L’arrêt cardiaque extra-hospitalier (ACREH) touche environ 30 à 40,000 personnes en France chaque année. Dans près de la moitié des cas, la cause de l’ACREH est une occlusion coronaire aiguë provoquant un trouble du rythme ventriculaire létal. Malgré les progrès réalisés ces dernières années en terme de prise en charge pré et intra-hospitalière, le pronostic de ces patients reste sombre, de par les lésions neurologiques se produisant très rapidement après l’arrêt circulatoire. Alors que le pronostic à court terme est relativement bien décrit, les données sur le devenir à long terme, en termes de survie, mais aussi de devenir fonctionnel, neurologique, et de qualité de vie, restent rares. Objectifs : L’objectif de ce travail est de décrire le devenir à long terme des patients victimes d’un ACREH et admis vivants à l’hôpital (qualité de vie liée à l’état de santé, devenir neurologique et fonctionnel) et d’évaluer les facteurs associés à ce devenir (biomarqueurs, revascularisation coronaire précoce). Patients et méthodes : Ce travail a consisté en l’analyse des données de la cohorte des patients victimes d’un ACREH et admis vivants en réanimation mé- dicale à l’hôpital Cochin. Cette cohorte a été constituée rétrospectivement entre 2000 et 2006 sur dossiers archivés puis prospectivement selon les recommandations internationales d’Utstein depuis 2007. Les données de survie ont été collectées. Le devenir neurologique et fonctionnel et les données de qualité de vie ont été collectées lors d’entretiens téléphoniques réalisés auprès des survivants sortis vivants de l’hôpital. Résultats principaux : La mortalité globale à J30 était de 68,2%. La revascu- larisation coronaire (ATL) immédiate était associée à une mortalité à J30 plus faible (ORcoro sans ATL vs. pas coro 0,79 [0,57;1,08], p=0,14 et ORcoro avec ATL vs. pas coro 0,61 [0,43;0,85], p<0,01). Les 466 patients vivants à J30 ont été suivis pendant une durée médiane de 3,2 ans [IQR : 0,7 ;6,7], avec une durée maximale de suivi de 13,5 ans. En analyse multivariée, la revascularisation coronaire immédiate restait inversement associée à la mortalité à long terme (HRcoro sans ATL vs. pas coro 0,78 [0,45 ;1,33], p=0,35 et HRcoro avec ATL vs. pas coro 0,40 [0,23 ;0,70], p<0,01).
La copeptine a été dosée chez 298/510 patients à l’admission et chez 224 patients à J3. Le taux médian à l’admission était de 261,3 [125,2 ;478,6] pmol/L. Le taux de survie à 1 an était inversement proportionnel au quintile de copeptine à l’admission (38,2, 32,6, 27,7, 31 et 13,6%, respectivement; p<0,01). En analyse multivariée, seul le cinquième quintile de copeptine à l’admission était associé à la mortalité à 1 an (HR5ème vs. 1er 1,64 [1,06;2,58], p=0,03). Après ajustement mutuel des taux de copeptine à l’admission et à J3, le taux de copeptine à l’admission n’était plus associé à la mortalité à 1 an mais le taux de copeptine à J3 restait asso- cié à la mortalité à 1 an par une relation concentration-dépendante (HR2ème vs. 1er 1,60 [0,90-3,17], p=0,10 ; HR3ème vs. 1er 1,94 [1,01 ;3,71], p=0,05 ; HR 4ème vs. 1er 2,01 [1,04 ;3,89], p=0,04 et HR5ème vs. er 2,38 [1,19 ;4,74], p=0,01 ; p de tendance =0,02). Au cours du suivi, 255 patients ont pu être recontactés. Le délai médian de recon- tact après la survenue de l’ACREH était de 50 [22-93] mois. 66% des patients sortis de réanimation avec un score CPC coté à 1 gardaient une performance neurolo- gique préservée au moment de l’interview (n=150/231). Les dimensions physiques et mentales agrégées du SF-36 étaient similaires chez les survivants d’ACREH en comparaison avec les individus de la population générale (47,0 vs. 47,1, p=0,88 et 46,4 vs. 46,9, p=0,45, respectivement). Les patients présentaient une altération plus marquée des dimensions physiques que des dimensions mentales du score SF- 36 en comparaison avec la population générale. L’activité physique (74,1 vs. 78,4, p=0,02) et la vitalité (50,7 vs. 56,2, p<0,01) étaient les dimensions les plus altérées. (...) / Out-of-hospital cardiac arrest (OHCA) occurs in about 30-40,000 people in France each year and is related to a culprit coronary occlusion in half cases. Although pre and in-hospital management of such patients dramatically improved last years, outcome remains poor because of the neurological damage related to brain anoxia. Short-term outcome is well-described but data are lacking on long-term outcome, functionnal and neurological outcome and health-related quality of life (HRQOL). Objectives : The main purpose of this work was to describe the long-term outcome of successfully resuscitated OHCA patients admitted alive at ICU. We aimed at picking up factors associated with HRQOL as well. Patients and methods : Data from the Paris registry were used. Consecutive sucessfully resuscitated OHCA patients admitted alive at Medical ICU of Cochin hospital, Paris, France are included in the database since 2000, January 1st, accor-ding to Utstein style. We also collected survival data. Neurological and functionnal outcome, as well as HRQOL (SF-36 questionnaire) were recorded during phone in- terviews in OHCA patients discharged alive from hospital. Main results : Overall mortality at day-30 was 68.2%. Immediate percutaneous coronary intervention (PCI) was associated with day-30 mortality (ORcoro w/o PCI vs. no coro 0.79 [0.57,1.08], p=0.14 et ORcoro w/ PCI vs. no coro 0.61 [0.43,0.85], p<0.01). The 466 patients alive at day-30 were followed-up for 3.2 years [IQR : 0.7-6.7]. After adjus- tement for cofounders, immediate PCI remained associated with long-term mor-
