Clinical concerns exist regarding the delivered tidal volume (Vt) during high-frequency oscillatory ventilation (HFOV). HFOV is increasingly being used as a lung protective mode of ventilation for patients with Adult Respiratory Distress Syndrome (ARDS), but caution must be utilized. The purpose of this study was to investigate the effect of airway compliance on Vt delivered by HFOV to the adult patient. Method: An in vitro model was used to simulate an adult passive patient with ARDS, using a high fidelity breathing simulator (ASL 5000, IngMar Medical). The simulation included independent lung ventilation with a fixed resistance and adjustable compliance for each lung. Compliances of 10, 15, 20 and 25 ml/cmH2O were used and resistance (Raw) was fixed at 15 cm H2O/L/s. The ventilator SensorMedics 3100B (Cardinal Health, Dublin, Ohio) was set to a fixed power setting of 6.0, insp-% of 33%, bias flow =30 L/min, and 50% oxygen and Hz of 5.0 (n=5) for each compliance setting. Mean airway pressure (mPaw) and amplitude (AMP) varied as the compliance changes were made. Approximately 250 breaths were recorded at each compliance setting and the data was collected via the host computer and transferred to a log to be analyzed by SPSS v. 10. Data Analysis: The data analysis was performed using SPSS v. 10 to determine the statistical significance of the delivered Vt with different compliances, different AMP and a fixed power setting. A probability of (p < 0.05) was accepted as statistically significant. Results: The average delivered Vt with each compliance was 124.181 mL (range of 116.4276 mL and 132.6637 mL) and average AMP of 84.85 cm/H2O (range 82.0 cm/H2O and 88.0801 cm/H2O) n=5. There was an inverse relationship between Vt and AMP at a fixed power of 6.0. As compliance improved Vt increased and there was a corresponding decrease in AMP. The one-way ANOVA test showed that there were significant differences between the delivered tidal volume and AMP at a fixed power setting. When the post hoc Bonferroni test was used the data showed significant differences between AMP achieved with each compliance change and a fixed power of 6.0. When the post hoc Bonferroni test was used the data showed significant differences between Vt delivered with each compliance change and a fixed power setting of 6.0. Conclusion: Vt is not constant during HFOV. Compliance is one determinant of Vt in adults with ARDS during HFOV. AMP and Vt are inversely related during HFOV at a fixed power setting and improving compliance.

Concerns exist regarding the ability of HFOV to provide the needed lung protective ventilation for adult patients with ARDS. HFOV is increasingly being used as a lung protecting ventilation mode even if some of its protective attributes may be lost as the airway resistance (Raw) increases or decreases. In fact, in cases of shifting air resistance, HFOV may have caused lung injury. PURPOSE: The purpose of this study was to investigate the effect of airway resistance on tidal volume (Vt) delivered by HFOV to adult patients. Also, the study intended to determine direction for volume change when resistance increases or decreases. METHODS: An in vitro model was used to simulate an adult passive patient with ARDS using a breathing simulator (Active Servo Lung 5000, Ingmar Medical, Pittsburgh, PA, USA). Adjustable resistance and compliance for each lung was used. The resistance levels of 15, 30, 45 (cm H2O/L/sec) were used for upper and lower Raw and CL was fixed at 40 mL/cm H2O. The ventilator (Sensormedics 3100B) was set to MAP = 35 cm H2O, to insp-time of 33%, to bias flow =30 L/min, to delta-P of 80, and to 50% oxygen. Vt was recorded (n=3) for each Raw, and the data was collected on the host computer. Approximately 200-250 breaths of data for each Raw were captured via the ASL software and then converted to Excel for analysis. An average of 80 breathes (following the steady Vt level) was used in each analysis. DATA ANALYSIS: The data analysis was performed with one way ANOVA and with a post hoc Bonferroni test in order to determine the statistical significance of the delivered Vt with each Raw. A probability of (p < 0.05) was accepted as statistically significant. RESULTS: The descriptive statistics of the average delivered Vt with regard to each Raw (15, 30, 45 cm H2O/L/sec) were the number of experiments (n=3), mean Vt (93.52, 89.09, 85.99 mL), and standard deviations (SD) (1.38, 1.11, 1.10) respectively. There was an inverse relationship between tidal volume and airway resistance during HFOV. With all other variables kept constant, higher resistance caused less volume, whereas lower resistance caused more volume. The one-way ANOVA test showed that there were significant differences between the delivered tidal volumes. When the post hoc Bonferroni test was used, the data showed significant differences between airway resistances of 15 cm H2O/L/sec and 30 cm H2O/L/sec and between 15 cm H2O/L/sec and 45 cm H2O/L/sec. In contrast, no significant differences were found between airway resistances of 30 cm H2O/L/sec and 45 cm H2O/L/sec. CONCLUSION: Vt is not constant during HFOV. Airway resistance is one of the determinants of delivered tidal volume in adults with ARDS during HFOV. Airway resistance should be an important factor in ventilator management and in clinical experiments of patients on HFOV. Without a proper Vt measurement device HFOV should not be used as lung protective ventilation for adult patients with ARDS.

