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1.
Am J Vet Res ; 83(6)2022 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-35524961

RESUMO

OBJECTIVE: To compare ketamine-butorphanol-azaperone-medetomidine (KBAM) to detomidine-etorphine-acepromazine (DEA) for field anesthesia in captive Przewalski horses (Equus przewalskii). ANIMALS: 10 adult Przewalski horses. PROCEDURES: A prospective randomized crossover trial was conducted. Each horse was immobilized once with KBAM (200 mg ketamine, 109.2 mg butorphanol, 36.4 mg azaperone, and 43.6 mg medetomidine) and once with DEA (40 mg detomidine premedication, followed 20 minutes later by 3.9 to 4.4 mg etorphine and 16 to 18 mg acepromazine). Both protocols were administered by IM remote dart injection with a washout period of 6 months between treatments. Selected cardiorespiratory variables and quality of anesthesia were recorded. Antagonists were administered IM (KBAM, 215 mg atipamezole and 50 mg naltrexone; DEA, 4 mg RX821002 and 100 mg naltrexone). RESULTS: All horses were anesthetized and recovered uneventfully. Inductions (DEA, 6.8 min; KBAM, 11.6 min; P = 0.04) and recoveries (DEA, 3.2 min; KBAM, 19.6 min; P < 0.01) were faster with DEA compared with KBAM. Quality scores for induction and recovery did not differ between protocols, but maintenance quality was poorer for DEA (P < 0.01). Clinical concerns during DEA immobilizations included apnea, severe hypoxemia (arterial partial pressure of oxygen < 60 mm Hg), muscle rigidity, and tremors. Horses treated with KBAM were moderately hypoxemic, but arterial partial pressures of oxygen were higher compared with DEA (P < 0.01). CLINICAL RELEVANCE: Captive Przewalski horses are effectively immobilized with KBAM, and this protocol results in superior muscle relaxation and less marked hypoxemia during the maintenance phase, but slower inductions and recoveries, compared with DEA.


Assuntos
Anestesia , Ketamina , Acepromazina/farmacologia , Anestesia/veterinária , Animais , Azaperona/farmacologia , Butorfanol/farmacologia , Etorfina/farmacologia , Frequência Cardíaca , Cavalos , Hipnóticos e Sedativos/farmacologia , Hipóxia/tratamento farmacológico , Hipóxia/veterinária , Imidazóis , Imobilização/métodos , Imobilização/veterinária , Ketamina/farmacologia , Medetomidina/farmacologia , Naltrexona/farmacologia , Oxigênio/farmacologia , Estudos Prospectivos
3.
BMC Anesthesiol ; 22(1): 138, 2022 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-35534825

RESUMO

BACKGROUND: Esketamine is an antagonist of the N-methyl-D-aspartate receptor (NMDA receptor) that is widely used for multimodal analgesia. In addition to analgesia, sedation is another important effect of esketamine. However, data are limited regarding the sedation effect of esketamine during general anaesthesia. The objective of this study was to determine whether sedation with a subanaesthetic does of esketamine affects anaesthesia recovery. METHODS: Fifty patients, ASA I to II patient scheduled to laparoscopic cholecystectomy, were randomly assigned to receive a single bolus of esketamine 0.2 mg kg-1 (esketamine group) or placebo (control group). Propofol, sufentanil and rocuronium were used during total intravenous anaesthesia. The patients' time of recovery from anaesthesia, postoperative pain, postoperative nausea and vomiting, and postoperative agitation were analysed. RESULTS: Data from 47 patients were analysed. The average time of anaesthetic recovery was 22.04 ± 1.48 min in the esketamine group(n = 23) and 17.54 ± 1.46 min in the control group(n = 24). The recovery time was significantly longer in the esketamine group. Postoperative pain in the PACU was lower in the esketamine group (NRS score range 0-2) than in the control group (NRS score range 0-3). There were no differences in postoperative nausea and vomiting, and postoperative agitation. CONCLUSION: Subanaesthetic doses of esketamine can reduce postoperative pain in the PACU but delay the aesthetic recovery during the laparoscopic cholecystectomy, without affecting postoperative nausea and vomiting, and postoperative agitation. TRIAL REGISTRATION: The study was registered at the Chinese Clinical Trial Registry http://www.chictr.org.cn/ (Registration date: 20/11/2020; TrialID: ChiCTR2000040077 ).


