity by modelling the synaptic architecture and restoring a functional pattern of interregional co-activation.

Evolution of reactive species and their contribution to the removal of ketamine and amine-containing pharmaceuticals during the sunlight/chlorine process.

Sunlight-induced photoirradiation of chlorine (sunlight/chlorine) can be observed in outdoor swimming pools and open-channel disinfection units for wastewater treatment. In this study, the degradation of ketamine, an environmentally persistent pharmaceutical, under sunlight irradiation in the presence of a low concentration of chlorine (1 mg/L as Cl2) was investigated to elucidate the evolution of reactive species and their contribution to ketamine removal. •OH dominates the initial stage of sunlight/chlorine; however, after chlorine depletion, reactions still progress with an observed rate constant (kobs = 7.6 ± 0.50 × 10-3 min-1) an order of magnitude higher than photolysis alone (kobs = 2.9 ± 0.15 × 10-4 min-1). When chlorine is depleted, O3 becomes the major reactant that degrades ketamine. High O3 yields were found in both sunlight/HOCl (12.5 ± 0.5% at pH 5) and sunlight/ClO- (10 ± 1% at pH 10) systems. At sub-µM levels, O3 resulted in substantial removal of ketamine, and even faster rates were observed in the presence of sunlight. A kinetic model was also established, and evaluate time-dependent concentration levels during sunlight/chlorine. The model simulation showed that the cumulative O3 concentration could reach 0.91 µM, and O3 contributed 31% ketamine removal during the sunlight/chlorine process. Primary and secondary amine functional groups were demonstrated to be the reaction sites of O3; other pharmaceuticals, such as atenolol and metoprolol, underwent similar phenomena. In addition, the experimental and model results further indicated that sunlight/ClO2- or ClO2 also participates in the degradation of ketamine with a minor role; trace amounts (below nM level) of ClO2- and ClO2 were estimated by the simulation.

Treatment and outcome following substantial ketamine overdose in a dog.

A 9-year-old, 3.7 kg (8.14 lb) neutered male Yorkshire terrier mix was treated following a ketamine overdose after subcutaneous ureteral bypass surgery. Due to an error in communication and misinterpretation of an electronic treatment sheet, the dog was inadvertently placed on a continuous rate infusion (CRI) of ketamine at 67.6 mg/kg per hour, rather than the intended 0.2 mg/kg per hour rate. Four hours after initiation of the ketamine CRI, the dog developed signs indicative of a ketamine overdose including tachycardia, hyperthermia, anisocoria, and hypoglycemia. It was determined the dog had received an iatrogenic overdose of ketamine; the infusion had been running at 67.6 mg/kg per hour, resulting in 270 mg/kg of ketamine over 4 h. Aggressive supportive measures were undertaken, and the dog gradually recovered over an 18-hour period, without lasting consequences of the overdose. To the authors' knowledge, there are no current published reports of a ketamine overdose of this magnitude in a dog. This case report documents an iatrogenic 338 times intravenous ketamine overdose in a dog, which was successfully managed with supportive care. In addition, it highlights the importance of doctor-technician communication and the potential errors in using electronic treatment sheets.

Traitement et résultat à la suite d'une surdose importante de kétamine chez un chien. Un Yorkshire terrier mélangé mâle de 9 ans et pesant 3,7 kg (8,14 lb) a été traité à la suite d'une surdose de kétamine après un pontage urétéral sous-cutané. En raison d'une erreur de communication et d'une mauvaise interprétation d'une feuille de traitement électronique, le chien a été placé par inadvertance sous une perfusion à débit continu (IRC) de kétamine à 67,6 mg/kg par heure, au lieu du débit prévu de 0,2 mg/kg par heure. Quatre heures après le début de l'IRC de kétamine, le chien a développé des signes indiquant une surdose de kétamine, notamment de la tachycardie, de l'hyperthermie, de l'anisocorie et de l'hypoglycémie. Il a été déterminé que le chien avait reçu une surdose iatrogène de kétamine; la perfusion fonctionnait à 67,6 mg/kg par heure, entraînant 270 mg/kg de kétamine en 4 h. Des mesures de soutien agressives ont été mises en place et le chien s'est progressivement rétabli sur une période de 18 heures, sans conséquences durables du surdosage.À la connaissance des auteurs, il n'existe actuellement aucun rapport publié sur une surdose de kétamine de cette ampleur chez un chien. Ce rapport de cas documente une surdose iatrogène de kétamine de 338 fois par voie intraveineuse chez un chien, qui a été gérée avec succès avec des soins de soutien. De plus, il met en évidence l'importance de la communication médecin-technicien et les erreurs potentielles dans l'utilisation des fiches de traitement électroniques.(Traduit par Dr Serge Messier).

