Novel Proline Transporter Inhibitor (LQFM215) Presents Antipsychotic Effect in Ketamine Model of Schizophrenia.

The glutamatergic hypothesis of schizophrenia suggests a correlation between NMDA receptor hypofunction and negative psychotic symptoms. It has been observed that the expression of the proline transporter (PROT) in the central nervous system (CNS) is associated with glutamatergic neurotransmission, as L-proline has the capacity to activate and modulate AMPA and NMDA receptors. In this study, we aimed to investigate whether inhibition of proline transporters could enhance glutamatergic neurotransmission and potentially exhibit antipsychotic effects in an experimental schizophrenia model. Using molecular dynamics analysis in silico, we validated an innovative PROT inhibitor, LQFM215. We quantified the cytotoxicity of LQFM215 in the Lund human mesencephalic cell line (LUHMES). Subsequently, we employed the ketamine-induced psychosis model to evaluate the antipsychotic potential of the inhibitor, employing behavioral tests including open-field, three-chamber interaction, and prepulse inhibition (PPI). Our results demonstrate that LQFM215, at pharmacologically active concentrations, exhibited negligible neurotoxicity when astrocytes were co-cultured with neurons. In the ketamine-induced psychosis model, LQFM215 effectively reduced hyperlocomotion and enhanced social interaction in a three-chamber social approach task across all administered doses. Moreover, the compound successfully prevented the ketamine-induced disruption of sensorimotor gating in the PPI test at all tested doses. Overall, these findings suggest that PROT inhibition could serve as a potential therapeutic target for managing symptoms of schizophrenia model.

Sleep disorders in patients with chronic pain: cross-sectional study / Distúrbios do sono em pacientes com dor crônica: estudo transversal

ABSTRACT BACKGROUND AND OBJECTIVES: Chronic pain and its relationship with sleep disturbance are common conditions with great influence on the individual's quality of life. The simultaneous occurrence of these two entities results in greater suffering, reduced functionality and well-being. The objective of this research was to evaluate the influence of chronic pain on sleep and its impact on quality of life. METHODS: This is an observational, cross-sectional, individual, uncontrolled study carried out at the Multidisciplinary Pain Center of the Clinical Hospital of the Federal University of Minas Gerais (Hospital das Clínicas da Universidade Federal de Minas Gerais - HC-UFMG). The patients answered a semi-structured, face-to-face interview via the pain center's own computer system (avaliaDor®), using internet-connected mobile devices. Socioeconomic and pain data was collected, and then instruments were applied to assess pain intensity (Visual Numerical Scale - VNS), quality of life (Medical Outcomes Study 36 - Short Form Health Survey - SF-36), presence of psychiatric disturbances (Hospital Depression Anxiety Scale - HAD) and sleep (Mini Sleep Questionnaire - MSQ). RESULTS: One hundred and three patients participated in the study. Seventy two percent were women, the median age was 55 years, and the patients were predominantly married, white and with a low level of schooling. Of the entire study population 74.76% presented "severe difficulty" in sleeping, while 22.33% had "good quality" sleep. Regarding pain intensity, patients in the moderate and severe pain groups had a higher percentage of "severe difficulty" in sleeping, when compared to patients with mild pain. About the presence of anxiety and depression, it was observed lower scores on: "restless sleep", "tiredness for no apparent reason", "wakes up with a headache", "wakes up and goes back to sleep", "wakes up tired in the morning", and finally "wakes up and does not go back to sleep". The general data from the SF-36 points to a low quality of life for the patients in the present study and, based on the multivariate analysis, the items "SF-36-Pain and SF-36-Vitalidade" were shown to be protective factors for the presence of sleep disturbances. CONCLUSION: Sleep disorders in patients with chronic pain are common and show a worsening in quality of life. The frequency of this disturbance was higher in patients with anxiety and depression compared to patients without these psychiatric disorders. The early identification of sleep disturbances in individuals with chronic pain is necessary to improve well-being.

