Critical care nurses experience stressful situations in their daily working environments. The question arises for nurses: are there adequate support systems in the critical care environment and what are critical care nurses doing to mantain their own health and well-being. Facilitating conscious awareness among critical care nurses could enhance their resiliency and their hardiness, strengthening their coping capacities in stressful working situations. The contextual framework adopted for this research was the Neuman Systems Model. A qualitative research approach (exploratory, descriptive and contextual) was used to explore and describe the stress experienced by critical care nurses. Focus group interviews were conducted with critical care nurses and individual interviews with nurse managers. The results revealed their perceptions and experiences about the effects of stress in the critical care environment, as well as some of their coping strategies. Raising critical care nurses' levels of conscious awareness about their coping strategies with stressful events in their daily working lives, could enhance their resiliency and hardiness, enabling them to continue working effectively in stressful environments. This could enhance the general well-being of individual critical care nurses, the nursing care rendered to critically ill patients, and save money for the health care services by reducing turnover rates among critical care nurses. / Health Studies / D.Litt. et Phil. (Health Studies)

Objectifs : Définir les paramètres pharmacocinétiques du pantoprazole intraveineux en soins intensifs pédiatriques et déterminer l’influence qu’exercent sur ceux-ci les facteurs démographiques, le syndrome de réponse inflammatoire systémique (SRIS), la dysfonction hépatique et l’administration d’un inhibiteur du cytochrome (CYP) 2C19. Méthode : Cent cinquante-six concentrations plasmatiques de pantoprazole provenant d’une population de 20 patients (âgés de 10 jours à 16.4 ans) à risque ou atteints d’une hémorragie gastroduodénale de stress, ayant reçu des doses quotidiennes de pantoprazole de 19.9 à 140.6 mg/1.73m2, ont été analysées selon les méthodes non compartimentale et de modélisation non linéaire à effets mixtes. Résultats : Une clairance médiane (CL) de 0.14 L/h/kg, un volume apparent de distribution de 0.20 L/kg et une demi-vie d’élimination de 1.7 h ont été déterminés via l’approche non compartimentale. Le modèle populationnel à deux compartiments avec une infusion d’ordre zéro et une élimination d’ordre un représentait fidèlement la cinétique du pantoprazole. Le poids, le SRIS, la dysfonction hépatique et l’administration d’un inhibiteur du CYP2C19 constituaient les covariables significatives rendant compte de 75 % de la variabilité interindividuelle observée pour la CL. Seul le poids influençait significativement le volume central de distribution (Vc). Selon les estimations du modèle final, un enfant de cinq ans pesant 20 kg avait une CL de 5.28 L/h et un Vc de 2.22 L. La CL du pantoprazole augmentait selon l’âge et le poids tandis qu’elle diminuait respectivement de 62.3%, 65.8% et 50.5% en présence d’un SRIS, d’un inhibiteur du CYP2C19 ou d’une dysfonction hépatique. Conclusion : Ces résultats permettront de guider les cliniciens dans le choix d’une dose de charge et dans l’ajustement des posologies du pantoprazole en soins intensifs pédiatriques dépendamment de facteurs fréquemment rencontrés dans cette population. / Aims : To characterize the pharmacokinetics of intravenous pantoprazole in a paediatric intensive care population and to determine the influence of demographic factors, systemic inflammatory response syndrome (SIRS), hepatic dysfunction and concomitantly used cytochrome (CYP) 2C19 inhibitors on the drug’s pharmacokinetics. Methods : A total of 156 pantoprazole concentrations from 20 patients (aged from 10 days to 16.4 years) at risk for or with upper gastrointestinal bleeding, who received pantoprazole doses ranging from 19.9 to 140.6 mg/1.73m2/day, were analyzed using non compartmental and non linear mixed effects modelling (NONMEM) approaches. Results : The non compartmental results showed that median clearance (CL), apparent volume of distribution and elimination half-life were 0.14 L/h/kg, 0.20 L/kg and 1.7 h, respectively. The best structural model for pantoprazole was a two-compartment model with zero order infusion and first order elimination. Body weight, SIRS, age, hepatic dysfunction and presence of CYP2C19 inhibitors were the significant covariates affecting CL, accounting for 75% of interindividual variability. Only body weight significantly influenced central volume of distribution (Vc). In the final population model, the estimated CL and Vc were 5.28 L/h and 2.22 L, respectively, for a typical five year old child weighing 20 kg. Pantoprazole CL increased with weight and age whereas the presence of SIRS, CYP2C19 inhibitors and hepatic dysfunction, when present separately, significantly decreased pantoprazole CL by 62.3%, 65.8% and 50.5%, respectively. Conclusion : These results provide important information to physicians regarding selection of a starting dose and dosing regimen of pantoprazole for paediatric intensive care patients based on various factors frequently encountered in this population.

