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INTRODUCTION: Catatonia, documented since the 19th century, remains a significant challenge in terms of recognition and treatment. Over the last two decades, ketamine has brought new perspectives to psychiatry, sparking widespread interest. Concurrently, catatonia has attracted heightened scientific attention. Preliminary evidence suggests the therapeutic potential of ketamine for catatonia. METHODS: We systematically searched Medline/PubMed, Embase, PsycINFO, Lilacs, and Cochrane Library databases, as well as Google Scholar, for studies with ketamine or its enantiomers as intervention for catatonia, with no restrictions to underlying diagnosis, date, language, or study design. RESULTS: Twenty articles were included, encompassing a total of 25 catatonic patients receiving ketamine or esketamine. Predominantly female (61.9 %), with a mean age of 44.4 years, patients mostly exhibited manifestations compatible with the retarded subtype of catatonia. Mood disorders were the most prevalent underlying diagnoses. Ketamine was primarily administered intravenously over a 40-minute period and in multiple-dosing schemes. Mean response and remission rates of catatonic manifestations for the whole sample were 80 % and 44 %, respectively, with no reports of worsening catatonic features or psychotic symptoms. Only one patient discontinued treatment due to intolerable dissociative effects. CONCLUSION: Challenging the conventional contraindication of ketamine in psychotic disorders, current evidence highlights its potential efficacy, particularly in treating catatonia. Pending further research, we advocate reevaluating this contraindication, as it may offer a promising therapeutic option, especially for challenging cases. Preliminary evidence suggests potentially greater benefits for catatonic patients with underlying mood disorders compared to primary psychotic disorders.

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INTRODUCTION: Major depressive disorder is related to unfavourable outcomes in patients with severe comorbidities. In transplant patients, major depression is associated with worse clinical outcomes. CASE REPORT: We present the case of a 55-year-old man with a heart transplant due to heart failure of ischaemic origin. Six months after the transplant he developed depressed mood, anhedonia and suicidal ideation with a score of 20/27 on the PHQ-9 depression screening scale. After receiving mirtazapine 30 mg/night for a week and persisting with a high suicide risk, it was decided to administer ketamine infusion for 24 h, with which a significant improvement in mood was observed, and the disappearance of suicidal ideation 24 h after the infusion. DISCUSSION: Depression in transplant patients is a factor associated with graft loss and post-transplant mortality, in addition to favouring other negative outcomes such as deep vein thrombosis. CONCLUSIONS: Ketamine infusion was shown to be an effective and safe option to treat major depression with suicidal risk in a heart transplant patient.

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OBJECTIVE: Fibromyalgia (FM) subjects are treated with antidepressant agents; in most cases, these drugs lose efficacy or have adverse effects. Ketamine is an anesthetic drug used in FM in some studies. This article aims to systematically review the safety and efficacy of ketamine in fibromyalgia (FM) patients. MATERIALS AND METHODS: We systematically searched articles on FM and ketamine published at Pubmed from 1966 to 2021. This study was registered at PROSPERO. RESULTS: There were only 6 articles published in this field, with a total of 115 patients. The female sex was predominant (88 to 100%). The age varied from 23 to 53 years old. Disease duration ranged from 1 month to 28 years. The dosage of ketamine changed from 0.1 mg/kg-0.3-0.5 mg/kg in intravenous infusion (4/5) and subcutaneous application (1/5). Regarding outcomes, the Visual analog scale (VAS) before ketamine was from 59 to 100 mm and after treatment from 2 to 95 mm. Most short-term studies had a good response. Only the study with 8 weeks of follow-up did not observe a good response. Side effects were common; all appeared during the infusion and disappeared after a few minutes of the ketamine injection. CONCLUSIONS: The present study demonstrates the effectiveness and safety of ketamine in FM patients in the short term. Although, more studies, including long-term follow-up studies, are still needed.

