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Ronald B. Hirschl - One of the best experts on this subject based on the ideXlab platform.
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Liquid Ventilation in an Infant With Pulmonary Alveolar Proteinosis
2016Co-Authors: Wan Chong Tsai, Dorothy Lewis, Samya Z. Nasr, Ronald B. HirschlAbstract:Summary. Partial Liquid Ventilation (PLV) has been applied in various pulmonary diseases. We describe the use of partial Liquid Ventilation as a lavage method following normal saline (NS) lavage in an infant with pulmonary alveolar proteinosis (PAP) and severe hypoxemia. A 6 weeks old 3.4 kg former 36 weeks gestation boy on supplemental oxygen was transferred to our NICU with persistent tachypnea, dry cough, and increasing oxygen requirements. A lingular open lung biopsy revealed PAP. He developed progressive respiratory failure requiring ventilatory support, necessitating conventional NS lavage, followed by lung lavage with perflubron (LiquiVent; Alli-ance Pharmaceutical Corp. and Hoechst Marion Roussel) while on venovenous extracorporeal life support (ECLS). Lung lavage with NS and perflubron yielded minimal cloudy effluent. Gas exchange and pulmonary function deteriorated following NS lavage and attempts to discontinue ECLS were poorly tolerated. In contrast, tidal volume, PaO2, and pulmonary compliance in-creased after PLV, while the (A-a) DO2 decreased to a point where ECLS was no longer required. Once perflubron was added repeatedly to the ventilator circuit to correct for evaporation over the 4 days of PLV. Cardiovascular status remained stable for several days; however, eventually he required reinitiation of ECLS and more mechanical ventilatory support with each trial off ECLS. He was maintained on high pressures and FiO2 without any possibility to wean him from me-chanical Ventilation. Life support was withdrawn 1 month after admission. The survival from PAP in infants remains dismal, even with total lung NS lavage. While both NS and perflubron lavage in this patient were not effective in removing the proteinaceous alveolar debris, PLV following NS lavage was associated with an improvement in gas exchange and lung compliance. Pediat
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Effects of respiratory rate and tidal volume on gas exchange in total Liquid Ventilation.
Asaio Journal, 2009Co-Authors: Joseph L. Bull, Stefano Tredici, Hideki Fujioka, E Komori, James B. Grotberg, Ronald B. HirschlAbstract:Using a rabbit model of total Liquid Ventilation (TLV), and in a corresponding theoretical model, we compared nine tidal volume-respiratory rate combinations to identify a ventilator strategy to maximize gas exchange, while avoiding choked flow, during TLV. Nine different Ventilation strategies were tested in each animal (n = 12): low [LR = 2.5 breath/min (bpm)], medium (MR = 5 bpm), or high (HR = 7.5 bpm) respiratory rates were combined with a low (LV = 10 ml/kg), medium (MV = 15 ml/kg), or high (HV = 20 ml/kg) tidal volumes. Blood gases and partial pressures, perfluorocarbon gas content, and airway pressures were measured for each combination. Choked flow occurred in all high respiratory rate-high volume animals, 71% of high respiratory rate-medium volume (HRMV) animals, and 50% of medium respiratory rate-high volume (MRHV) animals but in no other combinations. Medium respiratory rate-medium volume (MRMV) resulted in the highest gas exchange of the combinations that did not induce choke. The HRMV and MRHV animals that did not choke had similar or higher gas exchange than MRMV. The theory predicted this behavior, along with spatial and temporal variations in alveolar gas partial pressures. Of the combinations that did not induce choked flow, MRMV provided the highest gas exchange. Alveolar gas transport is diffusion dominated and rapid during gas Ventilation but is convection dominated and slow during TLV. Consequently, the usual alveolar gas equation is not applicable for TLV.
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Multicenter comparative study of conventional mechanical gas Ventilation to tidal Liquid Ventilation in oleic acid injured sheep.
