A new paradigm for lung-conservative total liquid ventilation.

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).

Gas transfer model to design a ventilator for neonatal total liquid ventilation.

The study was aimed to optimize the gas transfer in an innovative ventilator for neonatal Total Liquid Ventilation (TLV) that integrates the pumping and oxygenation functions in a non-volumetric pulsatile device made of parallel flat silicone membranes. A computational approach was adopted to evaluate oxygen (O2) and carbon dioxide (CO2) exchanges between the liquid perfluorocarbon (PFC) and the oxygenating gas, as a function of the geometrical parameter of the device. A 2D semi-empirical model was implemented to this purpose using Comsol Multiphysics to study both the fluid dynamics and the gas exchange in the ventilator. Experimental gas exchanges measured with a preliminary prototype were compared to the simulation outcomes to prove the model reliability. Different device configurations were modeled to identify the optimal design able to guarantee the desired gas transfer. Good agreement between experimental and simulation outcomes was obtained, validating the model. The optimal configuration, able to achieve the desired gas exchange (ΔpCO2 = 16.5 mmHg and ΔpO2 = 69 mmHg), is a device comprising 40 modules, 300 mm in length (total exchange area = 2.28 m(2)). With this configuration gas transfer performance is satisfactory for all the simulated settings, proving good adaptability of the device.

Total liquid ventilation offers ultra-fast and whole-body cooling in large animals in physiological conditions and during cardiac arrest.

INTRODUCTION: Total liquid ventilation (TLV) can cool down the entire body within 10-15 min in small animals. Our goal was to determine whether it could also induce ultra-fast and whole-body cooling in large animals using a specifically dedicated liquid ventilator. Cooling efficiency was evaluated under physiological conditions (beating-heart) and during cardiac arrest with automated chest compressions (CC, intra-arrest). METHODS: In a first set of experiments, beating-heart pigs were randomly submitted to conventional mechanical ventilation or hypothermic TLV with perfluoro-N-octane (between 15 and 32 °C). In a second set of experiments, pigs were submitted to ventricular fibrillation and CC. One group underwent continuous CC with asynchronous conventional ventilation (Control group). The other group was switched to TLV while pursuing CC for the investigation of cooling capacities and potential effects on cardiac massage efficiency. RESULTS: Under physiological conditions, TLV significantly decreased the entire body temperatures below 34 °C within only 10 min. As examples, cooling rates averaged 0.54 and 0.94 °C/min in rectum and esophageous, respectively. During cardiac arrest, TLV did not alter CC efficiency and cooled the entire body below 34 °C within 20 min, the low-flow period slowing cooling during CC. CONCLUSION: Using a specifically designed liquid ventilator, TLV induced a very rapid cooling of the entire body in large animals. This was confirmed in both physiological conditions and during cardiac arrest with CC. TLV could be relevant for ultra-rapid cooling independently of body weight.

Establishment of a total liquid ventilation system using saline-based oxygen micro/nano-bubble dispersions in rats.

Micro/nano-bubbles are practical nanomaterials designed to increase the gas content in liquids. We attempted to use oxygen micro/nano-bubble dispersions as an oxygen-rich liquid as a means for total liquid ventilation. To determine the oxygen content in the bubble dispersion, a new method based on a spectrophotometric change between oxy- and deoxy-hemoglobin was established. The oxygen micro/nano-bubble dispersion was supplied to an experimental total ventilation liquid in anesthetic rats. Though the amount of dissolving oxygen was as low as 6 mg/L in physiological saline, the oxygen content in the oxygen micro/nano-bubble dispersion was increased to 45 mg/L. The positive correlation between the oxygen content and the life-saving time under liquid ventilation clearly indicates that the life-saving time is prolonged by increasing the oxygen content in the oxygen micro/nano-bubble dispersion. This is the first report indicating that the oxygen micro/nano-bubbles containing a sufficient amount of oxygen are useful in producing oxygen-rich liquid for the process of liquid ventilation.

Core body temperature control by total liquid ventilation using a virtual lung temperature sensor.