Assuntos
Ketamina , Náusea e Vômito Pós-Operatórios , Anestesia Geral , Método Duplo-Cego , Humanos , Ketamina/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controle , Náusea e Vômito Pós-Operatórios/epidemiologia , Náusea e Vômito Pós-Operatórios/prevenção & controle
4.
Transl Psychiatry ; 12(1): 179, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35501309

RESUMO

Subanesthetic-dose racemic (R,S)-ketamine (ketamine) produces rapid, robust, and sustained antidepressant effects in major depressive disorder (MDD) and bipolar disorder (BD) and has also been shown to effectively treat neuropathic pain, complex regional pain syndrome, and post-traumatic stress disorder (PTSD). However, to date, its mechanism of action remains unclear. Preclinical studies found that (2 R,6 R;2 S,6 S)-hydroxynorketamine (HNK), a major circulating metabolite of ketamine, elicits antidepressant effects similar to those of ketamine. To help determine how (2 R,6 R)-HNK contributes to ketamine's mechanism of action, an exploratory, targeted, metabolomic analysis was carried out on plasma and CSF of nine healthy volunteers receiving a 40-minute ketamine infusion (0.5 mg/kg). A parallel targeted metabolomic analysis in plasma, hippocampus, and hypothalamus was carried out in mice receiving either 10 mg/kg of ketamine, 10 mg/kg of (2 R,6 R)-HNK, or saline. Ketamine and (2 R,6 R)-HNK both affected multiple pathways associated with inflammatory conditions. In addition, several changes were unique to either the healthy human volunteers and/or the mouse arm of the study, indicating that different pathways may be differentially involved in ketamine's effects in mice and humans. Mechanisms of action found to consistently underlie the effects of ketamine and/or (2 R,6 R)-HNK across both the human metabolome in plasma and CSF and the mouse arm of the study included LAT1, IDO1, NAD+, the nitric oxide (NO) signaling pathway, and sphingolipid rheostat.


Assuntos
Transtorno Depressivo Maior , Ketamina , Animais , Antidepressivos/uso terapêutico , Encéfalo/metabolismo , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/metabolismo , Humanos , Ketamina/uso terapêutico , Metabolômica , Camundongos
5.
J Clin Psychopharmacol ; 42(3): 254-259, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35499958

RESUMO

PURPOSE/BACKGROUND: Subanesthetic dosing of intravenous ketamine has shown to be an effective treatment for patients with major depressive disorder. It is unknown whether sympathetic response is related to treatment outcomes. The purpose of this study is to evaluate sympathetic response to ketamine infusions as it relates to treatment outcomes. METHODS/PROCEDURES: This retrospective study examines an outpatient population diagnosed with major depressive disorder or bipolar depression treated with ketamine infusions. Patient characteristics, depressive symptoms measured with the Patient Health Questionnaire (PHQ-9), and vital signs were retrieved by chart review. Patients (n = 145) were categorized as responders (50% reduction in PHQ-9 or less than 10 on final PHQ-9) or nonresponders. Changes in vital signs were recorded during each infusion for the initiation series. FINDINGS/RESULTS: Ketamine responders (51.7%) showed a significant greater increase in systolic blood pressure response during the first infusion when compared with nonresponders. There was no difference seen in diastolic pressure, heart rate, or rate pressure product. Changes in vital signs for subsequent infusions also did not approach significance. IMPLICATIONS/CONCLUSIONS: Physiologic sensitivity to the effects of ketamine may predict treatment responsiveness. Blood pressure and heart rate did not always increase. Further work should examine possible influences on physiologic responses.


Assuntos
Transtorno Depressivo Maior , Ketamina , Pressão Sanguínea , Depressão , Transtorno Depressivo Maior/tratamento farmacológico , Humanos , Prognóstico , Estudos Retrospectivos
6.
J Avian Med Surg ; 36(1): 21-27, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35526161

