Dose Of Ketamine Research Articles

Exploring ketamine’s reinforcement, cue-induced reinstatement, and nucleus accumbens cFos activation in male and female long evans rats

Ketamine (KET), a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist, has rapid onset of antidepressant effects in Treatment-Resistant Depression patients and repeated infusions are required to sustain its antidepressant properties. However, KET is an addictive drug, and so more preclinical and clinical research is needed to assess the safety of recurring treatments in both sexes. Thus, the aim of this study was to investigate the reinforcing properties of various doses of KET (0-, 0.125-, 0.25-, 0.5 mg/kg/infusion) and assess KET’s cue-induced reinstatement and neuronal activation in both sexes of Long Evans rats. Neuronal activation was assessed using the protein expression of the immediate early gene cFos in the nucleus accumbens (Nac), an important brain area implicated in reward, reinforcement and reinstatement to most drug-related cues. Our findings show that KET has reinforcing effects in both male and female rats, albeit exclusively at the highest two doses (0.25 and 0.5 mg/kg/infusion). Furthermore, we noted sex differences, particularly at the highest dose of ketamine, with female rats displaying a higher rate of self-administration. Interestingly, all groups that self-administered KET reinstated to drug-cues. Following drug cue-induced reinstatement test in rats exposed to KET (0.25 mg/kg/infusion) or saline, there was higher cFos protein expression in KET-treated animals compared to saline controls, and higher cFos expression in the core compared to the shell subregions of the Nac. As for reinstatement, there were no notable sex differences reported for cFos expression in the Nac. These findings reveal some sex and dose dependent effects in KET’s reinforcing properties and that KET at all doses induced similar reinstatement in both sexes. This study also demonstrated that cues associated with ketamine induce comparable neuronal activation in the Nac of both male and female rats. This work warrants further research into the potential addictive properties of KET, especially when administered at lower doses which are now being used in the clinic for treating various psychopathologies.

Predictive model for post-induction hypotension in patients undergoing transcatheter aortic valve implantation: a retrospective observational study

PurposePost-induction hypotension (PIH) is an independent risk factor for prolonged postoperative stay and hospital death. Patients undergoing transcatheter aortic valve implantation (TAVI) are prone to develop PIH. This study aimed to develop a predictive model for PIH in patients undergoing TAVI.MethodsThis single-center retrospective observational study included 163 patients who underwent TAVI. PIH was defined as at least one measurement of systolic arterial pressure <90 mmHg or at least one incident of norepinephrine infusion at a rate >6 µg/min from anesthetic induction until 20 min post-induction. Multivariate logistic regression analysis was performed to develop a predictive model for PIH in patients undergoing TAVI.ResultsIn total, 161 patients were analyzed. The prevalence of PIH was 57.8%. Multivariable logistic regression analysis showed that baseline mean arterial pressure ≥90 mmHg [adjusted odds ratio (aOR): 0.413, 95% confidence interval (95% CI): 0.193–0.887; p=0.023] and higher doses of fentanyl (per 1-µg/kg increase, aOR: 0.619, 95% CI: 0.418–0.915; p=0.016) and ketamine (per 1-mg/kg increase, aOR: 0.163, 95% CI: 0.062–0.430; p=0.002) for induction were significantly associated with lower risk of PIH. A higher dose of propofol (per 1-mg/kg increase, aOR: 3.240, 95% CI: 1.320–7.920; p=0.010) for induction was significantly associated with higher risk of PIH. The area under the curve (AUC) for this model was 0.802.ConclusionThe present study developed predictive models for PIH in patients who underwent TAVI. This model may be helpful for anesthesiologists in preventing PIH in patients undergoing TAVI.

Design, Synthesis and Biological Evaluation of Novel Ketamine Derivatives as NMDAR Antagonists.