In total liquid ventilation (TLV), the lungs are filled with a breathable liquid perfluorocarbon (PFC) while a liquid ventilator ensures proper gas exchange by renewal of a tidal volume of oxygenated and temperature-controlled PFC. Given the rapid changes in core body temperature generated by TLV using the lung has a heat exchanger, it is crucial to have accurate and reliable core body temperature monitoring and control. This study presents the design of a virtual lung temperature sensor to control core temperature. In the first step, the virtual sensor, using expired PFC to estimate lung temperature noninvasively, was validated both in vitro and in vivo. The virtual lung temperature was then used to rapidly and automatically control core temperature. Experimentations were performed using the Inolivent-5.0 liquid ventilator with a feedback controller to modulate inspired PFC temperature thereby controlling lung temperature. The in vivo experimental protocol was conducted on seven newborn lambs instrumented with temperature sensors at the femoral artery, pulmonary artery, oesophagus, right ear drum, and rectum. After stabilization in conventional mechanical ventilation, TLV was initiated with fast hypothermia induction, followed by slow posthypothermic rewarming for 1 h, then by fast rewarming to normothermia and finally a second fast hypothermia induction phase. Results showed that the virtual lung temperature was able to provide an accurate estimation of systemic arterial temperature. Results also demonstrate that TLV can precisely control core body temperature and can be favorably compared to extracorporeal circulation in terms of speed.

Total liquid ventilation: a new approach to improve 3D OCT image quality of alveolar structures in lung tissue.

Little is known about mechanical processes of alveolar tissue during mechanical ventilation. Optical coherence tomography (OCT) as a three-dimensional and high-resolution imaging modality can be used to visualize subpleural alveoli during artificial ventilation. The quality of OCT images can be increased by matching the refractive index inside the alveoli to the one of tissue via liquid-filling. Thereby, scattering loss can be decreased and higher penetration depth and tissue contrast can be achieved. We show the liquid-filling of alveolar structures verified by optical coherence tomography and intravital microscopy (IVM) and the advantages of index matching for OCT imaging of subpleural alveoli in a mouse model using a custom-made liquid ventilator.

Measurement of fractional order model parameters of respiratory mechanical impedance in total liquid ventilation.

This study presents a methodology for applying the forced-oscillation technique in total liquid ventilation. It mainly consists of applying sinusoidal volumetric excitation to the respiratory system, and determining the transfer function between the delivered flow rate and resulting airway pressure. The investigated frequency range was f ∈ [0.05, 4] Hz at a constant flow amplitude of 7.5 mL/s. The five parameters of a fractional order lung model, the existing "5-parameter constant-phase model," were identified based on measured impedance spectra. The identification method was validated in silico on computer-generated datasets and the overall process was validated in vitro on a simplified single-compartment mechanical lung model. In vivo data on ten newborn lambs suggested the appropriateness of a fractional-order compliance term to the mechanical impedance to describe the low-frequency behavior of the lung, but did not demonstrate the relevance of a fractional-order inertance term. Typical respiratory system frequency response is presented together with statistical data of the measured in vivo impedance model parameters. This information will be useful for both the design of a robust pressure controller for total liquid ventilators and the monitoring of the patient's respiratory parameters during total liquid ventilation treatment.

Total liquid ventilation provides superior respiratory support to conventional mechanical ventilation in a large animal model of severe respiratory failure.

Total liquid ventilation (TLV) has the potential to provide respiratory support superior to conventional mechanical ventilation (CMV) in the acute respiratory distress syndrome (ARDS). However, laboratory studies are limited to trials in small animals for no longer than 4 hours. The objective of this study was to compare TLV and CMV in a large animal model of ARDS for 24 hours. Ten sheep weighing 53 ± 4 (SD) kg were anesthetized and ventilated with 100% oxygen. Oleic acid was injected into the pulmonary circulation until PaO2:FiO2 ≤ 60 mm Hg, followed by transition to a protective CMV protocol (n = 5) or TLV (n = 5) for 24 hours. Pathophysiology was recorded, and the lungs were harvested for histological analysis. Animals treated with CMV became progressively hypoxic and hypercarbic despite maximum ventilatory support. Sheep treated with TLV maintained normal blood gases with statistically greater PO2 (p < 10(-9)) and lower PCO2 (p < 10(-3)) than the CMV group. Survival at 24 hours in the TLV and CMV groups were 100% and 40%, respectively (p < 0.05). Thus, TLV provided gas exchange superior to CMV in this laboratory model of severe ARDS.

A regulator for pressure-controlled total-liquid ventilation.

