Pattern of Psychiatric Emergencies in Children and Adolescents at a Tertiary Care Centre After Onset of COVID-19 Pandemic

Objective: To assess changes in profile of psychiatric emergencies in children and adolescents (aged <19 year) during the coronavirus disease 2019 (COVID-19) pandemic compared to pre-pandemic period. Methods: The psychiatric emergency records were analyzed for the period of April, 2019 – September, 2021 to assess the pattern and profile of mental health emergencies in children and adolescents in the period before and after the onset of the pandemic lockdown (i.e., 23 March, 2020). Results: 379 consecutive child and adolescent psychiatric emergencies were identified, of which 219 were seen after the onset of pandemic. Commonest reason for referral in the pandemic group was attempted self-harm (44.3%). The ICD-10 neurotic, stress-related and somatoform disorders constituted the commonest diagnostic category, similar to pre-pandemic period. A significantly higher proportion (44% vs 28%) of children was prescribed benzodiazepines in the pandemic period, compared to the pre-pandemic period. Conclusion: The average monthly psychiatric emergencies in children and adolescents showed no increase during the pandemic period. Self-harm was the commonest cause of psychiatric referral in emergency services mental health crisis in the younger population.

Benzodiazepines in complex biological matrices:Recent updates on pretreatment and detection methods / 药物分析学报

Benzodiazepines(BDZs)are used in clinics for anxiolysis,anticonvulsants,sedative hypnosis,and muscle relaxation.They have high consumptions worldwide because of their easy availability and potential addiction.They are often used for suicide or criminal practices such as abduction and drug-facilitated sexual assault.The pharmacological effects of using small doses of BDZs and their detections from complex biological matrices are challenging.Efficient pretreatment methods followed by accurate and sensitive detections are necessary.Herein,pretreatment methods for the extraction,enrichment,and preconcentration of BDZs as well as the strategies for their screening,identification,and quantitation developed in the past five years have been reviewed.Moreover,recent advances in various methods are summarized.Characteristics and advantages of each method are encompassed.Future directions of the pretreatment and detection methods for BDZs are also reviewed.

Évaluation de la prescription et de l'utilisation des benzodiazépines dans la ville de Sidi Bel-Abbès / Evaluation of the prescription and use of benzodiazepines in Sidi Bel-Abbes city

Introduction :Une forte consommation des benzodiazépines (BZDs) a été remarquée en dehors parfois des règles de recommandations de prescription, ce qui rend leur consommation un problème majeur de santé publique. La présente étude a eu pour objectif d'évaluer la prescription et l'usage des BZDs dans la ville de Sidi Bel-Abbès. Méthodes-Il s'agissait d'une étude descriptive transversale réalisée du 01 Février 2018 au 30 Juin 2018 évaluant la prescription et l'usage des BZDs dans la ville de Sidi Bel-Abbès au moyen d'un questionnaire distribué aux patients de l'hôpital psychiatrique, du service de psychiatrie du CHU et aux pharmaciens d'officine.Le critère de jugement principal était l'évaluation de la prescription et de l'utilisation des BZDs dans cette ville. La saisie et l'analyse des données ont été réalisées par le logiciel SPSS. Résultats-Au total, 353 patients traités au moins par une BZD ont été inclus dont 178 hommes. Le taux de prescription des BZDs était de 1.10, des jeunes (59,77 %) et des personnes mariées (60,34%) constituaient les consommateurs privilégiés. La prescription était l'apanage des psychiatres, en monothérapie (07,42%), la molé cule la plus fréquemment prescrite était le Bromazépam (31,07%) et la prise noc turne était la plus importante (49,01%). Les BZDs étaient utilisées pour combattre l'insomnie (25,21%), l'anxiété (16,43%), pour une durée de plus d'une année (57,79 %). Conclusion-La prescription et l'utilisation des BZDs dans la ville de Sidi Bel-Abbès s'est avérée importante. L'insomnie et l'anxiété constituaient les principales raisons de leur utilisation, et le Bromazépam était la molécule la plus fréquemment utilisée .

Introduction-A high consumption of benzodiazepines (BZDs) has been noticed so metimes outside the rules of prescription recommendations, which makes their consumption a major public health problem. The present study aimed to evaluate the prescription and use of BZDs in Sidi Bel-Abbès city. Methods-: This was a descriptive cross-sectional study carried out from February 01st, 2018 to June 30th, 2018 evaluating the prescription and use of BZDs in of Sidi Bel-Abbès by means of a questionnaire distributed to patients from the psychiatric hospital, the CHU psychiatry department and community pharmacists. The primary endpoint was the assessment of the prescription and use of BZDs in this city. Data entry and analysis were performed using SPSS software. Results-A total of 353 patients treated with at least one BZD were included, including 178 men. The prescription rate of BZDs was 1.10, young people (59.77%) and married people (60.34%) were the privileged consumers. The prescription was the prerogative of psychiatrists, in monotherapy (07.42%), the molecule most frequent ly prescribed was Bromazepam (31.07%) and night intake was the most important (49.01%). BZDs were used to combat insomnia (25.21%), anxiety (16.43%), for a period of more than a year (57.79%). Conclusion-The prescription and use of BZDs in Sidi Bel-Abbès has proven to be important. Insomnia and anxiety were the main reasons for their use, and Bromazepam was the most molecule frequently used.

