When the fever will not stop, stop the pills! A case report

ABSTRACT Neuroleptic malignant syndrome (NMS) is a neurologic emergency potentially fatal. This rare side effect is most commonly associated with first-generation antipsychotics and less frequently with atypical or second-generation antipsychotics. The diagnosis relies on both clinical and laboratory criteria, with other organic and psychiatric conditions being ruled out. CASE REPORT: A 39-year-old female patient, who is institutionalized and completely dependent, has a medical history of recurrent urinary infections and colonization by carbapenem-resistant Klebsiella pneumoniae. Her regular medication regimen included sertraline, valproic acid, quetiapine, risperidone, lorazepam, diazepam, haloperidol, baclofen, and fentanyl. The patient began experiencing dyspnea. Upon physical examination, she exhibited hypotension and a diminished vesicular murmur at the right base during pulmonary auscultation. Initially, after hospitalization, she developed high febrile peaks associated with hemodynamic instability, prompting the initiation of antibiotic treatment. Despite this, her fever persisted without an increase in blood inflammatory parameters, and she developed purulent sputum, necessitating antibiotherapy escalation. The seventh day of hospitalization showed no improvement in symptoms, suggesting NNMS as a differential diagnosis. All antipsychotic and sedative drugs, as well as antibiotherapy, were discontinued, after which the patient showed significant clinical improvement. CONCLUSION: Antipsychotic agents are commonly employed to manage behavioral changes linked to various disorders. However, their severe side effects necessitate a high degree of vigilance, the cessation of all medications, and the implementation of supportive care measures. A prompt and accurate diagnosis of NMS is crucial to alleviating the severe, prolonged morbidity and potential mortality associated with this syndrome.

Quedas na doença de Huntington / Falls in Huntington's Disease

Introdução: Quedas estão associadas com injúrias, medo de cair, diminuição da mobilidade funcional e piora na qualidade de vida. Entretanto, pouco se sabe sobre os fatores potencialmente contribuintes para ocorrência de quedas na Doença de Huntington (DH) assim como sobre as circunstâncias nas quais elas ocorrem. Objetivos: Investigar as características clínicas potencialmente associadas com o aumento do risco de quedas na DH, assim como as circunstâncias nas quais as quedas ocorrem e suas consequências. Métodos: Dados demográficos e clínicos foram obtidos através de entrevista, revisão do prontuário e exame físico. Instrumentos para avaliação de risco de quedas (TUG), sintomas motores (UHDRS, UPDRS), distúrbios da marcha (10MWT, FOG), distúrbios cognitivos (MEEM, FAB, FDT, Hayling,Ekman), alterações comportamentais (Irritability Scale, BIS-11, BDI-II, NPI-Q) e distúrbios do equilíbrio (BBS) foram aplicado em todos pacientes. Resultados: Foram obtidos dados de 40 pacientes e 24 (60%) apresentaram ≥ 2 quedas nos últimos 6 meses e foram considerados "caidores recorrentes". Idade, idade de início da doença e duração da doença (DCL) não diferiram entre os grupos. Em contrapartida, a dose de neurolépticos medida em equivalentes de Olanzapina (OE) foi maior no grupo dos "caidores recorrentes." Os pacientes "caidores recorrentes" também apresentaram pior performance no desempenho da UHDRS-TMS, UPDRS, BBS e mais coreia do que os "não-caidores". Houve também diferença estatística na comparação dos tempos de escolha e alternância do FDT indicando pior desempenho cognitivo do grupo dos "caidores recorrentes" no teste. "Caidores- recorrentes" também apresentaram mais comportamento motor aberrante do que os "não- caidores". Não houve diferença na comparação dos parâmetros espaço-temporais da marcha estudados, assim como no desempenho do TUG. Ambos os grupos apresentaram altos índices de medo de queda. Somente o modelo contento o BBS alcançou significância estatística na regressão logística. Cerca de 80% das quedas ocorreram dentro de casa, caminhar foi o ato mais comum durante as quedas. Ainda, 40% das quedas foram classificadas como intrínsecas. Conclusão: As quedas são frequentes na DH assim como o medo de cair. Nosso estudo sugere que o risco de quedas na doença de Huntington seja multifatorial. Altas doses de neurolépticos, coreia, sintomas cognitivos e comportamentais e particularmente distúrbios do equilíbrio contribuem para ocorrência de quedas na HD.

