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A fairly large portion of patients receiving surgical or intensive care will need mechanical ventilation at some point. The potential ventilator-induced lung injury (VILI) is thus of interest. One of the main causal factors in VILI is the cyclic energy shifts, i.e. tidal volumes, in the lung during mechanical ventilation. The problem can be approached in two ways. Firstly, one can utilize apneic oxygenation and thus not cause any tidal injuries at all. Secondly, and more traditionally, one can simply lower the tidal volumes and respiratory rates used. The following describes a series of animal experiments exploring these options. In the first two papers, I explored and improved upon the methodology of apneic oxygenation. There is a generally held belief that it is only possible to perform apneic oxygenation by prior denitrogenation and by using 100% oxygen during the apnea. As 100% oxygen is toxic, this has prevented apneic oxygenation from more widespread use. The first paper proves that it is indeed possible to perform apneic oxygenation with less than 100% oxygen. I also calculated the alveolar nitrogen concentration which would conversely give the alveolar oxygen concentration. The second paper addresses the second large limitation of apneic oxygenation, i.e. hypercapnia. Using a high dose infusion of tris(hydroxymethyl)aminomethane (THAM) buffer, a pH > 7.2 could be maintained during apneic oxygenation for more than 4.5 hours. In the last two papers, THAM’s properties as a proton acceptor are explored during respiratory acidosis caused by very low volume ventilation. In paper III, I found that THAM does not, in the long term, affect pH in respiratory acidosis after stopping the THAM infusion. It does, however, lower PVR, even though the PaCO2 of THAM-treated animals had rebounded to levels higher than that of the controls. In the last experiment, I used volumetric capnography to confirm our hypothesis that carbon dioxide elimination through the lungs was lower during the THAM infusion. Again, the PaCO2 rebounded after the THAM infusion had stopped and I concluded that renal elimination of protonated THAM was not sufficient.

Abstract Guidelines and instructions derived from adult randomized controlled trials are generally followed in pediatric ventilation, as there have been no large trials of this kind in children. Current treatment strategies aim at preventing ventilator-induced lung injury by avoiding too large tidal volumes, supporting patient's spontaneous breathing and preventing lung collapse with positive end-expiratory airway pressure. Neurally adjusted ventilatory assist (NAVA) is a novel ventilation mode that provides respiratory support proportional to the electrical activity of the diaphragm (Edi). The aims of this thesis were to assess daily practices in pediatric ventilation in Finland and to compare NAVA with conventional ventilation in terms of safety and quality of care. Current treatment practices were studied with a preliminary enquiry and a 3-month prospective survey that was offered to all hospital units providing ventilatory care for children <16 years of age. NAVA was compared with current standard ventilation in a crossover trial involving 18 pediatric patients and in a larger controlled trial in which 170 patients were randomized to receive either NAVA or conventional ventilation. Respiratory distress was the most common indication for invasive ventilation in neonates, and postoperative care in older children. The principles of lung-protective ventilation were generally accepted and the goals were achieved in the majority of treatment episodes. The low incidence of pediatric invasive ventilation favours centralization. NAVA proved to be a safe and feasible primary ventilation mode in pediatric intensive care. It improved patient-ventilator synchrony and led to lower peak inspiratory pressures and oxygen requirements. It also reduced the need for sedation during longer treatment periods. Information derived from the Edi-signal could be used to optimize the level of sedation and to identify patients with a potential risk of extubation failure. / Tiivistelmä Nykyisin käytössä olevat menetelmät lasten hengityskonehoidossa perustuvat suurelta osin aikuisilla tehtyihin tutkimuksiin ja totuttuihin tapoihin, sillä lasten hengityskonehoidosta on olemassa vain vähän tutkittua tietoa. Hengityskonehoidon