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Ketamine is an NMDA (N-methyl-d-aspartate) glutamate receptor antagonist, which has a myriad of dose-dependent pharmacological and behavioral effects, including anesthetic, sedative, amnestic, analgesic, and anti-inflammatory properties. Intriguingly, ketamine at subanesthetic doses displays a relevant profile both in mimicking symptoms of schizophrenia and also as the first fast-acting treatment for depression. Here, we present an overview of the state-of-the-art knowledge about ketamine as an antidepressant as well as a pharmacological model of schizophrenia in animal models and human participants. Ketamine's dual effect appears to arise from its mechanism of action involving NMDA receptors, with both immediate and downstream consequences being triggered as a result. Finally, we discuss the feasibility of a unified approach linking the glutamatergic hypothesis of schizophrenia to the promising preclinical and clinical success of ketamine in the treatment of refractory depression.

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This prospective, blinded, randomized crossover study aimed to assess the anesthetic effects of the combination of 30 mg/kg ketamine and 2 mg/kg midazolam via intranasal (IN) or intramuscular (IM) routes in twelve domestic chickens. Physiological parameters (respiratory rate - RR, heart rate - HR, and cloacal temperature -Tºcloacal) were monitored throughout the experiment, along with recovery time and sedation level (S0: awake, no recumbency, responsive to stimuli; S1: blinking eyes, recumbency, relaxed, response to stimulus, mild movement; S2: open eyes, recumbency, relaxed, mild response to stimuli; S3: closed eyes, recumbency, relaxed, no movement). In the IM group, all birds reached S3, while in IN 5/12 reached S3, 4/12 reached at most S1, and 1/12 at most S2. IM administration showed higher sedation at 5, 10, 15, 20, 30, 35, 40, and 45 minutes (p<0.05). IN administration exhibited a shorter total recovery time (26.3±21.4 min vs. 92.9±33.4 min; p<0.001). No time, group, or time-group interaction effects were observed in HR and cloacal Tº, with a trend to a decrease in RR both groups (p<0.001). Increased incidences of vocalization and agitation was observed via IM (4/12 vs. 0/12; p=0.028), with no difference in salivation. Despite faster recovery with less agitation and vocalization, the ketamine and midazolam combination via IN provided less consistent sedation compared to the IM route in chickens.

Este estudo crossover randomizado objetivou avaliar os efeitos anestésicos da associação de 30 mg/kg de cetamina e 2 mg/kg de midazolam via intranasal (IN) ou intramuscular (IM) em doze galinhas. Além dos parâmetros fisiológicos (frequência respiratória ­ FR e cardíaca ­ FC e temperatura cloacal ­ Tºcloacal), registrou-se o tempo de recuperação e o grau de sedação ao longo do experimento (S0: acordada, sem decúbito, responsiva a estímulos; S1: olhos piscando, decúbito, relaxada, resposta a estímulo, movimentação leve; S2: olhos abertos, decúbito, relaxada, resposta leve a estímulos; S3: olhos fechados, decúbito, relaxada, sem movimentação. Pela via IM, todas as aves atingiram o grau S3, enquanto pela via IN 5/12 alcançaram S3, 4/12 atingiram no máximo S1 e 1/12 no máximo S2. A via IM apresentou maior sedação em 5, 10, 15, 20, 30, 35, 40 e 45 min (p<0,05). A via IN apresentou menor tempo total até recuperação (26,3±21,4 min vs. 92,9±33,4 min; p<0,001). Não foram observados efeitos de tempo, grupo e interação tempo-grupo na FC e na Tºcloacal com uma tendência de queda da FR nos dois grupos (p<0,001). Observou-se maior incidência de vocalização e agitação pela via IM (4/12 vs. 0/12; p=0,028), não havendo diferença para sialorreia. Apesar da recuperação mais rápida e com menos agitação e vocalização, a associação cetamina e midazolam via IN levou a uma sedação menos consistente que a via IM em galinhas.