Depression is a chronic, severe, and often life-threatening neurological disorder. It not only causes depression in patients and affects daily life but, in severe cases, may lead to suicidal behavior and have adverse effects on families and society. In recent years, it has been found that sub-anesthetic doses of ketamine have a rapid antidepressant effect on patients with treatment-resistant depression and can significantly reduce the suicidal tendencies of patients with major depressive disorder. Current studies suggest that ketamine may exert antidepressant effects by blocking NMDAR ion channels, but its anesthetic and psychotomimetic side effects limit its application. Here, we report efforts to design and synthesize a novel series of ketamine derivatives of NMDAR antagonists, among which compounds 23 and 24 have improved activity compared with ketamine, introducing a new direction for the development of rapid-acting antidepressant drugs.

Comparison of Different Ketofol Procedural Sedation and Analgesic Doses during Orthopedic Procedures in Patients Referred to the Emergency Department: A Double-Blind Randomized Clinical Trial

Background: Orthopedic procedures are one of the most common medical procedures in the emergency department (ED) and are also among the most painful procedures performed on the conscious patient. This study aimed to compare different doses of ketofol in procedural sedation and analgesia (PSA) in patients referred to the EDs. Methods: In this double-blinded clinical trial, 296 patients aged 18 years or over who presented with the need for orthopedic procedures in the three academic EDs in 2020 were studied. After completing the written consent, the patients were randomly assigned to four treatment groups. Demographic information, underlying diseases, patients' physical condition, type of orthopedic injuries requiring intervention, and patients' vital signs were recorded in a checklist for each patient. Results: In this study, the mean age, gender, level of education, addiction, patients' physical condition, type of procedures performed, apnea, hypoventilation, bradycardia, hypotension, and agitation in all four treatment groups were not statistically different, but hallucination and hypoxia in group C (propofol 1 mg/kg plus ketamine 0.33 mg/kg) were much less than other groups; thus, oxygen administration was more common in other groups. Conclusion: By testing different doses of ketamine, we concluded that doses of 1 mg and 0.5 mg were associated with more side effects. A dose of 0.33 mg of ketamine has fewer side effects while causing analgesia and sedation as in the above doses. A dose of 0.25 mg of ketamine increases the likelihood of requiring subsequent doses. Therefore, it seems that 0.33 mg of ketamine is the best dose of choice.

Environmental enrichment enhances the antidepressant effect of ketamine and ameliorates spatial memory deficits in adult rats

Ketamine is a rapid-acting antidepressant associated with various cognitive side effects. To mitigate these side effects while enhancing efficacy, it can be co-administered with other antidepressants. In our study, we adopted a similar strategy by combining ketamine with environmental enrichment, a potent sensory-motor paradigm, in adult male Wistar rats. We divided the animals into four groups based on a combination of housing conditions and ketamine versus vehicle injections. The groups included those housed in standard cages or an enriched environment for 50 days, which encompassed a 13-day-long behavioral testing period. Each group received either two doses of ketamine (20 mg/kg, IP) or saline as a vehicle. We tested the animals in the novel object recognition test (NORT), forced swim test (FST), open field test (OFT), elevated plus maze (EPM), and Morris water maze (MWM), which was followed by ex vivo c-Fos immunohistochemistry. We observed that combining environmental enrichment with ketamine led to a synergistic antidepressant effect. Environmental enrichment also ameliorated the spatial memory deficits caused by ketamine in the MWM. There was enhanced neuronal activity in the habenula of the enrichment only group following the probe trial of the MWM. In contrast, no differential activity was observed in enriched animals that received ketamine injections. The present study showed how environmental enrichment can enhance the antidepressant properties of ketamine while reducing some of its side effects, highlighting the potential of combining pharmacological and sensory-motor manipulations in the treatment of mood disorders.

Retrospective Comparison of the Anesthetic Effects of Tiletamine-Zolazepam with Dexmedetomidine and Ketamine with Dexmedetomidine in Captive Formosan Serow (Capricornis swinhoei).

