Das akute Lungenversagen des Erwachsenen (Acute Respiratory Distress Syndrome - ARDS) bleibt trotz lungenprotektiver Beatmung und dem Einsatz moderner Therapieverfahren ein schwerwiegendes Krankheitsbild mit nicht selten letalem Ausgang. Ziel der hier durchgeführten experimentellen Studien war es, sowohl den Einfluss verschieden hoher Niveaus des positiven end-exspiratorischen Drucks (PEEP) als auch die Auswirkungen einer unterschiedlichen Volumentherapie hinsichtlich Oxygenierung und histopathologischem Lungenschaden zu untersuchen. Hierzu wurde an 24 weiblichen narkotisierten und druckkontrolliert beatmeten Pietrain-Schweinen ein Lungenversagen mittels repetitiver bronchoalveolärer Lavage mit Kochsalzlösung induziert. Je acht Tiere wurden randomisiert und einer von drei Versuchsgruppen zugeteilt. In der ARDSNet(V+)-Gruppe wurde gemäß dem ARDS-Netzwerk mit einem festen Kombinationsschema aus PEEP und inspiratorischer Sauerstofffraktion (FiO2) beatmet und eine liberale Volumentherapie angewandt. In den Gruppen mit Open-Lung-Konzept (OLC) OLC(V+)- und OLC(V-) wurde eine Beatmung mit einem PEEP von 3 cm H2O über dem unteren Umschlagspunkt der Druck-Volumen-Kurve sowie Rekrutierungsmanövern von 50 cm H2O über 30 Sekunden durchgeführt. Die beiden OLC-Gruppen unterschieden sich im Hinblick auf die Volumensubstitution: restriktive Volumentherapie in OLC(V-) und liberale Volumentherapie in OLC(V+). Der Versuchszeitraum nach Randomisierung betrug 6,5 Stunden. Es wurden Gasaustausch- und Hämodynamikparameter zu fünf verschiedenen Messzeitpunkten ausgewertet. Des Weiteren wurden nach dem Versuchsende die Lungen histologisch untersucht. Bei der Untersuchung der Effekte der Beatmungsstrategien zeigte sich beim Vergleich der Gruppen mit großzügiger Volumensubstitution in der Gruppe mit höherem PEEP (OLC(V+)) eine bessere Oxygenierung (PaO2/FiO2 416+/-80 mmHg), verglichen mit der Beatmung gemäß ARDS-Netzwerk (ARDSNet(V+): PaO2/FiO2 189+/-55 mmHg). Ein statistisch signifikanter Unterschied im histopathologischen Lungenschaden zwischen beiden Gruppen konnte nicht gefunden werden (Gesamtscore OLC(V+) 1,6+/ [1,2-1,9] vs. ARDSNet(V+) 1,9 [1,4-2,0]). Bei der Untersuchung der Effekte der Volumentherapie konnte beim Vergleich der Gruppen mit Beatmung nach Open-Lung-Konzept in der Gruppe mit einem restriktiven Volumenmanagement (OLC(V-)) ein signifikant reduzierter histopathologischer Lungenschaden (Gesamtscore 0,9 [0,8-1,4]), jedoch keine weitere Verbesserung der Oxygenierung (PaO2/FiO2 400+/-55 mmHg) gegenüber der Gruppe mit liberalem Volumenmanagement (OLC(V+)) festgestellt werden. Zusammenfassend konnten wir mit unserer Studie zeigen, dass im experimentellen ARDS eine restriktive Volumentherapie den Lungenschaden reduzieren kann. Das Volumen-management scheint im experimentellen Lungenversagen somit einen größeren Einfluss auf den Lungenschaden zu haben als die Höhe des PEEP. / The effects of positive end-expiratory pressure (PEEP) and intravascular volume administration on the histopathologic lung injury were not investigated in experimental lung injury previously. We hypothesized that high PEEP and a restrictive volume therapy would yield the best oxygenation and the least degree of lung injury. 24 Pigs underwent saline lavage-induced lung injury. The animals were ventilated either with low PEEP according to ARDS-network (mean PEEP 9 to 12 cm H2O) and liberal volume therapy using hydroxyethyl starch (ARDSNet (V+)) or with high PEEP (PEEP 3 cm H20 above the lower inflection point of the pressure-volume-curve) combined with recruitment maneuvers and liberal (OLC (V+)) or restrictive volume therapy (OCL(V-)). After 6.5 hours, lung injury was determined by using a histopathologic score evaluating overdistension, edema, exsudation, and inflammation. When volume therapy was liberal, high PEEP (OLC(V+)) improved the Pao₂/Fio₂ index (416+/-80 mmHg) compared to low PEEP (ARDSNet(V+), 189+/-55 mmHg) but there was no difference in the median (interquartile range) lung injury score: 1.6 (1.2-1.9) to 1.9 (1.4-2.0). High PEEP with restrictive volume therapy (OLC(V-)) did not further improve oxygenation (400+/-55 mmHg) but ameliorated the degree of lung injury: 0.9 (0.8-1.4). In summary in lavage-induced lung injury, high PEEP improved oxygenation, but restrictive volume administration markedly reduced the degree of histopathologic lung injury.