Dans le milieu clinique des soins intensifs, l’induction du coma médicamenteux (i.e. iatrogénique) par les sédatifs et les analgésiques est souvent associée à une augmentation significative du délirium. De plus, l’utilisation de sédatifs et d’analgésiques comme le fentanyl et le midazolam sans interruption et sans ajustement aux besoins du patient augmentent la durée de séjour, les coûts et la mortalité. Le but de cette étude était d’explorer les facteurs de variabilité pouvant influencer la survenue du coma iatrogénique et du délirium tel que : les facteurs génétiques/sociodémographiques et la co-administration de médicaments substrats ou inhibiteurs de CYP3A4/3A5 ou de la glycoproteine P. L’étude prospective à visée observationnelle a été effectuée à l’unité de soins intensifs de l’hôpital Maisonneuve-Rosemont avec 53 patients perfusés avec fentanyl ou midazolam. La faisabilité du modèle pharmacocinétique du fentanyl a été mise en évidence à partir des échantillons sanguins des patients et était compatible avec les données cliniques. Cette étude montre donc que contrairement au profil génomique de CYP3A5 (p value = 0,521) et MDR1 (p value = 0,828), les effets des interactions médicamenteuses entre les inhibiteurs CYP3A4/CYP3A5 et fentanyl/midazolam représentent un facteur de risque pour le coma iatrogénique (p value = 0,014). Ces effets peuvent être facilement identifiés et sont prévisibles; résultats qui seront utiles aux praticiens – intensivistes dans le choix d’une thérapie pharmacologique appropriée pour prévenir les complications morbides comme le coma iatrogénique et le délirium. / When sedatives such as midazolam or opiate analgesics such as fentanyl administered to critically ill patients and medication-induced coma occurs, increased delirium is observed. In addition, there is an increase in the length of stay in ICU, in costs and mortality. The purpose of this study was to explore the factors of variability affecting the incidence of iatrogenic coma and delirium: genetics/socio demographics factors, co-administration of substrates/inhibitors of CYP3A4/3A5 or P-gp. We performed a prospective cohort observational study of 53 hospitalized patients treated with fentanyl or/and midazolam in the intensive care unit of the Maisonneuve-Rosemont hospital The feasibility of pharmacokinetics modeling using blood samples from critically ill patients was demonstrated and was compatible with clinical data. This study suggests that contrary to genomic variants in the CYP3A5 (p value = 0,521) and MDR1 (p value = 0,828) genes, the effect of drugs and drugs interactions between inhibitors of CYP3A4/3A5 and fentanyl/ midazolam constitutes the main risk factor for iatrogenic coma (p value - 0,014). These effects are easily identifiable and predictable, and are very important for intensive care workers to make the appropriate choice of medication in order to prevent morbid complications such as iatrogenic coma and delirium.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

Les patients admis aux soins intensifs (SI) souffrent de comorbidités qui affectent leur pronostic. Deux problèmes sont potentiellement associés aux sédatifs et compliquent le séjour de 35 à 50% des malades : le délirium, un état confusionnel aigu; et le coma ‘iatrogénique’, une altération de la conscience induite pharmacologiquement. L’importance de l’association entre clinique et médicaments a un intérêt pour prévenir ces syndromes cliniques morbides. Nous voulions étudier le délirium et le coma iatrogénique, les doses administrées de midazolam et de fentanyl, leurs niveaux plasmatiques, les variantes génétiques de métabolisme et de transport et les facteurs inflammatoires et ce, chez 100 patients admis aux soins intensifs. Nos données soulignent l’importance des interactions médicamenteuses dans l’incidence du coma iatrogénique, et réfutent l’association entre les benzodiazépines et le délirium. Ces résultats clarifient la pathophysiologie du délirium, corroborent le manque d’association délirium-benzodiazépines avec un marqueur biologique, c.