RESUMO JUSTIFICATIVA E OBJETIVOS: A dor crônica e os distúrbios do sono são condições comuns. A ocorrência simultânea dessas duas entidades resulta em maior sofrimento pessoal e redução do bem-estar e da funcionalidade. O objetivo desta pesquisa foi avaliar a influência da dor crônica no sono e o seu impacto na qualidade de vida. MÉTODOS: Trata-se de um estudo observacional, transversal, individual e não controlado, realizado no Centro Multidisciplinar de Dor do Hospital das Clínicas da Universidade Federal de Minas Gerais (HC-UFMG). Os pacientes responderam a uma entrevista semiestruturada, face a face, por meio do sistema de computador do próprio centro de dor (avaliaDor®), utilizando dispositivos móveis conectados à internet. Foram coletados dados socioeconômicos e de dor; em seguida foram aplicados instrumentos para avaliar a intensidade da dor (Escala Visual Numérica - EVN), a qualidade de vida (Medical Outcomes Study 36 - Short Form Health Survey - SF-36), a presença de distúrbios psiquiátricos (Escala Hospitalar de Ansiedade e Depressão - HAD) e o sono (Mini Sleep Questionnaire - MSQ). RESULTADOS Cento e três pacientes participaram do estudo. Setenta e dois por cento eram do sexo feminino, com mediana de idade de 55 anos, com predominância de brancos com baixo nível de escolaridade. De toda a população estudada, 74,76% dos participantes apresentaram "dificuldade grave" para dormir, enquanto 22,33% tiveram "boa qualidade" de sono. Em relação à intensidade da dor, os pacientes dos grupos de dor moderada e intensa apresentaram maior percentual de "dificuldade grave" para dormir quando comparados aos pacientes com dor leve. Em relação à presença de ansiedade e depressão, observou-se maior pontuação nos itens: "sono agitado", "cansaço sem motivo aparente", "acorda com dor de cabeça", "acorda e volta a dormir", "acorda cansado pela manhã" e, por fim, "acorda e não volta a dormir". Os dados gerais do SF-36 apontam para uma baixa qualidade de vida dos doentes do presente estudo e, com base na análise multivariada, os itens "SF-36-Dor e SF-36-Vitalidade" revelaram-se fatores protetores da presença de perturbações do sono. CONCLUSÃO: Os distúrbios de sono em pacientes com dor crônica são comuns e determinam piora na qualidade de vida. A frequência desse distúrbio foi maior nos pacientes com ansiedade e depressão, em comparação com os pacientes que não apresentaram essas desordens psiquiátricas. A identificação precoce dos distúrbios do sono, em indivíduos com dor crônica, é fundamental para alcançar maior bem-estar.

Evaluation of functionality and socioeconomic status of patients with chronic pain.

OBJECTIVE: This study aimed to evaluate the influence of chronic pain on functionality and its consequences on work and patient income. METHODS: A total of 103 patients from the Multidisciplinary Pain Center of the Clinics Hospital of Universidade Federal de Minas Gerais were interviewed between January 2020 and June 2021, applying questionnaires on mobile devices. Socioeconomic data, multidimensional characterization of pain, and instruments for assessing pain functionality and intensity were analyzed. Pain intensity was categorized as mild, moderate, or intense for comparative analysis. Ordinal logistic regression was used to identify risk factors and variables that jointly influence the outcome of pain intensity. RESULTS: The patients had a median age of 55 years, were predominantly female, married or in a stable relationship, white race, and completed high school. The median family income was R$2,200. Most patients were retired due to disability and pain-related causes. Functionality analysis showed severe disability directly associated with pain intensity. The financial impacts observed were correlated with the pain intensity of the patients. Age was a risk factor for pain intensity, while sex, family income, and duration of pain served as protective factors. CONCLUSION: Chronic pain was associated with severe disability, decreased productivity, and exit from the labor market, with a negative impact on financial condition. Age, sex, family income, and duration of pain were directly associated with pain intensity.

Evaluation of functionality and socioeconomic status of patients with chronic pain

SUMMARY OBJECTIVE: This study aimed to evaluate the influence of chronic pain on functionality and its consequences on work and patient income. METHODS: A total of 103 patients from the Multidisciplinary Pain Center of the Clinics Hospital of Universidade Federal de Minas Gerais were interviewed between January 2020 and June 2021, applying questionnaires on mobile devices. Socioeconomic data, multidimensional characterization of pain, and instruments for assessing pain functionality and intensity were analyzed. Pain intensity was categorized as mild, moderate, or intense for comparative analysis. Ordinal logistic regression was used to identify risk factors and variables that jointly influence the outcome of pain intensity. RESULTS: The patients had a median age of 55 years, were predominantly female, married or in a stable relationship, white race, and completed high school. The median family income was R$2,200. Most patients were retired due to disability and pain-related causes. Functionality analysis showed severe disability directly associated with pain intensity. The financial impacts observed were correlated with the pain intensity of the patients. Age was a risk factor for pain intensity, while sex, family income, and duration of pain served as protective factors. CONCLUSION: Chronic pain was associated with severe disability, decreased productivity, and exit from the labor market, with a negative impact on financial condition. Age, sex, family income, and duration of pain were directly associated with pain intensity.

Effect of adding clonidine to lidocaine on ocular hemodynamics during sub-Tenon's anesthesia: randomized double-blind study.

