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1.
Medicine (Baltimore) ; 99(36): e21859, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899015

RESUMO

BACKGROUND: The purpose of this study was to evaluate the effects of adding ketamine to propofol on cognitive functions in patients undergoing sedation for colonoscopy. METHODS: In this randomized, double-blinded, and controlled study, 200 patients were randomly allocated to ketamine/propofol admixture group (Group KP, n = 100), and propofol group (Group P, n = 100). Patients in Group KP received 0.25 mg/kg of ketamine and 0.5 mg/kg of propofol. Patients in Group P received 0.5 mg/kg propofol. Cognitive functions were measured using CogState battery before and after the colonoscopy procedure. Ninety five patients in Group KP and 92 patients in Group P had completed the CogStates tests and were included in the data analysis. RESULTS: Compared with before procedure baseline, the performance on detection and identification tasks were significantly impaired after the procedure in both Group KP (P = .004, P = .001) and Group P patients (P = .005, P < .001). However, one-card learning accuracy and One-back memory was only impaired in Group KP patients (P = .006, P = .040) after the endoscopy but left intact in Group P patients. Group KP patients showed more severe impairment in one-card learning accuracy compared with Group P patients (P = .044). Group KP patients have better 5 minutes MAP (P = .005) and were also less likely to suffer from complications such as respiratory depression (P = .023) and hypotension (P = .015). OAA/S scores, BIS, MAP, complications, recovery times, and endoscopist and patient satisfaction were similar between the 2 groups. CONCLUSION: Although adding ketamine to propofol for sedation in colonoscopy provided fewer complications such as respiratory depression and hypotension, it also causes more impairment in cognitive functions.


Assuntos
Colonoscopia/métodos , Sedação Profunda/métodos , Hipnóticos e Sedativos/farmacologia , Ketamina/farmacologia , Complicações Cognitivas Pós-Operatórias/induzido quimicamente , Propofol/farmacologia , Adulto , Sedação Profunda/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Hipnóticos e Sedativos/administração & dosagem , Ketamina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Propofol/administração & dosagem , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
PLoS One ; 15(8): e0237174, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32776966

RESUMO

Postoperative sore throat is one of the most common complications following endotracheal intubation. Nebulization therapy, a preferable and safety method of drug delivery, has been shown to be effective in postoperative sore throat prevention in many studies. However, the relative efficacy of various nebulized agents remains unknown. In this review, we aimed to quantify and rank order the efficacy of available nebulized agents for various postoperative sore throat-related outcomes. A comprehensive literature search of PubMed, EMBASE, CENTRAL and Google Scholar was conducted to identify eligible studies from inception to 25 May 2020. Incidence of postoperative sore throat 1hour and 24hours postoperatively and severity of postoperative sore throat 24 hours postoperatively were the primary outcomes. We conducted a Bayesian network meta-analysis to combine direct and indirect evidence to estimate the relative effects between treatments as well as the probabilities of ranking for treatments based on their protective effects. We identified 32 trials assessing 6 interventions. Overall inconsistency and heterogeneity were acceptable. Nebulized corticosteroids, magnesium, and ketamine differed from non-analgesic methods on the three primary outcomes. Based on the surface under the cumulative ranking curve, nebulized corticosteroids ranked first in almost all outcomes among the nebulized drugs. Considering only high-quality and 2-arm design studies, nebulized corticosteroids still seemed best. In conclusion, prophylactic use of nebulized corticosteroids, magnesium, and ketamine can effectively prevent postoperative sore throat, and nebulized corticosteroids appears to be the overall best approach.