Risk Factors of Delirium in Children in Pediatric Intensive Care Unit

Objectives: To determine the prevalence of delirium and its risk factors among children admitted to a Pediatric intensive care unit (PICU). Method: A descriptive study in which consecutive patients admitted to the PICU over a period of 12 months were screened daily for delirium using the Cornell Assessment of Pediatric Delirium (CAPD) score. Treatmentrelated and demographic variables were collected and analyzed. The statistically significant risk factors for delirium were analyzed by multivariable logistic regression for independent associations. Results: Among the 476 screened patients, 96 (20.2%) developed delirium. The independent risk factors associated with the development of delirium were respiratory failure (P<0.001), administration of benzodiazepines during PICU stay (P<0.001), and presence of multiple (?2) risk factors for delirium (P<0.001). The mean length of PICU stay was significantly higher among delirious subjects with P<0.001. Conclusion: Delirium is a frequent complication in critically ill children, and recognition of associated factors may assist in early diagnosis and focussed management.

Prescribing Pattern of Benzodiazepine Receptor Agonists (BZRA) and Factors Associated With Duration of BZRA Use in a Malaysian Psychiatry Outpatient Clinic

@#Introduction: Benzodiazepine receptor agonist (BZRA) are among the most frequently used psychotropic medications worldwide. We aim to understand the pattern of prescription of BZRA in the government healthcare facilities and identify factors affecting the likelihood of BZRA prescription and duration of use. Method: This is a retrospective study. Data was obtained from record of outpatient clinical notes. Medications studied were midazolam, alprazolam, lorazepam, bromazepam, clonazepam, diazepam and zolpidem. Mean duration per prescription, mean dosage per prescription and duration per patient per year were calculated for each sedative hypnotic. The likelihood of factors affecting duration of prescription were also analysed. Results: The prevalence of sedative hypnotic use in psychiatry outpatient clinic was 12.16%. Clonazepam was found to have the longest duration per patient per year (306.5 days). Insomnia and anxiety are the two most common reasons for sedative hypnotic prescription. Factors found to affect duration of prescription were unemployment, borderline personality disorder, alcohol and substance use disorders. Conclusion: Implementation of effective monitoring system on sedative hypnotic prescribing and increase use of non-pharmacological interventions for insomnia and anxiety are necessary to curb prolonged use of sedative hypnotic.

Barriers and enablers to deprescribing benzodiazepines in older adults: elaborating an instrument and validating its content / Facilitadores e dificultadores do processo de desprescrição de benzodiazepínicos em idosos: elaboração de um instrumento e validação de seu conteúdo

OBJECTIVE: To elaborate and validate an instrument on barriers and enablers to deprescribing benzodiazepines in the patient's perspective. METHODS: This study was conducted in 3 stages: (1) a methodological stage, (2) a semi-structured pilot interview with 25 older adults undergoing clonazepam deprescribing, and (3) content validation with the Delphi technique. Content validation was performed by 50 specialists with degrees and/or experience with primary health care and/or health care of older adults, such as physicians, pharmacists, and nurses. For evaluating the obtained results, we analyzed the concordance of evaluations with the coefficient of content validity (CCV). We considered values equal to or higher than 0.8 as acceptable levels of concordance. RESULTS: The instrument was considered validated in the first round of evaluation, where all items obtained a CCV of more than 0.8 in the specialists' assessment. Nevertheless, they proposed improvements that were incorporated to the final version of the questionnaire. CONCLUSION: The instrument represents an important tool to be used by health care professionals for optimizing benzodiazepine deprescribing, with suitable levels of clarity and validity.

OBJETIVO: Elaborar e validar um instrumento sobre facilitadores e dificultadores do processo de desprescrição de benzodiazepínicos na perspectiva do paciente. METODOLOGIA: Estudo desenvolvido em três etapas, quais sejam: (1) metodológica, (2) entrevista piloto semiestruturada com 25 idosos em desprescrição de clonazepam e (3) validação de conteúdo por meio da técnica de Delphi. A validação deu-se por 50 especialistas com formação e/ou experiência na área da Atenção Primária à Saúde e/ou Saúde do Idoso, entre eles médicos, farmacêuticos e enfermeiros. Como medidas para avaliar os resultados obtidos, foi analisada a concordância da avaliação por meio do coeficiente de validade de conteúdo (CVC). Considerou-se como nível aceitável de concordância o valor maior ou igual a 0,8. RESULTADOS: O instrumento foi considerado validado na primeira rodada de avaliação, em que todos os itens avaliados obtiveram CVC superior a 0,8 na avaliação dos especialistas. Entretanto, estes propuseram sugestões de melhorias que foram incorporadas na versão final do questionário. CONCLUSÃO: O instrumento apresenta-se como uma importante ferramenta a ser utilizada pelos profissionais de saúde para a otimização do processo de desprescrição de benzodiazepínicos, possuindo índice de clareza e de validade adequados.

Deprescribing benzodiazepines: Do Brazilian package inserts address this issue? / Desprescrição de benzodiazepínicos: As bulas brasileiras abordam essa temática?