aiheuttamaa keuhkovauriota pyritään ehkäisemään välttämällä suuria kertahengitystilavuuksia, tukemalla potilaan omia hengityksiä ja säilyttämällä ilmateissä positiivinen paine uloshengityksen aikanakin. Neuraalisesti ohjattu ventilaatio (NAVA) on uusi hengityskonehoitomuoto, joka tukee potilaan omia hengityksiä ohjaamalla koneen antamaa tukea pallealihaksen sähköisen signaalin avulla. Tämän tutkimuksen tavoitteena oli selvittää lasten hengityskonehoidon nykytilaa Suomessa sekä tutkia, voidaanko NAVAa käyttämällä parantaa hoidon laatua ja turvallisuutta. Nykyisiä hoitokäytäntöjä selvitettiin vuonna 2010 kysely- ja seurantatutkimuksella, johon kutsuttiin mukaan kaikki Suomessa lapsia ja vastasyntyneitä hoitavat tehohoito-osastot. NAVAa verrattiin nykyiseen hengityskonehoitoon 18 potilaan vaihtovuoroisessa tutkimuksessa sekä suuremmassa 170 lapsipotilaan satunnaistetussa kontrolloidussa tutkimuksessa. Eri syistä johtuvat hengitysvaikeudet ovat yleisin syy hengityskonehoitoon vastasyntyneillä ja suurten leikkausten jälkeinen hoito isommilla lapsilla. Keuhkoja säästävän hoidon periaatteet ovat Suomessa yleisesti hyväksyttyjä ja toteutuvat valtaosassa hoitojaksoja. Hengityskonehoitojaksojen määrän vähäisyys puoltaa hoidon keskittämistä suuriin sairaaloihin. NAVAa käyttämällä hengityskoneen antama tuki ajoittuu paremmin potilaan omien hengitysten mukaan ja sen avulla saavutetaan matalammat ilmatiepaineet sekä vähäisempi lisähapen tarve. Pitkissä hoitojaksoissa NAVA vähentää rauhoittavan lääkityksen tarvetta, ja pallealihaksen signaalia seuraamalla on mahdollista optimoida sedaatioaste aikaisempaa tarkemmin. Palleasignaalia voidaan myös hyödyntää arvioitaessa potilaan valmiutta hengitystuesta vieroittamiseen.

Orientador: José Roberto Fioretto / Resumo: A Síndrome do Desconforto Respiratório Agudo (SDRA) cursa com alta morbi-mortalidade apesar dos avanços no entendimento de sua fisiopatologia e tratamento. A terapia ventilatória baseia-se na proteção pulmonar, sendo a ventilação oscilatória de alta frequência (VOAF) uma opção de método protetor. A posição prona (PP) é terapia adjuvante que possibilita homogeneização da distribuição do volume corrente (VC) e promove recrutamento alveolar. O objetivo do estudo foi investigar o efeito da posição prona associada à VOAF e ventilação mecânica convencional (VMC) protetora sobre a oxigenação, inflamação, dano oxidativo e histologia pulmonares, comparando-a à posição supina em ambos os modos ventilatórios. Foram instrumentados 75 coelhos com traqueostomia e acessos vasculares. A lesão pulmonar aguda (LPA) foi induzida por lavagem traqueal de salina aquecida (30mL/Kg, 38°C). Os animais foram então aleatorizados em cinco grupos (n=15): 1) GC (Controle): animais sadios em VMC protetora basal; 2) GVMS: animais com LPA em VMC protetora e posição supina; 3) GVMP: animais com LPA em VMC protetora e posição prona; 4) GVAFS: animais com LPA em VOAF e posição supina; 5) GVAFP: animais com LPA em VOAF e posição prona. Após, foram submetidos a quatro horas de VMC protetora (modo pressão regulada-volume controlado, PEEP 10 cmH2O, VC 6mL/kg, Ti 0,5s, FR 40 rpm e FiO2 1) ou VOAF (MAP 15 mmHg, FR 10Hz, amplitude 22 e FiO2 1). O nível de significância foi de 5%. Após a indução, os grupos apresentaram... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Acute Respiratory Distress Syndrome (ARDS) presents with high morbidity and mortality despite advances in the understanding of its pathophysiology and treatment. Ventilatory therapy is based on the intention of injuring less, with high frequency oscillatory ventilation (HFOV) being a protective method option. Prone position (PP) is an adjuvant therapy that enables homogenization of volume tidal (VT) distribution and promotes alveolar recruitment. The aim of this study was to investigate the effects of prone position associated with HFOV and protective conventional mechanical ventilation (CMV) on oxygenation and lung inflammation, oxidative damage and histology, comparing it with the supine position in both ventilatory modes. Seventy five rabbits were submitted to tracheostomy and vascular accesses. ALI was induced by tracheal infusion of heated saline (30mL/kg, 38° C). The subjects were then ramdomized in five groups (n=15): 1) CG (Control): healthy animals in basal protective CMV; 2) MVSG: animals with ALI in protective CMV and supine position; 3) MVPG animals with ALI in protective CMV and prone position; 4) HFSG: animals with ALI in HFOV and supine position; 5) HFPG: animals with ALI in HFOV and prone position. After that, they were submitted to four hours of protective VMC (PRV mode, PEEP 10 cmH2O, VC 6ml/kg, Ti 0,5s, FR=40 rpm and FiO2 1) or HFOV (MAP 15 mmHg, FR 10 Hz, amplitude 22 and FiO2 1). The level of significance was 5%. After induction, the groups presented simi... (Complete abstract click electronic access below) / Doutor