Universiẗat, Diss., 2007--Giessen.

Zugl.: Giessen, Universiẗat, Diss., 2008.

Diversas estratégias de ventilação mecânica que estabelecem limites na pressão e volume intratorácicas têm sido propostas para pacientes com síndrome de angustia respiratória aguda (SARA). Estas recomendações são baseadas na observação de que a ventilação mecânica com volume corrente excessivo ou pressão positiva expiratória final (PEEP) insuficiente pode ocasionar lesões pulmonares graves, decorrentes de superdistensão de unidades alveolares. O objetivo do atual estudo foi aplicar manobras de recrutamento alveolar e PEEP em pulmões submetidos à lesão pulmonar aguda (LPA) através da administração de HCl . Foram utilizados 24 suínos Landrace - Largewhite, do sexo feminino, pesando entre 25 e 35 Kg. Após a anestesia os animais foram submetidos à ventilação com volume controlado (6 a 8 ml/Kg) e foram randomizados em 4 grupos: GI (6 animais não submetidos a LPA e tratados com PEEP progressivo de 5, 10, 15 e 20 cmH2O e regressivo de 20 a 5 cmH2O); GII (6 animais não submetidos a LPA e tratados com PEEP progressivo de 5, 10, 15 e 20 cmH2O e regressivo de 20 a 5 cmH2O associado a 3 manobras de recrutamento consecutivas, com pressão de 30 cmH2O antes de cada alteração do PEEP); GIII (6 animais submetidos a 1 hora de LPA por HCl e tratados como GI) e GIV (6 animais submetidos a 1 hora de LPA por HCl e tratados como GII). A mecânica respiratória e oxigenação foram avaliadas a cada 20 minutos, acompanhando cada alteração do PEEP. A LPA foi observada através de severas alterações na oxigenação e mecânica respiratória. A administração de MR associada a PEEP foi capaz de restaurar os valores controle, porém, os elevados valores de PEEP e CPAP foram acompanhados de significantes alterações hemodinâmicas quando comparadas com os animais que não foram submetidos a LPA. O derrecrutamento alveolar ocorreu provavelmente quando os valores de PEEP foram retornados para 5cmH2O. As lesões pulmonares foram uniformes nos animais que foram submetidos ao HCl, evidenciadas pela presença de necrose, hemorragia, congestão e infiltrado de células inflamatórias no interstício e nos alvéolos. O modelo experimental de lesão pulmonar aguda foi adequado para estudar MR seguidas por PEEP, pois apresentou importantes alterações dos valores de oxigenação e complacência, observado 1 hora após a instilação do HCl.Os valores de PEEP de 5cmH2O foram incapazes de manter o recrutamento no momento final do estudo, enquanto que os valores de PEEP de 10cmH2O foram suficientes para restabelecer a oxigenação com mínima alteração hemodinâmica. A complacência não melhorou após as manobras. Futuros estudos são necessários para confirmar os resultados obtidos, especialmente para mostrar que a manutenção do PEEP de 10cmH2O é suficientes para manter o recrutamento após as MR / Different mechanical ventilation strategies which define limits of intrathoracic pressures and volumes are being proposed for patients with acute respiratory distress syndrome (ARDS). These recommendations are based on observations that mechanical ventilation with excessive tidal volumes or insufficient values of positive end expiratory pressure (PEEP) can cause severe lung injury due to overinflation. The aim of the present study was to apply recruitment maneuvers (RM) and PEEP in lungs submitted to acute lung injury (ALI) due to the administration of hydrochloride acid. Twenty four female Landrace – Largewhite pigs, weighing 25 to 35 Kg were used. After anesthesia, animals were submitted to volume controlled mechanical ventilation (6 to 8ml/kg) and were randomly allocated in four groups of 6 animals each: GI animals without ALI and treated with progressive values of PEEP (5, 10, 15 and 20 cmH2O) or regressive (20 to 5 cm H2O); GII animals without ALI and treated with progressive values of PEEP (5, 10, 15 and 20 cmH2O) or regressive (20 to 5 cm H2O) plus 3 consecutive recruitment maneuvers with 30 cmH2O; GIII animals submitted to 1 hour of ALI and treated as GI; GIV animals submitted to 1 hour of ALI and treated as GII. Parameters of respiratory mechanics, ventilation and oxygenation were measured each 20 minutes according to the change of the PEEP values. ALI could be observed by the severe changes of oxygenation and respiratory mechanics noted. The use of RM and PEEP were able to restore control values. Nevertheless, application of high values of PEEP and CPAP were accompanied by significant hemodynamic changes which could be evidenced in animals without ALI. Derecruitment