Assuntos
Corticosteroides/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Ketamina/uso terapêutico , Magnésio/uso terapêutico , Nebulizadores e Vaporizadores , Faringite/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Administração por Inalação , Corticosteroides/administração & dosagem , Adulto , Anestesia Geral/efeitos adversos , Teorema de Bayes , Feminino , Humanos , Incidência , Intubação Intratraqueal/efeitos adversos , Ketamina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Metanálise em Rede , Faringite/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento
3.
Adv Pharmacol ; 89: 131-162, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32616205

RESUMO

Major depressive disorder (MDD) is a debilitating illness with significant morbidity and mortality, leading to attempted and completed suicides. It affects interpersonal relationships and also contributes to decreased productivity, causing financial burden to individuals and society. Patients often fail to respond to various antidepressant medication trials resulting in treatment-resistant depression (TRD). Current antidepressant medications work by modulating the monoaminergic systems and takes several weeks to establish a clinical response. Ketamine has been used extensively as an anesthetic agent since the 1970s, and more recent research has shown its rapid and robust effectiveness in TRD the subject of this review. Ketamine is a racemic mixture comprised of two enantiomers (R)-ketamine and (S)-ketamine and acts as an NMDA receptor antagonist. Most research studies have explored its antidepressant and antisuicidal effects by using it as an intravenous infusion or via the intranasal route due to increased bioavailability. Recently an intranasal esketamine spray was approved by the United States Food and Drug Administration (FDA) for TRD as an adjunct to standard antidepressant treatment in a supervised setting. Regarding its safety profile, multiple research studies have established the short-term safety and efficacy of ketamine in TRD. The cardiorespiratory and neuropsychiatric adverse events observed in these studies were mostly transient. However, ketamine is a scheduled agent with abuse potential, making its long-term use challenging and mandating further research.


Assuntos
Depressão/tratamento farmacológico , Ketamina/uso terapêutico , Antidepressivos/uso terapêutico , Humanos , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Ketamina/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores de N-Metil-D-Aspartato/metabolismo , Suicídio
4.
Adv Pharmacol ; 89: 237-259, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32616208

RESUMO

Major depressive disorder (MDD) is the leading cause of disability worldwide and reduces life expectancy. Achieving and sustaining remission from depression is challenging after initial improvement of an acute episode with an antidepressant, especially for patients whose depressive episodes have proven treatment-resistant in response to conventional antidepressant pharmacotherapy. While standard antidepressants are at least partly effective for the short-term treatment of acute depressive episodes of MDD, many patients relapse within 6 months of apparent clinical remission, with faster and higher rates observed in those with treatment-resistant depression (TRD). Efficacy of IV ketamine, a rapid-acting N-methyl d-aspartate (NMDA) receptor antagonist, in maintaining antidepressant effect was suggested in a few small, single center, open-label studies and case series. More recently, maintenance of antidepressant effects beyond the initial acute (induction) treatment period has been shown with esketamine nasal spray, an enantiomer of ketamine, in conjunction with an oral antidepressant in three phase 2/3 registration studies (SYNAPSE, SUSTAIN-1, SUSTAIN-2) of adult patients with TRD. In these studies the maintenance of efficacy of an intermittently-dosed esketamine treatment regimen was established in which twice-weekly dose administration during a 4-week induction period was followed initially by weekly administration and later by either weekly or every-other-week administration. During long-term maintenance therapy the antidepressant effect persisted in most patients with this regimen, despite their history of being resistant to conventional antidepressants prior to entering esketamine studies. These data suggest that the neurobiological changes induced by initial esketamine treatment, which putatively underlie its antidepressant effect, can be maintained using repeated administration.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Prevenção Secundária , Antidepressivos/farmacologia , Ensaios Clínicos como Assunto , Humanos , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Ketamina/uso terapêutico
5.
Adv Pharmacol ; 89: 261-286, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32616209