tality (HRcoro w/o PCI vs. no coro 0.78 [0.45,1.33], p=0.35 et HRcoro w/ PCI vs. no coro 0.40 [0.23,0.70], p<0.01). Copeptin was assessed in 298/510 patients at ICU admission and in 224 patients at day-3. Median admission copeptin level was 261.3 [125.2,478.6] pmol/L. Survival rates were 38.2, 32.6, 27.7, 31 and 13.6% through admission copeptin quintiles (p<0,01). In multivariate analysis, only the fifth quin-
tile was associated with one-year mortality (HR5ème vs. 1st 1.64 [1.06-2.58], p=0.03). After mutual adjustement of admission and day-3 copeptin levels, admission co- peptin level was not associated anymore with one-year mortality whereas day-3 copeptin level remained associated with one-year mortality in a concentration- dependent manner (HR2nd vs. 1st 1.60 [0.90-3.17], p=0.10; HR3th vs. 1st 1.94 [1.01- 3.71], p=0.05; HR 4th vs. 1st 2.01 [1.04-3.89], p=0.04 et HR5th vs. st 2.38 [1.19-4.74], p=0.01 ; p for trend =0.02). During follow-up, 255 OHCA patients dicharged alive from hospital were phone in- terviewed, after a median duration from cardiac arrest of 50 [22-93] months. 66% of patients kept a good cerebral performance after hospital discharge (n=150/231). Overall physical and mental SF-36 dimensions were similar between OHCA pa- tients and age- and gender-matched individuals from French general population (47.0 vs. 47.1,p=0.88 and 46.4 vs. 46.9, p=0.45, respectively). Physical dimensions were more significantly altered in OHCA patients, especially physical functionning (74.1 vs. 78.4, p=0.02) and vitality (50.7 vs. 56.2, p<0.01). In multivariate analysis, age, male gender, initial shockable rhythm were associated with an improvement in most of the SF-36 dimensions. Immediate PCI was associated with a gain in physical functionning (+7.0, p=0.06), general health (+7.3, p=0.02) and vitality (+4.4, p=0.08). Conclusion : Overall survival in this large cohort of successfully resuscitated OHCA patients was about 20%. Immediate PCI was associated with a decrea- sed short and long-term mortality. HRQOL was similar between OHCA patients and age and gender matched individuals from general population but physical di- mensions appeared significantly altered. Age, male gender and initial shockable rhythm were associated with a better HRQOL. (...)

Introduction: The most appropriate airway management technique for use by paramedics in out-of-hospital cardiac arrest is yet to be determined and evidence relating to the influence of airway management strategy on outcome remains equivocal. In cases where return of spontaneous circulation (ROSC) occurs following out-of-hospital cardiac arrest, patients may undergo direct transfer to a specialist heart attack centre (HAC) where the post resuscitation 12 lead ECG demonstrates evidence of ST elevation myocardial infarction. To date, no studies have investigated the role of airway management strategy on outcomes in this sub-set of patients. The AMICABLE (Airway Management In Cardiac Arrest, Basic, Laryngeal mask airway, Endotracheal intubation) study therefore sought to investigate the influence of prehospital airway management strategy on outcomes in patients transferred by the ambulance service directly to a HAC post ROSC. Methods: Adults with ROSC post out-of-hospital cardiac arrest who met local criteria for transfer to a HAC were identified prospectively. Ambulance records were reviewed to determine prehospital airway management approach and collect physiological and demographic data. HAC notes were obtained to determine in-hospital course and quantify neurological outcome via the Cerebral Performance Category (CPC) scale. Neurologically intact survivors were contacted post discharge to assess quality of life via the SF-36 health survey. Statistical analyses were performed via Chi-square, Mann Whitney U test, odds ratios, and binomial logistic regression. Results: A total of 220 patients were recruited between August 2013 and August 2014, with complete outcome data available for 209. The age of patients ranged from 22-96 years and 71.3% were male (n=149). Airway management was undertaken using a supraglottic airway (SGA) in 72.7% of cases (n=152) with the remainder undergoing endotracheal intubation (ETI). There was no significant difference in the proportion of patients with good neurological outcome (CPC 1&2) between the SGA and ETI groups (p=.286). Similarly, binomial logistic regression incorporating factors known to influence outcome demonstrated no significant difference between the SGA and ETI groups (Adjusted OR 0.725, 95% CI 0.337-1.561). Clinical and demographic variables associated with good neurological outcome included the presence of a shockable rhythm (p < .001), exposure to angiography (p < .001), younger age (p < .001) and shorter time to ROSC (p < .001). Due to an inadequate response rate (25.4%, n=15) analysis of SF36 data was limited to descriptive statistics. Limitations: The study only included patients who achieved ROSC and met the criteria for direct transfer to a HAC. Results are therefore not generalisable to more heterogenous resuscitation populations. Accuracy of clinical decision making and ECG interpretation were not assessed and therefore some patients included in the study may have been inappropriately transferred to a HAC. The low SF-36 survey response rate limited the level of neurological outcome analysis that could be undertaken. Conclusion: In this study, there was no significant difference in the proportion of good neurological outcomes in patients managed with SGA versus ETI during cardiac arrest. Further research incorporating randomised controlled trials is required to provide more definitive evidence in relation to the optimal airway management strategy in out-of-hospital cardiac arrest.