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We conducted a systematic review and meta-analysis to investigate the comparative effectiveness of ketamine versus electroconvulsive therapy (ECT) for the treatment of major depressive episodes (MDEs). PubMed, EMBASE and Cochrane Library databases were systematically searched for randomized controlled trials (RCTs) comparing ketamine and ECT for MDE. The primary outcome was response rate, for which we prespecified a non-inferiority margin of -0.1, based on the largest and most recent RCT. Response was defined as a reduction of at least 50 % in the depression scale score. Six RCTs met the inclusion criteria, comprising 655 patients. In the overall population, ketamine was not non-inferior to ECT in response rate (RD -0.10; 95 % CI -0.26 to 0.05; p = 0.198; I2 = 72 %). The ECT group had a higher reduction in depression scores, but without difference in remission and relapse rates. Regarding safety outcomes, ketamine had better posttreatment cognition scores and reduced muscle pain rate compared with ECT, albeit with an increased rate of dissociative symptoms. In a subanalysis with only inpatients, ketamine was inferior to ECT in response rate (RD -0.15; 95 % CI -0.27 to -0.03; p = 0.014; I2 = 25 %), remission, and change in depression scores. These findings support the use of ECT over ketamine for inpatients. Further RCTs are warranted to clarify the comparative effect of these treatments for outpatients.

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BACKGROUND: This study aimed to investigate the analgesic impact of S(+)-ketamine on pain behavior and synovial inflammation in an osteoarthritis (OA) model. METHODS: Animals were grouped as follows: OA-Saline (n = 24) and OA-Ketamine (n = 24), OA induced via intra-articular sodium monoiodoacetate (MIA); a Non-OA group (n = 24) served as the control. On the 7th day post OA induction, animals received either saline or S(+)-ketamine (0.5 mg.kg-1). Behavioral and histopathological assessments were conducted up to day 28. RESULTS: S(+)-ketamine reduced allodynia from day 7 to 28 and hyperalgesia from day 10 to 28. It notably alleviated weight distribution deficits from day 10 until the end of the study. Significant walking improvement was observed on day 14 in S(+)-ketamine-treated rats. Starting on day 14, OA groups showed grip force decline, which was countered by S(+)-ketamine on day 21. However, S(+)-ketamine did not diminish synovial inflammation. CONCLUSION: Low Intra-articular (IA) doses of S(+)-ketamine reduced MIA-induced OA pain but did not reverse synovial histopathological changes. IRB APPROVAL NUMBER: 23115 012030/2009-05.

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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.

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Objective: Post-traumatic stress disorder (PTSD) is an enduring condition characterized by a chronic course and impairments across several areas. Despite its significance, treatment options remain limited, and remission rates are often low. Ketamine has demonstrated antidepressant properties and appears to be a promising agent in the management of PTSD. Method: A systematic review was conducted in PubMed/MEDLINE, Cochrane Library, Clinicaltrials.gov, Lilacs, Scopus, and Embase, covering studies published between 2012 and December 2022 to assess the effectiveness of ketamine in the treatment of PTSD. Ten studies, consisting of five RCTs, two crossover trials, and three non-randomized trials, were included in the meta-analysis. Results: Ketamine demonstrated significant improvements in PCL-5 scores, both 24 hours after the initial infusion and at the endpoint of the treatment course, which varied between 1 to 4 weeks in each study. Notably, the significance of these differences was assessed using the Two Sample T-test with pooled variance and the Two Sample Welch's T-test, revealing a statistically significant effect for ketamine solely at the endpoint of the treatment course (standardized effect size= 0.25; test power 0.9916; 95% CI = 0.57 to 17.02, p=0.0363). It is important to note that high heterogeneity was observed across all analyses. Conclusions: Our findings suggest that ketamine holds promise as an effective treatment option for PTSD. However, further trials are imperative to establish robust data for this intervention.