Formosan serows are endemic to the mountainous regions of Taiwan. This crossover study aimed to assess and compare the anesthetic induction and recovery using either dexmedetomidine-tiletamine-zolazepam (DZ) or dexmedetomidine-ketamine (DK) by intramuscular injection from a blow-dart in a zoo environment. Ten anesthetic procedures were performed with five adult Formosan serows. Each participant was anesthetized with both combinations at least once with a minimal 12-month washout. The average dosages were 22.6 ± 8.3 µg/kg and 35.8 ± 2.5 µg/kg for dexmedetomidine and 185.6 ± 123.6 and 357.8 ± 25.2 µg/kg for atipamezole for the DZ and DK groups, respectively. The doses of tiletamine-zolazepam and ketamine were 2.1 ± 0.25 mg/kg and 3.6 ± 0.3 mg/kg, respectively, in the DZ and DK groups. All participants were induced within 10 min (median: 8 min for both groups), except one serow in the DK group with an induction time of 22 min. Serows in the DZ group had a lower respiratory rate (p = 0.016) and lower rectal temperature (p = 0.008) than those in the DK group. The quality of recovery was poor for DZ because of paddling, prolonged recovery, and ataxia after antagonism of dexmedetomidine with atipamezole. The induction of anesthesia with dexmedetomidine-tiletamine-zolazepam was uneventful and rapid. However, recovery from this combination was not smooth.

Ketamine subcutaneous continuous infusion for depressive symptoms at home: A case report beyond pain use.

Ketamine has been widely used in refractory pain as an opioid adjuvant. Evidence suggests that ketamine can also have an essential role in easing depressive symptoms. Its rapid onset of action makes it a valuable choice in palliative care. We present a case of a 70-year-old man with stage IV renal carcinoma and bone metastasis. The main symptoms included neuropathic pain, depression, and a persistent and severe desire for death. We started continuous subcutaneous infusion with morphine 30 mg and ketamine 100 mg/day. The dose of ketamine was incremented to the maximum of 250 mg/day. During the 28-day treatment, we observed an overall improvement in neuropathic pain, depressive symptoms, and other end-of-life psychological aspects of distress. Only minor psychological side effects were identified, which were controlled by using midazolam in the continuous subcutaneous infusion. Some studies have already demonstrated the benefits of ketamine use in alleviating depression, using parental infusion or oral formulas, which are administered in hospice care. Our report enhances the benefit of the subcutaneous route for palliative patients cared for at home.

Therapeutic doses of ketamine acutely attenuate the aversive effect of losses during decision-making.

The discovery of rapid-acting antidepressant, ketamine has opened a pathway to a new generation of treatments for depression, and inspired neuroscientific investigation based on a new perspective that non-adaptive changes in the intrinsic excitatory and inhibitory circuitry might underlie the pathophysiology of depression. Nevertheless, it still remains largely unknown how the hypothesized molecular and synaptic levels of changes in the circuitry might mediate behavioral and neuropsychological changes underlying depression, and how ketamine might restore adaptive behavior. Here, we used computational models to analyze behavioral changes induced by therapeutic doses of ketamine, while rhesus macaques were iteratively making decisions based on gains and losses of tokens. When administered intramuscularly or intranasally, ketamine reduced the aversiveness of undesirable outcomes such as losses of tokens without significantly affecting the evaluation of gains, behavioral perseveration, motivation, and other cognitive aspects of learning such as temporal credit assignment and time scales of choice and outcome memory. Ketamine's potentially antidepressant effect was separable from other side effects such as fixation errors, which unlike outcome evaluation, was readily countered with strong motivation to avoid errors. We discuss how the acute effect of ketamine to reduce the initial impact of negative events could potentially mediate longer-term antidepressant effects through mitigating the cumulative effect of those events produced by slowly decaying memory, and how the disruption-resistant affective memory might pose challenges in treating depression. Our study also invites future investigations on ketamine's antidepressant action over diverse mood states and with affective events exerting their impacts at diverse time scales.