OBJECTIVE: To analyze the presence and quality of content on drug deprescribing in Brazilian package inserts for benzodiazepine drugs. METHODS: Documentary study where we analyzed data on deprescribing extracted from electronic package inserts of drugs containing benzodiazepines; these documents were available at the Brazilian Health Surveillance Agency website. Our search was performed independently by 2 researchers who used the following keywords: "deprescription," "withdrawal," and "tapering." The deprescribing plan, when presented by the package insert, was compared to deprescribing protocols for benzodiazepines found in the literature. Moreover, we assessed the presence of guidance on the maximum length of treatment and risks of long-term use. RESULTS: We found 12 package inserts for benzodiazepines and 100% of them suggested gradual withdrawal; only 1 (8.33%) suggested a systematized deprescribing plan. One document (8.33%) did not offer guidance on maximum treatment duration. Eleven (91.67%) had the information on long-term use possibly causing dependence or tolerance, and 1 (8.33%) did not describe the risks of continuous use. CONCLUSIONS: It is known that benzodiazepines should be withdrawn in a gradual and schematized manner, but package inserts do not currently bring this information in detail. It is of utmost importance that health professionals be educated on their conduct, hence the necessity for updating medication package inserts.

OBJETIVO: Analisar a presença e a qualidade do conteúdo sobre desprescrição em bulas brasileiras de benzodiazepínicos. METODOLOGIA:Estudo do tipo documental, em que foram analisados dados sobre a desprescrição extraídos de bulas eletrônicas de medicamentos que contêm benzodiazepínicos disponibilizadas na página eletrônica da Agência Nacional de Vigilância Sanitária. A busca foi realizada de forma independente por dois pesquisadores que utilizaram as palavras-chave "desprescrição", "retirada" e "redução". Para fins de comparação, quando a bula apresentou esquema de desprescrição, este foi comparado com protocolos de desprescrição de benzodiazepínicos encontrados na literatura. Além disso, foi analisada nas bulas a existência de orientações quanto ao tempo máximo de uso e os riscos do uso prolongado. RESULTADOS: Foram encontradas 12 bulas de benzodiazepínicos e 100% delas sugeriram a redução gradual do medicamento; apenas uma (8,33%) sugeria o esquema sistematizado de desprescrição. Uma (8,33%) não apresentou orientações quanto ao tempo máximo de uso. Onze (91,67%) continham a informação de que o uso prolongado pode causar dependência ou tolerância e uma (8,33%) não descrevia os riscos do uso contínuo. CONCLUSÕES: Sabe-se que os benzodiazepínicos devem ser retirados de forma gradual e esquematizada, porém, atualmente, as bulas não trazem essas informações de forma detalhada. É de suma importância que os profissionais de saúde sejam orientados quanto a sua conduta e, por isso, há grande necessidade de atualização das bulas.

Quality Of Life Amongst Benzodiazepine Users Pre And Post Deprescribing

Objective: The study aimed to analyze the Quality of Life (QoL) of patients utilizing benzodiazepines (BZDs). Methods: A prospective interventional study was conducted among 109 patients who met the inclusion criteria. The patients consuming BZDs more than the prescribed duration were identified and deprescribed. Deprescribing plan was advised after discussing with the prescribing psychiatrist and inappropriate BZD users. The QoL of patient’s pre and post-intervention amongst both the continuing and deprescribed groups was evaluated by WHO-QoL BREF questionnaire. Results: Mean scores in the domains of physical health (71.48), psychological health (68.74), social relationships (65.15) and environmental health (68) among the deprescribed group was higher compared to the maintenance group. Independent t-test statistic for QoL showed a statistical significance in all 4 domains with p value<0.05. Conclusion: The current study emphasizes that deprescribing of BZDs as shared decision model involving the physician, pharmacist and patients improves the QoL of the patient.

Anesthetic quality and cardiovascular and respiratory effects of continuous intravenous infusion of tiletamine-zolazepam in bitches / Qualidade anestésica e efeitos cardiovascular e respiratória da infusão intravenosa contínua de tiletamina-zolazepam em cadelas

The objective of this study was to evaluate the quality and recovery from anesthesia promoted by the tiletamine-zolazepam (TZ) combination administered intravenously (IV) continuously in bitches pre-medicated with acepromazine. Eight cross-bred, clinically healthy bitches weighing 13.7 ±1.9kg on average were used in this study. After a food fast of 12 h and a water fast of four hours, the animals were treated with acepromazine (0.1mg/kg, intramuscular) and, after 15 minutes, anesthesia was induced with a combination of tiletamine-zolazepam (2mg/kg, IV) immediately followed by continuous IV infusion thereof at a dose of 2mg/kg/h for 60 min. The following parameters were measured in all animals immediately before administration of acepromazine (M15), immediately before anesthetic induction (M0), and at 5, 10, 20, 30, 40, 50, and 60 min after initiation of continuous infusion (M5, M10, M20, M30, M40, M50, and M60): electrocardiography (ECG), heart rate (HR), mean arterial pressure (MAP), respiratory rate (RR), body temperature (BT), and arterial hemogasometry, with the last performed only at experimental times M15, M0, M30, and M60. A subcutaneous electrical stimulator was used to evaluate the degree of analgesia. Myorelaxation and quality of anesthetic recovery were also assessed, classifying these parameters as excellent, good, and poor. Anesthetic recovery time was recorded in minutes. HR increased significantly at time M10 in relation to that at M-15, and at times M5, M10, M40, and M50 in relation to that at M0. MAP decreased significantly at M20 and M30 compared with the baseline. BT decreased significantly at M50 compared with that at M0, but no hypothermia was observed. RR showed significant reduction at M5, M10, and M20 in relation to that at M-15, and at M5 and M10 in relation to that at M0, and bradypnoea was observed during the first 20 min after anesthetic induction. Significant decreases in the PR interval at times M10, M40, and M50 were observed in relation to that at M15. Amplitude of the R wave showed significant decrease at M20 compared with that at M-15. In the other ECG parameters, no significant difference was observed between the times evaluated. Hemogasometric parameters and analgesia did not show significant alterations. Myorelaxation and quality of anesthetic recovery were considered excellent. Recovery time was 15.1±7.7 min for positioning of sternal decubitus and 45.5±23.1 minutes for return of ambulation. Continuous IV administration of TZ combination does not produce satisfactory analgesia and does not cause severe cardiorespiratory and hemogasometric effects in bitches pre-medicated with acepromazine.(AU)

