A liquid ventilator is similar to a

medical ventilator A ventilator is a piece of health technology, medical technology that provides mechanical ventilation by moving breathable air into and out of the lungs, to deliver breaths to a patient who is physically unable to breathe, or breathing insuffici ...

except that it should be able to ensure reliable total

liquid ventilation Liquid breathing is a form of respiration in which a normally air-breathing organism breathes an oxygen-rich liquid (such as a perfluorocarbon), rather than breathing air. By selecting a liquid that is capable of holding large amounts of oxy ...

with a breatheable liquid (a

perfluorocarbon Fluorocarbons are chemical compounds with carbon-fluorine bonds. Compounds that contain many C-F bonds often has distinctive properties, e.g., enhanced stability, volatility, and hydrophobicity. Fluorocarbons and their derivatives are commerci ...

). Liquid ventilators are prototypes that may have been used for

animal experimentation Animal testing, also known as animal experimentation, animal research, and ''in vivo'' testing, is the use of non-human animals in experiments that seek to control the variables that affect the behavior or biological system under study. This ...

s but experts recommend continued development of a liquid ventilator toward clinical applications.

Function and technology

Driving liquid

In total

(TLV), the lungs are completely filled with a

(PFC) liquid while the liquid ventilator renews the tidal volume of PFC. The liquid ventilator operates in mandatory mode: it must force the PFC in and out of the lungs with a pumping system. * During the inspiratory phase, the pump generates a positive driving pressure in the

trachea The trachea, also known as the windpipe, is a Cartilage, cartilaginous tube that connects the larynx to the bronchi of the lungs, allowing the passage of air, and so is present in almost all air-breathing animals with lungs. The trachea extends ...

to ensure the PFC insertion of the tidal volume. * During the expiratory phase, the pump generates a negative driving pressure in the

to ensure PFC withdrawal of the tidal volume. The pumping system is either a

peristaltic pump A peristaltic pump, also commonly known as a roller pump, is a type of positive displacement pump used for pumping a variety of fluids. The fluid is contained in a flexible tube fitted inside a circular pump casing. Most peristaltic pumps work t ...

(in the simplest liquid ventilators) or two

piston pump A piston pump is a type of positive displacement pump where the high-pressure seal reciprocates with the piston. Piston pumps can be used to move liquids or compress gases. They can operate over a wide range of pressures. High pressure operation ...

s (in the most advanced liquid ventilators). Because of the PFC

viscosity The viscosity of a fluid is a measure of its resistance to deformation at a given rate. For liquids, it corresponds to the informal concept of "thickness": for example, syrup has a higher viscosity than water. Viscosity quantifies the inte ...

, the

head loss Hydraulic head or piezometric head is a specific measurement of liquid pressure above a vertical datum., 410 pages. See pp. 43–44., 650 pages. See p. 22. It is usually measured as a liquid surface elevation, expressed in units of length, ...

in the airways requires a low negative driving pressure during the expiration phase that can collapse the airways. This is the choked flow phenomenon in TLV which compromises the minute ventilation and consequently the gas exchanges. To address this limitation, liquid ventilator integrates a control of the pumping system.

Controlling liquid ventilator

The introduction of computers in liquid ventilators to control the pumping system provides different control modes, monitoring and valuable data for decision making. The liquid ventilator is always volume-controlled because the specified

tidal volume Tidal volume (symbol VT or TV) is the volume of air moved into or out of the lungs during a normal breath. In a healthy, young human adult, tidal volume is approximately 500 ml per inspiration or 7 ml/kg of body mass. Mechanical vent ...

of PFC must be accurately delivered and retrieved. It is also pressure-limited because it must stop the expiratory or inspiratory phase when a too low, or a too large, driving pressure is detected. However, during the expiratory phase, the expiratory flow can be commanded by an

open-loop controller In control theory, an open-loop controller, also called a non-feedback controller, is a control system in which the control action is independent of the "process output", which is the process variable that is being controlled."Feedback and contr ...

or a

closed-loop controller Control theory is a field of mathematics that deals with the control of dynamical systems in engineered processes and machines. The objective is to develop a model or algorithm governing the application of system inputs to drive the system to a ...

: * when the expiratory flow is open-loop controlled, it is fast initially and slowing down progressively after to minimize the risk of collapse generation. * when the expiratory flow is closed-loop controlled, it is commanded in real-time to maintain a specified driving pressure. This is a pressure-regulated mode. Such approach automatically avoids collapse generation. Also, during the inspiratory phase, the volume-controlled mode is realized by open-loop or closed loop control of the PFC flow.

Oxygenating and heating liquid

The liquid ventilator removes

Carbon dioxide Carbon dioxide (chemical formula ) is a chemical compound made up of molecules that each have one carbon atom covalently double bonded to two oxygen atoms. It is found in the gas state at room temperature. In the air, carbon dioxide is transpar ...

(CO₂) from the PFC by saturating it with

oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as wel ...

(O₂) and medical

air The atmosphere of Earth is the layer of gases, known collectively as air, retained by Earth's gravity that surrounds the planet and forms its planetary atmosphere. The atmosphere of Earth protects life on Earth by creating pressure allowing for ...