Total-liquid ventilation (TLV) is an innovative experimental method of mechanical-assisted ventilation in which lungs are totally filled and then ventilated with a tidal volume of perfluorochemical liquid by using a dedicated liquid ventilator. Such a novel medical device must resemble other conventional ventilators: it must be able to conduct controlled-pressure ventilation. The objective was to design a robust controller to perform pressure-regulated expiratory flow and to implement it on our latest liquid-ventilator prototype (Inolivent-4). Numerical simulations, in vitro experiments, and in vivo experiments in five healthy term newborn lambs have demonstrated that it was efficient to generate expiratory flows while avoiding collapses. Moreover, the in vivo results have demonstrated that our liquid ventilator can maintain adequate gas exchange, normal acid-base equilibrium, and achieve greater minute ventilation, better oxygenation and CO2 extraction, while nearing flow limits. Hence, it is our suggestion to perform pressure-controlled ventilation during expiration with minute ventilation equal or superior to 140 mL x min(-1) x kg(-1) in order to ensure PaCO2 below 55 mmHg. From a clinician's point of view, pressure-controlled ventilation greatly simplifies the use of the liquid ventilator, which will certainly facilitate its introduction in intensive care units for clinical applications.

A microprocessor-controlled tracheal insufflation-assisted total liquid ventilation system.

A prototype time cycled, constant volume, closed circuit perfluorocarbon (PFC) total liquid ventilator system is described. The system utilizes microcontroller-driven display and master control boards, gear motor pumps, and three-way solenoid valves to direct flow. A constant tidal volume and functional residual capacity (FRC) are maintained with feedback control using end-expiratory and end-inspiratory stop-flow pressures. The system can also provide a unique continuous perfusion (bias flow, tracheal insufflation) through one lumen of a double-lumen endotracheal catheter to increase washout of dead space liquid. FRC and arterial blood gases were maintained during ventilation with Rimar 101 PFC over 2-3 h in normal piglets and piglets with simulated pulmonary edema induced by instillation of albumin solution. Addition of tracheal insufflation flow significantly improved the blood gases and enhanced clearance of instilled albumin solution during simulated edema.

Clinical design functions: round table discussions on the bioengineering of liquid ventilators.

During the 6th International Symposium on Perfluorocarbon Application and Liquid Ventilation, a round table discussion on bioengineering was held in which different experts shared their opinions and experiences about the use of a total liquid ventilator design for clinical applications. To structure the discussion, all experts were invited to contribute their knowledge within the context of three matrixes related to the liquid ventilators: 1) function and technology, 2) ventilation modes, and 3) risk analyses. The outcome of this international conference recommends continued development of a total liquid ventilator toward clinical applications.

The use of chilled condensers for the recovery of perfluorocarbon liquid in an experimental model of perfluorocarbon vapour loss during neonatal partial liquid ventilation.

BACKGROUND: Perfluorocarbon (PFC) vapour in the expired gases during partial liquid ventilation should be prevented from entering the atmosphere and recovered for potential reuse. This study aimed to determine how much PFC liquid could be recovered using a conventional humidified neonatal ventilator with chilled condensers in place of the usual expiratory ventilator circuit and whether PFC liquid could be recovered when using the chilled condensers at the ventilator exhaust outlet. METHODS: Using a model lung, perfluorocarbon vapour loss during humidified partial liquid ventilation of a 3.5 kg infant was approximated. For each test 30 mL of FC-77 was infused into the model lung. Condensers were placed in the expiratory limb of the ventilator circuit and the amounts of PFC (FC-77) and water recovered were measured five times. This was repeated with the condensers placed at the ventilator exhaust outlet. RESULTS: When the condensers were used as the expiratory limb, the mean (+/- SD) volume of FC77 recovered was 16.4 mL (+/- 0.18 mL). When the condensers were connected to the ventilator exhaust outlet the mean (+/- SD) volume of FC-77 recovered was 7.6 mL (+/- 1.14 mL). The volume of FC-77 recovered was significantly higher when the condenser was used as an expiratory limb. CONCLUSION: Using two series connected condensers in the ventilator expiratory line 55% of PFC liquid (FC-77) can be recovered during partial liquid ventilation without altering the function of the of the ventilator circuit. This volume of PFC recovered was just over twice that recovered with the condensers connected to the ventilator exhaust outlet.