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ABSTRACT BACKGROUND AND OBJECTIVES: Bone fractures constitute a frequent cause of emergency care in the pediatric population. Opioid drugs are routinely used for analgesia during the hospitalization of children victims of trauma. Few studies have evaluated the importance of a multimodal approach to analgesia in this context. The aim of this study was to compare the analgesic effect and possible side effects of fentanyl compared to those of ketamine. METHODS: The study analyzed 50 children and adolescents, aged between 24 and 192 months, submitted to surgical treatment of upper limb fractures in a tertiary trauma care hospital. The participants were randomized into two groups: one that received Ketamine and the other Fentanyl. In the post-anesthetic recovery room (PARR), pain intensity and the occurrence of delirium were measured for a period of 30 minutes. The incidence of respiratory depression, nausea, vomiting and other side effects during the surgical procedure were assessed. RESULTS: The sample consisted mostly of male individuals (76.0%). The mean age of the participants was 90.1 months. The use of a low-flow oxygen cannula was necessary in 30.0% of the participants. The incidence of vomiting and laryngospasm was 2.0% among the participants, and 6.0% presented increased salivary secretion. The occurrence of pain, delirium and respiratory depression was not different between the two assessed groups, as well as the occurrence of nausea and laryngospasm. CONCLUSION: Ketamine is not an effective and safe option to opioids for analgesia in children undergoing surgical procedures to treat upper limb fractures.

RESUMO JUSTIFICATIVA E OBJETIVOS: As fraturas ósseas constituem causa frequente de atendimento de emergência na população pediátrica. Fármacos opioides são rotineiramente utilizados para analgesia durante a hospitalização de crianças vítimas de trauma. Poucos estudos avaliaram a importância de uma abordagem multimodal para analgesia nesse contexto. O objetivo deste estudo foi comparar o efeito analgésico e possíveis efeitos adversos do fentanil em relação aos da cetamina. MÉTODOS: Foram analisados 50 crianças e adolescentes, com idade entre 24 e 192 meses, submetidos ao tratamento cirúrgico das fraturas de membros superiores em um hospital terciário de atendimento ao trauma. Os participantes foram aleatorizados em dois grupos: um recebeu cetamina e outro fentanil. Na sala de recuperação pós-anestésica (SRPA), a intensidade da dor e a ocorrência de delirium foram mensuradas por um período de 30 minutos. A incidência de depressão respiratória, náuseas, vômitos e outros efeitos adversos durante o procedimento cirúrgico foram avaliados. RESULTADOS: A amostra foi composta, em sua maioria, por indivíduos do sexo masculino (76,0%). A média de idade dos participantes foi de 90,1 meses. O uso de cânula de oxigênio de baixo fluxo foi necessário em 30,0% dos participantes. A incidência de vômitos e laringoespasmo foi de 2,0% entre os participantes, sendo que 6,0% apresentaram aumento da secreção salivar. A ocorrência de dor, delirium e depressão respiratória não foi diferente entre os dois grupos avaliados, assim como a ocorrência de náuseas e laringoespasmo. CONCLUSAO: Acetamina não se mostrou uma opção eficaz e segura aos opioides para analgesia em crianças submetidas a procedimentos cirúrgicos para tratamento de fraturas de membros superiores.

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Abstract Background: Emergence Delirium (ED) is an essential condition in the immediate postoperative period. Systematic review and meta-analysis of randomized controlled trials have concluded that the effect of ketamine on postoperative delirium remains unclear. The present study sought to evaluate if the intraoperative use of ketamine for postoperative analgesia is associated with postoperative ED in laparoscopic surgeries. Methods: A prospective observational study was performed in the PostAnesthetic Care Unit (PACU) to evaluate patients who had undergone laparoscopic surgery under a rigid intraoperative anesthesia protocol from July 2018 to January 2019. Patients submitted to laparoscopic surgery for cholecystectomy, oophorectomy, or salpingectomy with a score ≥1 on the Richmond Assessment Sedation Scale (RASS) or ≥2 on the Nursing Delirium Screening Scale (Nu-DESC) were considered to have ED. t-test, Chi-Square test or Fisher's exact tests were used for comparison. Results: One hundred and fifteen patients were studied after laparoscopic surgery. Seventeen patients (14.8%) developed ED, and the incidence of ED in patients who received ketamine was not different from that of other patients (18.3% vs. 10.6%, p = 0.262). Patients with ED had more postoperative pain and morphine requirement at the PACU (p = 0.005 and p = 0.025, respectively). Type of surgery (general surgery, OR = 6.4, 95% CI 1.2‒35.2) and postoperative pain (OR = 3.7, 95% CI 1.2‒11.4) were risk factors for ED. Conclusion: In this study, no association was found between ED and intraoperative administration of ketamine in laparoscopic surgeries. Type of surgery and postoperative pain were risk factors for ED.