Therapeutic doses of ketamine acutely attenuate the aversive effect of losses during decision-making

The discovery of rapid-acting antidepressant, ketamine has opened a pathway to a new generation of treatments for depression, and inspired neuroscientific investigation based on a new perspective that non-adaptive changes in the intrinsic excitatory and inhibitory circuitry might underlie the pathophysiology of depression. Nevertheless, it still remains largely unknown how the hypothesized molecular and synaptic levels of changes in the circuitry might mediate behavioral and neuropsychological changes underlying depression, and how ketamine might restore adaptive behavior. Here, we used computational models to analyze behavioral changes induced by therapeutic doses of ketamine, while rhesus macaques were iteratively making decisions based on gains and losses of tokens. When administered intramuscularly or intranasally, ketamine reduced the aversiveness of undesirable outcomes such as losses of tokens without significantly affecting the evaluation of gains, behavioral perseveration, motivation, and other cognitive aspects of learning such as temporal credit assignment and time scales of choice and outcome memory. Ketamine’s potentially antidepressant effect was separable from other side effects such as fixation errors, which unlike outcome evaluation, was readily countered with strong motivation to avoid errors. We discuss how the acute effect of ketamine to reduce the initial impact of negative events could potentially mediate longer-term antidepressant effects through mitigating the cumulative effect of those events produced by slowly decaying memory, and how the disruption-resistant affective memory might pose challenges in treating depression. Our study also invites future investigations on ketamine’s antidepressant action over diverse mood states and with affective events exerting their impacts at diverse time scales.

Ketamine Sedation Decreases Survival after Extremity Trauma and Moderate Hemorrhage in Rats

Objective: Traumatic hemorrhage (HEM) is often associated with pain. The use of ketamine (KET) has increased both on the battlefield and in civilian emergency care for analgesia and sedation. We have reported that an analgesic dose of KET does not impact cardiorespiratory responses or survival after HEM (JAP 130: 1583-1593, 2021). In this study, we measured the effects of a larger, sedative, dose of KET on cardiovascular responses and survival to moderate (37% blood volume) HEM combined with extremity trauma (ET), and whether midazolam (MDZ), a drug often given in combination with KET alters these responses. Hypothesis: We hypothesized that either KET (50 mg/kg) or KET+MDZ (5 mg/kg) would compromise cardiovascular responses to HEM and thereby decrease survival. Methods: Male rats were implanted with a telemetry transmitter to measure mean arterial pressure (MAP) and heart rate (HR); buprenorphine SR was used to relieve pain associated with surgical procedures. Following 2 weeks recovery, rats were anesthetized using isoflurane, and a carotid catheter was implanted. The next day, rats were briefly anesthetized using isoflurane to perform ET (fibular fracture + hindlimb soft tissue crush injury) and were allowed to recover 90 min before starting conscious HEM (time = 0-25 min). Rats received either 1) saline vehicle (VEH, n=8); 2) KET (n=8); or 3) KET followed by MDZ (KET+MDZ; n=9) during a 15 min infusion (t = 25-40 min). The study continued for 200 minutes (time = 40-240 min). Data are mean ± SD. Results: There were no differences between groups in MAP or HR at either baseline (t = 0 min) or at end of HEM (t = 25 min). However, during the 20 min after treatment (t = 40-60 min), MAP and HR were significantly lower (P≤0.05) in KET (46 ± 3 mmHg; 220 ± 11 bpm) and KET+MDZ (45 ± 10 mmHg; 212 ± 24 bpm) compared to VEH (68 ± 20 mmHg; 297 ± 37 bpm). During this time, only 3 of 8 rats in the KET group survived HEM, while all rats survived in VEH and KET+MDZ groups. At the end of the study (t = 240 min), survival rate was significantly lower (P=0.003) in KET (37.5%) compared to VEH (87.5%) or KET+MDZ (100%). Similarly, survival time was significantly lower (P=0.004) in KET (115 ± 103 min) compared to VEH (227 ± 37 min) or KET+MDZ (240 ± 0 min). Summary of Results: A sedative dose of KET decreased survival following HEM, but the same dose of KET followed by MDZ was protective. The MDZ effect was not due to improvements in cardiovascular responses to the HEM. Conclusion: Sedation with ketamine alone after trauma and moderate HEM decreased survival. Further studies of the effects of sedation with KET alone or KET+MDZ on respiration and metabolic responses to HEM may provide insight on the overall effect on survival. Congressionally Directed Medical Research Program (CDMRP). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Protocol for a randomised controlled trial of ketamine versus ketamine and behavioural activation therapy for adults with treatment-resistant depression in the community