-à-d. les niveaux sériques, et ouvrent le débat quant aux agents les plus utiles pour traiter l’anxiété et le délirium. Finalement, plusieurs caractéristiques pharmacocinétiques des benzodiazépines administrées aux soins intensifs publiées récemment complètent les données de notre étude quant à la sédation en soins critiques. Un chapitre sur l’importance de la pharmacogénomique en soins intensifs et un débat publié quant au pro et con de l'utilisation des benzodiazépines aux SI, sont soumis en complément de l’étude clinique décrite ci-haut effectuée dans le cadre de cette maîtrise. / Critically ill patients suffer from co-morbid conditions that impact on their prognosis. Two problems complicate Intensive Care Unit (ICU) stay in 35-50% of patients and are potentially associated with sedatives: delirium, an acute confusional state, and 'iatrogenic' coma, when consciousness is altered pharmacologically. Establishing the association between these clinical syndromes and administering sedatives is key in planning effective prevention of these morbid complications. We studied iatrogenic delirium and coma in 100 ICU patients given midazolam and/or fentanyl, and tallied drug doses, measured plasma levels, genetic variations in metabolism and transport and inflammatory factors. Our data highlight the role drug-drug interactions play in iatrogenic coma, and refute the association between benzodiazepines and delirium. These results clarify the pathophysiology of delirium, corroborate the lack of delirium-benzodiazepine association with a benzodiazepine biological marker, i.e. serum levels, and open the debate as to which agents are useful for treating anxiety and delirium. Recent publications addressing benzodiazepine pharmacokinetics in critical care complement our data in the field of critical care sedation. A chapter on the importance of pharmacogenomics in intensive care, and a published pro-con debate as to benzodiazepine use in critical care are submitted in addition to the clinical study mentioned above as part of this master’s thesis.

The threat of antimicrobial resistance particularly in the intensive care unit has become a global issue. This study aimed to evaluate the effectiveness of antimicrobial stewardship in limiting the spread of antimicrobial resistance in the hospital’s ICU. The study further determined the deficiencies of the ASP and recommended strategies to remedy the identified deficiencies. A quasi-experimental descriptive quantitative design was used in this study. The study was conducted at the intensive care unit of an academic hospital. A structured questionnaire was used to extract information from patients’ medical records. This evaluation showed that the antimicrobial stewardship program had a sufficient impact on the appropriate use of antimicrobials in the hospital’s ICU. While there were a small (19.05 %) number of patients inappropriately prescribed antimicrobials, a moderate (35.59%) number of patients developed hospital acquired infections during the study period. In addition, the results revealed a lack of the facility’s leadership commitment to antimicrobial stewardship, which is crucial for ensuring the availability of human, financial and information technology resources Through the evaluation of the program the deficiency in the program’s performance can be identified and optimised. For the studied facility, the performance of the program could be improved by gaining the support of the facility leadership. The present study endorses the evaluation of health promotion initiatives to improve patients’ safety and outcome in healthcare institutions. Keywords / Health Studies / D. Litt. et Phil. (Health Studies)