RESUMO

The objective of this study was to compare the sedative effects of intramuscular alfaxalone combined with either ketamine or midazolam in chickens (Gallus gallus domesticus). A prospective, randomized blinded crossover study design with a 7-day washout period was used. Nine adult layer hens received alfaxalone 15 mg/kg with ketamine 5 mg/kg IM (treatment AK) or alfaxalone 15 mg/kg with midazolam 1 mg/kg IM (treatment AM). Time to lateral recumbency, time to loss of righting reflex, induction quality, duration of loss of righting reflex, time to sternal recumbency or vigorous response to stimulation, and time to standing were recorded. Muscle tone, response to noxious stimulation, heart rate, respiratory rate, and oxygen saturation were monitored once the righting reflex was absent. Induction and recovery times were not different between treatments. Lateral recumbency was induced in 8 of 9 birds receiving AK compared to 6 of 9 birds receiving AM. Righting reflex was absent in 7 of 9 and 5 of 9 chickens administered AK and AM, respectively. Median time to loss of righting reflex for AK and AM were 5.5 (4.3-9.3) minutes and 9.1 (4.8-15.0) minutes, respectively (P = .88). Median duration of loss of righting reflex was 21.6 (16.0-36.9) minutes for AK and 21.1 (11.9-26.4) minutes for AM (P = .38). Alfaxalone-ketamine resulted in moderate excitation during induction. Further investigations are warranted to investigate the effects of alfaxalone and midazolam or ketamine at different doses.


Assuntos
Ketamina , Midazolam , Animais , Galinhas , Estudos Cross-Over , Feminino , Hipnóticos e Sedativos/farmacologia , Ketamina/farmacologia , Midazolam/farmacologia , Pregnanodionas , Estudos Prospectivos
7.
Behav Neurol ; 2022: 9015842, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35600241

RESUMO

Methods: In this experimental study, 64 mice were divided into 8 groups and received the following: normal saline; EA at doses of 6.25, 12.5, and 25 mg/kg; NMDA agonist at a dose of 75 mg/kg; NMDA antagonist (ketamine) at a dose of 0.5 mg/kg; an effective dose of EA plus NMDA agonist; and a subeffective dose of EA plus ketamine. We induced seizure using intravenous administration of PTZ. 60 minutes before induction of seizure, drugs were administrated. Duration lasts to seizure-induced was measured. Finally, the gene expression of NMDA receptor subunits (Nr2a and Nr2b) was assessed in the prefrontal cortex. Results: Results showed that EA increased the seizure threshold and decreased the expression of Nr2a and Nr2b. We determined that ketamine potentiated and NMDA attenuated the effects of subeffective and effective doses of EA. Conclusion: EA probably via attenuation of the NMDA-R pathway possesses an anticonvulsant effect in PTZ-induced seizure in mice.


Assuntos
Ketamina , Pentilenotetrazol , Animais , Anticonvulsivantes/uso terapêutico , Relação Dose-Resposta a Droga , Ácido Elágico/efeitos adversos , Ketamina/efeitos adversos , Masculino , Camundongos , N-Metilaspartato/efeitos adversos , Pentilenotetrazol/efeitos adversos , Receptores de N-Metil-D-Aspartato/metabolismo , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico
8.
J Clin Psychiatry ; 83(2)2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35377565

RESUMO

Five randomized controlled trials (RCTs) have compared racemic ketamine, mostly administered intravenously in the dose of 0.5 mg/kg across 40-45 minutes, with right unilateral or bilateral electroconvulsive therapy (ECT). These RCTs were conducted in samples of severely ill patients with mostly unipolar depression (with or without psychotic features) who were referred for ECT. Of these, 2 RCTs were of reasonably adequate quality to inform clinical practice; one, in fact, was large (n = 186) and had a 1-year post-treatment follow-up. In these RCTs, ECT emerged as a clearly superior treatment with regard to response rate, remission rate, time to response, time to remission, and magnitude of improvement at treatment endpoint; however, relapse rate and time to relapse did not differ between ECT and ketamine groups. ECT appeared superior in older patients and in those with psychotic depression, as well. These findings notwithstanding, response and remission rates with ketamine appeared sufficiently impressive for ketamine to be viewed as a viable alternative to ECT in severely depressed patients who are referred for ECT. Notably, in such patients ketamine does not appear to have dramatic antidepressant action; rather, the benefits evolve across a course of 6 or more alternate day, thrice weekly sessions, validating the concept of a course of ketamine treatment that is administered much as ECT is. Finally, whereas the high relapse rates after successful remission encourage the use of ECT and ketamine as continuation therapy, continuation ketamine must be carefully supervised in patients who are prone to substance abuse.