RESUMO

A serious lack of effective pharmacotherapeutic interventions for posttraumatic stress disorder (PTSD) raises the urgent need for the development of novel treatments. Ketamine-a noncompetitive glutamate N-methyl-d-aspartate (NMDA) receptor antagonist in use for decades as an anesthetic and analgesic agent-has more recently been demonstrated to have rapid-onset antidepressant effects in patients with treatment-resistant depression (TRD). In the present review of ketamine as an emerging novel pharmacotherapeutic intervention for chronic PTSD, we discuss findings from the first proof-of-concept, randomized clinical trial (RCT) of single-dose intravenous ketamine in patients with chronic PTSD, as well as open-label studies and current practice. We introduce ongoing RCTs investigating the efficacy of repeated ketamine infusions in rapidly reducing symptoms and maintaining improvement in samples of individuals with PTSD stemming from civilian and military traumas. Additionally, we discuss mixed findings from published reports on ketamine administration in the acute aftermath of trauma. Studies in animal models of chronic stress have investigated molecular mechanisms underlying ketamine's effects, generating a shift in the conceptualization of PTSD as a disorder of impaired neural connectivity. We review animal studies examining the potential of ketamine to modify the expression of fear by altering memory reconsolidation or enhancing fear extinction, as well as others investigating ketamine administration prophylactically prior to stress exposure. We introduce the need for additional study in humans to evaluate whether ketamine might enhance the efficacy of psychotherapeutic interventions in individuals with chronic PTSD, harnessing a window of ketamine-induced neuroplasticity. While research on ketamine for PTSD is still in its early stages, it brings about the promise of novel and more effective treatments for this disabling condition.


Assuntos
Ketamina/uso terapêutico , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Modelos Animais de Doenças , Humanos , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Ketamina/farmacologia , Padrões de Prática Médica , Ensaios Clínicos Controlados Aleatórios como Assunto , Transtornos de Estresse Pós-Traumáticos/terapia
6.
Adv Pharmacol ; 89: 3-41, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32616211

RESUMO

A single sub-anesthetic intravascular dose of the use-dependent NMDAR antagonist, ketamine, improves mood in patients with treatment resistant depression within hours that can last for days, creating an entirely new treatment strategy for the most seriously ill patients. However, the psychomimetic effects and abuse potential of ketamine require that new therapies be developed that maintain the rapid antidepressant effects of ketamine without the unwanted side effects. This necessitates a detailed understanding of what cellular and synaptic mechanisms are immediately activated once ketamine reaches the brain that triggers the needed changes to elicit the improved behavior. Intense research has centered on the effects of ketamine, and the other rapidly acting antidepressants, on excitatory and inhibitory circuits in hippocampus and medial prefrontal cortex to determine common mechanisms, including key modifications in synaptic transmission and the precise location of the NMDARs that mediate the rapid and sustained antidepressant response. We review data comparing the effects of ketamine with other NMDAR receptor modulators and the muscarinic M1 acetylcholine receptor antagonist, scopolamine, together with evidence supporting the disinhibition hypothesis and the direct inhibition hypothesis of ketamine's mechanism of action on synaptic circuits using preclinical models.


Assuntos
Antidepressivos/farmacologia , Hipocampo/fisiologia , Ketamina/farmacologia , Inibição Neural/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Animais , Hipocampo/efeitos dos fármacos , Humanos , Ketamina/administração & dosagem , Ketamina/uso terapêutico , Caracteres Sexuais
9.
Medicine (Baltimore) ; 99(20): e20001, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443302