Introdução: Conhecida desde os tempos de Hipócrates, a varicela é autolimitada e isenta de complicações na maioria dos casos, mas responde por absenteísmo escolar das crianças e laboral dos cuidadores, além de hospitalizações e óbitos em pacientes previamente hígidos. Após a incorporação da vacina varicela no calendário americano em 1995, diversos países têm verificado suas epidemiologias para análise de custo-benefício da vacinação; alguns já vêm publicando resultados do impacto da vacina. O Brasil incluiu a vacina no calendário vacinal para crianças de 15 meses em 2013 e vem avaliando o seu impacto. Objetivos: Aprimorar dados pré-vacinais num hospital universitário de atenção secundária, descrevendo atendimentos de Pronto-Socorro Infantil (PSI), hospitalizações e internações em unidade de terapia intensiva (UTI) por varicela; caracterizar o perfil etário, sazonalidade e diagnósticos das complicações da doença, além de analisar possíveis fatores de risco para internação e evolução grave. Metodologia: Estudo retrospectivo descritivo de crianças e adolescentes menores de 15 anos com varicela, no período entre janeiro de 2003 e dezembro de 2012. Relacionamos os resultados à população local para calcular taxas de incidência, hospitalização, internação em UTI e óbito relacionadas à doença. O registro informatizado do hospital forneceu a lista de pacientes com diagnóstico de varicela no atendimento de PSI ou na internação; prontuários foram consultados para coleta de dados que foram submetidos a análise em programas estatísticos. Resultados: Ocorreram 8520 atendimentos em PSI com varicela, 508 destes (6,0%) sendo hospitalizados, 36 destes últimos (7,1%) necessitando de UTI e 2 óbitos (0,4% dos internados), fornecendo as seguintes taxas médias anuais: 887,5 atendimentos, 52,9 hospitalizações, 3,8 internações em UTI e 0,21 óbitos para 100.000 habitantes até 15 anos. Crianças abaixo de 5 anos representaram 75% dos atendimentos, 92,3% das hospitalizações e 88,9% das internações em UTI. Lactentes entre 12 e 15 meses representaram 4,5% dos atendimentos, 6,5% das hospitalizações e 6,1% das internações em UTI. O segundo semestre do ano representou 89,4% dos atendimentos de PSI. Os menores de 5 anos atendidos no PSI tiveram 4,3 vezes maior chance de internação que os maiores de 5 anos, mas a idade não representou diferença no risco para necessidade de UTI. Infecções de pele e partes moles causaram 72,6% das hospitalizações, enquanto problemas respiratórios e neurológicos responderam por 20,1% e 1%, respectivamente. O motivo principal da indicação de UTI foi instabilidade hemodinâmica; 58,3% necessitaram de drogas vasoativas. Comparando os que necessitaram de UTI e os que não necessitaram, os primeiros apresentavam maior tempo de varicela à admissão, febre mais prolongada após internação, maior quantidade absoluta e relativa de neutrófilos e suas formas jovens, Proteína C reativa mais alta e plaquetas reduzidas nos exames admissionais. Conclusão: As taxas epidemiológicas verificadas neste estudo se mostraram dentro do descrito em literatura; as infecções secundárias de pele e partes moles na varicela, sem CID10 específico, prevalecem sobre complicações como pneumopatia, meningite e encefalite, que possuem descritores específicos, como causas de internação e dados de história e exames admissionais podem ajudar a apontar gravidade / Introduction: Known since Hippocrates times, varicella is self-limited and complication-free in most cases, but it responds to school and labor absenteeism of children and caregivers, as well as previously healthy patients hospitalizations and deaths. After varicella vaccine was recommended for routine use in United States in 1995, several countries reviewed their epidemiology for cost-benefit analysis of vaccination; some of then published vaccine impact results. Brazil included varicella vaccine in immunization routine for 15 months child in 2013 and has been appraising its impact. Objectives: Improve pre-vaccination data from secondary care university hospital describing pediatric urgent care (PUC) assessment, inpatient department and pediatric intensive care unit (PICU) hospitalizations; define age profile, seasonality and varicella complications diagnoses and analyze hospitalization and severe evolution possible risk factors. Methods: This report is