L’insuffisance cardiaque aigue est une émergence médicale qui nécessite une prise en charge multidisciplinaire. L’Extracorporeal Life Support (ECLS) peut être envisagé comme option thérapeutique pour les formes d’insuffisance cardiaque aigue réfractaire au traitement conventionnel. L’objectif de ce projet de recherche clinique est de fournir une vue d’ensemble de l’ECLS dans la prise en charge du choc cardiogénique et de l’arrêt cardiaque réfractaire. L’intoxication médicamenteuse et la myocardite sont les meilleures indications à l’implantation de l’ECLS en considération de leur potentiel de récupération myocardique très élevé. La défaillance primaire du greffon après transplantation cardiaque et l’infarctus du myocarde présentent des résultats plus mitigés avec l’ECLS en raison d’une physiopathologie plus complexe. Le choc cardiogénique postcardiotomie après une intervention de chirurgie cardiaque montre des résultats décevants en raison du profile préopératoire des patients. L’arrêt cardiaque aussi exige une prise en charge immédiate et l’ECLS peut être considéré comme une solution thérapeutique de sauvetage. Une meilleure sélection des patients s’impose afin d’améliorer les résultats de l’ECLS pour l’arrêt cardiaque réfractaire intrahospitalier. Les résultats de l’ECLS pour l’arrêt cardiaque réfractaire extrahospitalier sont dictés principalement par le temps de réanimation cardio-pulmonaire et le rythme cardiaque. Les rythmes non choquables pourraient être considérés comme une contre-indication formelle à l’utilisation de l’ECLS autorisant une concentration de nos efforts sur les rythmes choquables où les chances de survie sont plus importantes / Acute heart failure is a clinical situation requiring a prompt multidisciplinary approach. Extracorporeal Life Support (ECLS) could represent a therapeutic option for acute heart failure refractory to standard maximal treatment. The aim of this report is to offer an overview of ECLS in the management of refractory cardiogenic shock and cardiac arrest. Drug intoxication and myocarditis are the best indications of ECLS in consideration of their high potential of myocardial recovery. Primary graft dysfunction after heart transplantation and acute myocardial infarction show reduced survival rates owing to their more complex pathophysiology. Postcardiotomy cardiogenic shock after cardiac surgery operations displays poor outcomes due to the preoperative profile of the patients. ECLS could be also considered as a rescue solution for refractory cardiac arrest. A better selection of in-hospital cardiac arrest patients is mandatory to improve ECLS outcomes. In-hospital cardiac arrest patients with a reversible cause like drug intoxication and acute coronary syndrome should benefit from ECLS whereas end-stage cardiomyopathy and postcardiotomy patients with an unclear cause of cardiac arrest should be contraindicated to avoid futile support. ECLS for refractory out-ofhospital cardiac arrest should be limited in consideration of its poor, especially neurological, outcome and the results are mainly limited by the low-flow duration and cardiac rhythm. Nonshockable rhythms could be considered as a formal contraindication to ECLS for refractory out-of-hospital cardiac arrest allowing a concentration of our efforts on the shockable rhythms, where the chances of success are substantial

Introdução: O prognóstico da parada cardiorrespiratória (PCR) em ritmo não chocável (assistolia/atividade elétrica sem pulso) é ruim e não melhorou significativamente nas últimas décadas. Embora a epinefrina seja o vasopressor recomendado, há evidências de que ela eleva o consumo de oxigênio, reduz a pressão de perfusão subendocárdica, causa grave disfunção miocárdica e piora a microcirculação cerebral durante a ressuscitação cardiopulmonar. Vasopressina foi muito estudada nos últimos anos e não se mostrou superior à epinefrina. Naloxona e terlipressina têm sido cogitadas como potenciais vasopressores no tratamento da PCR, entretanto há poucos estudos publicados e os resultados são controversos e inconclusivos. Objetivos: Avaliar os efeitos hemodinâmicos e metabólicos da terlipressina ou naloxona na PCR induzida por hipóxia e compará-las com o tratamento-padrão (epinefrina ou vasopressina). Métodos: Estudo experimental, randomizado, cego e controlado. Ratos Wistar adultos, machos, foram anestesiados, submetidos a traqueostomia e ventilados mecanicamente. A PCR foi induzida por obstrução da traqueia e mantida por 3,5 minutos. Em seguida, os animais foram ressuscitados de forma padronizada e randomizados em um dos grupos: placebo (n = 7), vasopressina (n = 7), epinefrina (n = 7), naloxona (n = 7) ou terlipressina (n = 21). Variáveis