INTRODUCTION AND OBJECTIVES: Different regional anesthesia techniques for ophthalmology can have hemodynamic effects on the eye. We assessed the effects of adding clonidine to lidocaine on Intraocular Pressure (IOP), Ocular Pulse Amplitude (OPA), and Ocular Perfusion Pressure (OPP) after the sub-Tenon's technique for cataract surgery. METHODS: The study included 40 patients randomly allocated into two groups: sub-Tenon's blockade with Lidocaine plus Saline Solution (LS) or Lidocaine plus Clonidine (LC). IOP, OPA and OPP were measured before anesthesia, and 1, 5 and 10 minutes after the injection of anesthetic solution. RESULTS: There was no difference between the groups in IOP, OPA, and OPP baseline values. After the injection of the anesthetic solution, the IOP increased in both groups at minute one, with a mean difference of +4.67 mmHg (p = 0.001) and +2.15 mmHg (p = 0.013) at 5 minutes. The increase was lower in the LC group when compared to LS (p = 0.027). OPA decreased in both groups, with a baseline difference, after 1 minute, of -0.85 mmHg (p =  -0.85 mmHg (p = 0.001), and at 5 and 10 minutes with differences of -1.17 (p = 0.001) and -0.89 mmHg (p = 0.001), respectively. The highest decrease was observed in group LC in relation to group LS (p = 0.03). There was no difference in OPP in relation to baseline measurements. CONCLUSIONS: Adding clonidine to lidocaine for sub-Tenon's anesthesia reduced IOP and OPA without significant changes in OPP.

The Role of Astrocytes in the Neurorepair Process.

Astrocytes are highly specialized glial cells responsible for trophic and metabolic support of neurons. They are associated to ionic homeostasis, the regulation of cerebral blood flow and metabolism, the modulation of synaptic activity by capturing and recycle of neurotransmitters and maintenance of the blood-brain barrier. During injuries and infections, astrocytes act in cerebral defense through heterogeneous and progressive changes in their gene expression, morphology, proliferative capacity, and function, which is known as reactive astrocytes. Thus, reactive astrocytes release several signaling molecules that modulates and contributes to the defense against injuries and infection in the central nervous system. Therefore, deciphering the complex signaling pathways of reactive astrocytes after brain damage can contribute to the neuroinflammation control and reveal new molecular targets to stimulate neurorepair process. In this review, we present the current knowledge about the role of astrocytes in brain damage and repair, highlighting the cellular and molecular bases involved in synaptogenesis and neurogenesis. In addition, we present new approaches to modulate the astrocytic activity and potentiates the neurorepair process after brain damage.

Residual neuromuscular blockade and late neuromuscular blockade at the post-anesthetic recovery unit: prospective cohort study.

INTRODUCTION AND OBJECTIVES: The use of neuromuscular blockers during surgery represented a landmark for anesthesiology. However, their use can prompt residual Neuromuscular Blockade (RNMB) and objective monitoring of neuromuscular function is crucial to warrant the recovery of muscle strength. The present study aimed to estimate the incidence of RNMB and late Neuromuscular Blockade (LNMB) at the Post-Anesthetic Recovery Unit (PACU). METHOD: The study included 85 patients, 43 of which received cisatracurium and 42 of which, rocuronium. The depth of the Neuromuscular Blockade (NMB) was assessed by Train Of Four (TOF). NMB reversal was performed with the administration of neostigmine and atropine.RNMB was defined when a patient presented TOF below 90% at the PACU. RESULTS: RNMB at the PACU was diagnosed in 39.5% and 40.5% of the patients receiving cisatracurium and rocuronium, respectively (p = 1.0). LNMB at the PACU was found in 32.6% and 16.7% of the patients receiving cisatracurium and rocuronium, respectively (p = 0.131). CONCLUSIONS: The incidence ofRNMB remains significant despite the use of intermediate-acting neuromuscular blockers and reversal agents. There was no statistically significant difference in the incidence of RNMB or LNMB in patients receiving cisatracurium or rocuronium. The use of objective NMB monitoring is effective for the diagnosis of RNMB, as well as for treatment management.

Ophthalmic artery resistance index after peribulbar block in the presence of epinephrine.

PURPOSE: There are controversies regarding ophthalmic artery (OA) flow after peribulbar block in the presence of epinephrine. Therefore, we aimed to evaluate OA flow via echo-Doppler before and after peribulbar block with lidocaine in the presence or absence of epinephrine. METHODS: Fifty-six patients who had an American Society of Anesthesiologists (ASA) classification of I, II or III and were eligible for cataract phacoemulsification surgery were selected. Patients with other eye diseases were excluded. Patients were divided into two groups: group 1-peribulbar block with lidocaine and 1/200,000 epinephrine; group 2-peribulbar block with lidocaine in the absence of epinephrine. The resistance index (RI), peak systolic velocity (PSV), end diastolic velocity (EDV) of the OA were evaluated using echo-Doppler before and 10 min after the peribulbar block. RESULTS: No differences between groups were observed in the RI before the peribulbar block as well regarding the presence of hypertension and the age or gender of the patient. After the peribulbar block, we observed a decrease in the RI in group 1 (p = 0.038, Cohen's d = 0.336) and no difference in the RI in group 2 (p = 0.109, Cohen's d = 0.172). When comparing group 1 and group 2, we observed a decrease in the RI in group 1 (p = 0.028, Cohen's d = 0,583). There was no difference between groups regarding the PSV and EDV after the peribulbar block. CONCLUSIONS: A decrease in RI was observed in the OA after peribulbar block with a vasoconstrictor, an effect that could be a benefit in some ocular surgeries.