aimed to retrospectively discriminate children and adolescents under 15 years with varicella from January 2003 to December 2012. Local population was considered to propose varicella-related PUC visit, hospitalization, PICU stay and death rates. Hospital registration provided computerized varicella-diagnosed PUC assessment, inpatient and PICU patient list; data collected from its charts were submitted to statistical program analysis. Results: 8520 PUC varicella cases were reported, 508 of them (6.0%) were hospitalized, 36 of them (7.1%) required PICU and 2 died (0.4% of hospitalized patients), providing following annual rates: 887.5 assessments, 52.9 hospitalizations, 3.8 PICU admissions and 0.21 deaths per 100,000 inhabitants up to 15 years. Children younger than 5 years accounted for 75% of PUC visits, 92.3% of hospitalizations and 88.9% of PICU admissions. Infants between 12 and 15 months represented 4.5% of PUC visits, 6.5% of hospitalizations and 6.1% of PICU admissions. Second half of the year accounted 89.4% of PUC attendances. Under 5 years PUC child had 4.3 more hospitalization risk than those older than 5 years, but age did not represent difference in PICU risk. Skin and soft tissue infections caused 72.6% of hospitalizations, while respiratory and neurological problems accounted for 20.1% and 1%, respectively. The main reason for PICU indication was hemodynamic instability; 58.3% required vasoactive drugs. Comparing those who needed PICU and those who did not need them, the former had longer time of varicella on admission, longer fever after hospitalization, greater absolute and relative amount of neutrophils and their young forms, higher C-reactive protein levels and reduced platelets in admission exams. Conclusion: epidemiological rates verified in this study were within described in literature; secondary skin infections and soft tissues in varicella, without specific ICD-10, overcome complications as pneumopathy, meningitis, and encephalitis, which have specific descriptors; anamnesis and admission examinations data may help predict severity

INTRODUÇÃO: A combinação de sepse e insuficiência renal com necessidade de diálise é bastante comum nas Unidades de Terapia Intensiva e esta situação tem elevada mortalidade. Um desafio neste cenário é prescrever a dose correta dos antimicrobianos para o tratamento destas infecções. Em pacientes críticos e hemodinamicamente instáveis que necessitam de terapia renal substitutiva, um dos métodos mais utilizados é a diálise contínua, entretanto, recentemente, tem-se utilizado a diálise de baixa eficiência - conhecida como SLED, da abreviação do inglês \"sustained low-efficiency dialysis\". Esta modalidade de terapia renal substitutiva combina características da hemodiálise contínua com a intermitente, utilizando o equipamento da diálise intermitente, com menores fluxos sanguíneos e de dialisato, e com vantagem de menor custo. Apesar do fluxo mais baixo, por ser utilizado tempo mais prolongado, a SLED frequentemente resulta em maior clearance e especula-se que a remoção dos fármacos seria maior. Há escassez de estudos que avaliaram a farmacocinética e farmacodinâmica de antimicrobianos em pacientes submetidos à SLED.OBJETIVOS: Avaliar adequação farmacodinâmica de meropenem e vancomicina em pacientes submetidos a diálise estendida de baixa eficiência. Avaliar a depuração paramêtros farmacocinéticos durante a sessão de SLED. MÉTODOS: Foi realizado estudo prospectivo descritivo observacional com coleta de material biológico julho de 2012 a julho de 2014 HC-FMUSP. Foram incluídos pacientes submetidos à SLED em uso de vancomicina e/ou meropenem. Foram coletadas amostras de sangue seriadas (tempos: imediatamente antes do início da sessão de diálise, 0,5h, 1h, 2h, 4h após o início do tratamento e ao final da sessão). A quantificação dos antimicrobianos foi realizada através dos métodos analíticos de quantificação em Cromatografia Líquida de Alta Eficiência (CLAE). Os parâmetros farmacocinéticos foram calculados apenas durante a sessão