IntroductionAlthough short-term benefits follow parenteral ketamine for treatment-resistant major depressive disorder (TR-MDD), there are challenges that prevent routine use of ketamine by clinicians. These include acute dissociative effects of parenteral...

252. Working-Memory Changes at Baseline and Following a Subanesthetic Dose of Intravenous Ketamine in Treatment-Resistant Depression Patients and Healthy Volunteers

252. Working-Memory Changes at Baseline and Following a Subanesthetic Dose of Intravenous Ketamine in Treatment-Resistant Depression Patients and Healthy Volunteers

The Effect of a Subsequent Dose of Dexmedetomidine or Other Sedatives following an Initial Dose of Dexmedetomidine on Sedation and Quality of Recovery in Cats: Part I.

Dexmedetomidine is an a2-agonist commonly used in veterinary practice. Occasionally, the administered dose of dexmedetomidine may result in insufficient sedation, and an additional dose or drug may be required. The sedative effects of seven different drugs administered at subsequent time points after an initial, insufficient dose of dexmedetomidine were evaluated. Seven adult cats participated in this crossover, blind, randomised study. The groups consisted of two consecutive doses of dexmedetomidine (15 + 10 μg/kg) (DD) or a dose of dexmedetomidine (15 μg/kg) followed by either NS 0.9% (DC-control group), tramadol 2 mg/kg (DT), butorphanol 0.2 mg/kg (DBT), buprenorphine 20 μg/kg (DBP), ketamine 2 mg/kg (DK), or midazolam 0.1 mg/kg (DM). Sedation was evaluated using the Grint sedation scale. In all groups, atipamezole was administered at the end of the evaluation, and recovery was assessed using the Lozano and Sams recovery scales. The DC and DM groups exhibited minimal sedative effects. The maximum sedative effect was observed in the DD and DK groups, while sedation in the DD and DK groups was significantly higher compared to the DC group. Recovery in all groups was uneventful, except in the DM group, where it was prolonged and difficult, although no statistically significant difference was detected. Therefore, insufficient sedation with dexmedetomidine can be enhanced by a subsequent dose of dexmedetomidine, ketamine, or butorphanol, whereas the addition of midazolam reduces sedation and prolongs recovery.

Subcutaneous ketamine reduces suicide risk and improves functioning in depression: A proof-of-concept study

This investigation explores the efficacy of subcutaneous ketamine for mitigating depressive symptoms and suicidal ideation, addressing a crucial need for rapid-onset treatments in severe depression cases. It introduces an innovative approach to administering an NMDA receptor antagonist, significantly advancing psychopharmacological methods for treating suicidal behaviors as distinct entities, even within depressive episodes. The study's objective is to assess the impact of subcutaneous ketamine on diminishing suicidal thoughts and mood symptoms during depressive episodes through a naturalistic, prospective observational design. Conducted at Hospital de Clínicas de Porto Alegre, Brazil, between 2021 and 2023, the study involved 26 patients undergoing a current depressive episode. Of these, 23 completed the acute phase of treatment, and 18 were followed up for 6 months. The treatment regimen commenced with a ketamine dose of 0.5 mg/kg, which was adjusted according to individual responses under psychiatric supervision. The findings revealed substantial decreases in Columbia Suicide Severity Rating Scale scores following multiple ketamine sessions, with most patients achieving remission after approximately eight sessions. A notable reduction in depressive symptoms was also observed. A clear dose-response relationship was established, indicating that higher doses of ketamine were associated with more significant improvements in depressive symptoms, suicidal ideation, and overall functionality. Follow-up assessments suggested that these improvements were sustained over time. The subcutaneous administration of ketamine was generally well-tolerated, with minor and short-lived side effects. The study posits that subcutaneous ketamine may present a promising solution for treating severe depression accompanied by suicidal tendencies, particularly considering its positive influence on patient functionality and well-being. This method could offer a cost-effective and accessible treatment alternative, especially relevant in settings with limited resources. Given its potential in reducing long-term disability and economic viability, the study advocates for its broader application and further validation through larger, controlled trials.Trial Registration: ClinicalTrials.gov NCT05249309.