Comparison of post-anesthesia recovery time in sedated patients for colonoscopy using midazolam or fentanyl associated with propofol / Comparação do tempo de recuperação pós-anestésica em pacientes sedados para colonoscopia usando midazolam ou fentanil associados a propofol

ABSTRACT Objective: Comparison of post-anesthesia recovery time in sedated patients for colonoscopy using two drug combinations: midazolam and propofol or fentanyl and propofol. Method: Fifty patients ASA I and II, from 18 to 65 years of age, candidates for elective colonoscopy under sedation administered by an anesthesiologist, were randomized in two groups: Group A (midazolam and propofol) and Group B (fentanyl and propofol). Each patient was evaluated as for the length of the exam (Exam length), length of stay in the post-anesthesia care unit 1 and 2 (LSPACU1 and LSPACU2) and hospital discharge. Episodes of awakening, and of movement, drop in SpO2 < 90%, need for mechanical ventilation, propofol consumption, heart rate (HR) and mean blood pressure (MBP) were also evaluated. Results: Patients of group B had a recovery time in LSPACU1 statistically shorter than that for those in group A. In both groups, LSPACU1 was considered inversely proportional to LSPACU2. Hospital discharge time was similar between groups. Patients of group B had a significant decrease in MBP during and at the end of the exam, when compared to the initial measurement and that during sedation. Nevertheless, this variation was lower than 20%. No adverse event was observed. All patients were discharged on the same day, with no unexpected hospitalization. Conclusions: The combined use of fentanyl and propofol for colonoscopy sedation had a post-anesthesia recovery time in LSPACU1 shorter than that with the combination of midazolam and propofol. Nevertheless hospital discharge time was similar between groups.

RESUMO Objetivo: Comparar o tempo de recuperação pós-anestésica de pacientes sedados para colonoscopia usando duas combinações de fármacos: midazolam e propofol ou fentanil e propofol. Método: Cinquenta pacientes ASA I e II, entre 18 e 65 anos, candidatos a colonoscopia eletiva sob sedação administrada por anestesiologista, foram randomizados em dois grupos: Grupo A (midazolam e propofol) e Grupo B (fentanil e propofol). Cada paciente foi avaliado quanto ao tempo de realização do exame (TExame), tempo de permanência na sala de recuperação pós-anestésica 1 e 2 (TSRPA 1 e TSRPA2) e a alta domiciliar. Episódios de despertar, movimentação, queda de SpO2 < 90%, necessidade de assistência ventilatória, consumo de propofol, frequência cardíaca (FC) e pressão arterial média (PAM) também foram avaliados. Resultados: Pacientes do grupo B apresentaram tempo de recuperação na SRPA1 inferior estatisticamente ao grupo A. Em ambos os grupos o TSRPA1 foi considerado inversamente proporcional ao TSRPA2. O tempo de alta domiciliar foi semelhante entre os grupos. Pacientes do grupo B apresentaram redução significativa na PAM no tempos exame e final, em relação ao inicial e sedação. Entretanto, essa variação foi inferior a 20%. Não foram observados eventos adversos. Todos os pacientes evoluíram com alta domiciliar no mesmo dia, sem ocorrência de internação não prevista. Conclusões: O uso combinado de fentanil e propofol para sedação em colonoscopia produziu tempo de recuperação pós-anestésica na SRPA1 inferior a combinação midazolam e propofol. No entanto, o tempo de alta domiciliar foi semelhante entre os grupos.

Neurobiology of glycine transporters: From molecules to behavior.

Glycine transporters (GlyTs) are Na+/Cl--dependent neurotransmitter transporters, responsible for l-glycine uptake into the central nervous system. GlyTs are members of the solute carrier family 6 (SLC6) and comprise glycine transporter type 1 (SLC6A9; GlyT1) and glycine transporter type 2 (SLC6A5; Glyt2). GlyT1 and GlyT2 are expressed on both astrocytes and neurons, but their expression pattern in brain tissue is foremost related to neurotransmission. GlyT2 is markedly expressed in brainstem, spinal cord and cerebellum, where it is responsible for glycine uptake into glycinergic and GABAergic terminals. GlyT1 is abundant in neocortex, thalamus and hippocampus, where it is expressed in astrocytes, and involved in glutamatergic neurotransmission. Consequently, inhibition of GlyT1 transporters can modulate glutamatergic neurotransmission through NMDA receptors, suggesting an alternative therapeutic strategy. In this review, we focus on recent progress in the understanding of GlyTs role in brain function and in various diseases, such as epilepsy, hyperekplexia, neuropathic pain, drug addiction, schizophrenia and stroke, as well as in neurodegenerative disorders.

Lipid dynamics in LPS-induced neuroinflammation by DESI-MS imaging.