de diálise utilizando-se o software WinNonlin. A área sob a curva foi determinada para a vancomicina. Para o meropenem, calculou-se o tempo acima da MIC. Resultados: Foram incluídos 24 pacientes tratados com vancomicina e 21 com meropenem eforam obtidas 170 amostras de plasma. As concentrações médias de vancomicina sérica e meropenem: antes da sessão de SLED foram 24,5 e 28,0 ?g / ml, respectivamente; e após SLED 14 e 6 ?g / ml, respectivamente. A depuração média foi de 41% para a vancomicina e 78% para o meropenem. Para vancomicina, 22 (96%), 19 (83%) e 16 (70%) pacientes teriam atingido o alvo (AUC0-24 > 400) considerando-se MIC 0,5; <= 1mg/l e <= 2 mg/l respectivamente. Para meropenem, 19 (95%), 18 (90%) e 11 (55%) pacientes teriam atingido a meta (70% de tempo acima da CIM) se infectados com isolados com MIC <= 1, <= 4 e <= 8 mg/l, respectivamente. Conclusões: Em pacientes críticos, meropenem evancomicina foram removidas durante o SLED. Entretando, a maioria dos pacientes alcançaria alvo PK-PD, excepto para CIMs mais altas. Sugerimos doses de manutenção de 1g a cada 12 ou 8 horaspara meropenem. Para a vancomicina, deve-se utilizar abordagem mais individualizada com monitorização sérica, uma vez que ensaios comerciais são disponíveis / Background: Antibiotic dosing is a challenge in critically ill patients undergoing renal replacement therapy. Our aim was to evaluate pharmacokinetics and pharmacodynamics of meropenem and vancomycin in patients undergoing SLED.Methods: ICU patients undergoing SLED, receiving meropenem and/or vancomycin, were prospectively evaluated. Blood samples were collected at the start of SLED and 0.5; 1; 2; 4 and 6 hours later. Antimicrobial levels were determined by HPLC. Noncompartimental pharmacokinetic analysis was performed. Area under the curve was determined for vancomycin. For meropenem, time above MIC was calculated. Results: 24 patients receiving vancomycin and 21 receiving meropenem were included; 170 plasma samples were obtained. Median serum vancomycin and meropenem concentrations: before SLED were 24.5 and 28.0 ?g/ml, respectively; and after SLED 14 and 6 ?g/ml, respectively. Mean removal was 41% for vancomycin and 78% for meropenem. For vancomycin, 22 (96%), 19(83%) and 16(70%) patients would have achieved the target (AUC0-24>400) considering MIC 0.5; <= 1mg/l and <= 2 mg/l, respectively. For meropenem, 19 (95%), 18 (90%) and 11(55%) patients would have achieved the target (70% of time above MIC) if infected with isolates with MIC <= 1, <= 4 and <= 8mg/l, respectively. Conclusions: In critically ill patients, meropenem and vancomycin were removed during SLED. Despite this, overall high PK/PD target attainment was obtained, except for higher MICs. We suggest maintenance doses of 1g tid or bid for meropenem. For vancomycin, more individualized approach using therapeutic drug monitoring should be used, as commercial assays are available

Zielsetzung: Der Nachweis eines Apallischen Syndroms (APS) ist trotz der diagnostischen Kriterien der Multi Society Task Force on persistent vegetative state (MSTF) selbst für erfahrene Kliniker eine diagnostische Herausforderung. Das Ziel der vorliegenden Arbeit ist, inwieweit etablierte neurologische Untersuchungstechniken die Anwendung der MSTF-Kriterien vereinfachen und so zur Diagnose des APS beitragen. Design: Prospektive diagnostische Studie Patienten: Von initial 24 Patienten mit der Differentialdiagnose eines APS wurden 16 Patienten endgültig in die Studie eingeschlossen und einer prospektiven klinischen Untersuchung unterzogen. Das Studienprotokoll umfasste die Untersuchung der spontanen Motorik sowie Reiz korrelierter motorischen Reaktionen, der Primitivreflexe, Habituation und der Okulomotorik. Ergebnisse: Die Diagnosekriterien der MSTF waren bei allen Patienten nachweisbar, die in die Studie eingeschlossenen wurden. Darüber hinaus wurde durch die Studie weitere, ebenfalls häufig auftretende klinischen Symptome identifiziert, die als Markersymptom für eine APS bewertet wurden: spontane