A prototype of volume-controlled tidal liquid ventilator using independent piston pumps.

Liquid ventilation using perfluorochemicals (PFC) offers clear theoretical advantages over gas ventilation, such as decreased lung damage, recruitment of collapsed lung regions, and lavage of inflammatory debris. We present a total liquid ventilator designed to ventilate patients with completely filled lungs with a tidal volume of PFC liquid. The two independent piston pumps are volume controlled and pressure limited. Measurable pumping errors are corrected by a programmed supervisor module, which modifies the inserted or withdrawn volume. Pump independence also allows easy functional residual capacity modifications during ventilation. The bubble gas exchanger is divided into two sections such that the PFC exiting the lungs is not in contact with the PFC entering the lungs. The heating system is incorporated into the metallic base of the gas exchanger, and a heat-sink-type condenser is placed on top of the exchanger to retrieve PFC vapors. The prototype was tested on 5 healthy term newborn lambs (<5 days old). The results demonstrate the efficiency and safety of the prototype in maintaining adequate gas exchange, normal acido-basis equilibrium, and cardiovascular stability during a short, 2-hour total liquid ventilator. Airway pressure, lung volume, and ventilation scheme were maintained in the targeted range.

An advanced expiratory circuit for the recovery of perfluorocarbon liquid from non-saturated perfluorocarbon vapour during partial liquid ventilation: an experimental model.

BACKGROUND: The loss of perfluorocarbon (PFC) vapour in the expired gases during partial liquid ventilation should be minimized both to prevent perfluorocarbon vapour entering the atmosphere and to re-use the recovered PFC liquid. Using a substantially modified design of our previously described condenser, we aimed to determine how much perfluorocarbon liquid could be recovered from gases containing PFC and water vapour, at concentrations found during partial liquid ventilation, and to determine if the amount recovered differed with background flow rate (at flow rates suitable for use in neonates). METHODS: The expiratory line of a standard ventilator circuit set-up was mimicked, with the addition of two condensers. Perfluorocarbon (30 mL of FC-77) and water vapour, at concentrations found during partial liquid ventilation, were passed through the circuit at a number of flow rates and the percentage recovery of the liquids measured. RESULTS: From 14.2 mL (47%) to 27.3 mL (91%) of the infused 30 mL of FC-77 was recovered at the flow rates studied. Significantly higher FC-77 recovery was obtained at lower flow rates (ANOVA with Bonferroni's multiple comparison test, p < 0.0001). As a percentage of the theoretical maximum recovery, 64 to 95% of the FC-77 was recovered. Statistically significantly less FC-77 was recovered at 5 Lmin(-1) (ANOVA with Bonferroni's multiple comparison test, p < 0.0001). Amounts of perfluorocarbon vapour recovered were 47%, 50%, 81% and 91% at flow rates of 10, 5, 2 and 1 Lmin(-1), respectively. CONCLUSION: Using two condensers in series 47% to 91% of perfluorocarbon liquid can be recovered, from gases containing perfluorocarbon and water vapour, at concentrations found during partial liquid ventilation.

A mechanical model lung for hydraulic testing of total liquid ventilation circuits.

A new model lung (ML), designed to reproduce the tracheal pressure vs. fluid flow relationship in animals undergoing total liquid ventilation (TLV) trials, was developed to be used as a mock bench test for neonatal TLV circuits. The ML is based on a linear inertance-resistance-compliance (LRC) lumped-parameter model of the respiratory system with different resistance values for inspiration (R insp ) or expiration (R exp ). The resistant element was set up using polypropylene hollow fibres packed inside a tube. A passive one-way valve was used to control the resistance cross-section area provided for the liquid to generate different values for R insp or R exp , each adjustable by regulating the active length of the respective fibre pack. The compliant element consists of a cylindrical column reservoir, in which bars of different diameter were inserted to adjust compliance (C). The inertial phenomena occurring in the central airways during TLV were reproduced by specifically dimensioned conduits into which the endotracheal tube connecting the TLV circuit to the ML was inserted. A number of elements with different inertances (L) were used to simulate different sized airways. A linear pressure drop-to-flow rate relationship was obtained for flow rates up to 5 l/min. The measured C (0.8 to 1.3 mL cmH2O (-1) kg(-1)), R insp (90 to 850 cmH2O s l(-1)), and R exp (50 to 400 cmH2O s l(-1)) were in agreement with the literature concerning animals weighing from 1 to 12 kg. Moreover, features observed in data acquired during in vivo TLV sessions, such as pressure oscillations due to fluid inertia in the upper airways, were similarly obtained in vitro thanks to the inertial element in the ML.