hemodinâmicas foram monitorizadas durante todo o experimento (via cateter intra-arterial e intraventricular) e mensuradas na base, no 10o (T10), 20o (T20), 30o (T30), 45o (T45) e 60o (T60) minutos pós-PCR. Amostras de sangue arterial foram coletadas para gasometria, hemoglobina, bioquímica e lactato em quatro momentos [base, 11o (T11), 31o (T31), e 59o (T59) minutos pós-PCR]. Resultados: Os grupos foram homogêneos e não houve diferença significativa entre eles nas variáveis de base. O retorno da circulação espontânea ocorreu em 57% dos animais no grupo placebo (4 de 7) e 100% nos demais grupos (p = 0,002). A ! sobrevida em 1 hora foi de 57% no grupo placebo, 71,4% no grupo epinefrina, 90,5% no grupo terlipressina e de 100% nos demais grupos. Comparado com o grupo epinefrina, o grupo terlipressina teve maiores valores de PAM no T10 (164 vs 111 mmHg; p = 0,02), T20 (157 vs 97 mmHg; p < 0,0001), T30 (140 vs 67 mmHg; p < 0,0001), T45 (117 vs 67 mmHg; p = 0,002) e T60 (98 vs 62 mmHg; p = 0,026). O lactato arterial no grupo naloxona foi significativamente menor quando comparado ao grupo epinefrina, no T11 (5,15 vs 8,82 mmol/L), T31 (2,57 vs 5,24 mmol/L) e T59 (2,1 vs 4,1 mmol/L)[p = 0,002]. Ao longo da 1a hora pós-PCR, o grupo naloxona apresentou o melhor perfil do excesso de bases (-7,78 mmol/L) quando comparado ao grupo epinefrina (-12,78 mmol/L; p = 0,014) e ao grupo terlipressina (-11,31 mmol/L; p = 0,024). Conclusões: Neste modelo de PCR induzida por hipóxia em ratos, terlipressina e naloxona foram eficazes como vasopressores na RCP e apresentaram melhor perfil metabólico que a epinefrina. A terlipressina resultou em uma maior estabilidade hemodinâmica na 1a hora pós-PCR comparada com a epinefrina ou a vasopressina. Os efeitos metabólicos favoráveis da naloxona não são explicados pelos valores da PAM / Introduction: The prognosis of cardiac arrest (CA) with nonshockable rhythm (asystole/pulseless electrical activity) is poor and not improved significantly in recent decades. Epinephrine is the most commonly used vasopressor, although there is evidence that its use correlates with myocardial dysfunction and worsens the cerebral microcirculation. Vasopressin has been widely studied in recent years and was not superior to epinephrine. Naloxone and terlipressin have been considered as potential vasopressors in the treatment of CA, however, there are few published studies and the results are controversial and inconclusive. Objectives: To evaluate the hemodynamic and metabolic effects of terlipressin or naloxone in CA induced by hypoxia and compare with standard treatment with epinephrine or vasopressin. Methods: Experimental, randomized, blinded and controlled trial. Adult male Wistar rats were anesthetized, the proximal trachea was surgically exposed, and a 14-gauge cannula was inserted 10 mm into the trachea to the larynx. They were mechanically ventilated and monitored. The CA was induced by tracheal obstruction and maintained for 3.5 minutes. Subsequently, the animals were resuscitated using standard maneuvers and randomized to one of groups: placebo (n=7), vasopressin (n=7), epinephrine (n=7), naloxone (n=7) or terlipressin (n=21). Hemodynamic variables were monitored throughout the study (intra-arterial and intra-ventricular catheter) and measured at baseline, in the 10th (T10), 20th (T20), 30th (T30), 45th (T45) and 60th (T60) minute post-cardiac arrest. Arterial blood samples were collected for hemoglobin, biochemistry, blood gases and lactate at four moments: baseline, 11th (T11), 31st (T31) and 59th (T59) minute post-cardiac arrest. Results: The groups were homogenous and there were no significant differences among them regarding the baseline variables. The return of spontaneous circulation (ROSC) occurred in 57% of the animals (4 of 7) in the placebo group and in 100% in the ! other groups (P=0.002). One-hour survival was 57% in the placebo group, 71.4% in the epinephrine group, 90.5% in the terlipressin and 100% in the naloxone group. Compared with the epinephrine group, the terlipressin groups had a significantly higher MAP at the T10 (164 x 111 mmHg; P=0.02), T20 (157 x 97 mmHg; P<0.0001), T30 (140 x 67 mmHg; P=0.0001), T45 (117 x 67 mmHg; P=0.002) and T60 (98 x 62 mmHg; P= 0.026). The blood lactate in naloxone group was significantly lower when compared to epinephrine group in the T11 (5.15 x 8.82 mmol/L), T31 (2.57 x 5.24 mmol/L) and T59 (2.1 x 4.1)[P=0.002]. Along the first hour after cardiac arrest, the naloxone group showed the best profile of base excess (- 7.78 mmol/L) when compared to epinephrine (-12.78 mmol/L, P= 0.014) and terlipressin group (-11.31 mmol/L, P=0.024). Conclusions: In this model of CA induced by hypoxia in rats, terlipressin and naloxone were effective as vasopressors in resuscitation and had better metabolic profile compared to epinephrine. Terlipressin resulted in higher hemodynamic stability in the first hour after CA and significantly better than epinephrine or vasopressin. The favorable metabolic effects of naloxone are not explained by the values of MAP