Automatismen (N=12), periodisch-alternierende Augenbewegungen (N=12), startle Reaktion nach externer Reizung (N=10) und Spastik (N=9). Klinische Symptome, die erhaltene Bewusstseinsleistung voraussetzen wie reflektorische Sakkaden, Habituation, der optokinetische Nystagmus und Augenfolgebewegungen oder Symptome, die auf eine schwere Hirnstammschädigung hinweisen wie eine Dezerebrationshaltung, wurden als Ausschlusskriterien eines APS vorgeschlagen. Zusammenfassung: Die Erweiterung der MSTF-Diagnosekriterien um obligatorische und unterstützende Schlüsselsymptome sowie klar definierte Ausschlusskriterien erleichtert die klinische Differentialdiagnose des APS und führt zu einer größeren Diagnosesicherheit des Syndroms. / Objective: Although the Multi Society Task Force (MSTF) on persistent vegetative state (PVS) published diagnostic criteria ten years ago, differentiation of PVS from similar syndromes remains a diagnostic challenge. The aim of our study was the prospective identification of clinically assessable symptoms supplementary to the MSTF criteria which supports or rejects the diagnosis of a PVS and to reevaluate the parameters after 30 month. Design: Prospective diagnostic study Setting: The 90-bed department of Neurology of the University hospital of Berlin. Patients and participants: Out of 24 screened patients with the differential diagnosis PVS, 16 patients were finally included to the study and prospectively assessed by a clinical examination, comprising spontaneous and reflexive motor activities, primitive reflexes, habituation and eye movements. Measurements and results: Mandatory symptoms of the MSTF were found in all 16 patients. In addition, clinical features like spontaneous automatisms (n=12), periodic alternating gaze deviation (n=12), startle reaction to external stimuli (n=10), and spastic muscular tone (n=9) were found frequently and considered supportive for the diagnosis. In contrast to previous observations, periodic alternating eye movements and increased muscular tone were found more frequently in our patients. Symptoms linked to a preserved consciousness like reflexive visually guided saccades, habituation, an optokinetic nystagmus and eye tracking or symptoms indicating a severe functional impairment of the brainstem like a decerebrated posture were proposed as excluding PVS. Conclusion: The application of mandatory and supportive symptoms lead to a further improvement of diagnostic certainty in PVS, particular in patient presenting exceptional clinical phenomena. Clearly defined exclusive criteria prevent from misdiagnosis.

Introdução: A Síndrome do Desconforto Respiratório Agudo (SDRA) apresenta alta incidência e mortalidade em pacientes de terapia intensiva. A ventilação mecânica é o principal suporte para os pacientes que apresentam-se com SDRA, entretanto ainda existe muito debate sobre a melhor estratégia ventilatória a ser adotada, pois a ventilação mecânica pode ser lesiva aos pulmões e aumentar a mortalidade se mal ajustada. Um dos principais mecanismos de lesão pulmonar induzida pela ventilação é o uso de volumes correntes altos, havendo evidência na literatura que a utilização de volumes correntes menores fornece uma ventilação dita protetora, a qual aumenta a probabilidade de sobrevivência. Objetivo: Explorar se uma estratégia ventilatória de alta frequência com pressão positiva (HFPPV) realizada através de um ventilador mecânico convencional (Servo-300) é capaz de permitir uma maior redução do volume corrente e estabilização da PaCO2 em um modelo de SDRA severa, inicialmente ventilado com uma estratégia protetora. Métodos: Estudo prospectivo, experimental que utilizou oito porcos que foram submetidos a uma lesão pulmonar através de lavagem pulmonar com soro fisiológico e ventilação mecânica lesiva. Em seguida, os animais foram ventilados com um volume corrente de 6 mL/kg, seguido de uma randomização de sequências diferentes de frequências respiratórias (30, 60, 60 com pausa inspiratória de 10 e 30%, 90, 120, 150, 60 com manobra de