RESUMO

Elderly patients with femoral fractures are anticipated to endure the most pain caused by positional changes required for spinal anesthesia. To improve pain relief, we compared the analgesic effects of intravenous dexmedetomidine-ketamine and dexmedetomidine-fentanyl combinations to facilitate patient positioning for spinal anesthesia in elderly patients with proximal femoral fractures. Forty-six patients were randomly assigned to two groups and received either 1 mg/kg of intravenous ketamine (group K) or 1 µg/kg of intravenous fentanyl (group F) concomitant with a loading dose of dexmedetomidine 1 µg/kg over 10 minutes, then dexmedetomidine infusion only was continued at 0.6 µg/kg/h for following 20 minutes, and titrated at a rate of 0.2 to 0.6 µg/kg/h until the end of surgery. After completion of the infusion of either ketamine or fentanyl, the patients were placed in the lateral position with the fracture site up. The pain score (0 = calm, 1 = facial grimacing, 2 = moaning, 3 = screaming, and 4 = unable to proceed because of restlessness or agitation) was used to describe the pain intensity in each step during the procedure (lateral positioning, hip flexion, and lumbar puncture), and quality score (0 = poor hip flexion, 1 = satisfactory hip flexion, 2 = good hip flexion, and 3 = optimal hip flexion) was used to describe the quality of posture. Group K showed a median pain score of 0 (0-1), 0 (0-0) and 0 (0-0) in lateral positioning, hip flexion and lumbar puncture, respectively, while group F showed a score of 3 (2.75-3), 3 (2-3) and 0 (0-1), respectively. The pain score in lateral positioning (P < .0001) and hip flexion (P < .0001) was significantly lower in group K than group F. Group K showed the significantly higher quality scores of spinal anesthesia positioning (P = .0044) than group F. Hemodynamic adverse effects, such as bradycardia, hypotension, and desaturation, were not significantly different between the groups. The administration of dexmedetomidine-ketamine showed a greater advantage in reducing pain intensity and increasing the quality with patient positioning during spinal anesthesia in elderly patients with proximal femoral fractures, without any serious adverse effects.


Assuntos
Analgesia/métodos , Analgésicos/administração & dosagem , Raquianestesia , Fraturas do Quadril/cirurgia , Posicionamento do Paciente , Idoso , Idoso de 80 Anos ou mais , Dexmedetomidina/administração & dosagem , Método Duplo-Cego , Feminino , Fentanila/administração & dosagem , Humanos , Ketamina/administração & dosagem , Masculino
12.
J Clin Psychiatry ; 81(3)2020 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-32412700

RESUMO

OBJECTIVE: To compare esketamine to placebo, each in addition to standard-of-care treatment, for rapidly reducing major depressive disorder symptoms, including suicidal ideation. METHODS: This phase 3, double-blind, multicenter study (ASPIRE I), conducted between June 2017 and December 2018, enrolled 226 adults having major depressive disorder based on Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5) criteria, active suicidal ideation with intent, and need for psychiatric hospitalization. Patients were randomized 1:1 to esketamine 84 mg or placebo nasal spray twice-weekly for 4 weeks, each with comprehensive standard-of-care treatment (initial psychiatric hospitalization and newly initiated or optimized oral antidepressant[s] therapy). Change from baseline to 24 hours post-first dose in Montgomery-Asberg Depression Rating Scale (MADRS) total score (primary endpoint) was analyzed using analysis of covariance (ANCOVA), and change in Clinical Global Impression of Severity of Suicidality Revised version (CGI-SS-r; key secondary endpoint) score was analyzed using ANCOVA on ranks with treatment difference estimated using the Hodges-Lehmann estimate. RESULTS: Greater improvement in MADRS total score was observed with esketamine + standard-of-care versus placebo + standard-of-care at 24 hours (least-squares mean difference [SE]: -3.8 [1.39]; 95% CI, -6.56 to -1.09; 2-sided P = .006), as well as at earlier (4 hours) and later time points during 4-week double-blind treatment. The difference between groups in the severity of suicidality was not statistically significant (median of treatment difference [95% CI]: 0.0 [-1.00 to 0.00]; 2-sided P = .107). The most common adverse events among esketamine-treated patients were dizziness, dissociation, headache, nausea, and somnolence. CONCLUSIONS: These findings demonstrate rapid and robust efficacy of esketamine nasal spray in reducing depressive symptoms in severely ill patients with major depressive disorder who have active suicidal ideation with intent. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03039192.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Ketamina/uso terapêutico , Ideação Suicida , Administração Intranasal , Adolescente , Adulto , Antidepressivos/administração & dosagem , Antidepressivos/efeitos adversos , Transtorno Depressivo Maior/psicologia , Método Duplo-Cego , Feminino , Humanos , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Sprays Nasais , Adulto Jovem
13.
J Clin Psychiatry ; 81(4)2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32459407