Objetivou-se avaliar a qualidade e a recuperação da anestesia promovida pela associação tiletamina-zolazepam, administrada por via intravenosa (IV) contínua, em cadelas pré-medicadas com acepromazina. Foram utilizadas oito cadelas, sem raças definidas, clinicamente sadias, pesando em média 13,7±1,9kg. Após jejum alimentar de 12 horas e hídrico de quatro horas, os animais foram medicados com acepromazina (0,1mg/kg, via intramuscular) e, após 15 minutos, a anestesia foi induzida com a associação tiletamina-zolazepam (2mg/kg, IV) seguida imediatamente pela infusão IV contínua da mesma, na dose de 2mg/kg/h, durante 60 minutos. Os parâmetros que foram mensurados em todos os animais, imediatamente antes da administração da acepromazina (M-15), imediatamente antes da indução anestésica (M0) e, aos 5, 10, 20, 30, 40, 50 e 60 minutos após o início da infusão contínua (M5, M10, M20, M30, M40, M50 e M60) foram os seguintes: eletrocardiografia (ECG), frequência cardíaca (FC), pressão arterial média (PAM), frequência respiratória (f), temperatura corpórea (TC) e hemogasometria arterial, esta sendo realizada apenas nos momentos M-15, M0, M30 e M60. Para avaliação do grau de analgesia foi empregado um estimulador elétrico subcutâneo. Também se avaliou o miorrelaxamento e a qualidade da recuperação anestésica, classificando estes parâmetros em: excelente, bom e ruim. O tempo de recuperação anestésica foi registrado em minutos. A FC aumentou significativamente no momento M10 em relação ao M-15, e nos momentos M5, M10, M40 e M50 em relação ao M0. A PAM diminuiu significativamente em M20 e M30 em comparação ao valor basal. A TC diminuiu significativamente em M50 em comparação ao M0, mas não foi observada hipotermia. A f apresentou uma redução significativa nos momentos M5, M10 e M20 em relação ao M-15, e em M5 e M10 em relação ao M0, sendo observado bradipneia durante os primeiros 20 minutos após a indução anestésica. Foram observadas diminuições significativas do intervalo PR nos momentos M10, M40 e M50, em relação ao M-15. A amplitude da onda R apresentou diminuição significativa em M20 em comparação ao M-15. Nos demais parâmetros da ECG não houve diferença significativa entre os momentos avaliados. Os parâmetros hemogasométricos e a analgesia não apresentaram alterações significativas. O miorrelaxamento e a qualidade da recuperação anestésica foram considerados excelentes. O período de recuperação foi de 15,1±7,7 minutos para posicionamento do decúbito esternal e 45,5±23,1 minutos para retorno da deambulação. A administração intravenosa contínua de tiletamina-zolazepam não produz analgesia satisfatória e não causa efeitos cardiorrespiratórios e hemogasométricos severos, em cadelas pré-tratadas com acepromazina.(AU)

Electroacupuncture improves insomnia by down-regulating peripheral benzodiazepine receptor expression in hippocampus, and up-regulating 5-HT, 5-HIAA, TNF-α and IL-1β contents in hypothalamus in insomnia rats / 针刺研究

OBJECTIVE: To observe the therapeutic effect of electroacupuncture (EA) at five Back-Shu points on sleep, hippocampal peripheral benzodiazepine receptor (PBR) expression and hypothalamic 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1β contents in insomnia rats, so as to explore its mechanisms underlying improvement of insomnia. METHODS: Forty male SD rats were randomly divided into control, model, EA and medication (Diazepam) groups (n=10 rats in each group). The insomnia model was established by intraperitoneal injection (i.p.) of para-Chlorophenylalanine (PCPA, 300 mg/kg) once daily for 2 days. EA (60 Hz, 1 mA) was applied to bilateral five Back-Shu points, i.e., Feishu (BL13), Xinshu (BL15), Ganshu (BL18), Pishu (BL20) and Shenshu (BL23) for 10 min, once daily for 6 days. Rats of the medication group were treated by gavage of Diazepam (0.92 mg/kg) once daily for 6 days. The sleep duration was recorded after i.p. of Pentobarbital Sodium (45 mg/kg). Histopathological changes of the hippocampus were displayed by H.E. staining. The contents of 5-HT, 5-HIAA, TNF-α and IL-1β in the hypothalamus were assessed by using ELISA. The expression levels of PBR mRNA and protein in the hippocampus were detected by quantitative real-time PCR, immunohistochemistry and Western blot, separately. RESULTS: Following modeling, the sleep duration was considerably shortened in rats of the model group relevant to the control group (P0.05), and significantly superior to that of the medication in increasing TNF-α and IL-1β levels (P<0.05), and considerably superior to that of medication in down-regulating PBR mRNA and protein expression (P<0.05). CONCLUSION: EA at five Back-Shu-points of the five Zang-organs can significantly improve the sleep in insomnia rats, which is closely associated with its effects in reducing the expression of PBR in hippocampus and up-regulating the levels of 5-HT, 5-HIAA, TNF-α and IL-1β in hypothalamus.