COMPARISON OF INTRAMUSCULAR VERSUS INTRAVENOUS KETAMINE FOR SEDATION IN CHILDREN UNDERGOING MAGNETIC RESONANCE IMAGING EXAMINATION.

OBJECTIVE: The aim: To compare efficacy of intramuscular (IM) versus intravenous (IV) ketamine for sedation in children undergoing brain MRI scanning in children. PATIENTS AND METHODS: Materials and methods: Children who required elective brain MRI were selected for this study. They were randomly divided into two groups; group I received 1.5 mg/kg IV Ketamine and group II received 4 mg/kg IM ketamine. In each group supplementary 0.1 mg/kg midazolam intravenously before positioning on MRI table was given. Patients were monitored for pulse rate, SPO2, and respiratory wave. RESULTS: Results: Children who received IM ketamine had significantly shorter scan time and a greater success rate of sedation with first dose than the IV group. The proportions of scan interruption and scan repeat were significantly higher among the IV group than in the IM group. The scan time was longer among the IV group than in the IM group with significantly more scan interruption and repeat. Satisfaction with sedation as expressed by the technicians was significantly more in the IM group than in IV group (98.1% vs. 80.8%, P= 0.004). CONCLUSION: Conclusions: Intramuscular ketamine injection was predicted to have a better sedative success rate and takes less time to complete than intravenous admin¬istration. This makes IM ketamine more appealing in certain conditions.

Effect of pre-administration of esketamine intraoperatively on postpartum depression after cesarean section: A randomized, double-blinded controlled trial.

BACKGROUND: To evaluate the effect of pre-administration of esketamine intraoperatively on the occurrence of postpartum depression after cesarean section under combined spinal-epidural anesthesia. METHODS: A total of 120 women aged 24 to 36 years undergoing cesarean section by spinal-epidural anesthesia with American Society of Anesthesiologists physical status II were enrolled. According to the intraoperative use of esketamine, all participants were randomly divided into 2 groups: test group (group E) and control group (group C). Esketamine was administered intravenously at a dose of 0.2 mg/kg after the infant was delivered in group E and equal volume of normal saline was given in group C. The incidence of postpartum depression was recorded at 1 week and 6 weeks after the operation. The occurrence of adverse reactions such as postpartum bleeding, nausea and vomiting, drowsiness, and nightmares were also recorded at 48 hours after surgery. RESULTS: Compared with group C, the incidence of postpartum depression was significantly lower at 1 week and 6 weeks after surgery in group E (P < .01). There was no significant difference of the adverse effects at 48 hours after the operation between the 2 groups. CONCLUSION: Intravenous infusion of 0.2 mg/kg esketamine in women during cesarean section can significantly reduce the incidence of postpartum depression at 1 week and 6 weeks after surgery without increasing related adverse effects.

Opposite Modulation of the NMDA Receptor by Glycine and S-Ketamine and the Effects on Resting State EEG Gamma Activity: New Insights into the Glutamate Hypothesis of Schizophrenia.

NMDA-receptor hypofunction is increasingly considered to be an important pathomechanism in schizophrenia. However, to date, it has not been possible to identify patients with relevant NMDA-receptor hypofunction who would respond to glutamatergic treatments. Preclinical models, such as the ketamine model, could help identify biomarkers related to NMDA-receptor function that respond to glutamatergic modulation, for example, via activation of the glycine-binding site. We, therefore, aimed to investigate the effects of opposing modulation of the NMDA receptor on gamma activity (30-100 Hz) at rest, the genesis of which appears to be highly dependent on NMDA receptors. The effects of subanesthetic doses of S-ketamine and pretreatment with glycine on gamma activity at rest were examined in twenty-five healthy male participants using 64-channel electroencephalography. Psychometric scores were assessed using the PANSS and the 5D-ASC. While S-ketamine significantly increased psychometric scores and gamma activity at the scalp and in the source space, pretreatment with glycine did not significantly attenuate any of these effects when controlled for multiple comparisons. Our results question whether increased gamma activity at rest constitutes a suitable biomarker for the target engagement of glutamatergic drugs in the preclinical ketamine model. They might further point to a differential role of NMDA receptors in gamma activity generation.