ASAIO journal (American Society for Artificial Internal Organs : 1992), 2008Co-Authors: Marla R. Wolfson, Ronald B. Hirschl, J. Craig Jackson, David S. Foley, Wayne J. E. Lamm, John P. Gaughan, Thomas H ShafferAbstract:We performed a multicenter study to test the hypothesis that tidal Liquid Ventilation (TLV) would improve cardiopulmonary, lung histomorphological, and inflammatory profiles compared with conventional mechanical gas Ventilation (CMV). Sheep were studied using the same volume-controlled, pressure-limited ventilator systems, protocols, and treatment strategies in three independent laboratories. Following baseline measurements, oleic acid lung injury was induced and animals were randomized to 4 hours of CMV or TLV targeted to "best PaO2" and PaCO2 35 to 60 mm Hg. The following were significantly higher (p < 0.01) during TLV than CMV: PaO2, venous oxygen saturation, respiratory compliance, cardiac output, stroke volume, oxygen delivery, ventilatory efficiency index; alveolar area, lung % gas exchange space, and expansion index. The following were lower (p < 0.01) during TLV compared with CMV: inspiratory and expiratory pause pressures, mean airway pressure, minute Ventilation, physiologic shunt, plasma lactate, lung interleukin-6, interleukin-8, myeloperoxidase, and composite total injury score. No significant laboratories by treatment group interactions were found. In summary, TLV resulted in improved cardiopulmonary physiology at lower ventilatory requirements with more favorable histological and inflammatory profiles than CMV. As such, TLV offers a feasible ventilatory alternative as a lung protective strategy in this model of acute lung injury.
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effect of repeated induced airway collapse during total Liquid Ventilation
Asaio Journal, 2007Co-Authors: Paola Bagnoli, Joseph L. Bull, Stefano Tredici, Kent J Johnson, Rupa Seetharamaiah, David O Brant, Lauren A Hewell, Maria Laura Costantino, Ronald B. HirschlAbstract:Negative pressure generated during the expiratory phase of total Liquid Ventilation (TLV) may induce airway collapse. Evaluation of the effect of repeated airway collapse is crucial to optimize this technique. A total of 24 New Zealand White rabbits were randomly divided into four groups. Ventilation was performed for 6 hours with different strategies: conventional gas Ventilation, TLV without airway collapse, and TLV with collapse induced in either 75 or 150 sequential breaths. In the treated groups, airway collapse was induced by increasing the perfluorocarbon drainage velocity while maintaining the minute Ventilation constant. Airway pressure, gas exchange, and blood pressure were monitored at 30-minute intervals. At the end of the experiment, airway and lung parenchyma specimens were processed for light microscopy. No evidence of fluorothorax was noticed in any of the four groups at autopsy examination. Minimal signs of inflammation were noticed in all airway and lung parenchyma specimens, but no evident structural alteration was visible. Adequate gas exchange and systemic blood pressure were maintained during all the studies. Repeated airway collapse is not associated with structural changes in the respiratory system and does not alter the gas exchange ability of the lungs.
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current experience with Liquid Ventilation
Paediatric Respiratory Reviews, 2004Co-Authors: Ronald B. HirschlAbstract:The concept of Liquid Ventilation has been investigated for almost 40 years. Kylstra,1 in 1962, demonstrated the ability to sustain gas exchange in dogs spontaneously breathing saline oxygenated at 6 atmospheres. Clark2 subsequently demonstrated that spontaneously breathing mice could survive when submerged in perfluorocarbon under normobaric conditions. Perfluorocarbons are structurally similar to hydrocarbons with the hydrogen replaced by fluorine. The carbon chains vary in length and an additional moiety often is attached to the molecule which, together, give unique properties to each perfluorocarbon. In general, perfluorocarbons have excellent oxygen and carbon dioxide carrying capacity (50mlO2/dl and 160−210mlCO2/dl, respectively).3 They are clear, odorless, inert fluids which are immiscible in aqueous and most other solutions. They are relatively dense (1.7−1.9 gm/mL), have a low surface tension (15−19 dynes/cm), and are relatively volatile with vapor pressures ranging from 11 to 85 torr at 37oC. The vapor pressure of the individual perfluorocarbon governs the rapidity with which it evaporates from the lungs after intratracheal administration. Liquid Ventilation has been performed by two methods.3 The first is total Liquid Ventilation (TLV) in which the lungs are filled with perfluorocarbon to a volume equivalent to functional residual capacity (FRC) upon which a device is utilised to ventilate the perfluorocarbon-filled lung with perfluorocarbon.4 The second technique of Liquid Ventilation involves administration of intratracheal perfluorocarbon to a volume equivalent to functional residual capacity followed by standard gas mechanical Ventilation of the perfluorocarbon-filled lung,
Matthias Kohlhauer - One of the best experts on this subject based on the ideXlab platform.