The use of flumazenil for benzodiazepine associated respiratory depression in postanesthesia recovery: risks and outcomes / O uso de flumazenil para depressão respiratória associada ao benzodiazepínico na recuperação pós-anestésica: riscos e resultados

Abstract Background and objectives The primary aim was to determine risk factors for flumazenil administration during postanesthesia recovery. A secondary aim was to describe outcomes among patients who received flumazenil. Methods Patients admitted to the postanesthesia recovery room at a large, academic, tertiary care facility after surgery under general anesthesia from January 1, 2010, to April 30, 2015, were identified and matched to 2 controls each, by age, sex, and surgical procedure. Flumazenil was administered in the recovery phase immediately after general anesthesia, according to the clinical judgment of the anesthesiologist. Demographic, procedural, and outcome data were extracted from the electronic health record. Conditional logistic regression, accounting for the 1:2 matched-set case-control study designs, was used to assess characteristics associated with flumazenil use. Results The incidence of flumazenil administration in the postanesthesia care unit was 9.9 per 10,000 (95% CI, 8.4-11.6) general anesthetics. History of obstructive sleep apnea (Odds Ratio [OR] = 2.27; 95% CI 1.02-5.09), longer anesthesia (OR = 1.13; 95% CI 1.03-1.24 per 30 minutes), use of total intravenous anesthesia (OR = 6.09; 95% CI 2.60-14.25), and use of benzodiazepines (OR = 8.17; 95% CI 3.71-17.99) were associated with risk for flumazenil administration. Among patients who received midazolam, cases treated with flumazenil received a higher median (interquartile range) dose than controls: 3.5 mg (2.0-4.0 mg) vs. 2.0 mg (2.0-2.0 mg), respectively (p < 0.001). Flumazenil use was correlated with a higher rate of unanticipated noninvasive positive pressure ventilation, longer postanesthesia care unit stay, and increased rate of intensive care unit admissions. Conclusions Patients who required flumazenil postoperatively had received a higher dosage of benzodiazepines and utilized more postoperative health care resources. More conservative perioperative use of benzodiazepines may improve postoperative recovery and use of health care resources.

Resumo Justificativa e objetivos Determinar os fatores de risco da administração de flumazenil durante a recuperação pós-anestésica e descrever os desfechos entre os pacientes que receberam flumazenil. Métodos Os pacientes admitidos em sala de recuperação pós-anestésica de um grande centro universitário em setor terciário de cuidados pós-cirurgia sob anestesia geral entre 1° de janeiro de 2010 e 30 de abril de 2015 foram identificados e pareados com dois controles cada por idade, sexo e procedimento cirúrgico. Flumazenil foi administrado na fase de recuperação imediatamente após a anestesia geral, de acordo com a avaliação clínica do anestesiologista. Os dados demográficos, dos procedimentos e dos desfechos foram extraídos do registro eletrônico de saúde. A regressão logística condicional para os desenhos do estudo de caso-controle pareado em 1:2 foi usada para avaliar as características associadas ao uso de flumazenil. Resultados A incidência da administração de flumazenil em sala de recuperação pós-anestésica foi de 9,9 por 10.000 (95% IC: 8,4-1,6) anestesias gerais. História da apneia obstrutiva do sono (razão de chances [OR] = 2,27; IC 95%: 1,02-5,09), anestesia de longa duração (OR = 1,13; IC 95%: 1,03-1,24 por 30 minutos), uso de anestesia intravenosa total (OR = 6,09; IC de 95%: 2,60-14,25) e uso de benzodiazepínicos (OR = 8,17; IC 95%: 3,71-17,99) foram associados a risco para a administração de flumazenil. Entre os pacientes que receberam midazolam, os casos tratados com flumazenil receberam uma dose mediana mais alta (intervalo interquartil) do que os controles: 3,5 mg (2,0-4,0 mg) vs. 2,0 mg (2,0-2,0 mg), respectivamente (p < 0,001). O uso de flumazenil foi correlacionado com uma taxa maior não prevista de ventilação não invasiva com pressão positiva, permanência mais longa em sala de recuperação pós-anestésica e aumento da taxa de admissões em unidade de terapia intensiva. Conclusão Os pacientes que precisaram de flumazenil no pós-operatório receberam uma dose maior de benzodiazepínicos e usaram mais recursos de cuidados da saúde no pós-operatório. O uso mais conservador de benzodiazepínicos no período perioperatório pode melhorar a recuperação e o uso de recursos de cuidados da saúde no pós-operatório.