A prototype of a liquid ventilator using a novel hollow-fiber oxygenator in a rabbit model.

OBJECTIVE: A functional total liquid ventilator should be simple in design to minimize operating errors and have a low priming volume to minimize the amount of perfluorocarbon needed. Closed system circuits using a membrane oxygenator have partially met these requirements but have high resistance to perfluorocarbon flow and high priming volume. To further this goal, a single piston prototype ventilator with a low priming volume and a new high-efficiency hollow-fiber oxygenator in a circuit with a check valve flow control system was developed. DESIGN: Prospective, controlled animal laboratory study. SETTING: Research facility at a university medical center. SUBJECTS: Seven anesthetized, paralyzed, normal New Zealand rabbits INTERVENTIONS: The prototype oxygenator, consisting of cross-wound silicone hollow fibers with a surface area of 1.5 m2 with a priming volume of 190 mL, was tested in a bench-top model followed by an in vivo rabbit model. Total liquid ventilation was performed for 3 hrs with 20 mL.kg(-1) initial fill volume, 17.5-20 mL.kg(-1) tidal volume, respiratory rate of 5 breaths/min, inspiratory/expiratory ratio 1:2, and countercurrent sweep gas of 100% oxygen. MEASUREMENTS AND MAIN RESULTS: Bench top experiments demonstrated 66-81% elimination of CO2 and 0.64-0.76 mL.min(-1) loss of perfluorocarbon across the fibers. No significant changes in PaCO2 and PaO2 were observed. Dynamic airway pressures were in a safe range in which ventilator lung injury or airway closure was unlikely (3.6 +/- 0.5 and -7.8 +/- 0.3 cm H2O, respectively, for mean peak inspiratory pressure and mean end expiratory pressure). No leakage of perfluorocarbon was noted in the new silicone fiber gas exchange device. Estimated in vivo perfluorocarbon loss from the device was 1.2 mL.min(-1). CONCLUSIONS: These data demonstrate the ability of this novel single-piston, nonporous hollow silicone fiber oxygenator to adequately support gas exchange, allowing successful performance of total liquid ventilation.

A novel expiratory circuit for recovery of perfluorocarbon liquid during partial liquid ventilation.

OBJECTIVE: To determine whether perfluorocarbon liquid can be condensed from gases containing perfluorocarbon vapour and whether the amount recovered varies with background flow rate. DESIGN AND SETTING: Bench-top experimental study in a neonatal laboratory. INTERVENTIONS: The expiratory limb of a standard ventilator circuit set-up was mimicked, with the addition of a chilled water jacket (Liebig) condenser. Perfluorocarbon vapour was passed through the circuit at a number of flow rates. MEASUREMENTS AND RESULTS: Perfluorocarbon vapour was passed through the circuit and the percentage recovery of liquid measured. More than 60% of the perfluorocarbon vapour was recovered at all flow rates (1, 2, 5 and 10 l/min), with significantly higher recovery obtained (up to 74%) at low flow rates (1 l/min). CONCLUSIONS: Using a simple condenser, more than 60% of perfluorocarbon liquid can be recovered without altering the function of an expiratory limb of a ventilator circuit.

Volume controlled apparatus for neonatal tidal liquid ventilation.