Assuntos
Transtorno Depressivo Maior , Eletroconvulsoterapia , Ketamina , Idoso , Depressão , Transtorno Depressivo Maior/tratamento farmacológico , Eletroconvulsoterapia/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Riv Psichiatr ; 57(2): 57-66, 2022.
Artigo em Italiano | MEDLINE | ID: mdl-35426424

RESUMO

About a third of patients with major depressive disorder (MDD) do not have an adequate response to first-line antidepressant treatment, i.e., develop a treatment-resistant depression (TRD). The partial understanding of MDD pathophysiology currently constitutes the major barrier to clinical and research progress on this topic. However, recent advances in genome editing techniques as well as in induced pluripotent stem cells (iPSC) technology are offering unprecedented opportunities in both human disease modelling and drug discovery. These technology progresses have been enabling to set up disease-relevant patient-specific in vitro disease modeling for various mental disorders. The resulting models have the potential to significantly improve pathophysiologic understanding of MDD and then overcome some limitations inherent to animal and post-mortem models. More recently, psychiatry started to deal with the fast acting antidepressant ketamine and its derivates. Although ketamine appears to have the potential to transform the treatment of depression, its specific mechanisms of action are only partially known. Such knowledge is necessary to develop a model to understand the mechanisms behind fast-acting antidepressants, which may enable the discovery of novel glutamatergic compounds for the treatment of MDD. After discussing both the current understanding of ketamine's mechanisms of action, and the state of the art of human iPSC technology, the authors will introduce the implementation of a TRD model based on iPSC human technology and aimed at studying the ketamine's fast acting antidepressant mechanisms of action.


Assuntos
Transtorno Depressivo Maior , Transtorno Depressivo Resistente a Tratamento , Ketamina , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Humanos , Ketamina/farmacologia , Ketamina/uso terapêutico
10.
Zhonghua Yi Xue Za Zhi ; 102(15): 1108-1113, 2022 Apr 19.
Artigo em Chinês | MEDLINE | ID: mdl-35436810

RESUMO

Objective: To investigate the effect of continuous intravenous infusion of subanesthetic dose of esketamine intraoperatively on postoperative opioid consumption in patients undergoing thoracoscopic surgery. Methods: A total of 71 patients with elective thoracoscopic lung surgery in the First Affiliated Hospital of Zhengzhou University from December 2020 to December 2021 were selected. Patients who were classified as grade Ⅰ or Ⅱ by the American Society of Anesthesiologists (ASA) and aged 18-70 years were included, including 32 males and 39 females, with a body mass index (BMI) of 18.5-30.0 kg/m2. The patients were randomly divided into three groups: (1) Control group (group C, n=24): continuous intravenous infusion of normal saline at the same rate during surgery; (2) Subanesthetic dose of esketamine 0.125 mg·kg-1·h-1 group (group ES1, n=23): continuous intravenous infusion of esketamine at a rate of 0.125 mg·kg-1·h-1 during surgery; (3) Subanesthetic dose of esketamine 0.250 mg·kg-1·h-1 group (group ES2, n=24): continuous intravenous infusion of esketamine at a rate of 0.250 mg·kg-1·h-1 during surgery. The main outcome measures were the total consumptions of hydromorphone of 3 groups within 24 and 48 hours after surgery. The secondary outcome measures were the extubation time, length of postanesthesia care unit (PACU) stay, the time of first feeding, and the incidences of adverse effects within 24 h after surgery in 3 groups. Results: The 24 h postoperative consumption of hydromorphone in group C, ES1 and ES2 was (5.4±1.0) mg, (4.5±1.5) mg and (4.0±0.8) mg, respectively. Likewise, the 48 h postoperative consumption of hydromorphone was (9.7±2.2) mg, (9.0±3.0) mg and (7.7±1.8) mg, respectively. Compared with group C, the 24 h postoperative hydromorphone consumptions were significantly reduced in group ES1 and ES2 (both P<0.05). The extubation time, length of PACU stay and the time of first feeding after surgery in group C were (23±10) min,(70±12) min,(17±3) h,in group ES1 were (22±4) min,(69±11) min,(14±5) h,in group ES2 were (16±8) min,(58±12) min,(14±3) h, respectively. Compared with group C and group ES1, both of the extubation time and length of PACU stay were shortened in group ES2 (both P<0.05). Compared with group C, the first postoperative feeding time of group ES1 and ES2 was shortened (both P<0.05). There were no differences in the incidences of adverse effects at postoperative 24 h among 3 groups (all P>0.05). Conclusion: Continuously intravenous infusion of subanesthetic esketamine at a rate of 0.250 mg·kg-1·h-1 can significantly reduce the postoperative opioid consumption and improve the patient's outcomes.