Avaliação do padrão de sono em insones usuários de benzodiazepínicos e análise da trazodona como medicação substitutiva / Evaluation of sleep pattern in insomnia in benzodiazepine users and analysis of trazodone as a substitute medication

RESUMO Objetivo Conhecer as modificações do padrão do sono em insones usuários crônicos de benzodiazepínicos (BZDs) após introdução da trazodona. Métodos Em um grupo de 11 pacientes, foi estabelecido esquema para retirada gradual do BZD com introdução progressiva da trazodona. Foram realizadas duas polissonografias, sendo a primeira com dose de BZD habitual do paciente e a segunda após supensão do BZD e com 150 mg de trazodona de liberação prolongada. Questionários de qualidade do sono (Pittsburgh), sonolência diurna (Epworth) e sintomas depressivos (Hamilton) e ansiosos (Beck) foram aplicados. Resultados Cinco indivíduos concluíram o estudo, tendo sido acompanhados por pelo menos seis semanas. Nesses pacientes, a trazodona aumentou significativamente a eficiência do sono e sono REM e diminuiu o tempo desperto após início do sono. Houve melhora da qualidade do sono, porém não houve alteração dos sintomas depressivos e ansiosos. Conclusão Trazodona de liberação prolongada demonstrou ser uma opção terapêutica para insones usuários crônicos de BZDs com retirada eficaz do ansiolítico. Houve melhora na qualidade do sono por questionário e polissonografia. Maior número de pacientes será necessário para determinar os benefícios da trazodona nesse tipo de intervenção.

ABSTRACT Objective To know the modifications of the sleep pattern in chronic benzodiazepine users after the introduction of trazodone. Methods In a group of 11 patients, a gradual withdrawal of benzodiazepine (BZD) was introduced with progressive introduction of trazodone. Two polysomnograms were performed, the first with BZD usual dose of the patient and the second after BZD suppression and with 150 mg of prolonged release trazodone. Sleep quality questionnaires (Pittsburgh), daytime sleepiness (Epworth) and depressive (Hamilton) and anxious (Beck) symptoms were applied. Results Five subjects completed the study and were followed up for at least six weeks. In these patients, trazodone significantly increased sleep efficiency and REM sleep and decreased wakefulness after sleep onset. There was an improvement in sleep quality, but there was no change in depressive and anxious symptoms. Conclusion Prolonged release trazodone has been shown to be a therapeutic option for chronic insomnia patients with benzodiazepines with effective withdrawal of the anxiolytic drug. There was improvement in sleep quality by questionnaire and polysomnography. More patients will be needed to determine the benefits of trazodone in this type of intervention.

Identification of New Designer Benzodiazepine Diclazepam in Drug Facilitated Sexual Assault / 法医学杂志

OBJECTIVES@#To identify the new designer drugs which are totally unknown and not in the routine testing list by the technologies such as high-resolution mass spectrometry in drug facilitated sexual assault, in order to solve the problem in actual cases.@*METHODS@#The milky fluid from an actual case was extracted and analyzed using LC-QE, ¹H-NMR and GC-MS, respectively. The accurate masses and cluster ions isotope patterns of unknown compound were obtained by LC-QE. The molecular formula was confirmed as C₁₆H₁₂C₂N₂O based on the protons number of ¹H-NMR. The isomers diclazepam and 4-chlorodiazepam were separated and detected with GC-MS.@*RESULTS@#The new designer benzodiazepine as diclazepam in the milky fluid was identified. The results provided direct evidence for the investigation and qualitative analysis of such cases.@*CONCLUSIONS@#The combined application of various methods, including LC-QE, ¹H-NMR and GC-MS, can be used to detect unknown new psychoactive substances.

Efeitos sedativos da administração intranasal ou intramuscular de midazolam associado ou não ao butorfanol em periquito autraliano (Melopsitacus undulatus) / Sedative effects of intranasal or intramuscular administration of midazolam with or without butorphanol in budgerigards (Melopsitacus undulatus)

Frequentemente o médico-veterinário é requisitado para realização de diversos procedimentos em aves, os quais geralmente necessitam de sedação ou anestesia geral. Este trabalho teve como objetivo comparar os efeitos sedativos do midazolam (5 mg.kg-1) associado ou não ao butorfanol (1 mg.kg-1) pelas vias de administração intranasal ou intramuscular. Sete periquitos australianos foram submetidos a quatro tratamentos em delineamento do tipo crossover com 15 dias de intervalo. Foram avaliados os períodos de latência, tempos de decúbito dorsal, tempos de sedação, tempos de recuperação, grau de sedação e qualidade de recuperação. Os resultados paramétricos foram avaliados por análise de variância de uma via seguida por teste de Student- Newman-Keuls e os dados não paramétricos foram submetidos ao teste Kruskal-Wallis ambos com 5% de significância. A técnica intranasal demonstrou melhores graus de sedação; no entanto, concluiu-se que ambos os protocolos e as vias de administração avaliados são seguras e viáveis para sedação em periquito australiano.