probably occurred when PEEP value reached 5 cmH2O. The lung lesions were uniform in the HCL-injured animals and consisted of necrosis, hemorrhage, congestion, and inflammatory cells infiltration that involved both the interstitium and the alveoli. The experimental model of lung injury was adequate to the study of RM followed by PEEP since significant changes of the oxygenation and compliance values could be observed 1 hour after acid instillation. PEEP values of 5cmH2O were incapable to maintain recruitment at the end of the observation period, while 10 cmH2O were sufficient to promote the reestablishment of oxygenation index with minimal hemodynamic changes. Compliance did not improve during the maneuvers. Further studies are necessary to confirm the results obtained, especially to show that the maintenance of a PEEP value of 10 cmH2O are sufficient to maintain recruitment after the RM

Diversas estratégias de ventilação mecânica que estabelecem limites na pressão e volume intratorácicas têm sido propostas para pacientes com síndrome de angustia respiratória aguda (SARA). Estas recomendações são baseadas na observação de que a ventilação mecânica com volume corrente excessivo ou pressão positiva expiratória final (PEEP) insuficiente pode ocasionar lesões pulmonares graves, decorrentes de superdistensão de unidades alveolares. O objetivo do atual estudo foi aplicar manobras de recrutamento alveolar e PEEP em pulmões submetidos à lesão pulmonar aguda (LPA) através da administração de HCl . Foram utilizados 24 suínos Landrace - Largewhite, do sexo feminino, pesando entre 25 e 35 Kg. Após a anestesia os animais foram submetidos à ventilação com volume controlado (6 a 8 ml/Kg) e foram randomizados em 4 grupos: GI (6 animais não submetidos a LPA e tratados com PEEP progressivo de 5, 10, 15 e 20 cmH2O e regressivo de 20 a 5 cmH2O); GII (6 animais não submetidos a LPA e tratados com PEEP progressivo de 5, 10, 15 e 20 cmH2O e regressivo de 20 a 5 cmH2O associado a 3 manobras de recrutamento consecutivas, com pressão de 30 cmH2O antes de cada alteração do PEEP); GIII (6 animais submetidos a 1 hora de LPA por HCl e tratados como GI) e GIV (6 animais submetidos a 1 hora de LPA por HCl e tratados como GII). A mecânica respiratória e oxigenação foram avaliadas a cada 20 minutos, acompanhando cada alteração do PEEP. A LPA foi observada através de severas alterações na oxigenação e mecânica respiratória. A administração de MR associada a PEEP foi capaz de restaurar os valores controle, porém, os elevados valores de PEEP e CPAP foram acompanhados de significantes alterações hemodinâmicas quando comparadas com os animais que não foram submetidos a LPA. O derrecrutamento alveolar ocorreu provavelmente quando os valores de PEEP foram retornados para 5cmH2O. As lesões pulmonares foram uniformes nos animais que foram submetidos ao HCl, evidenciadas pela presença de necrose, hemorragia, congestão e infiltrado de células inflamatórias no interstício e nos alvéolos. O modelo experimental de lesão pulmonar aguda foi adequado para estudar MR seguidas por PEEP, pois apresentou importantes alterações dos valores de oxigenação e complacência, observado 1 hora após a instilação do HCl.Os valores de PEEP de 5cmH2O foram incapazes de manter o recrutamento no momento final do estudo, enquanto que os valores de PEEP de 10cmH2O foram suficientes para restabelecer a oxigenação com mínima alteração hemodinâmica. A complacência não melhorou após as manobras. Futuros estudos são necessários para confirmar os resultados obtidos, especialmente para mostrar que a manutenção do PEEP de 10cmH2O é suficientes para manter o recrutamento após as MR / Different mechanical ventilation strategies which define limits of intrathoracic pressures and volumes are being proposed for patients with acute respiratory distress syndrome (ARDS). These recommendations are based on observations that mechanical ventilation with excessive tidal volumes or insufficient values of positive end expiratory pressure (PEEP) can cause severe lung injury due to overinflation. The aim of the present study was to apply recruitment maneuvers (RM) and PEEP in lungs submitted to acute lung injury (ALI) due to the administration of hydrochloride acid. Twenty four female Landrace – Largewhite pigs, weighing 25 to 35 Kg were used. After anesthesia, animals were submitted to volume controlled mechanical ventilation (6 to 8ml/kg) and were randomly allocated in four groups of 6 animals each: GI animals without ALI and treated with progressive values