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Abstract Background: This study aimed to investigate the analgesic impact of S(+)-ketamine on pain behavior and synovial inflammation in an osteoarthritis (OA) model. Methods: Animals were grouped as follows: OA-Saline (n = 24) and OA-Ketamine (n = 24), OA induced via intra-articular sodium monoiodoacetate (MIA); a Non-OA group (n = 24) served as the control. On the 7th day post OA induction, animals received either saline or S(+)-ketamine (0.5 mg.kg-1). Behavioral and histopathological assessments were conducted up to day 28. Results: S(+)-ketamine reduced allodynia from day 7 to 28 and hyperalgesia from day 10 to 28. It notably alleviated weight distribution deficits from day 10 until the end of the study. Significant walking improvement was observed on day 14 in S(+)-ketamine-treated rats. Starting on day 14, OA groups showed grip force decline, which was countered by S(+)-ketamine on day 21. However, S(+)-ketamine did not diminish synovial inflammation. Conclusion: Low Intra-articular (IA) doses of S(+)-ketamine reduced MIA-induced OA pain but did not reverse synovial histopathological changes. IRB approval number: 23115 012030/2009-05.

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Resumen: Introducción: el dolor agudo postoperatorio demora la recuperación funcional del paciente. Objetivo: evaluar utilidad de la ketamina asociada a morfina administrados en bolos intravenosos en el control del dolor agudo postoperatorio de pacientes sometidos a cirugía renal electiva. Material y métodos: realizamos estudio doble ciego en pacientes con dolor postoperatorio moderado-severo sometidos a cirugía renal electiva. Se conformaron dos grupos: grupo MK administramos morfina 0.05 mg/kg más ketamina 0.2 mg/kg y grupo M morfina 0.05 mg/kg más solución salina a 0.9%. Pacientes con dolor de intensidad moderada-severa según escala analógica visual recibieron dosis de morfina cada 20 minutos hasta lograr dolor ligero, registrándose el consumo total de morfina por paciente. La tensión arterial, frecuencia cardíaca y respiratoria, saturación de oxígeno y efectos adversos fueron evaluados con la misma periodicidad. Resultados: el grupo MK mostró menor intensidad del dolor con disminución significativa del consumo de morfina. Ambos grupos resultaron ser similares en cuanto a cifras de tensión arterial, frecuencia cardíaca, frecuencia respiratoria y saturación de oxígeno. Las náuseas y vómitos fueron los efectos adversos de mayor prevalencia, siendo superiores en el grupo morfina. Conclusiones: la asociación morfina-ketamina resultó útil en el control del dolor moderado-severo en pacientes sometidos a cirugía renal electiva.

Abstract: Introduction: acute postoperative pain delays the patient's functional recovery. Objective: to evaluate the utility of ketamine associated with morphine administered in intravenous boluses in the control of acute postoperative pain in patients undergoing elective renal surgery. Material and methods: we conducted a double-blind study in patients with moderate-severe postoperative pain undergoing elective renal surgery. Two groups were formed: group MK administered 0.05 mg/kg morphine plus 0.2 mg/kg ketamine and group M 0.05 mg/kg morphine plus 0.9% saline solution. Patients with pain of moderate-severe intensity according to the visual analogue scale received doses of morphine every 20 minutes until achieving light pain, recording the total consumption of morphine per patient. Blood pressure, heart and respiratory rates, oxygen saturation, and adverse effects were evaluated with the same periodicity. Results: MK group showed lower pain intensity with a significant decrease in morphine consumption. Both groups turned out to be similar in terms of blood pressure, heart rate, respiratory rate and oxygen saturation Figures. Nausea and vomiting were the most prevalent adverse effects, being higher in the morphine group. Conclusions: the morphine-ketamine association was useful in the control of moderate-severe pain in patients undergoing elective renal surgery.