Often veterinarians have attended various species of birds to perform clinical procedures, which require sedation or general anesthesia. The aim of this study was compare the intranasal or intramuscular sedative effects of midazolam (5 mg.kg-1) with or without butorphanol (1 mg.kg-1). Seven budgerigards (Melopsitacus undulates) were submitted in a crossover design to four treatments. The procedures were performed with 15 days washout. Were evaluated the on set time, dorsal recumbency time duration, total sedation period, total recovery time, sedation degree and recovery quality. The parametric results were analised by one way ANOVA following Student-Newman-Keuls test and non-parametric datas were submitted to Kruskal-Wallis test, both with 5% significance. The intranasal technical demonstrates best degrees of sedation, however, this study concluded that both protocols and the administration routes are safe and viable for sedation in budgerigards

Demographic Characteristics, Medication Profile and Treatment Outcome of Patients with Very Early-Onset Schizophrenia in One Hospital

OBJECTIVES: Very early-onset schizophrenia (VEOS) is a type of psychosis having a low frequency, insidious onset, and devastating clinical outcome. In this study, the demographic features, information on medication, clinical outcomes, and intellectual capability of patients diagnosed with VEOS in a hospital were analyzed to provide therapeutic strategies for this type of schizophrenia. METHODS: Using the electronic medical records of the National Center for Mental Health, 69 patients with VEOS were identified based on the DSM-5 criteria of schizophrenia. The data were summarized and analyzed according to the demographic characteristics, medications used, intellectual strength measured by the full intelligence quotient (FIQ) score, and current clinical status measured by the Clinical Global Impression-Severity (CGI-S) and various combinations of these parameters. RESULTS: The screened study group contained similar numbers of males and females. The younger the onset of psychosis, the lower the frequency. The study population included a significantly higher proportion of births in the winter season than that of the general population. The 3 most frequently used antipsychotic medications were risperidone and its derivatives, clozapine and olanzapine. Valproic acid and divalproex sodium were the most commonly added drugs for outcome augmentation. 53.5% of the study population had received benzodiazepines and/or hypnotics. The average FIQ of the study population was 69.4, which is quite low compared to previous Korean studies with similar populations. There was a weak negative correlation between FIQ and CGI-S, but it was not statistically significant. The average CGI-S score was 4.2, which meant that the patients were moderately ill. CONCLUSION: This study demonstrated that patients with VEOS showed more frequent intellectual deficits at baseline and poorer outcomes than the control group. Risperidone, clozapine, valproic acid and their combinations were the most preferred medications for the treatment of psychosis. Benzodiazepines were quite commonly added for various reasons.

Benzodiazepine Use among Patients with Schizophrenia in Korea: Analysis of Database of Health Insurance Review Agency / 신경정신의학

OBJECTIVE: This study was designed to examine the pattern of benzodiazepine use in a representative sample of patients with schizophrenia in Korea. METHOD: Data generated by the Health Insurance Review Agency of Korea was used to examine the frequency of benzodiazepine use. Demographic and geographic factors, hospital types in which patients received prescriptions, health insurance coverage, and the number of concomitant antipsychotics associated with benzodiazepine use were explored by multivariate logistic regression analysis. RESULTS: Among the 183427 patients with schizophrenia, the frequency of benzodiazepine use was 67.5% (n=122859). Use of benzodiazepines was highly associated with female patients treated in hospitals located in Gyeonggi, Gyeongsang, and Gangwon provinces, medicaid patients, patients treated in mental hospitals and private psychiatric clinics, and patients using concomitant antipsychotic agents. CONCLUSION: The study demonstrated that benzodiazepine use was highly prevalent among patients with schizophrenia. Long-term use of benzodiazepine may be at higher risk of neurocognitive side effects and risk of mortality. Therefore, patients with schizophrenia taking benzodiazepine concomitantly should be closely monitored for benefits and risks of benzodiazepine use. For the medicaid patients, policy change is urgently needed in order for patients to receive equal quality of treatment with that of non-medicaid patents.

Monoterpenoids (thymol, carvacrol and S-(+)-linalool) with anesthetic activity in silver catfish (Rhamdia quelen): evaluation of acetylcholinesterase and GABAergic activity

This study evaluated the anesthetic potential of thymol and carvacrol, and their influence on acetylcholinesterase (AChE) activity in the muscle and brain of silver catfish (Rhamdia quelen). The AChE activity of S-(+)-linalool was also evaluated. We subsequently assessed the effects of thymol and S-(+)-linalool on the GABAergic system. Fish were exposed to thymol and carvacrol (25, 50, 75, and 100 mg/L) to evaluate time for anesthesia and recovery. Both compounds induced sedation at 25 mg/L and anesthesia with 50-100 mg/L. However, fish exposed to carvacrol presented strong muscle contractions and mortality. AChE activity was increased in the brain of fish at 50 mg/L carvacrol and 100 mg/L thymol, and decreased in the muscle at 100 mg/L carvacrol. S-(+)-linalool did not alter AChE activity. Anesthesia with thymol was reversed by exposure to picrotoxin (GABAA antagonist), similar to the positive control propofol, but was not reversed by flumazenil (antagonist of benzodiazepine binding site), as observed for the positive control diazepam. Picrotoxin did not reverse the effect of S-(+)-linalool. Thymol exposure at 50 mg/L is more suitable than carvacrol for anesthesia in silver catfish, because this concentration did not cause any mortality or interference with AChE activity. Thymol interacted with GABAA receptors, but not with the GABAA/benzodiazepine site. In contrast, S-(+)-linalool did not act in GABAA receptors in silver catfish.