Effects of Mild Closed-Head Injury and Subanesthetic Ketamine Infusion on Microglia, Axonal Injury, and Synaptic Density in Sprague-Dawley Rats.

Mild traumatic brain injury (mTBI) affects millions of people in the U.S. Approximately 20-30% of those individuals develop adverse symptoms lasting at least 3 months. In a rat mTBI study, the closed-head impact model of engineered rotational acceleration (CHIMERA) produced significant axonal injury in the optic tract (OT), indicating white-matter damage. Because retinal ganglion cells project to the lateral geniculate nucleus (LGN) in the thalamus through the OT, we hypothesized that synaptic density may be reduced in the LGN of rats following CHIMERA injury. A modified SEQUIN (synaptic evaluation and quantification by imaging nanostructure) method, combined with immunofluorescent double-labeling of pre-synaptic (synapsin) and post-synaptic (PSD-95) markers, was used to quantify synaptic density in the LGN. Microglial activation at the CHIMERA injury site was determined using Iba-1 immunohistochemistry. Additionally, the effects of ketamine, a potential neuroprotective drug, were evaluated in CHIMERA-induced mTBI. A single-session repetitive (ssr-) CHIMERA (3 impacts, 1.5 joule/impact) produced mild effects on microglial activation at the injury site, which was significantly enhanced by post-injury intravenous ketamine (10 mg/kg) infusion. However, ssr-CHIMERA did not alter synaptic density in the LGN, although ketamine produced a trend of reduction in synaptic density at post-injury day 4. Further research is necessary to characterize the effects of ssr-CHIMERA and subanesthetic doses of intravenous ketamine on different brain regions and multiple time points post-injury. The current study demonstrates the utility of the ssr-CHIMERA as a rodent model of mTBI, which researchers can use to identify biological mechanisms of mTBI and to develop improved treatment strategies for individuals suffering from head trauma.

Fixed dose ketamine for prehospital management of hyperactive delirium with severe agitation

IntroductionPatients exhibiting signs of hyperactive delirium with severe agitation (HDSA) may require sedating medications for stabilization and safe transport to the hospital. Determining the patient's weight and calculating the correct weight-based dose may be challenging in an emergency. A fixed dose ketamine protocol is an alternative to the traditional weight-based administration, which may also reduce dosing errors. The objective of this study was to evaluate the frequency and characteristics of adverse events following pre-hospital ketamine administration for HDSA. MethodsEmergency Medical Services (EMS) records from four agencies were searched for prehospital ketamine administration. Cases were included if a 250 mg dose of ketamine was administered on standing order to an adult patient for clinical signs consistent with HDSA. Protocols allowed for a second 250 mg dose of ketamine if the first dose was not effective. Both the 250 mg initial dose and the total prehospital dose were analyzed for weight based dosing and adverse events. ResultsReview of 132 cases revealed 60 cases that met inclusion criteria. Patients' median weight was 80 kg (range: 50-176 kg). No patients were intubated by EMS, one only requiring suction, three required respiratory support via bag valve mask (BVM). Six (10%) patients were intubated in the emergency department (ED) including the three (5%) supported by EMS via BVM, three (5%) others who were sedated further in the ED prior to requiring intubation. All six patients who were intubated were discharged from the hospital with a Cerebral Performance Category (CPC) 1 score. The weight-based dosing equivalent for the 250 mg initial dose (OR: 2.62, CI: 0.67–10.22) and the total prehospital dose, inclusive of the 12 patients that were administered a second dose, (OR: 0.74, CI: 0.27, 2.03), were not associated with the need for intubation. ConclusionThe 250 mg fixed dose of ketamine was not >5 mg/kg weight-based dose equivalent for all patients in this study. Although a second 250 mg dose of ketamine was permitted under standing orders, only 12 (20%) of the patients were administered a second dose, none experienced an adverse event. This indicates that the 250 mg initial dose was effective for 80% of the patients. Four patients with prehospital adverse events likely related to the administration of ketamine were found. One required suction, three (5%) requiring BVM respiratory support by EMS were subsequently intubated upon arrival in the ED. All 60 patients were discharged from the hospital alive. Further research is needed to determine an optimal single administration dose for ketamine in patients exhibiting signs of HDSA, if employing a standardized fixed dose medication protocol streamlines administration, and if the fixed dose medication reduces the occurrence of dosage errors.