Assuntos
Analgésicos Opioides , Ketamina , Feminino , Humanos , Hidromorfona , Ketamina/uso terapêutico , Masculino , Dor Pós-Operatória/tratamento farmacológico , Toracoscopia
11.
Drug Des Devel Ther ; 16: 1131-1142, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35478936

RESUMO

Background: Being the S-enantiomer of racemic ketamine, esketamine is found to be effective for sedation, analgesia, and treating depression. However, there is no comprehensive bibliometric analysis about esketamine research. In this study, we aimed to determine the scientific output and emerging topics related to esketamine. Methods: Esketamine-related articles and reviews that published between 2000 and 2020 were obtained from the Web of Science Core Collection database, using key word search of "esketamine" "esketamine hydrochloride", "s-ketamine", "S(+)-ketamine", "(S)-ketamine", or "(-)-ketamine". Various bibliographic elements were collected, including the annual number of publications, citation frequency, countries/regions, institutions, authors, journals, and keywords. Two sorts of scientometric software, namely VOS viewer and CiteSpace, were used to conduct bibliometric and knowledge-map analyses. Results: A total of 683 publications were included in the current study. We found the number of publications in esketamine research field had increased annually since 2016. The United States was the leader in this field, with the highest publications number (162, 23.72%), total citations (3504/9713, 36.08%) and H-index (40). The most productive institution was Chiba University in Japan, and esketamine-related papers were mainly published in the journal Anesthesia & Analgesia. The keyword co-occurrence analysis showed that keywords relevant to depression were the most frequent. Moreover, all identified keywords could be divided into four clusters, with the research focus gradually shifting from cluster of "anesthesia and analgesia detection" to "depression treatment effect.". Conclusion: The past two decades have shown a marked increase in esketamine research. The United States maintained a top position worldwide, making the most significant contributions in the field of esketamine research. The contributions and collaborations of Asian countries have continuously increased and is a strong area of growth as well as development in recent years. Additionally, the emerging hotspots of esketamine research concentrate on clarifying its depression treatment effect.


Assuntos
Ketamina , Bibliometria , Bases de Dados Factuais , Humanos , Dor , Estados Unidos
13.
Pain Res Manag ; 2022: 1507097, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401887

RESUMO

Objective: Although low-dose ketamine has been shown to be generally beneficial in terms of pain control in a variety of major surgery, there is no consensus regarding the effectiveness of supplemental ketamine analgesic use exclusively in spine surgery. The objective of this systematic review and meta-analysis of randomized controlled trials (RCTs) was to assess the efficacy and safety of perioperative low-dose ketamine for pain management and analgesic consumption in patients undergoing spine surgery. Methods: A comprehensive literature search was performed for relevant studies using PubMed, EMBASE, Web of Science, and Cochrane Library. Patients who received perioperative low-dose ketamine were compared to the control group in terms of postoperative pain intensity, opioid consumption, and adverse events. Patients were further categorized by ages and administration times for subgroup analysis. Results: A total of 30 RCTs comprising 1,865 patients undergoing elective spine surgery were included. Significantly lower pain intensity and less opioid consumption at 12 h, 24 h, and 48 h postoperatively and lower incidence of postoperative nausea and vomiting (PONV) were observed in the ketamine group (all P < 0.05). There was no significant difference of central nervous system (CNS) adverse events between groups. However, different efficacy of low-dose ketamine was detected when patients were categorized by ages and administration times. Conclusion: Perioperative low-dose ketamine demonstrated analgesic and morphine-sparing effect with no increased adverse events after spine surgery. However, this effect was not significant in pediatric patients. Only postoperative or intraoperative and postoperative administration could prolong the analgesic time up to 48 h postoperatively. Further studies should focus on the optimal protocol of ketamine administration and its effect on old age participants.