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a new paradigm for lung conservative total Liquid Ventilation
EBioMedicine, 2020Co-Authors: Matthias Kohlhauer, Alice Hutin, Mathieu Nadeau, Fanny Lidouren, Emilie Boissady, Ludovic De Rochefort, Jerome Rambaud, Rosemarie Dubuisson, Genevieve Guillot, Pascaline PeyAbstract:Abstract Background Total Liquid Ventilation (TLV) of the lungs could provide radically new benefits in critically ill patients requiring lung lavage or ultra-fast cooling after cardiac arrest. It consists in an initial filling of the lungs with perfluorocarbons and subsequent tidal Ventilation using a dedicated Liquid ventilator. Here, we propose a new paradigm for a lung-conservative TLV using pulmonary volumes of perfluorocarbons below functional residual capacity (FRC). Methods and findings Using a dedicated technology, we showed that perfluorocarbon end-expiratory volumes could be maintained below expected FRC and lead to better respiratory recovery, preserved lung structure and accelerated evaporation of Liquid residues as compared to complete lung filling in piglets. Such TLV below FRC prevented volutrauma through preservation of alveolar recruitment reserve. When used with temperature-controlled perfluorocarbons, this lung-conservative approach provided neuroprotective ultra-fast cooling in a model of hypoxic-ischemic encephalopathy. The scale-up and automating of the technology confirmed that incomplete initial lung filling during TLV was beneficial in human adult-sized pigs, despite larger size and maturity of the lungs. Our results were confirmed in aged non-human primates, confirming the safety of this lung-conservative approach. Interpretation This study demonstrated that TLV with an accurate control of perfluorocarbon volume below FRC could provide the full potential of TLV in an innovative and safe manner. This constitutes a new paradigm through the tidal Liquid Ventilation of incompletely filled lungs, which strongly differs from the previously known TLV approach, opening promising perspectives for a safer clinical translation. Fund ANR (COOLIVENT), FRM (DBS20140930781), SATT IdfInnov (project 273).
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abstract 172 ultra fast cooling through total Liquid Ventilation is safe and feasible in non human primates
Circulation, 2019Co-Authors: Matthias Kohlhauer, Philippe Micheau, Bijan Ghaleh, Mathieu Nadeau, Fanny Lidouren, Emilie Boissady, Estelle Faucher, Renaud TissierAbstract:Introduction: Total Liquid Ventilation (TLV) with temperature-controlled perfluorocarbons (PFC) provides ultra-rapid and protective cooling in animal models of cardiac arrest. However, the ideal ve...
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abstract 19 ultra fast cooling induced by total Liquid Ventilation provides neuroprotection through a delay in the acute systemic inflammatory response after cardiac arrest in rabbits
Circulation, 2019Co-Authors: Emilie Boissady, Bijan Ghaleh, Matthias Kohlhauer, Fanny Lidouren, Renaud TissierAbstract:Introduction: Ultra-fast cooling with total Liquid Ventilation (TLV) is potently protective in animal models of cardiac arrest. Hypothesis: Here, we hypothesized that this protection involves a mit...
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abstract 201 neuroprotective effect of hypothermic total Liquid Ventilation in newborn piglets subjected to neonatal cardiac arrest
Circulation, 2018Co-Authors: Emilie Boissady, Alain Berdeaux, Philippe Micheau, Bijan Ghaleh, Matthias Kohlhauer, Fanny Lidouren, Nicolas Mongardon, Jerome Rambaud, Renaud TissierAbstract:Introduction: Hypothermic total Liquid Ventilation (TLV) has been shown to be highly protective in adult models of cardiac arrest. Hypothesis: TLV could also provide benefits through ultrafast cool...
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targeted temperature management with total Liquid Ventilation after ischemic spinal cord injury
The Annals of Thoracic Surgery, 2018Co-Authors: Nicolas Mongardon, Matthias Kohlhauer, Fanny Lidouren, Mariana BarrettoAbstract:Background Ischemic spinal cord injury is a devastating condition after aortic surgery. We determined whether ultrafast and short whole-body hypothermia provided by total Liquid Ventilation (TLV) attenuated lower limb paralysis after aortic cross-clamping with a targeted temperature management at 33°C versus 36°C. Methods Anesthetized rabbits were submitted to infrarenal aortic cross-clamping during 15 min. A control group (n = 7) was maintained at normothermia (38°C to 38.5°C) with conventional mechanical Ventilation. In TLV groups, TLV was started after reperfusion and maintained during 30 min with a target temperature at either 33°C or 36°C (TLV-33°C and TLV-36°C, respectively; n = 7 in each condition). After TLV, animals were resumed to conventional Ventilation. Hypothermia was maintained during 120 min, before rewarming and awakening. Hind limb motor function was assessed with modified Tarlov score at day 2 and infarct size in the spinal cord was determined using triphenyltetrazolium chloride staining. Results Target temperature was achieved within 20 minutes in the two TLV groups. At day 2, the modified Tarlov score was significantly lower in the control group, as compared with TLV-33°C and TLV-36°C groups (0.0 ± 0.0 versus 3.1 ± 0.7 and 2.6 ± 0.6, respectively). The infarct size of the spinal cord was also significantly higher in the control group compared with TLV-33°C and TLV-36°C groups (75% ± 10% versus 32% ± 7% and 28% ± 10%, respectively). Neither motor function nor infarct size differed significantly between TLV-33°C and TLV-36°C groups. Conclusions Ultrafast hypothermic TLV attenuates spinal cord injury when applied after ischemic insult. Neurological outcome was similar with targeted temperature management at either 33°C or 36°C.