Clonazepam associated hypothyroidism: Aforethought on a concealed dilemma.

Subclinical hypothyroidism or mild thyroid failure is a familiar problem, with a prevalence of 3-15% in a population without any known overt thyroid disorder. The prevalence increases with age and is relatively higher among females. Subclinical hypothyroidism is defined as serum thyroid stimulating hormone (TSH) levels above the upper limit of normal (4 mU/L) while the triiodothyronine (T3) and thyroxine (T4) enduring within the normal range. Additionally, there exists a log-linear relationship between TSH and circulating T3 and T4; hence, measurement of serum TSH becomes mandatory for diagnosing mild thyroid failure when free T3and T4 are lying within normal limits. Though, autoimmune thyroid disease is the most common cause for elevated TSH; thyroid functions can be afflicted by long-term consumption of drugs like lithium, amiodarone. The causal relationship between benzodiazepine class of drugs, particularly clonazepam and subclinical hypothyroidism has never been established clinically, yet there are some pre-clinical studies to claim the effect of benzodiazepine on thyroid functions; operating at various levels – hypothalamus, thyroid gland, peripheral cells and nuclear receptors. Henceforth, we would like to report a rare occurrence of subclinical hypothyroidism in an elderly female receiving clonazepam for her underlying psychiatric illness.

Prescrição de benzodiazepínicos para adultos e idosos de um ambulatório de saúde mental / Prescription of benzodiazepines for adults and older adults from a mental health clinic

Resumo Foi objetivo deste estudo comparar as prescrições de benzodiazepínicos (bzd) em adultos e idosos quanto aos indicadores do uso apropriado. Estudo transversal de coleta de dados de pacientes atendidos no Ambulatório Municipal de Saúde Mental de Sorocaba/SP, entre março e novembro de 2013. Foram utilizados indicadores de uso apropriado: medicamento apropriado, com adequada posologia e duração de uso; como também, o uso de apenas um bzd, como ansiolítico por menos de 3 meses, no tratamento da depressão com antidepressivo, uso por menos de 2 meses se associado ao antidepressivo e o não uso de bzd de longa ação em idoso. Dos 330 participantes, a maioria era mulheres, com histórico familiar de transtorno mental e uso de bzd, não realizava acompanhamento com psicólogo e fazia uso de outros psicotrópicos e de polifarmácia (p > 0,05). A minoria das prescrições tinha indicação de uso do bzd (37,5% para idosos e 32,4% para adultos) (p > 0,05). Apenas 5,8% das prescrições para idosos e 1,9% para adultos eram racionais (p > 0,05). O uso crônico foi observado em todos os adultos e idosos com transtornos depressivos e ansiosos (p > 0,05). Uma minoria das prescrições de bzd para adultos e idosos era apropriada.

Abstract The aim of this study was to compare benzodiazepine (bzd) prescriptions for adults and older adults regarding appropriate use indicator. It is a cross-sectional study for collecting data on patients treated at the City’s Mental Health Clinic in Sorocaba/SP, between March and December 2013. Appropriate use indicators were used: appropriate drug, with adequate posology and period of use; as well as the use of a single bzd, as anxiolytic for less than 3 months in depression treatment with antidepressants, use for less than 2 months if associated to an antidepressant and no use of long-acting bzd in older adults. From the 330 participants, most were women, with a family history of mental disorders and bzd use, without monitoring of a psychologist and using other psychotropic and polypharmacy (p>0.05).The minority of prescriptions had indication for the use of bzd (37.5% for older adults and 32.4% for adults) (p>0.05). Only 5.8% of the prescriptions for older adults and 1.9 for adults were rational (p>0.05). The chronic use was observed in all adults and older adults with depressive and anxiety disorders (p>0.05). A minority of prescriptions for adults and older adults was appropriate.

Effects of Early Administration of Dexmedetomidine on Benzodiazepine Requirements of ICU Patients with Alcohol Withdrawal Syndrome / 中国药师

Objective:To evaluate the effects of early administration of dexmedetomidine on benzodiazepine ( BZD) requirements of intensive care unit ( ICU) patients with alcohol withdrawal syndrome ( AWS) .Methods:Totally 60 adult patients with severe AWS were chosen and randomly divided into groups A and group B with 30 patients in each .The patients in group A received benzodiazepine simultaneously with early administration of dexmedetomidine , and those in group B received only benzodiazepine .After the first admin-istration of dexmedetomidine , the 24-h cumulative BZD requirement , stay length in ICU and hospital , condition of mechanical ventila-tion and incidence of hypotension and bradycardia were recorded .Results:The 24-h cumulative BZD requirement in group A was obvi-ously lower than that in group B [(8.6 ±1.2) mg vs (25.6 ±4.9) mg, P<0.05].The number of patients with mechanical ventila-tion in the two groups was similar, while the duration of intubation in group A was less than that in group B [(24.9 3.1) h vs (48.8 6.9) h, P<0.05].Additionally, group A had higher incidence of bradycardia when compared with group B (57% vs 13%, P<0.05).Conclusion:As the adjuvant treatment for alcohol withdrawal syndrome , early administration of dexmedetomidine can notably decrease the benzodiazepine requirement of ICU patients .