Submitted by KAREN SANTOS BRAGHIROLI null (ka_braghiroli@hotmail.com) on 2016-03-14T00:21:49Z No. of bitstreams: 1 NOVO CORRETO-CORREÇÃO PÓS DEFESA- WORD-DISSERTAÇÃO DE MESTRADO-KAREN S BRAGHIROLI-DEFESA 24-2-2016.pdf: 812463 bytes, checksum: 5d0fe477b5ee642d2fd42d5a02dd5a18 (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-03-15T12:13:23Z (GMT) No. of bitstreams: 1 braghiroli_ks_me_bot.pdf: 812463 bytes, checksum: 5d0fe477b5ee642d2fd42d5a02dd5a18 (MD5) / Made available in DSpace on 2016-03-15T12:13:23Z (GMT). No. of bitstreams: 1 braghiroli_ks_me_bot.pdf: 812463 bytes, checksum: 5d0fe477b5ee642d2fd42d5a02dd5a18 (MD5) Previous issue date: 2016-02-24 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Pró-Reitoria de Pesquisa (PROPe UNESP) / A população mundial está envelhecendo e o número de procedimentos anestésico-cirúrgicos está aumentando na faixa etária de 60 anos, comparando-se com outros grupos etários. Considerando essa realidade e a existência de diferenças na segurança do paciente entre países desenvolvidos e em desenvolvimento, a presente revisão comparou a incidência de Parada Cardíaca (PC) perioperatória e por fator anestésico em pacientes geriátricos em países desenvolvidos e em desenvolvimento de acordo com o IDH (Índice de Desenvolvimento Humano) e em dois períodos de tempo. Comparou-se também a literatura mundial da incidência de PC perioperatória e por fator anestésico ao longo do tempo (pré-1990s e 1990-2014) e em relação ao IDH. Métodos: Realizou-se uma revisão sistemática de estudos transversais da literatura mundial sobre a incidência de PC perioperatória e por fator anestésico em pacientes geriátricos. Foi realizada meta-análise da incidência de PC perioperatória e por fator anestésico em 10.000 anestesias, de acordo com o IDH dos países e o período de tempo (pré-1990s e 1990-2014). Utilizou-se a análise de metarregressão para analisar a incidência de PC perioperatória e por fator anestésico ao longo do tempo e do IDH dos países. A meta-análise e a metarregressão foram realizadas considerando um intervalo de confiança (IC) de 95%. Resultados: Foram incluídos 16 estudos de nove países diferentes, com um total de 1.758.153 pacientes geriátricos submetidos à anestesia. A meta-análise mostrou que a incidência de PC perioperatória e por fator anestésico diminuiu significativamente nos países com alto-IDH (38,6 [IC 95%, 37,8-39,6] no período pré-1990s para 7,7 [IC 95%, 7,6-7,8] em 1990-2014, p<0,001; e 9,2 [ IC 95%, 8,9-9,5], no período pré-1990s para 1,3 [ IC 95%, 0,2-6,5] em 1990-2014, p<0,001, respectivamente). Em países com baixo-IDH, não há estudos disponíveis na literatura com a incidência de PC perioperatória e por fator anestésico no período pré-1990, não permitindo a comparação entre os períodos de tempo. A incidência de PC perioperatória em 1990-2014 foi quatro vezes maior nos países com baixo-IDH, em comparação com países de alto IDH (p<0,001). A metarregressão mostrou uma relação significativa com redução da incidência de PC por fator anestésico e o tempo independentemente do IDH do país (slope= -0,0699; 95% IC= -0,1394 a -0,0003; p=0,049) assim como em países com alto-IDH (slope= -0,1049; 95% IC= -0,1762 a -0,0336; p=0,015). Por outro lado, a metarregressão não mostrou relação significativa entre a incidência da PC por fator anestésico e o IDH dos países. Também não houve relação significativa da PC perioperatória em relação ao tempo e ao IDH dos países. Conclusão: A incidência de PC por fator anestésico em pacientes geriátricos diminuiu significativamente nos últimos 60 anos, especialmente em países com alto-IDH. Existe uma redução clara e significativa na incidência de PC por fator anestésico e perioperatória somente em países com alto-IDH, comparando-se os dois períodos de tempo (cinco vezes e sete vezes, respectivamente). / The world population is ageing and the number of anesthesia and surgical procedures are increasing in the sixty-years-old compared to other age groups. Considering this and the differences in patient safety in low- and high-income countries, the current study compared the perioperative and anesthesia-related CA rates in geriatric patients in low- and high-income countries in two time periods. Additionally, we compared global data on anesthesia-related and perioperative cardiac arrest (CA) rates according to Human Development Index (HDI) status and by time. Methods: A systematic review was performed to identify worldwide observational studies in which geriatric patients were submitted to anesthesia with perioperative and/or anesthesia-related CA rates. Meta-analysis per 10,000 anesthetics and meta-regression were performed with 95% confidence intervals (CIs) to compare the perioperative and anesthesia-related CA rates by country’s HDI status (low-HDI versus high-HDI) and by time period (pre-1990s versus 1990-2014), and to evaluate data on perioperative and anesthesia-related CA rates according to country’s HDI status and by time. Results: Sixteen studies from 9 countries assessing 1,758,153 anesthetic administrations in geriatric patients were included. The meta-analysis showed that the perioperative and anesthesia-related CA rates declined in high-HDI (38.6 [95% CI, 37.8-39.6] before the 1990s to 7.7 [95% CI, 7.6-7.8] in the 1990-2014, P<0.001; and 9.2 [95% CI, 8.9-9.5] before the 1990s to 1.3 [95% CI, 0.2-6.5] in the 1990-2014, P<0.001, respectively). In low-HDI countries, there were no studies in perioperative and anesthesia-related CA before 1990 disabling the comparison between the periods. The perioperative CA rate in the 1990-2014 was 4-fold higher in low-HDI compared with high-HDI countries (P<0.001). Meta-regression showed the significant relationship between anesthesia-related CA rate and time independently of HDI status (slope= -0.0699; 95% CI= -0.1394 to -0.0003; P=0.049) as well as in high-HDI countries (slope= -0.1049; 95% CI= -0.1762 to -0.0336; P=0.015), but not according HDI status. The relationship between perioperative CA by time and by HDI status was not significant. Conclusions: Anesthesia-related CA rate in geriatric patients has declined significantly in the past 60 years, especially in high-HDI countries. There is a clear and consistently reduction in perioperative and anesthesia-related CA rates only in high-HDI countries comparing the two time periods (5-fold and 7-fold, respectively). / FAPESP: 2013/11007-6 / PROPe/CDC UNESP: #0143/004/13

The study is focused on advanced life support (ALS) performed by rescue team physicians in an out-of-hospital setting. The first part of the study analyzes diagnostic possibilities and correctness of assumed aetiology of the sudden cardiac arrest during cardiopulmonary resuscitation (CPR) in the field. It introduces an original method of "Crosscheck Tables" and applies this method to 211 cases of CPR provided by physicians of the Emergency Care Service. The study demonstrates that significantly misleading conclusions can result from a global analysis of a set of cases. It stresses importance of diagnostic analyses applied to individual cases. The second part of the study concentrates on changes in PETCO2 level as related to the return of spontaneous circulation (ROSC - Return of Spontaneous Circulation) as opposed to the circulation fully dependent on chest compressions. The study demonstrates that in constantly ventilated patients undergoing CPR in an out-of-hospital setting, PETCO2 is significantly higher (about 10 mmHg) after ROSC than before ROSC. It demonstrates that a sudden increase in PETCO2 exceeding 10 mmHg is likely to indicate the moment of ROSC. The study also support a view that steadily low levels of PETCO2 values (<10 mmHg) indicate a low chance for a successful resuscitation outcome. Key...

5 Summary: Currently, the outcomes from traumatic exsanguination cardiac arrest (CA) show that over 50% of deaths due to trauma occur at the scene, where medical care is limited. Less than 10% of patients who become pulseless from trauma survive. However, in an appropriate setting, some of those traumatic injuries could be surgically repairable. Emergency preservation and resuscitation (EPR) is a novel approach for resuscitation of exsanguination CA victims. EPR uses deep hypothermic preservation for prolonged CA to buy time for transport, damage control surgery, and delayed resuscitation with cardiopulmonary bypass (CPB). Initially, we used a dog model to maximize clinical relevance. We showed that the efficacy of EPR is related to the depth of hypothermia and duration of CA. Pharmacologic adjuncts tested to augment hypothermia generally failed. Extended hemorrhagic shock did not prevent the success of EPR vs. conventional resuscitation if extended post-resuscitative hypothermia was provided. Oxygenation of the flush allowed extending of survivable duration of deep hypothermic CA. Because of the lack of molecular tools available for use in dogs, we developed a rat EPR model to study the cellular and molecular mechanisms underlying deep hypothermic neuroprotection to allow us to define specific targets for...