Submitted by Rafaelle Batistella Pires (rafaelle.pires@gmail.com) on 2018-03-07T15:41:30Z No. of bitstreams: 1 Tese Rafaelle Batistella Pires.pdf: 2978722 bytes, checksum: f79b8076fd69934911d1a338cd131aa3 (MD5) / Approved for entry into archive by Luciana Pizzani null (luciana@btu.unesp.br) on 2018-03-08T20:07:06Z (GMT) No. of bitstreams: 1 pires_rb_dr_bot.pdf: 2978722 bytes, checksum: f79b8076fd69934911d1a338cd131aa3 (MD5) / Made available in DSpace on 2018-03-08T20:07:06Z (GMT). No. of bitstreams: 1 pires_rb_dr_bot.pdf: 2978722 bytes, checksum: f79b8076fd69934911d1a338cd131aa3 (MD5) Previous issue date: 2018-02-20 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A Síndrome do Desconforto Respiratório Agudo (SDRA) cursa com alta morbi-mortalidade apesar dos avanços no entendimento de sua fisiopatologia e tratamento. A terapia ventilatória baseia-se na proteção pulmonar, sendo a ventilação oscilatória de alta frequência (VOAF) uma opção de método protetor. A posição prona (PP) é terapia adjuvante que possibilita homogeneização da distribuição do volume corrente (VC) e promove recrutamento alveolar. O objetivo do estudo foi investigar o efeito da posição prona associada à VOAF e ventilação mecânica convencional (VMC) protetora sobre a oxigenação, inflamação, dano oxidativo e histologia pulmonares, comparando-a à posição supina em ambos os modos ventilatórios. Foram instrumentados 75 coelhos com traqueostomia e acessos vasculares. A lesão pulmonar aguda (LPA) foi induzida por lavagem traqueal de salina aquecida (30mL/Kg, 38°C). Os animais foram então aleatorizados em cinco grupos (n=15): 1) GC (Controle): animais sadios em VMC protetora basal; 2) GVMS: animais com LPA em VMC protetora e posição supina; 3) GVMP: animais com LPA em VMC protetora e posição prona; 4) GVAFS: animais com LPA em VOAF e posição supina; 5) GVAFP: animais com LPA em VOAF e posição prona. Após, foram submetidos a quatro horas de VMC protetora (modo pressão regulada-volume controlado, PEEP 10 cmH2O, VC 6mL/kg, Ti 0,5s, FR 40 rpm e FiO2 1) ou VOAF (MAP 15 mmHg, FR 10Hz, amplitude 22 e FiO2 1). O nível de significância foi de 5%. Após a indução, os grupos apresentaram comportamentos semelhantes, com diminuição da relação PaO2/FiO2 e da complacência pulmonar, e aumento do índice de oxigenação (IO) e da pressão média de via aérea (p > 0,05). Ao final do experimento, houve aumento da PaO2/FiO2 nos grupos VOAF comparado aos grupos em VMC (p < 0,05). Houve queda do IO para os grupos em VOAF comparados ao GVMS (p < 0,05), porém o GVMP não diferiu deles (p > 0,05). Não houve diferença estatística quanto à contagem de células polimorfonucleares no lavado broncoalveolar (BAL) nos grupos com LPA. Não houve diferença estatística entre os grupos com lesão para a medida de TNF-alfa no plasma e para sua expressão gênica em tecido pulmonar. Entretanto, a medida de TNF-alfa no lavado broncoalveolar (BAL) e no tecido pulmonar no grupo GVMP foi menor, assemelhando-se ao controle (p > 0,05). Não houve diferença no dano oxidativo avaliado no tecido pulmonar entre os grupos (p > 0,05) e, também, na comparação entre regiões ventral e dorsal dos pulmões. O escore de lesão histológica foi menor nos grupos em VOAF, efeito potencializado no grupo em prona quando comparado aos grupos em VMC (GC = GVAFP < GVMS = GVMP), sem diferença na regionalização pulmonar. Concluimos que, em modelo de LPA por lavagem alveolar com salina aquecida em coelhos: a VOAF melhora a oxigenação quando comparados à VMC; na VMC, a PP atenua a lesão inflamatória avaliada pela medida de TNF-alfa no BAL e tecido pulmonar; os modos ventilatórios e as posições não modificam o grau de estresse oxidativo quando avaliados pelo método de malondialdeído; a VOAF melhora o escore histopatológico de lesão pulmonar, independemente da posição, mas a associação de VOAF e PP atenua a lesão histopatológica quando comparada com a VMC protetora, seja em posição prona ou supina. / Acute Respiratory Distress Syndrome (ARDS) presents