It is well-established that bacterial lipopolysaccharides (LPS) can promote neuroinflammation through receptor Toll-like 4 activation and induces sickness behavior in mice. This phenomenon triggers changes in membranes lipid dynamics to promote the intracellular cell signaling. Desorption electrospray ionization mass spectrometry (DESI-MS) is a powerful technique that can be used to image the distribution of lipids in the brain tissue directly. In this work, we characterize the LPS-induced neuroinflammation and the lipid dynamics in C57BL/6 mice at 3 and 24 h after LPS injection. We have observed that intraperitoneal administration of LPS (5 mg/kg body weight) induces sickness behavior and triggers a peripheral and cerebral increase of pro- and anti-inflammatory cytokine levels after 3 h, but only IL-10 was upregulated after 24 h. Morphological analysis of hypothalamus, cortex and hippocampus demonstrated that microglial activation was present after 24 h of LPS injection, but not at 3 h. DESI-MS revealed a total of 14 lipids significantly altered after 3 and 24 h and as well as their neuroanatomical distribution. Multivariate statistical analyzes have shown that ions associated with phosphatidylethanolamine [PE(38:4)] and docosatetraenoic acid [FA (22:4)] could be used as biomarkers to distinguish samples from the control or LPS treated groups. Finally, our data demonstrated that monitoring cerebral lipids dynamics and its neuroanatomical distribution can be helpful to understand sickness behavior and microglial activation after LPS administration.

Combination of clonidine-bupivacaine in caudal epidural anesthesia for hypospadias surgery in children: prospective, randomized, blind study / Associação clonidina-bupivacaína na anestesia peridural caudal para cirurgia de hipospádia em crianças: estudo prospectivo, randomizado, encoberto

Abstract Background and objectives: The combination of clonidine with local anesthetic administered for epidural anesthesia via caudal route seems to improve the quality of postoperative analgesia, but with conflicting results. This study compared the postoperative analgesia of three different doses of clonidine combined with bupivacaine in caudal epidural anesthesia in children undergoing hypospadias repair. Methods: Eighty children aged 1-10 years, candidates for surgical repair of hypospadias, were randomly divided into four groups of 20 patients to receive general anesthesia combined with caudal epidural anesthesia with bupivacaine 0.165% alone or in combination with 1, 2 or 3 µg.kg- 1 of clonidine. The primary outcome was morphine consumption in the first 24 h postoperatively. Mean arterial pressure, heart rate, end-tidal concentration of sevoflurane, time to awakening, pain severity (FLACC scale), level of sedation (RAMSAY), duration of analgesia, and occurrence of adverse effects were also compared. Results: Intraoperatively, there was no difference between groups regarding mean arterial pressure, heart rate, end-tidal concentration of sevoflurane, and time to awakening. Postoperative morphine consumption and pain severity were similar between groups, but the group receiving clonidine (3 µg.kg-1) had lower heart rate and higher sedation level than the group receiving bupivacaine alone. Conclusions: The combination of clonidine at doses of 1, 2 or 3 µg.kg-1 with bupivacaine 0.16% via caudal epidural route did not alter the consumption of morphine in the early postoperative period of children undergoing hypospadias repair.

Resumo Justificativa e objetivos: A associação de clonidina ao anestésico local administrado por via peridural caudal parece melhorar a qualidade da analgesia pós-operatória, mas com resultados conflitantes. Este estudo comparou a analgesia pós-operatória de três diferentes doses de clonidina associada à bupivacaína na anestesia peridural caudal em crianças submetidas à correção de hipospádia. Método: Oitenta crianças entre um e dez anos, candidatas à correção cirúrgica de hipospádia, foram divididas, aleatoriamente, em quatro grupos de 20 pacientes para receber anestesia geral associada à anestesia peridural caudal com bupivacaína 0,166% isolada ou associada a 1, 2 ou 3 µg.Kg-1 de clonidina. Como desfecho principal avaliou-se o consumo de morfina nas primeiras 24 horas de pós-operatório. Compararam-se também pressão arterial média, frequência cardíaca, concentração expirada de sevoflurano, tempo de despertar da anestesia, intensidade da dor pela escala FLACC, nível de sedação (Ramsay), tempo de duração da analgesia e ocorrência de efeitos adversos. Resultados: No transoperatório, não houve diferença entre os grupos quanto à pressão arterial média, frequência cardíaca, concentração expirada de sevoflurano e ao tempo de despertar. No pós-operatório, o consumo de morfina e a intensidade da dor foram similares entre os grupos, mas o grupo que recebeu 3 µg.Kg-1 de clonidina apresentou menor frequência cardíaca e maior sedação do que o grupo que recebeu somente bupivacaína. Conclusões: A associação de clonidina nas doses de 1, 2 ou 3 µg.Kg-1 à bupivacaína 0,166% por via peridural caudal não alterou o consumo de morfina no pós-operatório imediato de crianças submetidas à correção de hipospádia.

[Combination of clonidine-bupivacaine in caudal epidural anesthesia for hypospadias surgery in children: prospective, randomized, blind study]. / Associação clonidina­bupivacaína na anestesia peridural caudal para cirurgia de hipospádia em crianças: estudo prospectivo, randomizado, encoberto.