A comparison of anesthesia induction by two different administration routes and doses of ketamine and medetomidine in red-eared sliders (Trachemys scripta elegans)

This study aimed to assess the efficiency of ketamine and medetomidine by two different doses and routes on anesthesia depth and cardiac stability in red-eared sliders. Each turtle was anesthetized two times, with seven days wash-out period. Induction of anesthesia consisted of a bolus combination of ketamine (10 mg/kg) and medetomidine (0.2 mg/kg) administered in the left brachial biceps in the intramuscular protocol, or a bolus combination of ketamine (20 mg/kg) and medetomidine (0.2 mg/kg) administered in subcarapacial sinus after clear blood presence confirmation in the intravenous protocol. Vital signs, reaction on the skin palpation, manual mouth opening for endotracheal intubation, palpebral and cloacal reflex, and the withdrawal reflex of the front and hind limbs were measured and recorded every 5 minutes for 60 minutes after anesthesia injection. Atipamezole (1 mg/kg) was administered in the right brachial biceps one hour after ketamine and medetomidine administration. Needle insertion and possible painful reactions to drug administration were also evaluated and recorded. Obtained data were analyzed for normality and paired t-tests, Wilcoxon, or McNamar tests were performed where appropriate. The values of P≤0.05 were considered significant. A significantly less pronounced decrease in heart rate was observed with intravenous anesthesia protocol. Both protocols recorded complete anesthesia recovery 60 minutes after intramuscular atipamezole administration. A ketamine-medetomidine dose combination administered intravenously provides a more stable and consistent anesthetic plane in red-eared sliders than ketamine-medetomidine administered intramuscularly.

Influence of intravenous fentanyl or dexmedetomidine infusions, combined with lidocaine and ketamine, on cardiovascular response, sevoflurane requirement and postoperative pain in dogs anesthetized for unilateral mastectomy