Renaud Tissier - One of the best experts on this subject based on the ideXlab platform.
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abstract 172 ultra fast cooling through total Liquid Ventilation is safe and feasible in non human primates
Circulation, 2019Co-Authors: Matthias Kohlhauer, Philippe Micheau, Bijan Ghaleh, Mathieu Nadeau, Fanny Lidouren, Emilie Boissady, Estelle Faucher, Renaud TissierAbstract:Introduction: Total Liquid Ventilation (TLV) with temperature-controlled perfluorocarbons (PFC) provides ultra-rapid and protective cooling in animal models of cardiac arrest. However, the ideal ve...
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abstract 19 ultra fast cooling induced by total Liquid Ventilation provides neuroprotection through a delay in the acute systemic inflammatory response after cardiac arrest in rabbits
Circulation, 2019Co-Authors: Emilie Boissady, Bijan Ghaleh, Matthias Kohlhauer, Fanny Lidouren, Renaud TissierAbstract:Introduction: Ultra-fast cooling with total Liquid Ventilation (TLV) is potently protective in animal models of cardiac arrest. Hypothesis: Here, we hypothesized that this protection involves a mit...
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perflubron distribution during transition from gas to total Liquid Ventilation
Frontiers in Physiology, 2018Co-Authors: Michaël Sage, Philippe Micheau, Mathieu Nadeau, Renaud Tissier, Claire Berger, Symon Stowe, Andy Adler, Claudia Forandchoiniere, Sofia Marouan, Jeanpaul PraudAbstract:Total Liquid Ventilation (TLV) using perfluorocarbons has shown promising results for the management of neonatal respiratory distress. However, one important safety consideration for TLV is a better understanding of the early events during the transition to TLV, especially regarding the fate of residual air in the non-dependent-lung regions. Our objective was to assess perflubron distribution during transition to TLV using electrical impedance tomography, complemented by fluoroscopy, in a neonatal lamb model of induced surfactant deficiency. Eight lambs were anesthetized and ventilated in supine position. Surfactant deficit was induced by saline lung lavage. After deflation, lungs were filled with 25 ml/kg perflubron over 18 s, and TLV was initiated. Electrical impedance tomography data was recorded from electrodes placed around the chest, during the first 10 and at 120 min of TLV. Lung perfusion was also assessed using hypertonic saline injection during apnea. In addition, fluoroscopic sequences were recorded during initial lung filling with perfluorocarbons, then at 10 and 60 min of TLV. Twelve lambs were used as controls for histological comparisons. Transition to TLV involved a short period of increased total lung volume (p = 0.01) secondary to recruitment of the dependent lung regions. Histological analysis shows that TLV was protective of these same regions when compared to gas-ventilated lambs (p = 0.03). The non-dependent lung regions filled with perflubron over at least 10 min, without showing signs of overdistention. Tidal volume distribution was more homogenous in TLV than during the preceding gas Ventilation. Perflubron filling was associated with a non-significant increase in the anterior distribution of the blood perfusion signal, from 46 ± 17% to 53 ± 6% (p = 0.4). However, combined to the effects on Ventilation, TLV had an instantaneous effect on Ventilation-perfusion relationship (p = 0.03), suggesting better coupling. Conclusion: transition to TLV requires at least 10 min, and involves air evacuation or dissolution in perflubron, dependent lung recruitment and rapid Ventilation-perfusion coupling modifications. During that time interval, the total lung volume transiently increases. Considering the potential deleterious effect of high lung volumes, one must manage this transition phase with care and, we suggest using a real-time monitoring system such as electrical impedance tomography.