of PEEP (5, 10, 15 and 20 cmH2O) or regressive (20 to 5 cm H2O); GII animals without ALI and treated with progressive values of PEEP (5, 10, 15 and 20 cmH2O) or regressive (20 to 5 cm H2O) plus 3 consecutive recruitment maneuvers with 30 cmH2O; GIII animals submitted to 1 hour of ALI and treated as GI; GIV animals submitted to 1 hour of ALI and treated as GII. Parameters of respiratory mechanics, ventilation and oxygenation were measured each 20 minutes according to the change of the PEEP values. ALI could be observed by the severe changes of oxygenation and respiratory mechanics noted. The use of RM and PEEP were able to restore control values. Nevertheless, application of high values of PEEP and CPAP were accompanied by significant hemodynamic changes which could be evidenced in animals without ALI. Derecruitment probably occurred when PEEP value reached 5 cmH2O. The lung lesions were uniform in the HCL-injured animals and consisted of necrosis, hemorrhage, congestion, and inflammatory cells infiltration that involved both the interstitium and the alveoli. The experimental model of lung injury was adequate to the study of RM followed by PEEP since significant changes of the oxygenation and compliance values could be observed 1 hour after acid instillation. PEEP values of 5cmH2O were incapable to maintain recruitment at the end of the observation period, while 10 cmH2O were sufficient to promote the reestablishment of oxygenation index with minimal hemodynamic changes. Compliance did not improve during the maneuvers. Further studies are necessary to confirm the results obtained, especially to show that the maintenance of a PEEP value of 10 cmH2O are sufficient to maintain recruitment after the RM

Sabe-se que a anestesia geral por si só já é capaz de causar substancial depressão cardiovascular e respiratória em equinos e tal característica pode ser potencializada ainda mais pelo posicionamento do paciente em decúbito dorsal e pela a administração de elevadas pressões intratorácicas durante as manobras de recrutamento utilizadas para reverter a hipoxemia. Sendo assim, o objetivo do atual estudo foi avaliar a mecânica respiratória e hemogasometria arterial após manobra de recrutamento alveolar e aplicação de PEEP para manutenção, em equinos ASA I e II submetidos à anestesia geral inalatória para cirurgia artroscópica, bem como qual o melhor valor da PEEP para manutenção do recrutamento alveolar. Para tanto foram utilizados 30 equinos, pesando em média 454 kg, submetidos a cirurgia artroscópica em decúbito dorsal, divididos aleatoriamente em 4 grupos, sendo eles: Controle; PEEP 7; PEEP 12; e PEEP 17. Os animais receberam xilazina (0,6 mg/kg) como MPA, seguida de indução anestésica (quetamina 2,2 mg/kg associado ao diazepam 0,05 mg/kg e EGG 10% 50 mg/kg) e anestesia inalatória com isofluorano. Os animais foram posicionados em decúbito dorsal e submetidos a ventilação com volume controlado (14ml/kg), FR de 7 mpm, relação I:E 1:3, PEEP 7 cmH2O e FiO2 de 0,7. Após período de instrumentação foi realizada MRA por titulação da PEEP a cada 5 minutos até alcançar PEEP de 22 cmH2O, sendo que os animais do grupo Controle não receberam MRA, apenas manutenção com PEEP de 7 cmH2O. Os animais dos outros grupos passaram pela MRA seguido de manutenção com suas PEEP de tratamento (7, 12 ou 17 cmH2O). Os parâmetros de mecânica respiratória e hemogasometria arterial foram avaliados imediatamente antes da MRA; e 5, 10, 15, 20, 40, 60 e 80 minutos após a MRA. Foram também avaliadas a FC, PAS, PAM e PAD, porcentagem de anestésico inalatório inspirado e expirado, ETCO2 e consumo de fármaco vasoativo. Os animais que receberam MRA apresentaram aumento na complacência estática e nos parâmetros de oxigenação após a manobra, nos animais do grupo PEEP 12 e 17 foi observada manutenção do incremento oriundo da MRA por pelo menos 80 minutos. Já os animais do grupo PEEP 7 apresentaram queda do incremento após 20 minutos da manobra, assim como o grupo Controle apresentou queda nos parâmetros de oxigenação e ventilação ao longo do tempo, ambos indicando uma provável fechamento pulmonar devido a PEEP insuficiente para manutenção dos alvéolos abertos. Não foram observadas alterações cardiovasculares nos animais do estudo, apenas leve taquicardia transitória no grupo PEEP 17 logo após a MRA. Portanto as PEEP de 12 e 17 cmH2O utilizadas após a MRA foram capazes de manter os alvéolos abertos, promovendo assim melhor trocas gasosas e o incremento na oxigenação e ventilação dos pacientes. Já os animais que