Introduction: Falls are associated with injuries, fear of falling, decreased functional mobility and worsening in quality of life. However, little is known about the potentially contributing factors to the occurrence of falls in Huntington's Disease (HD) as well as the circumstances in which they occur. Objectives: To investigate clinical features potentially associated with an increased risk of falls in HD, as well as the circumstances in which falls occur and their consequences.Methods: Demographic and clinical data was obtained through interviews, chart review and physical examination. Instruments for fall risk assessment (TUG), motor symptoms (UHDRS, UPDRS), gait disorders (10MWT, FOG), cognitive disorders (MMSE, FAB, FDT, Hayling, Ekman), behavioral changes (Irritability Scale, BIS- 11, BDI-II, NPI-Q) and balance disorders (BBS) were applied to all patients.Results: Data from 40 patients was obtained and 24 (60%) had ≥ 2 falls in the last 6 months and were considered "recurrent fallers". Age, age of disease onset and disease duration (DCL) did not differ between groups. In contrast, the dose of neuroleptics measured in olanzapine equivalents (EO) was higher in the "recurrent fallers" group. The "recurrent fallers" also showed worse performance in the execution of the UHDRS-TMS, UPDRS, BBS and more chorea than the "non-fallers". There was also a statistical difference in the comparison of times of choice and alternation of the FDT, indicating worse cognitive performance of the "recurrent fallers" group in the test. "Recurrent fallers" also showed more aberrant motor behavior than "non-fallers". There was no difference in the comparison of the spatio-temporal gait parameters studied, nor in the TUG performance. Both groups had high rates of fear of falling. Only the model containing the BBS reached statistical significance in the logistic regression. About 80% of falls occurred indoors, walking was the most common act during falls. In addition, 40% of falls were classified as intrinsic. Conclusion: Falls are frequent in HD as well as the fear of falling. Our study suggests that the risk of falls in Huntington's disease is multifactorial. High doses of neuroleptics, chorea, cognitive and behavioral symptoms and particularly balance disorders contribute to the occurrence of falls in HD.

Acatisia inducida por antipsicóticos: recomendaciones para la práctica clínica / Antipsychotic-induced akathisia: recommendations for clinical practice

La acatisia es uno de los eventos adversos inducidos por antipsicóticos más prevalentes y puede generar severa angustia en quien lo experimente. Se caracteriza por inquietud psicomotora objetiva y subjetiva. Pertenece al gran paraguas de los "síntomas extrapiramidales", sin embargo, tiene sus particularidades clínicas lo que representa un desafío clínico, tanto en su diagnóstico como en su manejo específico. La presente revisión sintetiza la información disponible a la fecha y ofrece al clínico recomendaciones para prevenir, reconocer y manejar esta complicación frecuente de una de las familias de psicofármacos de mayor prescripción clínica en la actualidad.

Abstract. Akathisia is one of the most prevalent antipsychotic-induced adverse events and causes severe distress in those who experience it. It is characterized by objective and subjective psychomotor restlessness. Usually classified under the great umbrella of extrapyramidal symptoms; however, it has its own clinical peculiarities, which might represent a challenge for the clinician in diagnosis as well as specific management. This review synthesizes the information available to date on antipsychotic-induced akathisia and offers the clinician recommendations to prevent, recognize and treat this prevalent complication of one of the most widely prescribed psychotropic medications today.

Hemodynamic effects of incremental doses of acepromazine in isoflurane-anesthetized dogs.