RESUMO

OBJECTIVE: Esketamine, the S-enantiomer of ketamine, was recently approved as a rapid-acting intranasal therapy for depression and is currently under development for suicidality. The authors sought to determine the efficacy of adjunctive intranasal esketamine in major depressive disorder (MDD). DATA SOURCES: A systematic search of PubMed/MEDLINE was conducted up to January 2019, in addition to abstracts of major psychiatric meetings held since 2010. Searches were conducted by cross-referencing the term intranasal with the term esketamine. Where necessary, authors and/or study sponsors were contacted in order to obtain a copy of the presentation as well as any pertinent study details. STUDY SELECTION: 241 study abstracts were initially identified and reviewed. Selected studies were randomized, double-blind clinical trials comparing adjunctive intranasal esketamine to adjunctive placebo for MDD. DATA EXTRACTION: Data were extracted independently by two of the authors. A random effects model was used to calculate the standardized mean difference (SMD) between esketamine and placebo (intranasal saline) in the Montgomery-Asberg Depression Rating Scale (MADRS) score change from baseline to endpoint, serving as the primary outcome of the study. RESULTS: Five trials with 774 patients were pooled. Adjunctive esketamine was significantly more effective than placebo for MADRS score change, response, and remission (N = 774, SMD = 0.36, 95% CI = 0.24-0.49, P < .0001; response: risk ratio [RR] = 1.40, 95% CI = 1.22-1.61, P < .0001; remission: RR = 1.45, 95% CI = 1.20-1.75, P < .0001). Results remained statistically significant regardless of differences in the study sample, fixed vs new/optimized baseline antidepressants. CONCLUSIONS: Adjunctive intranasal esketamine for patients with MDD who are either treatment-resistant or acutely suicidal appears to be an effective treatment strategy.


Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Ketamina/uso terapêutico , Administração Intranasal , Antidepressivos/administração & dosagem , Antidepressivos/uso terapêutico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Quimioterapia Combinada/métodos , Humanos , Ketamina/administração & dosagem , Resultado do Tratamento
14.
Zhonghua Er Ke Za Zhi ; 58(4): 295-300, 2020 Apr 02.
Artigo em Chinês | MEDLINE | ID: mdl-32234136

RESUMO

Objective: To investigate the effectiveness of ketamine in the treatment of refractory status epilepticus (RSE) and super refractory status epilepticus (SRSE) in children. Methods: A retrospective study was conducted to collect and analyze the medical data of 18 children with RSE or SRSE who received ketamine in intensive care unit of Beijing Children's Hospital from January 2016 to December 2018. According to the different regimen of ketamine, all children were divided into the loading-maintenance group (7 cases) and the maintenance group (11 cases). According to the control of status epilepticus, the patients were divided into controlled group (11 cases) and non-responsive group (7 cases).Wilcoxon's rank sum test or Fisher's exact test were used to compare the effectiveness between groups. Results: There were 9 males and 9 females in the study group, aged 6.7 (4.5, 9.0) years. Seven cases had RSE and the remaining had SRSE. Four cases died during hospitalization. After the initiation of ketamine treatment, RSE and SRSE were controlled in 11 children. The duration of ketamine administration was 4 (2, 11) days. The dose was 2.2 (1.2, 5.3) mg/(kg·h) in all patients, and 2.4 (1.3, 6.0) mg/(kg·h), 2.0 (1.0, 4.0) mg/(kg · h) in the controlled and non-responsive group, respectively (Z=-0.272, P=0.791). The RSE or SRSE were terminated in all the 7 patients who received loading dose of ketamine, with the dose of 1.5 (0.3,1.6) mg/kg. In the 11 patients who only received maintenance treatment, 4 had the RSE and SRSE terminated, which showed a significantly lower effectiveness than in loading-maintenance group (7/7 vs. 4/11, P=0.01). Regarding the adverse reactions, saliva secretion increased in 8 children during the ketamine administration, otherwise unremarkable. Conclusion: Loading dose followed by maintenance of ketamine can control children's RSE and SRSE well, without significant adverse reactions.