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abstract 201 neuroprotective effect of hypothermic total Liquid Ventilation in newborn piglets subjected to neonatal cardiac arrest
Circulation, 2018Co-Authors: Emilie Boissady, Alain Berdeaux, Philippe Micheau, Bijan Ghaleh, Matthias Kohlhauer, Fanny Lidouren, Nicolas Mongardon, Jerome Rambaud, Renaud TissierAbstract:Introduction: Hypothermic total Liquid Ventilation (TLV) has been shown to be highly protective in adult models of cardiac arrest. Hypothesis: TLV could also provide benefits through ultrafast cool...
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patient specific optimal cooling power command for hypothermia induction by Liquid Ventilation
Control Engineering Practice, 2018Co-Authors: Mathieu Nadeau, Hervé Walti, Renaud Tissier, Jeanyves Denaclara, Philippe MicheauAbstract:Abstract While it is known that total Liquid Ventilation can rapidly cool animal subjects and improve outcomes after cardiac arrest, the temperature control strategy of the Liquid ventilator for clinical use remains unknown. This work proposes to control the cooling power of the Liquid ventilator in two phases. The first phase consists in a null cooling power command in order to estimate cardiac output. During the second phase, the optimal cooling power command dedicated to the estimated cardiac output is sent to the cooling system. The simulated results in human adults allow predicting the cooling performances and the overall safety.
Robert H Bartlett - One of the best experts on this subject based on the ideXlab platform.
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effect of ventilatory variables on gas exchange and hemodynamics during total Liquid Ventilation in a rat model
Critical Care Medicine, 2003Co-Authors: Kenichi Matsuda, Shigeki Sawada, Robert H Bartlett, Ronald B. HirschlAbstract:OBJECTIVES: To investigate the settings necessary to achieve maximum gas exchange and pulmonary function while minimizing effects on cardiovascular hemodynamics during total Liquid Ventilation with a pressure-limited, time-cycled ventilator in a rat model. DESIGN: Prospective, randomized controlled animal study. SETTING: A university research laboratory. SUBJECTS: Male Sprague-Dawley rats (n = 48). INTERVENTIONS: All animals had a tracheostomy tube designed for total Liquid Ventilation placed under anesthesia. The carotid artery was cannulated for blood pressure monitoring and for assessing blood gas data. MEASUREMENTS AND MAIN RESULTS: Forty 492 +/- 33 g rats were assigned to one of four inspiratory/expiratory ratio groups (inspiratory/expiratory ratio of 1:2, 1:2.5, 1:3, and 1:4). Total Liquid Ventilation was performed with a pressure-limited, time-cycled total Liquid ventilator. Outcome measures were evaluated as a function of respiratory rate and included tidal volume, maximal alveolar Ventilation, inspiratory and expiratory mean arterial pressures, the difference of mean arterial pressure between the inspiratory and expiratory phase, static end-inspiratory/expiratory pressures, Paco(2), Pao(2), tidal volume + approximate expiratory reserve volume, and lung volume-induced suppression of mean arterial pressure. Maximal alveolar Ventilation increased and decreased in parabolic fashion as a function of respiratory rate and was maximal at rates of 4.3-6.8 breaths/min and high inspiratory/expiratory ratios that corroborated with optimal levels of Pao(2) and Paco(2). Lung overdistention occurred at high respiratory rates and high inspiratory/expiratory ratios. Deleterious effects were observed on the difference of mean arterial pressure between the inspiratory and expiratory phase during total Liquid Ventilation at low respiratory rates, apparently due to increased tidal volume, and on suppression of mean arterial pressure at high inspiratory/expiratory ratios and high respiratory rate apparently due to "auto-positive end-expiratory pressure." These effects were minimized in this model at respiratory rates >/=5.7 and Liquid Ventilation in rodents. A balance must be identified where gas exchange is optimal yet hemodynamics are least affected. In the specific system studied, an inspiratory/expiratory ratio of 1:2.5 and respiratory rate of 6.8 breaths/min appeared to provide optimal gas exchange while minimizing the effects on hemodynamics.