Assuntos
Ketamina , Analgésicos , Analgésicos Opioides , Criança , Humanos , Ketamina/efeitos adversos , Ketamina/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto
14.
BMC Vet Res ; 18(1): 134, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35410207

RESUMO

BACKGROUND: The present study aimed to investigate the effect of endotracheal intubation on nasal and tracheal endogenous NO concentrations, gas exchange and oxygenation in horses undergoing general anaesthesia. In many species a major part of physiological nitric oxide (NO) production takes place in the nasopharynx. Inhaled NO acts as a pulmonary vasodilator and regulates lung perfusion and endotracheal intubation bypasses the nasopharynx. Six horses were randomly assigned to either the "intubated" (INT) or the "non-intubated" (nINT) treatment group. Horses were premedicated with dexmedetomidine (5 µg/kg IV). Anaesthesia was induced with 2.5 mg/kg ketamine and 0.05 mg/kg diazepam IV, and it was maintained by administration of a triple-drip (100 mg/kg/h guaifenesin, 4 mg/kg/h ketamine, 7 µg/kg/h dexmedetomidine). The horses were spontaneously breathing room air. Heart rate, cardiac output, arterial blood pressure, pulmonary arterial blood pressures and respiratory rate were recorded during a 100-min anaesthesia period. Arterial, venous and mixed venous blood samples were taken every 10 minutes and analysed for partial pressure of oxygen (PO2) and carbon dioxide (PCO2), oxygen saturation and haemoglobin content. Standard oxygenation indices were calculated. Nasal and tracheal endogenous NO concentration was determined by chemiluminescence. RESULTS: Cardiovascular variables, respiratory rate, PO2, PCO2, oxygen saturation, haemoglobin content, CaO2, O2ER, P(a-ET)CO2 and Qs/Qt did not differ significantly between the two treatment groups. The P(A-a)O2 was significantly higher in INT (6.1 ± 0.3 kPa) compared to nINT (4.9 ± 0.1 kPa) (p = 0.045), respectively. The nasal (8.0 ± 6.2 ppb) and tracheal (13.0 ± 6.3 ppb) endogenous NO concentration differed significantly in INT (p = 0.036), but not in nINT (nasal: 16.9 ± 9.0 ppb; tracheal: 18.5 ± 9.5 ppb) (p = 0.215). CONCLUSION: Endotracheal intubation reduces the nasal and tracheal endogenous NO concentration. The influence on pulmonary gas exchange and oxygenation is negligible in horses breathing room air.


Assuntos
Dexmedetomidina , Ketamina , Anestesia Geral/veterinária , Anestesia Intravenosa/veterinária , Animais , Dexmedetomidina/farmacologia , Cavalos , Ketamina/farmacologia , Pulmão , Óxido Nítrico , Oxigênio , Respiração
15.
Behav Brain Res ; 428: 113895, 2022 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-35439523

RESUMO

Current pharmacotherapy for post-traumatic stress disorder (PTSD), a debilitating psychiatric condition that develops in a subset of traumatized individuals, is inadequate. Over the past two decades, numerous studies have shown that ketamine, a non-competitive NMDA receptor antagonist, exerts rapid antidepressant effects in both humans and rodents, but the anxiolytic profile of ketamine, as well as its ability to treat PTSD-related symptoms, is still unclear. Thus, we examined the ability of a single administration of ketamine to prevent the onset of PTSD-like sequelae in a chronic psychosocial stress model of PTSD. Adult male and female Sprague-Dawley rats were exposed to a cat on two occasions, in combination with chronic social instability. Immediately following the cat exposure on Day 1, rats were given intraperitoneal injections of 10 mg/kg or 15 mg/kg ketamine or vehicle; control rats were injected with vehicle. Three weeks after the second cat exposure, we assessed symptoms of hyperarousal and anxiety-like behavior in the rats. In males, chronic stress led to greater anxiety on the elevated plus maze and in the open field; in females, chronic stress resulted in an exaggerated startle response and greater anxiety in the open field. These effects were most effectively prevented by the administration of 10 mg/kg ketamine. These findings demonstrate that ketamine can prophylactically prevent the onset of PTSD-like behaviors in males and females. Their sex-dependent nature is consistent with previous preclinical research and highlights the need for future research to examine their neurobiological basis.