receberam MRA e manutenção com PEEP de 7 cmH2O, foram capazes de manutenção dos alvéolos abertos por apenas 20 minutos / It is known that general anaesthesia by it’s self is capable of causing substantial cardiovascular and respiratory depression in horses and this characteristic can be enhanced even more by patient positioned in dorsal recumbence and the administration of high intrathoracic pressures during recruitment manoeuvres used to reverse hypoxemia. Therefore, the aim of this study was to evaluate the respiratory mechanics and arterial blood gas analysis after recruitment manoeuvre and PEEP for maintenance, in horses ASA I and II undergoing general isoflurane-anaesthesia for arthroscopic surgery and what is the best value PEEP to maintain alveolar recruitment. Therefore, we used 30 horses, weighing on average 454 kg, which underwent arthroscopic surgery in the dorsal recumbence, randomly allocated into one of the 4 groups, as follows: Control; PEEP 7; PEEP 12; and PEEP 17. Animals received xylazine (0,6 mg/kg) as pre anaesthetic medication followed by anaesthesia induction (ketamine 2,2 mg/kg associated to diazepam 0,05 mg/kg and EGG 10% 50 mg/kg) and maintenance with isoflurane-anaesthesia. The animals were positioned in dorsal recumbence and submitted the volume-controlled ventilation (14ml/kg), RR: 7 mpm, I:E ratio 1:3, 7 cmH2O of PEEP and FiO2 0,7. After instrumentation period was performed RM by PEEP titration every 5 minutes until reach 22 cmH2O of PEEP, and the animals of control group did not receive RM, only maintenance with PEEP 7 cmH2O. The animals of other groups went through the RM followed by maintenance with their treatment PEEP (7, 12 or 17 cmH2O). The respiratory parameters and blood gas samples were assessed immediately before the RM; and 5, 10, 15, 20, 40, 60 and 80 minutes after the manoeuvre. We also assessed the HR, SAP, MAP and DAP, percentage of inhaled anaesthetic: inhaled and exhaled, ETCO2 and vasoactive drug consumption. Animals receiving RM showed an increase in static compliance and oxygenation parameters after the manoeuvre, maintenance of the increase coming from the RM were observed in animals from PEEP 12 and 17 group, for at least 80 minutes. The animals in PEEP 7 group decreased the increase after 20 minutes of manoeuvre and the control group decreased the parameters of oxygenation and ventilation over time, both indicating a probable pulmonary closure due to insufficient PEEP to maintain the alveoli opened. Cardiovascular changes were observed in the study animals, only mild transient tachycardia in PEEP 17group soon after RM. Therefore, the PEEP 12 and 17 cmH2O used after RM were able to keep the lung opened, thereby performing better gas exchange and the increase in the oxygenation and ventilation of patients. The animals receiving RM and maintenance PEEP 7 cmH2O were able to maintain the alveoli open for only 20 minutes

Made available in DSpace on 2015-03-26T13:47:15Z (GMT). No. of bitstreams: 1 texto completo.pdf: 1647046 bytes, checksum: 60df96193b1cb4bd963ea9c44f3a6f1e (MD5) Previous issue date: 2013-02-26 / Pneumoperitoneum using carbon dioxide (CO2) is used for better visualization of surgical field during laparoscopic surgeries and it has been associated to hemodynamic, respiratory and metabolic changes. The major complications are intraabdominal pressure increasing (IAP) and CO2 absorption. To maintain the appropriate respiratory function can be used positive end-expiratory pressure (PEEP). This study evaluate if ventilation controlled with 0, 5 and 10 cmH2O PEEP minimize changes promoted by pneumoperitoneum with 15 cmH2O IAP in cardiovascular and respiratory functions and arterial gasometry on the pulmonary parenchyma in rabbits anesthetized with isoflurane. Thirty-six rabbits were randomly divided into three groups according to PEEP level: GZP (0 cmH2O), G5P (5 cmH2O) and G10P (10 cmH2O). The variables partial oxygen pressure in arterial blood [pO2(a)], partial carbon dioxide pressure in arterial blood [pCO2(a)], arterial blood pH [pH(a)], plasma bicarbonate concentration in arterial blood [cHCO3 -(a)], base concentration in arterial blood [cBase(a)], K+ (cK+), Ca2+(cCa+2), Na+ (cNa+) and Cl- (cCl-) concentrations, GAP, partial carbon dioxide pressure in end expiratory (EtCO2), heart rate (HR), diastolic blood pressure (DBP), systolic blood pressure (SBP), mean arterial blood pressure (MAP) and temperature were evaluated at different times of anesthesia. The animals were euthanized at the following times: 0, 6, 