OBJECTIVE: To evaluate the effects of incremental doses of acepromazine on hemodynamics in isoflurane-anesthetized dogs. STUDY DESIGN: Prospective, experimental study. ANIMALS: Healthy, adult, mixed-breed dogs (two male and four female) weighing 16.8 ± 5.1 kg (mean ± standard deviation). METHODS: Dogs were anesthetized with propofol (7 mg kg-1) intravenously (IV) and isoflurane. Thermodilution and arterial catheters were placed for hemodynamic monitoring and arterial blood sampling for blood gas analysis. Baseline measurements were performed with stable expired concentration of isoflurane (Fe'Iso) at 1.8%. Each dog was then administered four incremental acepromazine injections (10, 15, 25 and 50 µg kg-1) IV, and measurements were repeated 20 minutes after each acepromazine injection with Fe'Iso decreased to 1.2%. The four acepromazine injections resulted in cumulative doses of 10, 25, 50 and 100 µg kg-1 (time points ACP10, ACP25, ACP50 and ACP100, respectively). RESULTS: Compared with baseline, cardiac index (CI) increased significantly by 34%, whereas systemic vascular resistance index (SVRI) decreased by 25% at ACP50 and ACP100. Arterial oxygen content (CaO2) was significantly lower than baseline after all acepromazine injections (maximum decreases of 11%) and was lower at ACP50 and ACP100 than at ACP10. No significant change was found in heart rate, stroke index, oxygen delivery index and systolic, mean and diastolic blood pressures. Hypotension (mean arterial pressure < 60 mmHg) was observed in one dog at baseline, ACP10, ACP25 and ACP100, and in two dogs at ACP50. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with isoflurane alone, anesthesia with acepromazine-isoflurane resulted in increased CI and decreased SVRI and CaO2 values. These effects were dose-related, being more pronounced at ACP50 and ACP100. Under the conditions of this study, acepromazine administration did not change blood pressure.

¿Es aún válida la división entre antipsicóticos "clásicos" y "atípicos"? / Is the division between "classic" and "atypical" antipsychotics still valid?

El desarrollo de los antipsicóticos "atípicos" o "de segunda generación" despertó grandes expectativas a partir de la década de 1990, al atribuírseles mayor eficacia y tolerabilidad que los antipsicóticos "típicos", "clásicos" o "de primera generación", merced al impacto de una enorme campaña publicitaria por parte de la industria farmacéutica. Sin embargo, diferentes estudios no han podido demostrar en forma fehaciente la pretendida superioridad de aquel grupo de medicamentos en términos de eficacia, prevención de recaídas o producción de efectos adversos. Por otro lado, la clasificación de antipsicóticos "clásicos" y "atípicos" tampoco se puede sustentar en base a estructura química, mecanismos de acción, costos o antigûedad, dada la heterogeneidad que exhiben ambos grupos. Por tales motivos, se plantea que la dicotomía existente debería descartarse.

The development of "atypical" or "second generation" antipsychotics, generated great expectations from the 1990s, as they were attributed more efficacy and tolerability than the "typical", "classic" or "first generation" antipsychotics, due mostly to the impact of a huge advertising campaign by the pharmaceutical industry. However, different studies have not been able to prove, in a categorical way, the alleged superiority of that group of drugs in terms of efficacy, prevention of relapses or production of adverse effects. On the other hand, the classification of "classic" and "atypical" antipsychotics cannot be supported either by factors such as chemical structure, mechanisms of action, costs or years in the market, , given the heterogeneity that both groups exhibit. For such reasons, it is suggested that the existing dichotomy should be ruled out.

Continuous palliative sedation for patients with advanced cancer at a tertiary care cancer center.