Assuntos
Ketamina , Transtornos de Estresse Pós-Traumáticos , Animais , Ansiedade/tratamento farmacológico , Ansiedade/etiologia , Modelos Animais de Doenças , Feminino , Ketamina/farmacologia , Masculino , Ratos , Ratos Sprague-Dawley , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Estresse Psicológico/complicações , Estresse Psicológico/tratamento farmacológico
16.
J Affect Disord ; 308: 44-46, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35405177

RESUMO

OBJECTIVES: On a background of the rapidly expanding clinical use of ketamine and esketamine for treatment of depression and other conditions, we examined safety monitoring, seeking to identify knowledge gaps relevant to clinical practice. METHODS: An international group of psychiatrists discussed the issue of safety of ketamine and esketamine and came to a consensus on key safety gaps. RESULTS: There is no standard safety monitoring for off-label generic ketamine. For intranasal esketamine, each jurisdiction providing regulatory approval may specify monitoring. Treatment is often provided beyond the period for which safety has been demonstrated, with no agreed framework for monitoring of longer term side effects for either generic ketamine or intranasal esketamine. LIMITATIONS: The KSET has established face and content validity, however it has not been validated against other measures of safety. CONCLUSIONS: We recommend the Ketamine Side Effect Tool (KSET) as a comprehensive safety monitoring tool for acute and longer term side effects.


Assuntos
Transtorno Depressivo Resistente a Tratamento , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Ketamina , Psiquiatria , Administração Intranasal , Antidepressivos/uso terapêutico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Humanos , Ketamina/efeitos adversos
17.
J Affect Disord ; 308: 243-248, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35429526

RESUMO

BACKGROUND: Early markers preceding suicide ideation (SI) may provide valuable information for both assessment and treatment. The glutamatergic modulator ketamine has rapid, transient effects on SI, creating an opportunity to observe potential antecedents of the re-emergence of SI. This analysis evaluated whether the interaction between two suicide risk factors-psychological pain and hopelessness-were prospectively associated with SI post-ketamine administration. METHODS: Data were drawn from three ketamine clinical trials of participants with treatment-resistant major depressive disorder or bipolar disorder (n = 108) with short- and/or long-term follow-up (three or 11 days). A random intercept cross-lagged panel model evaluated the longitudinal relationship between the correlated concepts, specifically whether the interaction between hopelessness and psychological pain was associated with future SI. RESULTS: Psychological pain and hopelessness were not prospectively associated with SI in short-term or long-term analyses; rather, long-term analyses found that SI was associated with later psychological pain and hopelessness. Similarly, no relationship was observed for other suicide risk factors, including anhedonia, depressed mood, and impaired sleep. LIMITATIONS: Secondary analysis of clinical trial data not collected for this purpose; hopelessness and psychological pain were assessed via proxy measures from existing depression rating scales; the small sample size required a restricted statistical model. CONCLUSIONS: Psychological pain and hopelessness were not associated with the re-emergence of SI post-ketamine. These results may be due to limited variability in the data. The re-emergence of SI post-ketamine may also not follow patterns typically seen in non-pharmacologic contexts. Individuals with a history of SI warrant careful monitoring post-ketamine administration.


Assuntos
Transtorno Depressivo Maior , Transtorno Depressivo Resistente a Tratamento , Ketamina , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/psicologia , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Humanos , Ketamina/uso terapêutico , Dor/tratamento farmacológico , Ideação Suicida
18.
J Affect Disord ; 308: 289-297, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35429529

RESUMO

BACKGROUND: The glutamate N-methyl-d-aspartate (NMDA) receptor antagonist ketamine rapidly ameliorates posttraumatic stress disorder (PTSD) and depression symptoms in individuals with comorbid PTSD and major depressive disorder (MDD). However, concerns over ketamine's potential neurocognitive side effects have yet to be assessed in this population. The current study investigated 1) changes in neurocognitive performance after a repeated ketamine dosing regimen and 2) baseline neurocognitive performance as a predictor of ketamine treatment effect. METHOD: Veterans with comorbid PTSD and MDD (N = 15) received six infusions of 0.5 mg/kg ketamine over a 12-day period. Neurocognitive and clinical outcomes assessments occurred at baseline and within 7 days of infusion-series completion using the CogState battery. RESULTS: Repeated ketamine infusions did not significantly worsen any measures of cognition. Rather, significant improvement was observed in working memory following completion of the infusion series. In addition, greater improvements in PTSD and MDD symptoms were associated with lower working memory, slower processing speed and faster set shifting at baseline. Lower verbal learning was also predictive of improvement in depression. LIMITATIONS: This study applied an open-label design without a placebo control. As such, it is not known to what extent the correlations or improvement in neurocognitive performance may have occurred under placebo conditions. CONCLUSION: This is the first study to examine the neurocognitive effects of repeated ketamine in participants with comorbid PTSD and MDD. Our findings suggest potential baseline neurocognitive predictors of ketamine response for comorbid PTSD and MDD symptoms.