with high morbidity and mortality despite advances in the understanding of its pathophysiology and treatment. Ventilatory therapy is based on the intention of injuring less, with high frequency oscillatory ventilation (HFOV) being a protective method option. Prone position (PP) is an adjuvant therapy that enables homogenization of volume tidal (VT) distribution and promotes alveolar recruitment. The aim of this study was to investigate the effects of prone position associated with HFOV and protective conventional mechanical ventilation (CMV) on oxygenation and lung inflammation, oxidative damage and histology, comparing it with the supine position in both ventilatory modes. Seventy five rabbits were submitted to tracheostomy and vascular accesses. ALI was induced by tracheal infusion of heated saline (30mL/kg, 38° C). The subjects were then ramdomized in five groups (n=15): 1) CG (Control): healthy animals in basal protective CMV; 2) MVSG: animals with ALI in protective CMV and supine position; 3) MVPG animals with ALI in protective CMV and prone position; 4) HFSG: animals with ALI in HFOV and supine position; 5) HFPG: animals with ALI in HFOV and prone position. After that, they were submitted to four hours of protective VMC (PRV mode, PEEP 10 cmH2O, VC 6ml/kg, Ti 0,5s, FR=40 rpm and FiO2 1) or HFOV (MAP 15 mmHg, FR 10 Hz, amplitude 22 and FiO2 1). The level of significance was 5%. After induction, the groups presented similar behaviors, with a decrease in the PaO2/FiO2 ratio and lung compliance, and an increase in oxygenation index (OI) and mean airway pressure (p > 0.05). At the end of experimental time, PaO2/FiO2 increased in the HFOV groups compared to the CMV groups (p < 0.05). There was a decrease in OI for HFOV groups compared to MVSG (p < 0.05), but MVPG did not differ from them (p > 0.05). There was no statistically significant difference in polymorphonuclear cell counts in bronchoalveolar lavage (BAL) in the groups with ALI. There was no difference between ALI groups regarding the TNF-alfa dosage in plasma and its gene expression in lung tissue. However, TNF-alpha measurement in BAL and in lung tissue was smaller, resembling control (p > 0.05). There was no difference in the oxidative damage assessed in the lung tissue between the groups (p > 0.05), nor between the lung regions. The histological damage score was lower in the HFOV groups, potentiated effect in the prone group when compared to the CMV groups (CG = HFPG < MVSG = MVPG), no difference in pulmonary regionalization. We conclude that, in the model of ALI induced by alveolar lavage with heated saline in rabbits: HFOV improves oxygenation if compared to CMV; PP in CMV attenuates lung inflammation, evaluated by TNF-alfa dosage in BAL and in lung tissue; ventilatory modes and positions don’t modify the oxidative stress whan evaluated by malondialdehyde method; HFOV improves histopathological lung lesion score, regardless of position, but HFOV and prone position association attenuates histopathological injury compared to protective CMV, either in the prone or supine positions. / FAPESP: 2010/06242-8

MUDr. Michal Otáhal Biomechanický model interakce oběhu a ventilace za podmínek UPV Abstract: Conventional mechanical ventilation provides gas exchange in conditions of respiratory failure by application positive airway pressure in the respiratory system. Due to the significant change in pressure conditions inside the thorax during conventional artificial ventilation the circulation can be significantly affected. Recruitment maneuver (RM) techniques can be a part of ventilation strategy in patients with the Acute Respiratory Distress Syndrome (ARDS), that are used to re-aerate collapsed parts of the lung parenchyma. During these RMs a significantly higher airway pressure is used than in protective ventilation strategy, which can limit the flow through the lung capillary network and can significantly affect the systemic hemodynamics of the patient. The aim of this work was to develop an optimized animation model of ARDS, then to compare the influence that has the application of different types of recruitment maneuvers on hemodynamics and to create a biomechanical simulation model of interaction and blood circulation and its verification with data obtained during the implementation of different types of RM in the experimental animal ARDS model. Results from the experimental animal model and simulations...