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Propofol is used for anesthetic induction in cats and procedural sedation in countries where alfaxalone is not available. Studies have reported propofol-related effects in echocardiography variables in dogs and humans. However, there is a lack of echocardiography studies investigating propofol-related effects on cats. This study aimed to use echocardiography to investigate echocardiographic changes in three protocols using propofol: propofol-slow (2 mg/kg/min, PS); propofol-fast (8 mg/kg/min, PF); propofol-ketamine (S-ketamine 2 mg/kg bolus followed by propofol 2 mg/kg/min; PK) in healthy premedicated (gabapentin-buprenorphine-acepromazine; 200 mg/cat, 0.4, and 0.1 mg/kg, respectively), non-intubated cats. Echocardiographic measurements were obtained at three time points: baseline (before the administration of propofol), end of propofol titration (end-point, T0), and 15 min after T0 (T15). Propofol at a lower rate continued from T0 to T15. Echocardiographic and physiological variables included fractional shortening (FS%), ejection fraction (EF%), HR, BP, and others. Propofol requirements at T0 for PF, PS, and PK groups were 5.0 ± 0.9, 3.8 ± 0.7, and 2.4 ± 0.5 mg/kg, respectively. EF% neither change over time nor between groups. PF and PK showed a reduction in FS% at T0 (47 ± 6 to 34 ± 6 and 42 ± 6 to 36 ± 5, respectively). BP reduced significantly in PF and PS groups (136 ± 26 to 105 ± 13 and 137 ± 22 to 115 ± 15 mmHg, respectively). It is unclear whether changes in echocardiography variables were of clinical relevance related to treatment groups or a result of within-group individual responses.

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Background: Ketamine is an analgesic adjuvant useful in acute pain preventive treatment. However, there are few studies evaluating its efficacy in local administration for postoperative pain management. Objective: To compare ketamine´s efficacy plus 2% lidocaine versus placebo plus 2% lidocaine infiltrated into surgical wound as postoperative analgesia in patients undergoing mastectomy. Material and methods: An experimental, randomized, single-blind study was carried out in 18 patients older than 18 years scheduled for mastectomy under general anesthetic technique. The surgical wound was infiltrated before to its closure with 0.5 mg/kg of ketamine plus 10 mL of simple 2% lidocaine volumetric to 20 mL with saline solution (group 1) or 10 mL saline solution + 10 mL of simple 2% lidocaine (group 2). Each patient was randomly assigned to one of the two intervention groups by draw (from which a piece of paper was drawn indicating the group to which they would belong). The pain intensity was assessed by Analog Numerical Scale (ANS) at 2, 8 and 12 hours after surgery and the need for analgesic rescue doses. Results: The scores on the ANS scale in both groups were similar at leaving (p 0.26) and 2 hours later (p 0.05). The ENA value was lower with 2% ketamine/lidocaine infiltration at 8 hours (ketamine 2.5 [2-3]; placebo 4 [3-7], p 0.01) and 12 hours (ketamine 3 [1-5]; placebo 5 [4-6], p < 0.001). Conclusions: Ketamine infiltrated into the surgical wound provides superior analgesia and improves ENA scores in the post-surgical period.