Introduction: The use of high frequency oscillatory ventilation is increasing in treatment ofacute respiratory distress syndrome over the past decade. The technique of HFOV of ventilatingthe lungs at volumes less than the anatomical dead space calms the clinical concerns surroundingventilating stiff ARDS lungs with high pressures and volumes. This largely reduces theprobability of barotraumas and/or atelectrauma. Purpose: The study was on an in vitro bench model that answered the following researchquestions: 1. The effect of three inline closed suction adapters on delivered tidal volume duringHFOV with varying lung compliance 2. The effect of varying compliance on the amplitudedelivered by HFOV; and 3. The effect of compliance on tidal volume delivered by HFOV. Method: An in vitro bench model using high fidelity breathing simulator (ASL 5000, IngMarMedical) simulating an adult patient with ARDS was set up with 3100B SensorMedic highfrequency ventilator. The simulation included varying the compliance for each lung at 50, 40, 30and 20cmH2O while maintaining fixed resistance of 15 cmH2O/L/sec. The ventilator was set tothe following parameters: power of 6, frequency (f) of 5, inspiratory time (Ti) of 33%, bias flow(BF) of 30 LPM and oxygen concentration of 50%. The breathing simulator was connected withthe high frequency ventilator using a standard HFOV circuit and a size 8.0mm of endotrachealtube. Fourteen French Kimberly Clark suction catheters (with T and Elbow adapters) and Air-Life suction catheters (Y adapter) were placed in-line with the circuit successively to carry outthe study. Each run lasted for 1 minute after achieving stable state conditions. Thisapproximated to 300 breaths. The data was collected from the stimulator and stored by the hostcomputer. Data Analysis: The data was analyzed using SPSS v.11 to determine the statistical significance.A probability value (P value) of ≤ 0.001 was considered to be statistically significant. Results: The data analysis showed that Air-Life Y-adapter suction catheters caused the least lostin tidal volume when placed in line with HFOV and hence proved to be the most efficient. Thestudy also showed a direct relationship between amplitude and lung compliance i.e. an increasein lung compliance caused an associated increase in amplitude (power setting remainingunaltered). Lastly, the study did not show a statistically significant change in tidal volume withchanges in lung compliance. Future studies may be required to further evaluate the clinicalsignificance of the same. Conclusion:1. Many factors affect delivery of tidal volume during high frequency ventilation and thus it isnot constant. Choice of in-line suction system to be placed in line is one of the determinants ofthe same.2. Lung compliance changes lead to associated changes in amplitude delivery by HFOV. Thisshould be adjusted as patient condition improves by altering the power settings to ensure optimalventilation and to avoid trauma to the lungs.

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

Background: Ventilatory pressures should target the range between the upper and lower inflection point of the pressure volume curve in order to avoid atelecto- and volutrauma. During high-frequency oscillatory ventilation (HFOV), this range is difficult to determine. Quadrant impedance measurement (QIM) has recently been shown to allow accurate and precise measurement of lung volume changes during conventional mechanical ventilation. Objectives: To investigate if QIM can be used to determine a static pressure-residual impedance curve during a recruitment-derecruitment manoeuvre on HFOV and to monitor the time course of alveolar recruitment after changing mean airway pressure (MAP). Methods: An incremental and decremental MAP trial (6 cm H₂O to 27 cm H₂O) was conducted in five surfactantdepleted newborn piglets during HFOV. Ventilatory, gas exchange and haemodynamic parameters were recorded. Continuous measurement of thoracic impedance change was performed. Results: Mean residual impedance (RI) increased with each stepwise increase of MAP resulting in a total mean increase of +26.5% (±4.0) at the highest MAP (27 cm H₂O) compared to baseline ventilation at 6 cm H₂O. Upon decreasing MAP levels, RI fell more slowly compared to its ascent; 83.4% (±19.1) and 84.8% (±16.4) of impedance changes occurred in the first 5 min after an increase or decrease in airway pressure, respectively. Conclusions: QIM could be used for continuous monitoring of thoracic impedance and determination of the pressure-RI curve during HFOV. The method could prove to be a promising bedside method for the monitoring of lung recruitment during HFOV in the future.