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

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

Background: General anesthesia usually requires mechanical ventilation, which is traditionally accomplished with constant tidal volumes in volume- or pressure-controlled modes. Experimental studies suggest that the use of variable tidal volumes (variable ventilation) recruits lung tissue, improves pulmonary function and reduces systemic inflammatory response. However, it is currently not known whether patients undergoing open abdominal surgery might benefit from intraoperative variable ventilation. Methods/Design: The PROtective VARiable ventilation trial ('PROVAR') is a single center, randomized controlled trial enrolling 50 patients who are planning for open abdominal surgery expected to last longer than 3 hours. PROVAR compares conventional (non-variable) lung protective ventilation (CV) with variable lung protective ventilation (VV) regarding pulmonary function and inflammatory response. The primary endpoint of the study is the forced vital capacity on the first postoperative day. Secondary endpoints include further lung function tests, plasma cytokine levels, spatial distribution of ventilation assessed by means of electrical impedance tomography and postoperative pulmonary complications. Discussion: We hypothesize that VV improves lung function and reduces systemic inflammatory response compared to CV in patients receiving mechanical ventilation during general anesthesia for open abdominal surgery longer than 3 hours. PROVAR is the first randomized controlled trial aiming at intra- and postoperative effects of VV on lung function. This study may help to define the role of VV during general anesthesia requiring mechanical ventilation.

Thoracic surgical procedures require partial or complete airway separation and the opportunity to exclude one lung from ventilation (one-lung ventilation, OLV). OLV is commonly associated with profound pathophysiological changes that may affect the postoperative outcome. It is injurious in terms of increased mechanical stress including alveolar cell stretch and overdistension, shear forces secondary to repeated tidal collapse and reopening of alveolar units and compression of alveolar vessels. Ventilation and perfusion distribution may thus be affected during and after OLV. The present studies investigated the influence of OLV on ventilation and perfusion distribution, on the gas/tissue distribution and on the lung histomorphology in a pig model of thoracic surgery. Anaesthetised and mechanically ventilated piglets were examined. The ventilation and perfusion distribution within the lungs was assessed by single photon emission computed tomography. Computed tomography was used to establish the effects of OLV on dependent lung gas/tissue distribution. The pulmonary histopathology of pigs undergoing OLV and thoracic surgery was compared with that of two-lung ventilation (TLV) and spontaneous breathing. OLV induced hyperperfusion and significant V/Q mismatch in the ventilated lung persistent in the postoperative course. It increased cyclic tidal recruitment that was associated with a persistent increase of gas content in the ventilated lung. OLV and thoracic surgery as well resulted in alveolar damage.  In the present model of OLV and thoracic surgery, alveolar recruitment manoeuvre (ARM) and protective ventilation approach using low tidal volume preserved the ventilated lung density distribution and did not aggravate cyclic recruitment of alveoli in the ventilated lung. In conclusion, the present model established significant alveolar damage in response to OLV and thoracic surgery. Lung injury could be related to the profound pathophysiological consequences of OLV including hyperperfusion, ventilation/perfusion mismatch and increased tidal recruitment of lung tissue in the dependent, ventilated lung.  These mechanisms may contribute to the increased susceptibility for respiratory complications in patients undergoing thoracic surgery. A protective approach including sufficient ARM, application of PEEP, and the use of lower tidal volumes may prevent the ventilated lung from deleterious consequences of OLV.