Assuntos
Transtorno Depressivo Maior , Ketamina , Transtornos de Estresse Pós-Traumáticos , Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/epidemiologia , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Humanos , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Transtornos de Estresse Pós-Traumáticos/epidemiologia
19.
BMJ Open ; 12(4): e056713, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35473735

RESUMO

INTRODUCTION: Depressive symptoms are common for patients undergoing major surgery and may worsen their mental health and lead to poor clinical outcomes. It is essential to seek a safe rapid-acting treatment for relieving moderate-to-severe depressive symptoms in patients undergoing major surgery. METHODS AND ANALYSIS: This study is a randomised, placebo-controlled and double-blinded trial aiming to determine the effect of esketamine on moderate-to-severe depressive symptoms in patients undergoing major surgery. Five hundred and sixty-four participants, aged 18-65 years old, undergoing major surgery will be randomly allocated into the esketamine and placebo groups at a 1:1 ratio. Esketamine or placebo will be given intravenously at the same speed on suturing the incision by anaesthesiologists in charge who are blinded to the randomisation. In the esketamine group, the total dosage of esketamine will be 0.2 mg/kg body weight. To estimate the efficacy and safety endpoints, blinded evaluation by trained researchers will be completed at 3 days, 5 days, 1 month, 3 months and 6 months after surgery. The primary outcome is the remission rate at the third postoperative day. The secondary outcomes include depression-related scores, severe pain events and safety-related endpoints such as psychotic symptoms, manic symptoms and dissociative symptoms. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board of Beijing Tiantan Hospital, Capital Medical University, Beijing, China on 30 October 2020 (KY-2020-058-02). This trial is designed to explore whether the administration of esketamine could improve the mental health of patients with depressive symptoms undergoing major surgery. The conclusions of this study will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04425473.


Assuntos
Depressão , Ketamina , Adolescente , Adulto , Idoso , Antidepressivos/uso terapêutico , China , Depressão/psicologia , Humanos , Ketamina/uso terapêutico , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
20.
BMC Anesthesiol ; 22(1): 114, 2022 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-35448950

RESUMO

BACKGROUND: Etomidate was associated with an inhibition of adrenal steroid synthesis. This study aimed to evaluate the effects of adding low-dose ketamine to etomidate to minimize the decrease in serum cortisol level in critically ill cardiac patients. METHODS: Sixty adult cardiac patients, ≥ 18 years, who underwent upper endoscopy and Colonoscopy to manage acute anemia in the cardiac intensive care units were enrolled. Patients were randomly divided into two groups: (group (E): n = 30) received etomidate 0.2 mg/kg IV followed by etomidate 0.05 mg/kg IV, and (group (KE): n = 30) received ketamine 0.5 mg/kg IV, then etomidate 0.1 mg/kg IV, followed by etomidate 0.05 mg/kg IV. The primary outcome was Serum cortisol level at 6 h after the procedure. RESULTS: The mean postoperative cortisol level was significantly lower in group E (295.60 ± 49.218 nmol/L) versus group KE (461.00 ± 67.946 nmol/L), with 95% CI = 351.94 to 404.66; p = 0.000. In addition, the estimated serum cortisol reduction level was also significant between groups; In group E, the estimated cortisol level decreased nearly 53% from 632.40 ± 35.066 nmol/L to 295.60 ± 49.218 nmol/L 6 hours postoperative. While in group KE, the estimated cortisol level decreased only 27% from 639.13 ± 43.035 nmol/L to 461.00 ± 67.946 nmol/L. CONCLUSIONS: Single-dose ketamine (0.5 mg/kg) was helpful to decrease the total dose of etomidate and hence decreased the percentage of serum cortisol level in such critically ill patients with preservation of patient satisfaction. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov ( NCT04857450 ; principal investigator: Mostafa Mohammed Elsaid Elhamamsy; registration date: 23/04/ 2021).


Assuntos
Etomidato , Ketamina , Adulto , Anestésicos Intravenosos/farmacologia , Estado Terminal , Etomidato/farmacologia , Humanos , Hidrocortisona
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