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prospective randomized controlled pilot study of partial Liquid Ventilation in adult acute respiratory distress syndrome
American Journal of Respiratory and Critical Care Medicine, 2002Co-Authors: Ronald B. Hirschl, Joseph B Zwischenberger, Herbert P Wiedemann, Martin Croce, Dennis C Gore, K E N Davis, Robert H BartlettAbstract:We evaluated the safety and efficacy of partial Liquid Ventilation (PLV) with perflubron in adult patients with acute lung injury and the acute respiratory distress syndrome (ARDS) in a multicenter, prospective, controlled, randomized exploratory clinical trial. Ninety adult patients with PaO2 /Fi O2 ratios > 60 and < 300 with ARDS for no more than 24 hours were randomized to receive PLV (n = 65) with administration of perflubron through an endotracheal tube sideport or conventional mechanical Ventilation (CMV, n = 25) for a maximum of five days. Although a significant reduction in progression to ARDS was noted among patients with PLV, no significant differences in the number of days free from the ventilator at 28 days (CMV = 6.7 ± 1.8, PLV = 6.3 ± 1.0 days, p = 0.85), the incidence of mortality (CMV = 36%, PLV = 42%, p = 0.63), or any pulmonary-related parameter were observed. During a post hoc subgroup analysis, significantly more rapid discontinuation of mechanical Ventilation (p = 0.045) and a trend t...
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the pulmonary and systemic distribution and elimination of perflubron from adult patients treated with partial Liquid Ventilation
Chest, 2001Co-Authors: Craig A Reickert, Robert H Bartlett, Ella A Kazerooni, Thomas Pranikoff, Michael C Overbeck, Kenneth D Massey, Ronald B. HirschlAbstract:Objective To assess the pulmonary and systemicdistribution and elimination of perflubron(C 8 F 17 Br 1 ; Liqui Vent; Alliance Pharmaceutical; San Diego, CA) during and following the period ofpartial Liquid Ventilation. Design Prospective phase, I and II clinical trial. Setting Adult surgical, ICU. Patients Eighteen adult patients(mean ± SEM age, 37.9 ± 3.4 years) with severe respiratoryfailure, some of whom required extracorporeal life support (72%), andwho were managed with partial Liquid Ventilation with perflubron. Interventions Perflubron was administered into thetrachea, and gas Ventilation of the perfluorocarbon-filled lung(partial Liquid Ventilation) was then performed. Additional doses wereadministered daily for from 1 to 7 days, with a median cumulative doseof 31 m, L/kg (range, 3 to 60 m, L/kg). Measurements andmain results Patient blood samples were evaluated by gaschromatography for serum perflubron levels. Sequential lateral andanteroposterior radiographs were assessed, using a 5-point ratingscale, for the degree of perflubron fill following the final dose. Samples of expired gas were collected, and the rate of loss ofperflubron in the expired gas was measured by gas chromatography. Meanserum perflubron levels increased to 0.16 ± 0.05 mg/dL at 24 hfollowing administration of the initial dose. A mean maximum level of0.26 ± 0.05 mg/dL of perflubron was present in the serum 24 hfollowing the administration of the last dose. This level slowlytrended downward to 0.18 ± 0.06 mg/dL over the ensuing 7 days(p = 0.281). Perflubron elimination via expired gas occurred at amean rate of 9.4 ± 3.0 m, L/h at 1 h, and 1.0 ± 0.4 m, L/h at48 h after the last dose (p = 0.012). By radiologic evaluation, perflubron was eliminated from the lungs progressively from4.2 ± 0.2 at the time of administration of the last dose, to2.8 ± 0.3 at 4 days later (p Conclusions Perflubron is eliminated ata maximum rate of 9.4 ± 3.0 m, L/h by evaporative loss from theairways and is retained in greater amounts in the dependent lungregions when compared to the nondependent lung regions. There is a lowbut measurable maximum blood concentration of 0.26 ± 0.05 mg/dL inpatients after perflubron administration, which did not decreasesignificantly after cessation of partial LiquidVentilation.
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partial Liquid Ventilation in adult patients with ards a multicenter phase i ii trial
Annals of Surgery, 1998Co-Authors: Ronald B. Hirschl, Robert H Bartlett, Steven A Conrad, Roger Kaiser, Joseph B Zwischenberger, Frank Mcl V Booth, Victor J CardenasAbstract:OBJECTIVE: To evaluate the safety and efficacy of partial Liquid Ventilation (PLV) in adult patients with the acute respiratory distress syndrome (ARDS). SUMMARY BACKGROUND DATA: Previous studies have evaluated gas exchange and the safety of PLV in adult patients with severe respiratory failure whose gas exchange was partially provided by extracorporeal life support (ECLS). This is the first experience with adult patients who were not on ECLS. METHODS: Intratracheal perflubron in a total dose of 30.1 +/- 7.1 ml/kg was administered over a period of 45 +/- 9 hours to nine adult patients with mean age = 49 +/- 4 years and mean PaO2/FiO2 ratio = 128 +/- 7 as part of a prospective, multicenter, phase I-II noncontrolled trial. RESULTS: Significant decreases in mean (A-a)DO2 (baseline = 430 +/- 47, 48 hour = 229 +/- 17, p = 0.0127 by ANOVA) and FiO2 (baseline = 0.82 +/- 0.08, 48 hour = 0.54 +/- 0.06, p = 0.025), along with an increase in mean SvO2 (baseline = 75 +/- 3, 48 hour = 85 +/- 2, p = 0.018 by ANOVA) were observed. No significant changes in pulmonary compliance or hemodynamic variables were noted. Seven of the nine patients in this study survived beyond 28 days after initiation of partial Liquid Ventilation whereas 5 patients survived to discharge. Three adverse events [hypoxia (2) and hyperbilirubinemia (1)] were determined to be severe in nature. CONCLUSIONS: These data suggest that PLV may be performed safely with few related severe adverse effects. Improvement in gas exchange was observed in this series of adult patients over the 48 hours after initiation of PLV.