12 and 24 hours after anesthesia. During autopsy, the lung lobes fragments were collected to do histological slides for histological evaluation of: lymphohistiocytic infiltrate, intraalveolar hemorrhage, congestion, pulmonary edema, interstitial and intra-alveolar neutrophils infiltration and atelectasis areas, with injuries been scored as absent, mild, moderate or intense. The variables [pCO2(a)], HR, DBP, SBP, MAP, (cNa+), (cK+), (cCa+2), (cCl-), GAP, [cHCO3 -(a)] e [cBase(a)] remained within the physiological values, an [pCO2 (a)] increase and consequent [pH (a)] decrease happens in all animals, and elevated EtCO2 was observed in groups ventilated with higher PEEP and CO2 elimination. It was observed in all groups lymphohistiocytic infiltrate typical of lymphocytic interstitial pneumonia, and low scores for neutrophil infiltration and alveolar interstitial edema, congestion and atelectasis consistent with alveolar capillary endothelium injury. These lesions were more intense in the early times after anesthetic-surgical procedure in the groups GZP and G5P. It is concluded that the increase of the PEEP at 0, 5 and 10 cmH2O cannot prevent acid / base changes promoted by peritoneal CO2 absorption. Positive end-expiratory pressure of 10 cmH2O improves CO2 elimination and reduces CO2 blood pressure, but does not prevent hypercapnia and promotes less intense inflammatory lesions in the lung parenchyma. / O pneumoperitônio com CO2, utilizado para melhor visualização do campo cirúrgico em cirurgias laparoscópicas, tem sido associado a alterações hemodinâmicas, respiratórias e metabólicas. As principais complicações são decorrentes do aumento da pressão intra-abdominal (PIA) e da absorção do CO2. Para que a função respiratória seja mantida de forma adequada, pode ser utilizada a pressão positiva expiratória final (PEEP). No trabalho foi avaliado se a ventilação controlada com PEEP (0, 5 e 10 cmH2O) minimiza as alterações promovidas pelo pneumoperitônio com PIA de 15 cmH2O nas funções cardiovascular e respiratória, na gasometria arterial e sobre o parênquima pulmonar de coelhos anestesiados com isofluorano. Foram utilizados 36 coelhos divididos aleatoriamente em três grupos conforme com o valor da PEEP utilizada: GZP (PEEP de 0 cmH2O), GP5 (PEEP de 5 cmH2O) e GP10 (PEEP de 10 cmH2O). As variáveis pressão parcial de oxigênio no sangue arterial [pO2(a)], pressão parcial de dióxido de carbono no sangue arterial [pCO2(a)], pH do sangue arterial [pH(a)], concentração de bicarbonato plasmático no sangue arterial [cHCO3 -(a)], concentração de base no sangue arterial [cBase(a)], concentração de potássio (cK+), concentração de cálcio (cCa+2), concentração de sódio (cNa+), concentração de cloro (cCl-), GAP, pressão parcial de CO2 no final da expiração (EtCO2), frequência cardíaca (FC), pressão arterial diastólica (PAD), pressão arterial sistólica (PAS), pressão arterial média (PAM) e temperatura foram avaliadas em diferentes momentos da anestesia. Os animais foram submetidos à eutanásia nos seguintes tempos: 0 e 6, 12 e 24 horas após o fim da anestesia. Na necropsia foram coletados fragmentos dos lobos pulmonares e confeccionadas as lâminas para avaliação histológica das variáveis: infiltrado linfo-histiocitário, hemorragia intra-alveolar, congestão, edema pulmonar, infiltrado de neutrófilos intersticiais, infiltrado de neutrófilos intra-alveolares e áreas de atelectasia, sendo atribuído às lesões escores de ausente, leve, moderado ou intenso. As variáveis [pCO2(a)], FC, PAD, PAS, PAM, (cNa+), (cK+), (cCa+2), (cCl-), GAP, [cHCO3 -(a)] e [cBase(a)] se mantiveram dentro dos valores fisiológicos. Após o pneumoperitônio, houve aumento da [pCO2(a)] e consequente diminuição do [pH(a)] em todos os animais e elevação da EtCO2 nos grupos ventilados por PEEP e maior eliminação do CO2. Foi observado em todos os grupos infiltrado linfo-histiocitário característico de pneumonia intersticial linfocítica, além de baixos escores para o infiltrado neutrofílico alveolar e intersticial, edema, congestão e atelectasia, compatíveis com lesões ao endotélio capilar alveolar. Tais lesões foram mais intensas nos primeiros momentos após o procedimento anestésico- cirúrgico nos grupos GZP e G5P. Conclui-se que o incremento da PEEP em 0, 5 e 10 cmH2O não é capaz de evitar alterações ácido/base promovidas pela absorção peritoneal de CO2. A PEEP de 10 cmH2O melhora a eliminação de CO2 e reduz a pressão arterial de CO2, mas não evita a hipercapnia e promove lesões inflamatórias menos intensas no parênquima pulmonar.