Assuntos
Epilepsia Resistente a Medicamentos/tratamento farmacológico , Ketamina/administração & dosagem , Estado Epiléptico/tratamento farmacológico , Anticonvulsivantes , Criança , Pré-Escolar , Feminino , Hospitalização , Humanos , Unidades de Terapia Intensiva , Masculino , Estudos Retrospectivos
15.
Anesthesiology ; 132(5): 992-1002, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32235144

RESUMO

BACKGROUND: Various multimodal analgesic approaches have been proposed for spine surgery. The authors evaluated the effect of using a combination of four nonopioid analgesics versus placebo on Quality of Recovery, postoperative opioid consumption, and pain scores. METHODS: Adults having multilevel spine surgery who were at high risk for postoperative pain were double-blind randomized to placebos or the combination of single preoperative oral doses of acetaminophen 1,000 mg and gabapentin 600 mg, an infusion of ketamine 5 µg/kg/min throughout surgery, and an infusion of lidocaine 1.5 mg/kg/h intraoperatively and during the initial hour of recovery. Postoperative analgesia included acetaminophen, gabapentin, and opioids. The primary outcome was the Quality of Recovery 15-questionnaire (0 to 150 points, with 15% considered to be a clinically important difference) assessed on the third postoperative day. Secondary outcomes were opioid use in morphine equivalents (with 20% considered to be a clinically important change) and verbal-response pain scores (0 to 10, with a 1-point change considered important) over the initial postoperative 48 h. RESULTS: The trial was stopped early for futility per a priori guidelines. The average duration ± SD of surgery was 5.4 ± 2.1 h. The mean ± SD Quality of Recovery score was 109 ± 25 in the pathway patients (n = 150) versus 109 ± 23 in the placebo group (n = 149); estimated difference in means was 0 (95% CI, -6 to 6, P = 0.920). Pain management within the initial 48 postoperative hours was not superior in analgesic pathway group: 48-h opioid consumption median (Q1, Q3) was 72 (48, 113) mg in the analgesic pathway group and 75 (50, 152) mg in the placebo group, with the difference in medians being -9 (97.5% CI, -23 to 5, P = 0.175) mg. Mean 48-h pain scores were 4.8 ± 1.8 in the analgesic pathway group versus 5.2 ± 1.9 in the placebo group, with the difference in means being -0.4 (97.5% CI; -0.8, 0.1, P = 0.094). CONCLUSIONS: An analgesic pathway based on preoperative acetaminophen and gabapentin, combined with intraoperative infusions of lidocaine and ketamine, did not improve recovery in patients who had multilevel spine surgery.


Assuntos
Analgésicos não Entorpecentes/administração & dosagem , Analgésicos Opioides/administração & dosagem , Manejo da Dor/métodos , Dor Pós-Operatória/prevenção & controle , Doenças da Coluna Vertebral/cirurgia , Acetaminofen/administração & dosagem , Idoso , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Gabapentina/administração & dosagem , Humanos , Ketamina/administração & dosagem , Lidocaína/administração & dosagem , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/diagnóstico , Doenças da Coluna Vertebral/diagnóstico
16.
Am J Emerg Med ; 38(7): 1544.e5-1544.e6, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32317201