BACKGROUND AND OBJECTIVES: The combination of clonidine with local anesthetic administered for epidural anesthesia via caudal route seems to improve the quality of postoperative analgesia, but with conflicting results. This study compared the postoperative analgesia of three different doses of clonidine combined with bupivacaine in caudal epidural anesthesia in children undergoing hypospadias repair. METHODS: Eighty children aged 1 to 10 years, candidates for surgical repair of hypospadias, were randomly divided into four groups of 20 patients to receive general anesthesia combined with caudal epidural anesthesia with bupivacaine 0.165% alone or in combination with 1, 2 or 3µg.kg-1 of clonidine. The primary outcome was morphine consumption in the first 24hours postoperatively. Mean arterial pressure, heart rate, end-tidal concentration of sevoflurane, time to awakening, pain severity (FLACC scale), level of sedation (RAMSAY), duration of analgesia, and occurrence of adverse effects were also compared. RESULTS: Intraoperatively, there was no difference between groups regarding mean arterial pressure, heart rate, end-tidal concentration of sevoflurane, and time to awakening. Postoperative morphine consumption and pain severity were similar between groups, but the group receiving clonidine (3µg.kg-1) had lower heart rate and higher sedation level than the group receiving bupivacaine alone. CONCLUSIONS: The combination of clonidine at doses of 1, 2 or 3µg.kg-1 with bupivacaine 0.16% via caudal epidural route did not alter the consumption of morphine in the early postoperative period of children undergoing hypospadias repair.

Guia prático para o manejo da dor / Guia prático para o manejo da dor

O estudo da dor e suas particularidades é de grande importância para o tratamento de diversas patologias e para a melhora na qualidade de vida dos pacientes. A maioria das disfunções orgânicas tem a dor como um ponto importante da sua manifestação. Dessa maneira, é justificável a elaboração de conteúdo para auxiliar os profissionais da saúde no entendimento e tratamento das principais causas de dores agudas e crônicas. Este livro foi elaborado com o objetivo de servir como um guia prático para o manejo da dor por profissionais e acadêmicos de Medicina. Engloba temas como conceitos e aspectos biopsicossociais da dor, além de questões mais complexas como a fisiologia da dor e o tratamento medicamentoso com o arsenal terapêutico existente. Finalmente, também trata dos diversos tipos de dor mais prevalentes e o conhecimento básico que envolve seu manejo.

Anesthesia recovery comparison between remifentanil-propofol and remifentanil-desflurane guided by Bispectral Index® monitoring / Comparação da recuperação pós-anestésica entre remifentanil-propofol e remifentanil-desflurano guiada pela monitoração do Índice Bispectral®

Abstract Background and objectives There is a strong demand for fast and predictable anesthesia recovery with few side effects. Choice of the hypnotic agent could impact on that. This study investigated the differences between recoveries after remifentanil-propofol and remifentanil-desflurane anesthesias guided by bispectral index (BIS®). Methods Forty patients were randomly assigned into 2 groups according to the anesthesia technique applied: remifentanil-propofol (REM-PRO) and remifentanil-desflurane (REM-DES). After the discontinuation of the anesthetics, the times to extubation, to obey commands and to recover the airway protection reflex were recorted. In the post-anesthetic recovery room (PACU) it was recorded the occurrence of nausea and vomiting (PONV), scores of Ramsay sedation scale and of numeric pain scale (NPS), morphine dose and length of stay in the unit. Results Data from 38 patients were analyzed: 18 from REM-PRO and 20 from REM-DES group. Anesthesia times were similar (REM-PRO = 193 min, SD 79.9 vs. 175.7 min, SD 87.9 REM-DES; p = 0.5). REM-DES had shorter times than REM-PRO group: time to follow command (8.5 min; SD 3.0 vs. 5.6 min; SD 2.5; p = 0.0) and extubation time (6.2 min; 3.1-8.5 vs. 9.5 min; 4.9-14.4; p = 0.0). Times to recover airway protective reflex were similar: 16 patients from REM-PRO (88.9%) restored the airway protective reflex 2 min after extubation vs. 17 from REM-DES (89.5%); and 2 patients from REM-PRO (11.1%) vs. 2 from REM-DES (10.5%) 6 min after extubation, p = 1. Ramsay sedation score, NPS, PONV incidents, morphine dose and PACU stay of length PACU were also similar. Conclusion Remifentanil-desflurane-based anesthesia has a faster extubation time and to follow command than remifentanil-propofol-based anesthesia when both guided by BIS®.