Orientador: Leandro Gobbo Braz / Resumo: A população mundial está envelhecendo e o número de procedimentos anestésico-cirúrgicos está aumentando na faixa etária de 60 anos, comparando-se com outros grupos etários. Considerando essa realidade e a existência de diferenças na segurança do paciente entre países desenvolvidos e em desenvolvimento, a presente revisão comparou a incidência de Parada Cardíaca (PC) perioperatória e por fator anestésico em pacientes geriátricos em países desenvolvidos e em desenvolvimento de acordo com o IDH (Índice de Desenvolvimento Humano) e em dois períodos de tempo. Comparou-se também a literatura mundial da incidência de PC perioperatória e por fator anestésico ao longo do tempo (pré-1990s e 1990-2014) e em relação ao IDH. Métodos: Realizou-se uma revisão sistemática de estudos transversais da literatura mundial sobre a incidência de PC perioperatória e por fator anestésico em pacientes geriátricos. Foi realizada meta-análise da incidência de PC perioperatória e por fator anestésico em 10.000 anestesias, de acordo com o IDH dos países e o período de tempo (pré-1990s e 1990-2014). Utilizou-se a análise de metarregressão para analisar a incidência de PC perioperatória e por fator anestésico ao longo do tempo e do IDH dos países. A meta-análise e a metarregressão foram realizadas considerando um intervalo de confiança (IC) de 95%. Resultados: Foram incluídos 16 estudos de nove países diferentes, com um total de 1.758.153 pacientes geriátricos submetidos à anestesia. A meta-análise most... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The world population is ageing and the number of anesthesia and surgical procedures are increasing in the sixty-years-old compared to other age groups. Considering this and the differences in patient safety in low- and high-income countries, the current study compared the perioperative and anesthesia-related CA rates in geriatric patients in low- and high-income countries in two time periods. Additionally, we compared global data on anesthesia-related and perioperative cardiac arrest (CA) rates according to Human Development Index (HDI) status and by time. Methods: A systematic review was performed to identify worldwide observational studies in which geriatric patients were submitted to anesthesia with perioperative and/or anesthesia-related CA rates. Meta-analysis per 10,000 anesthetics and meta-regression were performed with 95% confidence intervals (CIs) to compare the perioperative and anesthesia-related CA rates by country’s HDI status (low-HDI versus high-HDI) and by time period (pre-1990s versus 1990-2014), and to evaluate data on perioperative and anesthesia-related CA rates according to country’s HDI status and by time. Results: Sixteen studies from 9 countries assessing 1,758,153 anesthetic administrations in geriatric patients were included. The meta-analysis showed that the perioperative and anesthesia-related CA rates declined in high-HDI (38.6 [95% CI, 37.8-39.6] before the 1990s to 7.7 [95% CI, 7.6-7.8] in the 1990-2014, P<0.001; and 9.2 [95% CI, 8.9-9.5] befor... (Complete abstract click electronic access below) / Mestre

La transplantation d'organe améliore durablement la qualité de vie de patients en défaillance organique terminale. Malheureusement le nombre de greffons disponibles est insuffisant pour traiter tous les patients inscrits en liste d'attente. En France, les organes greffés proviennent essentiellement de donneurs en mort encéphalique. En cas de maladie grave, incurable et rapidement mortelle, il est également possible dans certains pays (dont la France) d'arrêter les thérapeutiques qui maintiennent artificiellement un patient en vie et de prélever ses organes une fois le décès par arrêt circulatoire constaté. La loi n°2005-370 du 22 Avril 2005 (dite loi Léonetti) autorise l'arrêt des traitements lorsqu'ils apparaissent « inutiles, disproportionnés ou n'ayant d'autre effet que le seul maintien artificiel de la vie ». Pour certains, cette fin de vie médicalement planifiée devrait prendre en compte les souhaits du patient en matière de don d'organes et l'intérêt de la greffe pour la société. La position française était néanmoins jusqu'en 2014 de ne pas considérer le patient en fin de vie comme un donneur potentiel afin d'éviter toute confusion entre la décision d'arrêter les traitements curatifs et l'intention de prélever ses organes. Alors que ce type de prélèvement a débuté fin 2014 dans quelques sites pilotes français, nous avons examiné les aspects pratiques, juridiques et éthiques du prélèvement d'organe en situation de fin de vie médicalisée, en focalisant notre réflexion sur les droits du patient, la définition de la mort, la temporalité du processus de prélèvement, et les éléments qui déterminent les modalités d'arrêt des suppléances vitales. / Organ transplantation saves lives of many persons who otherwise would die from end-stage organ disease. In the past decades the need for transplants has grown faster than the number of available organs. This increasing requirement for donated organs has led to a renewed interest in donation after circulatory determination of death (DCDD). In some countries including France, terminally ill patients who die of cardiac arrest after a planned withdrawal of life support may be considered as organ donors (controlled DCDD). Before 2005 French rules were not designed for such practices. With regard to patients in final stage of incurable diseases, the law number 2005-370 of April 22, 2005 authorizes the withholding or withdrawal of treatments when they appear "useless, disproportionate or having no other effect than solely the artificial preservation of life". Advocates of the controlled DCDD argue that the end-of-life care plan should incorporate the patient's wishes concerning organ donation and the public interest of transplantation. Until 2014, most French medical academics regarded the perceived conflict of interest that would arise for clinicians treating potential donors as a major ethical question. As the French program started at the end of 2014 in a few pilot sites, we thus examine the practical, legal and ethical issues that arise in considering controlled DCDD, including determination of the donor's overall benefit, debates relating to the diagnosis and time of death, and factors determining how life-sustaining treatment is to be withdrawn.