RESUMO

Low doses of ketamine have been shown to be safe and effective for pain relief. Adverse effects are generally mild and transient. A 69-year-old woman suffered a witnessed ground-level fall without report of head injury, loss of consciousness, or intoxication. She was in severe pain despite 10 mg of intravenous morphine and paramedics provided intravenous ketamine 16 mg (0.19 mg/kg). Upon arrival to the ED, she was alert and oriented. An X-ray demonstrated an acute comminuted nondisplaced right humeral head and neck fracture. Her pain improved after an additional 4 mg of morphine and placement of a sling. Prior to discharge, the patient developed confusion, difficulty finding words, amnesia to the event, and anterograde amnesia evidenced by repetitive questioning. A head CT and a CT angiogram of the patient's head and neck demonstrated no acute abnormalities and an EEG demonstrated no epileptiform activity. The patient was admitted for observation and her mental status gradually improved overnight. She was discharged the following morning. Low dose ketamine is an important therapeutic option. Delayed or prolonged neuropsychiatric effects may be possible following combined ketamine and opioid analgesia. Clinicians utilizing low dose ketamine should be aware of this potential complication as it could result in the need for additional diagnostic testing and prolonged length of stay.


Assuntos
Analgésicos/administração & dosagem , Analgésicos/efeitos adversos , Anemia/induzido quimicamente , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Acidentes por Quedas , Idoso , Relação Dose-Resposta a Droga , Serviços Médicos de Emergência , Feminino , Humanos , Dor/tratamento farmacológico
17.
Zoolog Sci ; 37(2): 159-167, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32282147

RESUMO

Kawai et al. (2011) recently introduced a mixture of three anesthetic agents (here called MMB) that has an effect similar to ketamine/xylazine in mice, which might allow more effective reaction to changes in the animal condition, as an antagonist is available, and which can be used without license for handling narcotic drugs. Using Kawai's study as a baseline, we tested whether this anesthesia and its antagonist can also be used in avian studies. In the present study, we used two species, the zebra finch and the Bengalese finch, of the avian family Estrildidae. In zebra finches, anesthesia effects similar to the use of ketamine/xylazine and to those obtained in mice can be reached by the use of MMB if a higher dose is applied. MMB leads to more variable anesthesia, but has the advantage of a longer time window of deep anesthesia. An antagonist to one component of MMB reduced the awaking time, but was not as effective as in mice. For Bengalese finches, MMB cannot be generally recommended because of difficult handling and high mortality rate when used without antagonist, but could be used for perfusions instead of pentobarbital.


Assuntos
Antagonistas de Receptores Adrenérgicos alfa 2/farmacologia , Anestésicos Combinados/administração & dosagem , Butorfanol/administração & dosagem , Imidazóis/farmacologia , Medetomidina/administração & dosagem , Midazolam/administração & dosagem , Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Antagonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Analgésicos Opioides/administração & dosagem , Animais , Feminino , Tentilhões , Hipnóticos e Sedativos/administração & dosagem , Imidazóis/administração & dosagem , Injeções Intramusculares , Ketamina/administração & dosagem , Masculino , Medetomidina/antagonistas & inibidores , Xilazina/administração & dosagem
19.
Psiquiatr. biol. (Internet) ; 27(1): 9-15, ene.-abr. 2020. graf
Artigo em Espanhol | IBECS | ID: ibc-193255

RESUMO

Los trastornos depresivos representan la principal causa de discapacidad en el mundo, siendo una de las enfermedades que requieren mayor número de bajas laborales y costes asociados. Los antidepresivos pueden tardar incluso meses en lograr respuesta y remisión. De hecho, se estima que el 30% de pacientes con trastorno depresivo mayor son resistentes al tratamiento. Recientemente se ha aprobado la esketamina intranasal como tratamiento de este tipo de pacientes. El desarrollo de este medicamento incluye numerosos estudios que apoyan su seguridad a corto y largo plazo en pacientes con depresión resistente al tratamiento. Por ello, el objetivo del presente estudio es realizar una revisión sistemática de estudios de fase III con esketamina intranasal. Tras realizar una búsqueda en Medline en la que se obtuvieron 5 estudios, 3 a corto plazo y 2 a largo, el tratamiento de esketamina intranasal en combinación con un antidepresivo oral ha demostrado ser eficaz y seguro en pacientes con depresión resistente al tratamiento. Los resultados de seguridad fueron consistentes en todos los estudios sin presentar efectos adversos inesperados a largo plazo