ObjectiveTo compare the effects of constant rate infusions (CRI) of fentanyl or dexmedetomidine, combined with lidocaine and ketamine, on cardiovascular response during surgery, sevoflurane requirement and postoperative pain in dogs undergoing mastectomy. Study designProspective, randomized, blinded, clinical trial. AnimalsA total of 29 female dogs with mammary tumors. MethodsPremedication consisted of intramuscular acepromazine and morphine. General anesthesia was induced with intravenous propofol and maintained with sevoflurane. Dogs were randomized to be administered intravenous DLK [dexmedetomidine 1 μg kg–1 loading dose (LD) and 1 μg kg–1 hour–1; lidocaine 2 mg kg–1 LD and 3 mg kg–1 hour–1; ketamine 1 mg kg–1 LD and 0.6 mg kg–1 hour–1; n = 14] or FLK (fentanyl 5 μg kg–1 LD and 9 μg kg–1 hour–1; same doses of lidocaine and ketamine; n = 15) during anesthesia. Cardiorespiratory variables and end-tidal sevoflurane (Fe′Sevo) were recorded during surgery. The number of dogs administered ephedrine to treat arterial hypotension [mean arterial pressure (MAP) < 60 mmHg] was recorded. Meloxicam was administered to both groups. Postoperative pain and rescue analgesia requirement were assessed for 24 hours using the short form of the Glasgow Composite Measure Pain Scale. Data were compared using a mixed effects model or a Mann–Whitney test. ResultsMore dogs required ephedrine in FLK than in DLK (67% versus 7%). Heart rate was not significantly different between groups, whereas lower values of MAP (p ≤ 0.01) and Fe′Sevo (p = 0.018) were observed in FLK than in DLK. Rescue analgesia was administered to 2/15 dogs in FLK and 0/14 dogs in DLK. Conclusions and clinical relevanceBased on the cardiovascular response during surgery, intraoperative infusions of FLK and DLK provided adequate antinociception. Infusion of DLK provided greater stability of blood pressure. Both protocols resulted in minimal need for additional analgesia within 24 hours postoperatively.

Ketamine enhanced ECT in refractory recurrent depression.

IntroductionRecurrent Depressive Disorder is a chronic condition that significantly impacts the quality of life. Despite various treatment options, some patients face severe and treatment-resistant relapses. This case is related to research on ketamine in Electroconvulsive Therapy (ECT) for RDD. One study highlighted the efficacy and safety of ketamine compared to other anaesthetic agents in ECT for major depression. Additionally, another study explored subanesthetic doses of ketamine before each ECT session to improve therapeutic outcomes and sleep quality in patients with major depressive disorder.ObjectivesTo present a clinical case of a patient with Recurrent Depressive Disorder (RDD) who improved following a change in the Electroconvulsive Therapy (ECT) protocol using ketamine as an anaesthetic inducer.Methods We examined the patient’s medical records, including her medical history, previous treatments, and therapeutic responses.ResultsA 65-year-old childless woman with a history of stroke, bilateral carotid atheromatosis, and hypothyroidism suffered from RDD. Despite multiple prior treatments and ECT, she experienced a severe depressive relapse. Eight intensive ECT sessions were administered, with observed memory lapses. Due to the lack of response, the anaesthetic inducer etomidate was replaced with ketamine, resulting in a positive response. The patient continued pharmacological treatment with improved mood, but recent and evident memory alterations persisted, possibly related to anterograde amnesia.Conclusions This case highlights the complexity of RDD in patients with comorbidities and treatment-resistant relapses. The change in the ECT protocol using ketamine was effective, emphasizing the importance of alternative therapeutic approaches in refractory cases. The successful treatment of RDD in this patient using ketamine in ECT underscores the need for personalized therapeutic options in treatment-resistant patients. These scientific resources reinforce the relevance of exploring therapeutic alternatives in contemporary clinical practice. We need more research to understand the underlying mechanisms and how this approach could be enhanced in similar cases.Disclosure of InterestNone Declared

Is anti-NMDA receptor encephalitis real? II. Therapeutic challenges

The first part of the review challenges the diagnostic concept of anti-NMDA receptor encephalitis (ANMDARE). The second part focuses on analyzing current therapeutic approaches. It is demonstrated that the use of antipsychotics or immunosuppressants poses the risk of severe complications, potentially leading to fatal outcomes, in the near or distant future. Comparing clinical and neurobiological effects associated with antibodies to the GluN1 subunit of the glutamate N-methyl-D-aspartate receptors (NMDAR1-AB) and the administration of subanesthetic doses of the non-competitive NMDA receptor antagonist Ketamine highly suggests a neuroprotective, health-promoting role of NMDAR1-AB, which should not be suppressed but rather potentiated. Benzodiazepines and electroconvulsive therapy (ECT) remain the treatment of choice for acute polymorphic hyperkinetic psychoses.