Resumo Justificativa e objetivos Há uma forte demanda por recuperação pós-anestésica rápida e previsível com poucos efeitos adversos. A escolha do agente hipnótico pode influenciar isso. Este estudo investigou as diferenças da recuperação no pós-operatório entre as técnicas anestésicas com remifentanil-propofol e com remifentanil-desflurano ambas com monitoração guiada pelo índice bispectral (BIS ®). Métodos Foram randomicamente distribuídos 40 pacientes em dois grupos de acordo com a técnica anestésica aplicada: remifentanil-propofol (REM-PRO) e remifentanil-desflurano (REM-DES). Após a descontinuação dos anestésicos foram registrados os tempos para extubação, obedecer a comandos e recuperar o reflexo de proteção das vias aéreas. Na sala de recuperação pós-anestésica (SRPA) foi registrado a ocorrência de náuseas e vômitos (NVPO), os escores na escala de sedação de Ramsay e na escala numérica de dor (END), a dose de morfina utilizada e o tempo de permanência nesta unidade. Resultados Os dados de 38 pacientes foram analisados: 18 do grupo REM-PRO e 20 do grupo REM-DES. Os tempos de anestesia foram semelhantes (REM-PRO = 193 minutos, DP 79,9 vs. 175,7 minutos, DP 87,9 REM-DES; p = 0,5). O grupo REM-DES apresentou tempos mais curtos do que o grupo REM-PRO: tempo para obedecer a comandos (8,5 minutos; DP 3,0 vs. 5,6 minutos; DP 2,5; p = 0,0) e tempo de extubação (6,2 minutos; 3,1-8,5 vs. 9,5 minutos; 4,9-14,4; p = 0,0). Os tempos para recuperação do reflexo de proteção das vias aéreas foram semelhantes: 16 pacientes do grupo REM-PRO (88,9%) recuperaram o reflexo de proteção das vias aéreas dois minutos após a extubação vs. 17 do grupo REM-DES (89,5%) e dois pacientes do grupo REM-PRO (11,1%) vs. dois do REM-DES (10,5%) seis minutos após a extubação, p = 1. Os escores de Ramsay, NPS, a incidência de NVPO, a dose de morfina e o tempo de permanência na SRPA também foram semelhantes. Conclusão A anestesia com remifentanil-desflurano tem um perfil de recuperação da anestesia pós-anestésica mais rápido do que o da anestesia com remifentanil-propofol quando ambas guiadas pelo BIS®.

Choroid plexus cauterization on treatment of hydranencephaly and maximal hydrocephalus.

INTRODUCTION: The standard treatment for hydranencephaly and maximal hydrocephalus consists of inserting shunts, although complications frequently occur. Choroid plexus cauterization (CPC) is an alternative, but its long-term efficacy and the factors associated with the success and failure of controlling head circumference (HC) are not well defined. OBJECTIVE: This study aims to evaluate the long-term efficacy and factors related to the success rate of CPC in the treatment of hydranencephaly and maximal hydrocephalus. METHOD: Forty-two children with maximal hydrocephalus and hydranencephaly underwent CPC from 2006 to 2014 and were retrospectively evaluated. Children with less than 3 months of follow-up were excluded. The long-term efficacy and success rate of possible variables (i.e., sex, type of malformation, type of surgery performed, treatment hospital, age, and HC at the time of surgery and birth) were evaluated. RESULTS: Thirty-four children were considered for the effectiveness analysis. Treatment was successful in 24 children (70.6%), and failure occurred in 10 children (29.4%). Failure was detected soon after the endoscopic procedure (average 116 days). There was no difference in effectiveness when comparing the age at the moment of surgery (p = 0.473), type of malformation (p = 1), HC at birth (0.699), and HC at the time of surgery (p = 0.648). The surgical death rate was 7.14%. CONCLUSION: Endoscopic CPC was a valid procedure used to treat hydranencephaly and maximal hydrocephaly, and it was effective in 70.6% of cases, with an average follow-up period of 32 months. When failures occurred, they occurred early. None of the analyzed variables interfered with the success of the treatment.

[Anesthesia recovery comparison between remifentanil-propofol and remifentanil-desflurane guided by Bispectral Index® monitoring]. / Comparação da recuperação pós-anestésica entre remifentanil­propofol e remifentanil­desflurano guiada pela monitoração do Índice Bispectral®.

BACKGROUND AND OBJECTIVES: There is a strong demand for fast and predictable anesthesia recovery with few side effects. Choice of the hypnotic agent could impact on that. This study investigated the differences between recoveries after remifentanil-propofol and remifentanil-desflurane anesthesias guided by bispectral index (BIS®). METHODS: Forty patients were randomly assigned into 2 groups according to the anesthesia technique applied: remifentanil-propofol (REM-PRO) and remifentanil-desflurane (REM-DES). After the discontinuation of the anesthetics, the times to extubation, to obey commands and to recover the airway protection reflex were recorted. In the post-anesthetic recovery room (PACU) it was recorded the occurrence of nausea and vomiting (PONV), scores of Ramsay sedation scale and of numeric pain scale (NPS), morphine dose and length of stay in the unit. RESULTS: Data from 38 patients were analyzed: 18 from REM-PRO and 20 from REM-DES group. Anesthesia times were similar (REM-PRO=193min, SD 79.9 vs. 175.7min, SD 87.9 REM-DES; p=0.5). REM-DES had shorter times than REM-PRO group: time to follow command (8.5min; SD 3.0 vs. 5.6min; SD 2.5; p=0.0) and extubation time (6.2 minutes; 3.1-8.5 vs. 9.5 minutes; 4.9-14.4; p=0.0). Times to recover airway protective reflex were similar: 16 patients from REM-PRO (88.9%) restored the airway protective reflex 2min after extubation vs. 17 from REM-DES (89.5%); and 2 patients from REM-PRO (11.1%) vs. 2 from REM-DES (10.5%) 6min after extubation, p=1. Ramsay sedation score, NPS, PONV incidents, morphine dose and PACU stay of length PACU were also similar. CONCLUSION: Remifentanil-desflurane-based anesthesia has a faster extubation time and to follow command than remifentanil-propofol-based anesthesia when both guided by BIS®.