Depressive disorders are the main cause of incapacity at a world level on being one of the illnesses that require a large number of days off work and associated costs. Antidepressants may even take months to achieve a response and remission. In fact, it is estimated that 30% of patients with a Major Depressive Disorder are resistant to the treatment. Intranasal eskatamine has recently been approved as treatment for this type of patient. The development of this drug includes numerous studies that support its safety in the short- and long-term in patients with Treatment-Resistant Depression. For this reason, the aim of the present article is to perform a systematic review of phase III studies with intranasal eskatamine. After carrying out a search on Medline, in which 5 studies were obtained. Three of them were short-term, and 2 long-term. The intranasal esketamine treatment in combination with an oral antidepressant was shown to be effective and safe in patients with treatment-resistant depression. The safety results were consistent in all the studies, without there being any unexpected adverse effects in the long-term


Assuntos
Humanos , Depressão/tratamento farmacológico , Administração Intranasal , Antidepressivos/administração & dosagem , Ketamina/administração & dosagem
20.
J Clin Psychiatry ; 81(3)2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32316080

RESUMO

OBJECTIVE: To evaluate long-term safety and efficacy of esketamine nasal spray plus a new oral antidepressant (OAD) in patients with treatment-resistant depression (TRD). METHODS: This phase 3, open-label, multicenter, long-term (up to 1 year) study was conducted between October 2015 and October 2017. Patients (≥ 18 years) with TRD (DSM-5 diagnosis of major depressive disorder and nonresponse to ≥ 2 OAD treatments) were enrolled directly or transferred from a short-term study (patients aged ≥ 65 years). Esketamine nasal spray (28-mg, 56-mg, or 84-mg) plus new OAD was administered twice a week in a 4-week induction (IND) phase and weekly or every-other-week for patients who were responders and entered a 48-week optimization/maintenance (OP/MAINT) phase. RESULTS: Of 802 enrolled patients, 86.2% were direct-entry and 13.8% were transferred-entry; 580 (74.5%) of 779 patients who entered the IND phase completed the phase, and 150 (24.9%) of 603 who entered the OP/MAINT phase completed the phase. Common treatment-emergent adverse events (TEAEs) were dizziness (32.9%), dissociation (27.6%), nausea (25.1%), and headache (24.9%). Seventy-six patients (9.5%) discontinued esketamine due to TEAEs. Fifty-five patients (6.9%) experienced serious TEAEs. Most TEAEs occurred on dosing days, were mild or moderate in severity, and resolved on the same day. Two deaths were reported; neither was considered related to esketamine. Cognitive performance generally either improved or remained stable postbaseline. There was no case of interstitial cystitis or respiratory depression. Treatment-emergent dissociative symptoms were transient and generally resolved within 1.5 hours postdose. Montgomery-Åsberg Depression Rating Scale total score decreased during the IND phase, and this reduction persisted during the OP/MAINT phase (mean [SD] change from baseline of respective phase to endpoint: IND, -16.4 [8.76]; OP/MAINT, 0.3 [8.12]). CONCLUSIONS: Long-term esketamine nasal spray plus new OAD therapy had a manageable safety profile, and improvements in depression appeared to be sustained in patients with TRD. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02497287.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Ketamina/uso terapêutico , Administração Intranasal , Administração Oral , Adolescente , Adulto , Idoso , Antidepressivos/administração & dosagem , Cognição/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Humanos , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Sprays Nasais , Adulto Jovem
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