recrutamento alveolar mais titulação da PEEP e HFOV com 5 Hertz), até obter estabilização da PaCO2 entre 57 63 mmHg por 30 minutos. O ventilador Servo-300 foi utilizado para HFPPV e o ventilador SensorMedics 3100B utilizado para fornecer a ventilação oscilatória de alta frequência (HFOV). Dados são apresentados como mediana [P25th,P75th]. Principais Resultados: O peso dos animais foi de 34 [29,36] kg. Após a lesão pulmonar, a relação P/F, o shunt pulmonar e a complacência estática dos animais ficaram em 92 [63,118] mmHg, 26 [17,31] % e 11 [8,14] mL/cmH2O respectivamente. O PEEP total usado foi de 14 [10,17] cmH2O durante o experimento. Da frequência respiratória de 35 (e com volume corrente de 6 mL/kg) até a frequência ventilatória de 150 rpm, a PaCO2 foi 81 [78,92] mmHg para 60 [58,63] mmHg (P=0.001), o volume corrente (VT) progressivamente caiu de 6.1 [5.9,6.2] para 3.8 [3.7,4.2] mL/kg (P<0.001), a pressão de platô de 29 [26,30] para 27 [25,29] cmH2O (P=0.306) respectivamente. Não houve nenhum comprometimento hemodinâmico ou da oxigenação, enquanto os animais utilizaram a FiO2 = 1. Conclusões: Utilizando-se de uma ventilação mecânica protetora, a estratégia de HFPPV realizada com um ventilador mecânico convencional em um modelo animal de SDRA severa permitiu maior redução do volume corrente, bem como da pressão de platô. Esta estratégia também permitiu a manutenção de PaCO2 em níveis clinicamente aceitáveis / Introduction: Acute respiratory distress syndrome (ARDS) has a high incidence and mortality between critical ill patients. The mechanical ventilation is the most important support for these patients with ARDS. However, until now there is an important debate about how is the best ventilatory strategy to use, because the mechanical ventilation if not well set can cause lung injury and increase mortality. The use of high tidal volume is one of the most important mechanics of ventilation induced lung injury and there is evidence in the literature that using low tidal volume is a protective ventilation with better survival. Objective: To explore if high frequency positive pressure ventilation (HFPPV) delivered by a conventional ventilator (Servo-300) is able to allow further tidal volume reductions and to stabilize PaCO2 in a severe acute respiratory distress syndrome (ARDS) model initially ventilated with a protective ventilation. Methods: A prospective and experimental laboratory study where eight Agroceres pigs were instrumented and followed by induction of acute lung injury with sequential pulmonary lavages and injurious ventilation. Afterwards, the animals were ventilated with a tidal volume of 6 mL/kg, followed by a randomized sequence of respiratory rates (30, 60, 60 with pauses of 10 and 30% of the inspiratory time, 90, 120, 150, 60 with alveolar recruitment maneuver and PEEP titration and 5 Hertz of HFOV), until PaCO2 stabilization between 57 63 mmHg for 30 minutes. The Servo-300 ventilator was used for HFPPV and the ventilator SensorMedics 3100B was used for HFOV. Data are shown as median (P25th,P75th). Measurements and Main Results: Animals weight was 34 [29,36] kg. After lung injury, the P/F ratio, pulmonary shunt and static compliance of animals were 92 [63,118] mmHg, 26 [17,31] % and 11 [8,14] mL/cmH2O respectively. The total PEEP used was 14 [10,17] cmH2O throughout the experiment. From the respiratory rates of 35 (while ventilating with 6 mL/kg) to 150 breaths/ minute, the PaCO2 was 81 [78,92] mmHg and 60 [58,63] mmHg (P=0.001), the tidal volume progressively felt from 6.1 [5.9,6.2] to 3.8 [3.7,4.2] mL/kg (P<0.001), the plateau pressure was 29 [26,30] and 27[25,29] cmH2O (P=0.306) respectively. There were no detrimental effects in the hemodynamics and blood oxygenation, while the animals were using a FiO2 = 1. Conclusions: During protective mechanical ventilation, HFPPV delivered by a conventional ventilator in a severe ARDS swine model allows further tidal volume reductions. This strategy also allowed the maintenance of PaCO2 in clinically acceptable levels