Sedation with dexmedetomidine for conducting electroencephalogram in a patient with Angelman syndrome: a case report / Sedação com dexmedetomidina para realização de eletroencefalograma em paciente portadora de síndrome de Angelmann: relato de caso

ABSTRACT INTRODUCTION: Angelman syndrome is characterized by severe mental retardation and speech and seizure disorders. This rare genetic condition is associated with changes in GABAA receptor. Patients with Angelman syndrome need to be sedated during an electroencephalogram ordered for diagnostic purposes or evolutionary control. Dexmedetomidine, whose action is independent of GABA receptor, promotes a sleep similar to physiological sleep and can facilitate the performing of this examination in patients with Angelman syndrome. CASE REPORT: Female patient, 14 years old, with Angelman syndrome; electroencephalogram done under sedation with dexmedetomidine. The procedure was uneventful and bradycardia or respiratory depression was not recorded. The examination was successfully interpreted and epileptiform activity was not observed. CONCLUSION: Dexmedetomidine promoted satisfactory sedation, was well tolerated and enabled the interpretation of the electroencephalogram in a patient with Angelman syndrome and seizure disorder.

RESUMO INTRODUÇÃO: a síndrome de Angelman (SA) é caracterizada por retardo mental grave, distúrbio da fala e desordem convulsiva. Essa condição genética rara está associada a alterações do receptor GABA-A. Pacientes portadores de SA necessitam ser sedados durante a feitura de eletroencefalograma (EEG), indicado para fins diagnósticos ou controle evolutivo. A dexmedetomidina, cuja ação independe do receptor GABA, promove sono semelhante ao fisiológico e pode viabilizar a feitura desse exame em pacientes com SA. RELATO DE CASO: paciente feminina, 14 anos, portadora de SA, fez EEG sob sedação com dexmedetomidina. O procedimento transcorreu sem intercorrências e não foi registrada bradicardia ou depressão respiratória. O exame foi interpretado com sucesso e atividade epileptiforme não foi observada. CONCLUSÃO: a dexmedetomidina promoveu sedação satisfatória, foi bem tolerada e possibilitou a interpretação do EEG em paciente com SA e desordem convulsiva.

Sedation with dexmedetomidine for conducting electroencephalogram in a patient with Angelman syndrome: a case report.

INTRODUCTION: Angelman syndrome is characterized by severe mental retardation and speech and seizure disorders. This rare genetic condition is associated with changes in GABAA receptor. Patients with Angelman syndrome need to be sedated during an electroencephalogram ordered for diagnostic purposes or evolutionary control. Dexmedetomidine, whose action is independent of GABA receptor, promotes a sleep similar to physiological sleep and can facilitate the performing of this examination in patients with Angelman syndrome. CASE REPORT: Female patient, 14 years old, with Angelman syndrome; electroencephalogram done under sedation with dexmedetomidine. The procedure was uneventful and bradycardia or respiratory depression was not recorded. The examination was successfully interpreted and epileptiform activity was not observed. CONCLUSION: Dexmedetomidine promoted satisfactory sedation, was well tolerated and enabled the interpretation of the electroencephalogram in a patient with Angelman syndrome and seizure disorder.

Ischemia-reperfusion model in rat spinal cord: cell viability and apoptosis signaling study.

This work aimed at determining the ideal ischemia time in an in vitro ischemia-reperfusion model of spinal cord injury. Rat spinal cord slices were prepared and then exposed or not to oxygen deprivation and low glucose (ODLG) for 30, 45, 60, 75 and 90 minutes. Cell viability was assessed by triphenyltetrazolium (TTC), lactate dehydrogenase (LDH) release, and fluorochrome dyes specific for cell dead (ethidium homodimer) using the apotome system. Glutamate release was enzymatically measured by a fluorescent method. Gene expression of apoptotic factors was assessed by real time RT-PCR. Whereas spinal cord slices exposed to ODLG exhibited mild increase in fluorescence for 30 minutes after the insult, the 45, 60, 75 and 90 minutes caused a 2-fold increase. ODLG exposure for 45, 60, 75 or 90 minutes, glutamate and LDH release were significantly elevated. nNOS mRNA expression was overexpressed for 45 minutes and moderately increased for 60 minutes in ODLG groups. Bax/bcl-xl ratio, caspase 9 and caspase 3 mRNA expressions were significantly increased for 45 minutes of ODLG, but not for 30, 60, 75 and 90 minutes. Results showed that cell viability reduction in the spinal cord was dependent on ischemic time, resulting in glutamate and LDH release. ODLG for 45 minutes was adequate for gene expression evaluation of proteins and proteases involved in apoptosis pathways.