Sabe-se que a anestesia geral por si só já é capaz de causar substancial depressão cardiovascular e respiratória em equinos e tal característica pode ser potencializada ainda mais pelo posicionamento do paciente em decúbito dorsal e pela a administração de elevadas pressões intratorácicas durante as manobras de recrutamento utilizadas para reverter a hipoxemia. Sendo assim, o objetivo do atual estudo foi avaliar a mecânica respiratória e hemogasometria arterial após manobra de recrutamento alveolar e aplicação de PEEP para manutenção, em equinos ASA I e II submetidos à anestesia geral inalatória para cirurgia artroscópica, bem como qual o melhor valor da PEEP para manutenção do recrutamento alveolar. Para tanto foram utilizados 30 equinos, pesando em média 454 kg, submetidos a cirurgia artroscópica em decúbito dorsal, divididos aleatoriamente em 4 grupos, sendo eles: Controle; PEEP 7; PEEP 12; e PEEP 17. Os animais receberam xilazina (0,6 mg/kg) como MPA, seguida de indução anestésica (quetamina 2,2 mg/kg associado ao diazepam 0,05 mg/kg e EGG 10% 50 mg/kg) e anestesia inalatória com isofluorano. Os animais foram posicionados em decúbito dorsal e submetidos a ventilação com volume controlado (14ml/kg), FR de 7 mpm, relação I:E 1:3, PEEP 7 cmH2O e FiO2 de 0,7. Após período de instrumentação foi realizada MRA por titulação da PEEP a cada 5 minutos até alcançar PEEP de 22 cmH2O, sendo que os animais do grupo Controle não receberam MRA, apenas manutenção com PEEP de 7 cmH2O. Os animais dos outros grupos passaram pela MRA seguido de manutenção com suas PEEP de tratamento (7, 12 ou 17 cmH2O). Os parâmetros de mecânica respiratória e hemogasometria arterial foram avaliados imediatamente antes da MRA; e 5, 10, 15, 20, 40, 60 e 80 minutos após a MRA. Foram também avaliadas a FC, PAS, PAM e PAD, porcentagem de anestésico inalatório inspirado e expirado, ETCO2 e consumo de fármaco vasoativo. Os animais que receberam MRA apresentaram aumento na complacência estática e nos parâmetros de oxigenação após a manobra, nos animais do grupo PEEP 12 e 17 foi observada manutenção do incremento oriundo da MRA por pelo menos 80 minutos. Já os animais do grupo PEEP 7 apresentaram queda do incremento após 20 minutos da manobra, assim como o grupo Controle apresentou queda nos parâmetros de oxigenação e ventilação ao longo do tempo, ambos indicando uma provável fechamento pulmonar devido a PEEP insuficiente para manutenção dos alvéolos abertos. Não foram observadas alterações cardiovasculares nos animais do estudo, apenas leve taquicardia transitória no grupo PEEP 17 logo após a MRA. Portanto as PEEP de 12 e 17 cmH2O utilizadas após a MRA foram capazes de manter os alvéolos abertos, promovendo assim melhor trocas gasosas e o incremento na oxigenação e ventilação dos pacientes. Já os animais que receberam MRA e manutenção com PEEP de 7 cmH2O, foram capazes de manutenção dos alvéolos abertos por apenas 20 minutos / It is known that general anaesthesia by it’s self is capable of causing substantial cardiovascular and respiratory depression in horses and this characteristic can be enhanced even more by patient positioned in dorsal recumbence and the administration of high intrathoracic pressures during recruitment manoeuvres used to reverse hypoxemia. Therefore, the aim of this study was to evaluate the respiratory mechanics and arterial blood gas analysis after recruitment manoeuvre and PEEP for maintenance, in horses ASA I and II undergoing general isoflurane-anaesthesia for arthroscopic surgery and what is the best value PEEP to maintain alveolar recruitment. Therefore, we used 30 horses, weighing on average 454 kg, which underwent arthroscopic surgery in the dorsal recumbence, randomly allocated into one of the 4 groups, as follows: Control; PEEP 7; PEEP 12; and PEEP 17. Animals received xylazine (0,6 mg/kg) as pre anaesthetic medication followed by anaesthesia induction (ketamine 2,2 mg/kg associated to diazepam 0,05 mg/kg and EGG 10% 50 mg/kg) and maintenance with isoflurane-anaesthesia. The animals were positioned in dorsal recumbence and submitted the volume-controlled ventilation (14ml/kg), RR: 7 mpm, I:E ratio 1:3, 7 cmH2O of PEEP and FiO2 0,7. After instrumentation period was performed RM by PEEP titration every 5 minutes until reach 22 cmH2O of PEEP, and the animals of control group did not receive RM, only maintenance with PEEP 7 cmH2O. The animals of other groups went through the RM followed by maintenance with their treatment PEEP (7, 12 or 17 cmH2O). The respiratory parameters and blood gas samples were assessed immediately before the RM; and 5, 10, 15, 20, 40, 60 and 80 minutes after the manoeuvre. We also assessed the HR, SAP, MAP and DAP, percentage of inhaled anaesthetic: inhaled and exhaled, ETCO2 and vasoactive drug consumption. Animals receiving RM showed an increase in static compliance and oxygenation parameters after the manoeuvre, maintenance of the increase coming from the RM were observed in animals from PEEP 12 and 17 group, for at least 80 minutes. The animals in PEEP 7 group decreased the increase after 20 minutes of manoeuvre and the control group decreased the parameters of oxygenation and ventilation over time, both indicating a probable pulmonary closure due to insufficient PEEP to maintain the alveoli opened. Cardiovascular changes were observed in the study animals, only mild transient tachycardia in PEEP 17group soon after RM. Therefore, the PEEP 12 and 17 cmH2O used after RM were able to keep the lung opened, thereby performing better gas exchange and the increase in the oxygenation and ventilation of patients. The animals receiving RM and maintenance PEEP 7 cmH2O were able to maintain the alveoli open for only 20 minutes