Ketofol as an Anesthetic Agent in Patients With Isolated Moderate to Severe Traumatic Brain Injury: A Prospective, Randomized Double-blind Controlled Trial.

BACKGROUND: The effects of ketofol (propofol and ketamine admixture) on systemic hemodynamics and outcomes in patients undergoing emergency decompressive craniectomy for traumatic brain injury (TBI) are unknown and explored in this study. METHODS: Fifty patients with moderate/severe TBI were randomized to receive ketofol (n=25) or propofol (n=25) for induction and maintenance of anesthesia during TBI surgery. Intraoperative hemodynamic stability was assessed by continuous measurement of mean arterial pressure (MAP) and need for rescue interventions to maintain MAP within 20% of baseline. Brain relaxation scores, serum biomarker-glial fibrillary acidic protein levels, and extended Glasgow Outcome Scale (GOSE) at 30 and 90 days after discharge were also explored. RESULTS: MAP was lower and hemodynamic fluctuations more frequent in patients receiving propofol compared with those receiving ketofol (P<0.05). MAP fell >20% below baseline in 22 (88%) patients receiving propofol and in 10 (40%) receiving ketofol (P=0.001), with a greater requirement for vasopressors (80% vs. 24%, respectively; P=0.02). Intraoperative brain relaxation scores and GOSE at 30 and 90 day were similar between groups. Glial fibrillary acidic protein was lower in the ketofol group (3.31±0.43 ng/mL) as compared with the propofol (3.41±0.17 ng/mL; P=0.01) group on the third postoperative day. CONCLUSION: Compared with propofol, ketofol for induction and maintenance of anesthesia during decompressive surgery in patients with moderate/severe TBI was associated with improved hemodynamic stability, lower vasopressor requirement, and similar brain relaxation.

Intravenous ketamine for severe alcohol use disorder at Moi Teaching & Referral Hospital, Kenya: a case report.

BACKGROUND: Alcohol use disorder is prevalent globally and in Kenya, and is associated with significant health and socio-economic consequences. Despite this, available pharmacological treatment options are limited. Recent evidence indicates that intravenous (IV) ketamine can be beneficial for the treatment of alcohol use disorder, but is yet to be approved for this indication. Further, little has been done to describe the use of IV ketamine for alcohol use disorder in Africa. The goal of this paper, is to: 1) describe the steps we took to obtain approval and prepare for off-label use of IV ketamine for patients with alcohol use disorder at the second largest hospital in Kenya, and 2) describe the presentation and outcomes of the first patient who received IV ketamine for severe alcohol use disorder at the hospital. CASE PRESENTATION: In preparing for the off-label use of ketamine for alcohol use disorder, we brought together a multi-disciplinary team of clinicians including psychiatrists, pharmacists, ethicists, anesthetists, and members of the drug and therapeutics committee, to spearhead the process. The team developed a protocol for administering IV ketamine for alcohol use disorder that took into account ethical and safety issues. The national drug regulatory authority, the Pharmacy and Poison's Board, reviewed and approved the protocol. Our first patient was a 39-year-old African male with severe alcohol use disorder and comorbid tobacco use disorder and bipolar disorder. The patient had attended in-patient treatment for alcohol use disorder six times and each time had relapsed between one to four months after discharge. On two occasions, the patient had relapsed while on optimal doses of oral and implant naltrexone. The patient received IV ketamine infusion at a dose of 0.71 mg/kg. The patient relapsed within one week of receiving IV ketamine while on naltrexone, mood stabilizers, and nicotine replacement therapy. DISCUSSION & CONCLUSIONS: This case report describes for the first time the use of IV ketamine for alcohol use disorder in Africa. Findings will be useful in informing future research and in guiding other clinicians interested in administering IV ketamine for patients with alcohol use disorder.