Introducción: la ketamina es un fármaco ahorrador de opioides y adyuvante analgésico, útil en el tratamiento preventivo del dolor agudo postoperatorio. Sin embargo, existen pocos estudios que evalúen su eficacia en su administración local para el manejo de dolor postoperatorio. Objetivo: comparar la eficacia de la ketamina más lidocaína al 2% frente a placebo más lidocaína al 2% infiltrada en herida quirúrgica como analgesia postoperatoria en pacientes sometidas a cirugía de mama. Material y métodos: se realizó un estudio experimental, prospectivo y aleatorizado en 18 pacientes mayores de 18 años programadas para mastectomía bajo técnica anestésica general. El sitio quirúrgico se infiltró con 0.5 mg/kg de ketamina más 10 mL de lidocaína al 2% aforado a 20 mL con solución salina (grupo 1) o solución salina 10 mL + 10 mL de lidocaína simple al 2% (grupo 2). Se valoró la intensidad del dolor mediante la Escala Numérica Análoga (ENA) a las 2, 8, y 12 horas posteriores a la cirugía y la necesidad de dosis de rescate analgésico. Resultados: las puntuaciones en la ENA en ambos grupos fueron similares al salir (p 0.26) y 2 horas posteriores (p 0.05). El valor de la ENA fue menor con la infiltración de ketamina/lidocaína 2% a las 8 horas (ketamina 2.5 [2-3]; placebo 4 [3-7], p 0.01) y 12 horas (ketamina 3 [1-5]; placebo 5 [4-6], p < 0.001). Conclusiones: la ketamina infiltrada en la herida quirúrgica provee analgesia superior, brinda seguridad y mejora las puntuaciones de la ENA en el periodo postquirúrgico.

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Major depressive disorder (MDD) is a debilitating illness that affects millions of people worldwide. Currently available antidepressants often take weeks to months to reach their full effect, which leads to an increased risk of suicidal behavior in patients with MMD. Intranasally, esketamine has emerged as an alternative to current antidepressants because of its rapid onset and long-lasting effects in patients with MDD. Animal models are useful for the initial pharmacological screening and for a better understanding of the mechanisms underlying the effects of new drugs with potential against MDD. There is a lack of data on alternative routes of drug administration, either oral or injectable, that can be used in preclinical studies. This study aimed to test whether ketamine has antidepressant-like effects in mice when administered via nebulization using a low-cost apparatus. When mice whose depressive-like behavior was induced by corticosterone were treated with nebulized ketamine at concentrations of 1.3, 2.6, and 5.2 mg/mL, immobility was reduced by 38.6 %, 62.0 %, and 61.1 %, respectively, in the forced swimming test (FST) and 43.6 %, 42.1 %, and 57.9 %, respectively, in the tail suspension test (TST). When depression-like behavior was induced by dexamethasone, nebulization with ketamine reduced immobility by 79.7 %, 49.2 %, and 44.4 % in the FST and 80.9 %, 71.4 %, and 80.4 %, respectively, in the TST. When depression-like behavior was induced by the association between dexamethasone and unpredictable chronic mild stress (UCMS) exposure, immobility was reduced by 26.1 %, 55.3 %, and 19.1 % in FST. Mice treated with nebulized ketamine did not show significant changes in the distance covered or in the time spent moving in the open field test. The efficacy of intraperitoneal and nebulized ketamine is equivalent, which shows that nebulization can be an alternative inexpensive route of drug administration for behavioral studies in rodents.

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BACKGROUND: Dexmedetomidine (DEX) and low-dose ketamine (KET) present neuroprotective effects in acute ischemic stroke (AIS); however, to date, no studies have evaluated which has better protective effects not only on the brain but also lungs in AIS. METHODS: AIS-induced Wistar rats (390 ± 30 g) were randomized after 24-h, receiving dexmedetomidine (STROKE-DEX, n = 10) or low-dose S(+)-ketamine (STROKE-KET, n = 10). After 1-h protective ventilation, perilesional brain tissue and lungs were removed for histologic and molecular biology analysis. STROKE animals (n = 5), receiving sodium thiopental but not ventilated, had brain and lungs removed for molecular biology analysis. Effects of DEX and KET mean plasma concentrations on alveolar macrophages, neutrophils, and lung endothelial cells, extracted primarily 24-h after AIS, were evaluated. RESULTS: In perilesional brain tissue, apoptosis did not differ between groups. In STROKE-DEX, compared to STROKE-KET, tumor necrosis factor (TNF)-α and vascular cell adhesion molecule-1 (VCAM-1) expressions were reduced, but no changes in nuclear factor erythroid 2-related factor-2 (Nrf2) and super oxide dismutase (SOD)-1 were observed. In lungs, TNF-α and VCAM-1 were reduced, whereas Nrf2 and SOD-1 were increased in STROKE-DEX. In alveolar macrophages, TNF-α and inducible nitric oxide synthase (M1 macrophage phenotype) were lower and arginase and transforming growth factor-ß (M2 macrophage phenotype) higher in STROKE-DEX. In lung neutrophils, CXC chemokine receptors (CXCR2 and CXCR4) were higher in STROKE-DEX. In lung endothelial cells, E-selectin and VCAM-1 were lower in STROKE-DEX. CONCLUSIONS: In the current AIS model, dexmedetomidine compared to low-dose ketamine reduced inflammation and endothelial cell damage in both brain and lung, suggesting greater protection.