BACKGROUND: Palliative sedation (PS) is an intervention to treat refractory symptoms and to relieve suffering at the end of life. Its prevalence and practice patterns vary widely worldwide. The aim of our study was to evaluate the frequency, clinical indications and outcomes of PS in advanced cancer patients admitted to our tertiary comprehensive cancer center. METHODS: We retrospectively studied the use of PS in advanced cancer patients who died between March 1st, 2012 and December 31st, 2014. PS was defined as the use of continuous infusion of midazolam or neuroleptics for refractory symptoms in the end of life. This study was approved by the Research Ethics Committee of our institution (project number 2481-15). RESULTS: During the study period, 552 cancer patients died at the institution and 374 met the inclusion criteria for this study. Main reason for exclusion was death in the Intensive Care Unit. Among all included patients, 54.2% (n = 203) received PS. Patients who received PS as compared to those not sedated were younger (67.8 vs. 76.4 years-old, p < 0.001) and more likely to have a diagnosis of lung cancer (23% vs. 14%, p = 0.028). The most common indications for sedation were dyspnea (55%) and delirium (19.7%) and the most common drugs used were midazolam (52.7%) or midazolam and a neuroleptic (39.4%). Median initial midazolam infusion rate was 0.75 mg/h (interquartile range - IQR - 0.6-1.5) and final rate was 1.5 mg/h (IQR 0.9-3.0). Patient survival (length of hospital stay from admission to death) of those who had PS was more than the double of those who did not (33.6 days vs 16 days, p < 0.001). The palliative care team was involved in the care of 12% (n = 25) of sedated patients. CONCLUSIONS: PS is a relatively common practice in the end-of-life of cancer patients at our hospital and it is not associated with shortening of hospital stay. Involvement of a dedicated palliative care team is strongly recommended if this procedure is being considered. Further research is needed to identify factors that may affect the frequency and outcomes associated with PS.

Psicosis inducida por corticoides en un adolescente: reporte de un caso clínico / Corticosteroid – induced psychosis in an adolescent: a clinical case report

La psicosis inducida por corticoides es una entidad clínica muy poco frecuente dentro de la práctica psiquiátrica infanto-juvenil. Presentamos el caso de un adolescente de 14 años que recibió terapia corticoidal intramuscular, endovenosa y oral para tratar un cuadro alérgico, que debuta posteriormente con un episodio psicótico a los pocos días de haber finalizado dicho tratamiento. Se muestrla presentación clínica, el enfrentamiento diagnóstico-terapéutico inicial, el manejo de especialidad y el seguimiento posterior.

The Corticosteroid induced psychosis is a rare clinical entity within the child and adolescent psychiatric practice. We report a case of a 14 years adolescent that received intramuscular, intravenous and oral corticosteroid therapy to treat an allergy, who debuts later with a psychotic episode a few days after finishing such treatment. It is shown the clinical presentation, the initial diagnostic and therapeutic confrontation, the specialist management and the follow up.

Novos antipsicóticos para o tratamento da esquizofrenia / New antipsychotics for the treatment of schizophrenia

CONTEXTO: Os antipsicóticos de segunda geração representam o grande avanço na terapêutica da esquizofrenia das últimas décadas, porém nos últimos anos foram sintetizados novos antipsicóticos que estão abrindo maiores perspectivas no campo do tratamento da esquizofrenia. Alguns desses medicamentos já foram lançados, enquanto outros estão em fase de testes. OBJETIVO: Apresentar uma síntese do conhecimento dos novos antipsicóticos de segunda geração. MÉTODOS: Busca por meio do PubMed e literatura específica fornecida pelos fabricantes dos medicamentos. RESULTADOS E CONCLUSÕES: São apresentadas as principais características farmacológicas, de eficácia, segurança e tolerabilidade dos seguintes antipsicóticos: Asenapina, ACP-103, Bifeprunox, Paliperidona, Risperidona de Ação Prolongada e Sertindol.

BACKGROUND: The second generation antipsychotics represent the great achievement in the treatment of schizophrenia of the last decades. However in the last years some new antipsychotics were synthesized and such new compounds may represent great perspectives for the field of the treatment of schizophrenia. Some of these compounds are in use while others are still on evaluation through clinical trials. OBJECTIVE: Summarize the current knowledge of new antipsychotics. METHODS: PubMed search as well literature provided by the manufactures. RESULTS AND CONCLUSIONS: We present the main pharmacological characteristics as well as profiles of efficacy, security and tolerability of the following compounds: Asenapine, ACP-103, Bifeprunox, Paliperidone, Long Acting Injectable Risperidone and Sertindole.