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neutrophil accumulation is reduced during partial Liquid Ventilation
Critical Care Medicine, 1998Co-Authors: Danny M Colton, Kent J Johnson, Robert H Bartlett, Gerd O Till, Shay B Dean, Ronald B. HirschlAbstract:OBJECTIVE This study evaluates the ability of perflubron to inhibit pulmonary neutrophil accumulation during partial Liquid Ventilation (PLV) in the setting of acute lung injury. DESIGN Randomized, controlled, nonblinded study. SETTING Research laboratory at a university. SUBJECTS Male, Sprague-Dawley rats (n = 120, 506 +/- 42 g). INTERVENTIONS Animals were divided into eight groups (n = 15 in each group, of which n = 12 for myeloperoxidase content and n = 3 for histologic neutrophil counting): a) GV-CVF group, animals received gas Ventilation (GV) with the induction of lung injury using cobra venom factor (CVF); b) PLV-CVF group, animals received partial Liquid Ventilation before the induction of lung injury; c) PEEP-CVF group, animals received positive end-expiratory pressure (PEEP) before the administration of cobra venom factor; d) CVF-PLV group, animals received partial Liquid Ventilation after cobra venom factor; e) CVF-PEEP group, animals received PEEP after cobra venom factor; f) PLV only group, animals received partial Liquid Ventilation only; g) GV only group, animals received gas Ventilation only; and h) NVSBA group, nonventilated spontaneous breathing animals. MEASUREMENTS AND MAIN RESULTS After the experimental period, total lung myeloperoxidase content was significantly decreased in the PLV-CVF (0.29 +/- 0.08, p = .02) and PEEP-CVF (0.34 +/- 0.04, p = .01) groups when compared with the GV-CVF group (0.62 +/- 0.07). When compared with the GV-CVF group, a trend toward a reduction in myeloperoxidase was observed in the CVF-PLV (0.42 +/- 0.05, p = .07) and the CVF-PEEP (0.39 +/- 0.06, p = .07) groups. When compared with the cobra venom factor only group (GV-CVF 47 +/- 2 neutrophils/high-power field), reductions in neutrophil count were observed in all groups (neutrophils/high-power field): PLV-CVF (20 +/- 2, p = .009); PEEP-CVF (24 +/- 1, p = .01); CVF-PLV (30 +/- 2, p = .03); and CVF-PEEP (37 +/- 1, p = .04). CONCLUSION These data suggest that both partial Liquid Ventilation and PEEP result in a reduction in neutrophil accumulation in the setting of acute lung injury.
Fanny Lidouren - One of the best experts on this subject based on the ideXlab platform.
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a new paradigm for lung conservative total Liquid Ventilation
EBioMedicine, 2020Co-Authors: Matthias Kohlhauer, Alice Hutin, Mathieu Nadeau, Fanny Lidouren, Emilie Boissady, Ludovic De Rochefort, Jerome Rambaud, Rosemarie Dubuisson, Genevieve Guillot, Pascaline PeyAbstract:Abstract Background Total Liquid Ventilation (TLV) of the lungs could provide radically new benefits in critically ill patients requiring lung lavage or ultra-fast cooling after cardiac arrest. It consists in an initial filling of the lungs with perfluorocarbons and subsequent tidal Ventilation using a dedicated Liquid ventilator. Here, we propose a new paradigm for a lung-conservative TLV using pulmonary volumes of perfluorocarbons below functional residual capacity (FRC). Methods and findings Using a dedicated technology, we showed that perfluorocarbon end-expiratory volumes could be maintained below expected FRC and lead to better respiratory recovery, preserved lung structure and accelerated evaporation of Liquid residues as compared to complete lung filling in piglets. Such TLV below FRC prevented volutrauma through preservation of alveolar recruitment reserve. When used with temperature-controlled perfluorocarbons, this lung-conservative approach provided neuroprotective ultra-fast cooling in a model of hypoxic-ischemic encephalopathy. The scale-up and automating of the technology confirmed that incomplete initial lung filling during TLV was beneficial in human adult-sized pigs, despite larger size and maturity of the lungs. Our results were confirmed in aged non-human primates, confirming the safety of this lung-conservative approach. Interpretation This study demonstrated that TLV with an accurate control of perfluorocarbon volume below FRC could provide the full potential of TLV in an innovative and safe manner. This constitutes a new paradigm through the tidal Liquid Ventilation of incompletely filled lungs, which strongly differs from the previously known TLV approach, opening promising perspectives for a safer clinical translation. Fund ANR (COOLIVENT), FRM (DBS20140930781), SATT IdfInnov (project 273).