Le taux de survie des patients souffrant d’un arrêt cardiaque extrahospitalier est inférieur à 10% même avec les meilleures pratiques en réanimation. Une nouvelle technique de réanimation, soit la réanimation par circulation extracorporelle, a été mise à l’essai et s’avère prometteuse pour améliorer le pronostic chez cette population. Par contre, des réponses à plusieurs enjeux doivent être obtenues avant de tester de façon prospective les avantages de cette technique, notamment quant aux impacts collatéraux sur les pratiques de réanimation préhospitalière qu’elle impliquerait, à la sélection des patients et aux potentielles stratégies de monitorage à utiliser chez ces patients. Cette thèse vise à répondre à ces questions avant d’éventuellement démontrer la valeur ajoutée de cette technique de réanimation et ainsi améliorer la survie pour ces patients. Le premier volet présente les résultats de trois études de cohorte explorant les impacts qu’aurait l’incorporation de la réanimation par circulation extracorporelle sur les protocoles de soins. Les résultats d’une première étude de cohorte ont démontré que la durée des manœuvres de réanimation avancées pratiquées en préhospitalier pourrait être réduite pour permettre un départ plus rapide vers un centre hospitalier pouvant initier la réanimation par circulation extracorporelle puisqu’il n’y avait pas d’association positive entre la durée de ces manœuvres et la survie chez ces patients. Les résultats d’une deuxième étude ont démontré que de rediriger les patients en arrêt cardiaque vers les centres hospitaliers pouvant pratiquer la réanimation par circulation extracorporelle pourrait augmenter leur taux de survie. Ce bénéfice potentiel subsistait jusqu’à un ajout de 14 minutes de la durée du trajet par ambulance dû à la redirection. Troisièmement, la modification de ces deux protocoles de soins permettrait à potentiellement trois fois plus de patients de bénéficier d’une réanimation par circulation extracorporelle. Le second volet présente les résultats de deux études visant à optimiser la sélection des patients pour une réanimation par circulation extracorporelle. Les résultats d’une première étude de cohorte descriptive ont démontré que les patients nécessitant plus de 10 défibrillations conservaient un pronostic de survie adéquat, et ainsi devraient demeurer éligible à une réanimation par circulation extracorporelle. Dans une deuxième étude de cohorte, nous avons étudié l’impact pronostique d’une conversion de rythme pendant la réanimation et avons démontré que le rythme initial était un meilleur marqueur de pronostic que la conversion du rythme. Ainsi, les patients ayant une conversion d’un rythme non-défibrillable à un rythme défibrillable ne devraient pas être retenus en première intention pour une réanimation par circulation extracorporelle, contrairement à ceux dont le rythme initial était déjà défibrillable. Les études du troisième volet visaient à explorer l’usage d’une technologie de monitorage de l’oxymétrie tissulaire, la spectroscopie proche-infrarouge, en raison de son potentiel pour mesurer en continu le degré d’oxygénation des candidats à une réanimation par circulation extracorporelle. Une revue systématique de la littérature a démontré l’utilité pronostique de cette technologie pour les patients en arrêt cardiaque. Ensuite, nous avons décrit à l’aide d’une cohorte prospective les propriétés métrologiques de deux appareils et les facteurs associés permettant d’optimiser leur utilité dans le contexte de patients en arrêt cardiaque. Les connaissances développées par l’entremise des études composant la présente thèse ont déjà été intégrées aux protocoles de prise en charge des patients souffrant d’un arrêt cardiaque extrahospitalier ce qui jette des bases solides pour poursuivre des recherches pour ultimement améliorer leur pronostic. / Despite advances in medical care, survival amongst out of hospital cardiac arrest patients remains low, with only 10% of patients surviving. The use of extracorporeal cardiopulmonary resuscitation, a novel resuscitation procedure, has recently garnered interest and showed promise to improve resuscitation outcomes. However, questions remain to be answered before this technology can be prospectively evaluated, notably regarding the collateral impacts of its implementation, appropriate patient selection and the monitoring strategies to use for these patients. The main objective of this thesis is to answer these questions to eventually improve the outcome of patients suffering from an out-of-hospital cardiac arrest. In the first part, the results of three cohort studies exploring the potential impact of the implementation of extracorporeal resuscitation on prehospital resuscitation protocols are presented. A first cohort study showed that the duration of prehospital advanced cardiac life support could be reduced to allow for an earlier transport to an extracorporeal resuscitation centre. A second cohort study showed that patients being transported to specialized resuscitation centres might have increased survival. This increase in survival would remain despite an additional 14 minutes of prehospital transport time due to the redirection. A third study showed that prehospital redirection could triple the number of patients who could benefit from extracorporeal resuscitation. In the second part, the results of two studies aiming to improve the selection of adequate patients for extracorporeal resuscitation are presented. A first cohort study showed that patients requiring more than 10 defibrillations still had an adequate chance at survival and should remain eligible for an extracorporeal resuscitation. A second cohort study showed that the initial rhythm was a much better prognosticating factor than subsequent rhythms. Patients with an initial non- shockable rhythm who experience a conversion to a shockable rhythm should not be considered first-line candidates for extracorporeal resuscitation. In the third part, three studies exploring the potential uses of near-infrared spectroscopy for the monitoring of extracorporeal resuscitation patients are presented. A systematic review was first performed and showed the prognosticating ability of this technology for patients suffering from a cardiac arrest. Then, using a prospective cohort, the metrological properties and their determinants of two frequently used near-infrared spectroscopy devices were described, in order to optimize their uses in the context of cardiac arrest. The knowledge acquired by the studies comprised in this thesis has already been integrated in protocols guiding the care for patients suffering from an out-of-hospital cardiac arrest and has laid the foundation for the prospective evaluation of extracorporeal resuscitation for this population, which will hopefully ultimately lead to improvement in their prognosis.