. This procedure can be performed with either a membrane oxygenator (a technology used in

extracorporeal An extracorporeal is a medical procedure which is performed outside the body. Extracorporeal devices are the artificial organs that remain outside the body while treating a patient. Extracorporeal devices are useful in hemodialysis and cardiac surg ...

oxygenators) or a bubble oxygenator. The liquid ventilator heats the PFC to body temperature. This is performed with a

heat exchanger A heat exchanger is a system used to transfer heat between a source and a working fluid. Heat exchangers are used in both cooling and heating processes. The fluids may be separated by a solid wall to prevent mixing or they may be in direct contac ...

connected to the oxygenator or with dedicated heaters integrated in the oxygenator. The oxygenator and the heater produce PFC vapor which is recuperated with a condenser in order to limit the evaporation loss (the PFC is a

greenhouse gas A greenhouse gas (GHG or GhG) is a gas that Absorption (electromagnetic radiation), absorbs and Emission (electromagnetic radiation), emits radiant energy within the thermal infrared range, causing the greenhouse effect. The primary greenhouse ...

Example

An example of a liquid ventilator is the Inolivent-4. It is composed of two independent piston pumps and integrated unit allowing for oxygenation of PFC, temperature control, and recovery of evaporated PFC. This liquid ventilator also includes volume and pressure control strategies to optimize the ventilatory cycle: it performs a ''pressure-regulated volume-controlled'' ventilation mode. It is designed for experimental research on animal models weighing between 0.5 kg to 9 kg. A typical cycle is composed of four steps : # Inspiratory pump inserts a volume of PFC in the lungs (valve 1 open, valve 2 closed), and the expiratory pump pushes PFC in the oxygenator via the filter (valve 3 closed, valve 4 open). # During the inspiratory pause (all valves are closed), the lung volume is at its maximal value. The measured pressure is the Positive End-Inspiratory Pressure (PEIP). # Expiratory pump retrieves a volume of PFC in the lungs (valve 3 open, valve 4 closed), and the inspiratory pump draws PFC from the reservoir (valve 1 closed, valve 2 open). # During the expiratory pause (all valves are closed), the lung volume is at its minimal value. The measured pressure is the Positive End-expiratory Pressure (PEEP).

Potential applications

Studies have shown both the efficacy and safety of liquid ventilation in normal, mature and immature newborn lungs. Overall, liquid ventilation improves gas exchange and lung compliance and prevents the lungs against ventilation-induced lung injury.

Respiratory support

Studies suggest clear benefits of liquid ventilation in

acute respiratory distress syndrome Acute respiratory distress syndrome (ARDS) is a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. Symptoms include shortness of breath (dyspnea), rapid breathing (tachypnea), and bluish skin colo ...

(ARDS). For example, total liquid ventilation could be used for

newborns An infant or baby is the very young offspring of human beings. ''Infant'' (from the Latin word ''infans'', meaning 'unable to speak' or 'speechless') is a formal or specialised synonym for the common term ''baby''. The terms may also be used to ...

with severe neonatal respiratory distress syndrome in which conventional treatment has failed. Typical cases are late

preterm Preterm birth, also known as premature birth, is the birth of a baby at fewer than 37 weeks gestational age, as opposed to full-term delivery at approximately 40 weeks. Extreme preterm is less than 28 weeks, very early preterm birth is between 2 ...

newborns who have an increased risk of

intracranial hemorrhage Intracranial hemorrhage (ICH), also known as intracranial bleed, is bleeding within the skull. Subtypes are intracerebral bleeds ( intraventricular bleeds and intraparenchymal bleeds), subarachnoid bleeds, epidural bleeds, and subdural bleeds. ...

and for whom their small vessel size poses technical limitations for

Extracorporeal membrane oxygenation Extracorporeal membrane oxygenation (ECMO), also known as extracorporeal life support (ECLS), is an extracorporeal technique of providing prolonged cardiac and respiratory support to persons whose heart and lungs are unable to provide an adequat ...

(ECMO).

Therapeutic lung lavage

Liquid ventilator can perform therapeutic

lung lavage Bronchoalveolar lavage (BAL) (also known as bronchoalveolar washing) is a diagnostic method of the lower respiratory system in which a bronchoscope is passed through the mouth or nose into an appropriate airway in the lungs, with a measured amou ...

, the washout of endogenous and exogenous debris from the lungs, without suspension of ventilation support (without

apnea Apnea, BrE: apnoea, is the temporal cessation of breathing. During apnea, there is no movement of the muscles of inhalation, and the volume of the lungs initially remains unchanged. Depending on how blocked the airways are ( patency), there ...

). For example, literature data suggest a radical change in the treatment of

meconium aspiration syndrome Meconium aspiration syndrome (MAS) also known as neonatal aspiration of meconium is a medical condition affecting newborn infants. It describes the spectrum of disorders and pathophysiology of newborns born in meconium-stained amniotic fluid (MSAF ...

(MAS) by considering the use of a liquid ventilator. The demonstration of its efficacy was performed in the neonatal lamb..

Therapeutic hypothermia with rapid cooling

The liquid ventilator with advanced control temperature of PFC allows the rapid cooling of the body. Consequently,

therapeutic hypothermia Targeted temperature management (TTM) previously known as therapeutic hypothermia or protective hypothermia is an active treatment that tries to achieve and maintain a specific body temperature in a person for a specific duration of time in an e ...

is an expected clinical application. For example, studies present that rapid cooling instituted by TLV can improve cardiac and mitochondrial function or can induce favorable neurological and cardiac outcomes after cardiac arrest in rabbits.

References

External links

* Research group Inoliven

*

{{Intensive care medicine Respiratory therapy Medical pumps de:Flüssigkeitsbeatmung fr:Respirateur liquidien