Assuntos

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Refinement of experimental procedures in animal research has the objective of preventing and minimizing pain/distress in animals, including the euthanasia period. This study aimed to evaluate pain associated with six methods of euthanasia in Wistar rats (injectable, inhalational, and physical), by applying the Rat Grimace Scale (RGS), comparing the scores, and determining the method with the highest score that might indicate pain for laboratory rodents. Sixty adult male and female Wistar rats were used and assigned to six treatments: pentobarbital, CO2, decapitation, isoflurane, ketamine + xylazine, and ketamine + CO2. Video recording to assess the RGS scores was performed in four events: basal: 24 h before the procedure; Ti1: three minutes before the procedure; Ti2: during the application of the euthanasia method; and Ti3: immediately after the application until LORR. The main findings of this study showed that, during Ti2, decapitation and ketamine + xylazine had the highest scores (0.6 ± 0.26 and 0.6 ± 0.16, respectively) (p < 0.0001), while at Ti3, CO2 (0.9 ± 0.18) and isoflurane (1.2 ± 0.20) recorded the highest scores (p < 0.0001). According to the present results, decapitation and ketamine + xylazine elicited short-term acute pain, possibly due to tissue damage caused by both methods (injection and guillotine). In contrast, isoflurane's RGS scores recorded during Ti3 might be associated with nociception/pain due to the pungency of the drug or to the pharmacological muscle relaxant effect of isoflurane. Further research is needed to establish a comprehensive study of pain during euthanasia, where RGS could be used minding the limitations that anesthetics might have on facial expression.

RESUMO

Introduction: Opioid-induced hyperalgesia (OIH) is a paradoxical phenomenon in which exposure to opioids can increase sensitivity to painful stimuli. Currently, several drugs have been used in an attempt to prevent OIH. We design this study to address the effect of preemptive treatment with ketamine, lidocaine, and ascorbic acid in a rat preclinical model of perioperative opioid-induced hyperalgesia. Methods: To reproduce OIH in a model of postoperative pain, rats received successive doses of fentanyl subcutaneously and underwent an incision in the paw. In an attempt to prevent OIH, ketamine, lidocaine, and ascorbic acid were administered before treatment with fentanyl. The von Frey test and the hot-plate test were used to evaluate mechanical allodynia and thermal hyperalgesia, respectively, with a follow-up period from 1 hour up to 7 days after surgery. Spinal cord nerve terminals (synaptosomes) were used to assess glutamate release under our experimental conditions. Results: Consecutive fentanyl injections increased the postoperative pain as indicated by increased thermal hyperalgesia and allodynia 48 hours after incision. Ketamine, lidocaine, and the combination of ketamine + lidocaine were able to prevent thermal hyperalgesia but not mechanical allodynia. Ascorbic acid did not prevent the hyperalgesia induced by fentanyl. We found no correlation between spinal glutamate release and the pharmacological treatments. Conclusion: Fentanyl induced a hyperalgesic effect that last few days in a postoperative model of pain. Hyperalgesic effect was not totally inhibited by ketamine and lidocaine in rats. Increased glutamate release was not the main molecular mechanism of fentanyl-induced hyperalgesia.