Conventional gas ventilation is often unsuccessful for premature neonatal patients suffering from respiratory distress syndrome (RDS). For such patients, liquid ventilation (LV) with perfluorocarbon (PFC) liquids has been proposed. By eliminating the air-liquid interface in saccules (the premature gas exchange structures), where scarce or absent surfactant production exists, pulmonary instability is avoided, lung compliance is improved, and atelectatic saccules are recruited, ultimately lowering the saccular pressure. Tidal LV involves administrating a liquid tidal volume to the patient at each respiratory cycle, and therefore requires a dedicated circuital setup to deliver, withdraw, and refresh the PFC during the treatment. We have developed a prototype liquid breathing system (LBS). The apparatus comprises two subcircuits managed by a personal computer based control system. The ventilation subcircuit performs inspiration/expiration with two sets of peristaltic pumps. A system to evaluate the true inspired/expired volumes was devised that consists of two reservoirs equipped with pressure transducers measuring the hydraulic head of the fluid therein. Volume accuracy was +/- 0.3 ml. The refresh subcircuit properly processes the PFC by performing filtration (DFA, Pall, NY), oxygenation, CO2 scavenge, and heat exchange (SciMed 2500, Life Systems, MN). The new apparatus has been used in preliminary animal tests on five newborn mini pigs with induced acquired RDS. The PFC used was RM-101 (Miteni, Milano, Italy). The animals were successfully supported for 4 hours each. Mean arterial O2 pressure was 131.4 mm Hg (range 79.0-184.2), and mean arterial CO2 pressure was 64.8 mm Hg (range 60.0-73.4).

Rapid (0.5 degrees C/min) minimally invasive induction of hypothermia using cold perfluorochemical lung lavage in dogs.

OBJECTIVE: Demonstrate minimally invasive rapid body core and brain cooling in a large animal model. DESIGN: Prospective controlled animal trial. SETTING: Private research laboratory. SUBJECTS: Adult dogs, anesthetized, mechanically ventilated. INTERVENTIONS: Cyclic lung lavage with FC-75 perfluorochemical (PFC) was administered through a dual-lumen endotracheal system in the new technique of 'gas/liquid ventilation' (GLV). In Trial-I, lavage volume (V-lav) was 19 ml/kg, infused and withdrawn over a cycle period (tc) of 37 s. (effective lavage rate V'-lav=31 ml/kg/min.) Five dogs received cold (approximately 4 degrees C) PFC; two controls received isothermic PFC. In Trial-II, five dogs received GLV at V-lav=8.8 ml/kg, tc=16 s, V'-lav=36 ml/kg/min. MEASUREMENTS AND MAIN RESULTS: Trial-I tympanic temperature change was -3.7+/-0.6 degrees C (SD) at 7.5 min, reaching -7.3+/-0.6 degrees C at 18 min. Heat transfer efficiency was 60%. In Trial-II, efficiency fell to 40%, but heat-exchange dead space (VDtherm) remained constant. Lung/blood thermal equilibration half-time was <8 s. Isothermic GLV caused hypercapnia unless gas ventilation was increased. At necropsy after euthanasia (24 h), modest lung injury was seen. CONCLUSIONS: GLV cooling times are comparable to those for cardiopulmonary bypass. Heat and CO(2) removal can be independently controlled by changing the mix of lavage and gas ventilation. Due to VDtherm of approximately 6 ml/kg in dogs, efficient V-lav is >18 ml/kg. GLV cooling power appears more limited by PFC flows than lavage residence times. Concurrent gas ventilation may mitigate heat-diffusion limitations in liquid breathing, perhaps via bubble-induced turbulence.

Development of a time-cycled volume-controlled pressure-limited respirator and lung mechanics system for total liquid ventilation.

Total liquid ventilation can support gas exchange in animal models of lung injury. Clinical application awaits further technical improvements and performance verification. Our aim was to develop a liquid ventilator, able to deliver accurate tidal volumes, and a computerized system for measuring lung mechanics. The computer-assisted, piston-driven respirator controlled ventilatory parameters that were displayed and modified on a real-time basis. Pressure and temperature transducers along with a lineal displacement controller provided the necessary signals to calculate lung mechanics. Ten newborn lambs (<6 days old) with respiratory failure induced by lung lavage, were monitored using the system. Electromechanical, hydraulic, and data acquisition/analysis components of the ventilator were developed and tested in animals with respiratory failure. All pulmonary signals were collected synchronized in time, displayed in real-time, and archived on digital media. The total mean error (due to transducers, analog-to-digital conversion, amplifiers, etc.) was less than 5% compared with calibrated signals. Components (tubing, pistons, etc.) in contact with exchange fluids were developed so that they could be readily switched, a feature that will be important in clinical settings. Improvements in gas exchange and lung mechanics were observed during liquid ventilation, without impairment of cardiovascular profiles. The total liquid ventilator maintained accurate control of tidal volumes and the sequencing of inspiration/expiration. The computerized system demonstrated its ability to monitor in vivo lung mechanics, providing valuable data for early decision making.