Mechanical ventilation (MV) therapy has been utilised in the intensive care unit (ICU) for 50 years to treat patients with respiratory illness by supporting the work of breathing, providing oxygen and removing carbon dioxide. MV therapy is utilised by 30-50% of ICU patients, and is a major driver of increased length of stay, increased cost and increased mortality. For patients suffering from acute respiratory distress syndrome (ARDS), the optimal MV settings are highly debated. ARDS patients suffer from a lack of recruited alveoli, and the application of positive end expiratory pressure (PEEP) is often used to maintain recruitment to maximise gas exchange and minimise lung damage. However, determining what level of PEEP is best for the patient is difficult. In particular, it involves a complex trade off between patient safety and ventilation efficacy. Currently, no clinical protocols exist to determine a patient-specific “best” PEEP. Model-based approaches provide an alternative patient-specific method to help clinical diagnosis and therapy selection. In particular, model-based methods can utilise a mix of both engineering and medical principles to create patient-specific models. The models are used for optimising ventilation settings and providing greater physiological insight into lung status than is currently available. Two model-based approaches are presented here. First, a quasi-static, minimal model of lung mechanics is presented based solely on fundamental lung physiology and mechanics. Secondly, a model of dynamic functional residual capacity (dFRC) is developed and presented based on model-based status of lung stress and strain. These models are validated with retrospective clinical data to evaluate the potential of such model-based approaches. Finally, the models are further validated with real time clinical data over a broader spectrum of pressure-volume ranges than prior studies to evaluate the clinical viability of model-based approaches to optimise MV therapy. When validated with real-time clinical trials data, the outputs of the recruitment model provide a range of optimal patient-specific values of PEEP based on different clinically and physiologically derived criteria. The recruitment model is also shown to have the ability to track the disease state of ARDS over time. The dFRC model introduces the PEEP stress parameter, β, which represents a unique population constant. The dFRC model suggests that clinically reasonable estimates of dFRC can be achieved by using this novel value of β, rather than the current, potentially hazardous, methods of deflating the lung to atmospheric pressure. Finally, a third model, combining the principles of recruitment and gas exchange is introduced. The combined model has the ability to estimate cardiac output (CO) changes with respect to PEEP changes during MV therapy. In addition, the model relates the coupled areas of circulation and pulmonary management, as well as linking these MV decision support models to oxygenation based clinical endpoints. A proof of concept is shown for this model by combining two different retrospective datasets and highlighting its ability to capture clinically expected drops in CO as PEEP increases. The model allows valuable cardiovascular circulation data to be predicted and also provides an alternative method and clinical end point by which PEEP could be optimised. The model requires further clinical validation before clinical use, but shows significant promise. The models developed and tested in this research enable rapid parameter identification from minimal, readily available clinical data, and thus provide a novel way of guiding therapy. The models can potentially provide clinicians with information to select an optimal patient-specific level of PEEP using only standard ventilation data, such as pressure-volume curves. In addition, the development of a dFRC stress model provides a unique population constant, β. Overall, the modelling approaches developed and validated in this research provide several novel methods of guiding therapy setting mechanical ventilation parameters and tracking and assess a patient’s lung condition. This research thus creates and provides novel validated methods for improving MV therapy with minimal cost or added invasiveness.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.