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abstract 172 ultra fast cooling through total Liquid Ventilation is safe and feasible in non human primates
Circulation, 2019Co-Authors: Matthias Kohlhauer, Philippe Micheau, Bijan Ghaleh, Mathieu Nadeau, Fanny Lidouren, Emilie Boissady, Estelle Faucher, Renaud TissierAbstract:Introduction: Total Liquid Ventilation (TLV) with temperature-controlled perfluorocarbons (PFC) provides ultra-rapid and protective cooling in animal models of cardiac arrest. However, the ideal ve...
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abstract 19 ultra fast cooling induced by total Liquid Ventilation provides neuroprotection through a delay in the acute systemic inflammatory response after cardiac arrest in rabbits
Circulation, 2019Co-Authors: Emilie Boissady, Bijan Ghaleh, Matthias Kohlhauer, Fanny Lidouren, Renaud TissierAbstract:Introduction: Ultra-fast cooling with total Liquid Ventilation (TLV) is potently protective in animal models of cardiac arrest. Hypothesis: Here, we hypothesized that this protection involves a mit...
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abstract 201 neuroprotective effect of hypothermic total Liquid Ventilation in newborn piglets subjected to neonatal cardiac arrest
Circulation, 2018Co-Authors: Emilie Boissady, Alain Berdeaux, Philippe Micheau, Bijan Ghaleh, Matthias Kohlhauer, Fanny Lidouren, Nicolas Mongardon, Jerome Rambaud, Renaud TissierAbstract:Introduction: Hypothermic total Liquid Ventilation (TLV) has been shown to be highly protective in adult models of cardiac arrest. Hypothesis: TLV could also provide benefits through ultrafast cool...
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targeted temperature management with total Liquid Ventilation after ischemic spinal cord injury
The Annals of Thoracic Surgery, 2018Co-Authors: Nicolas Mongardon, Matthias Kohlhauer, Fanny Lidouren, Mariana BarrettoAbstract:Background Ischemic spinal cord injury is a devastating condition after aortic surgery. We determined whether ultrafast and short whole-body hypothermia provided by total Liquid Ventilation (TLV) attenuated lower limb paralysis after aortic cross-clamping with a targeted temperature management at 33°C versus 36°C. Methods Anesthetized rabbits were submitted to infrarenal aortic cross-clamping during 15 min. A control group (n = 7) was maintained at normothermia (38°C to 38.5°C) with conventional mechanical Ventilation. In TLV groups, TLV was started after reperfusion and maintained during 30 min with a target temperature at either 33°C or 36°C (TLV-33°C and TLV-36°C, respectively; n = 7 in each condition). After TLV, animals were resumed to conventional Ventilation. Hypothermia was maintained during 120 min, before rewarming and awakening. Hind limb motor function was assessed with modified Tarlov score at day 2 and infarct size in the spinal cord was determined using triphenyltetrazolium chloride staining. Results Target temperature was achieved within 20 minutes in the two TLV groups. At day 2, the modified Tarlov score was significantly lower in the control group, as compared with TLV-33°C and TLV-36°C groups (0.0 ± 0.0 versus 3.1 ± 0.7 and 2.6 ± 0.6, respectively). The infarct size of the spinal cord was also significantly higher in the control group compared with TLV-33°C and TLV-36°C groups (75% ± 10% versus 32% ± 7% and 28% ± 10%, respectively). Neither motor function nor infarct size differed significantly between TLV-33°C and TLV-36°C groups. Conclusions Ultrafast hypothermic TLV attenuates spinal cord injury when applied after ischemic insult. Neurological outcome was similar with targeted temperature management at either 33°C or 36°C.