This document discusses partial liquid ventilation, a technique where the lungs are filled with an oxygenated perfluorochemical liquid at the functional residual capacity during mechanical ventilation. Two key types are discussed: total liquid ventilation where the entire lung is filled with liquid, and partial liquid ventilation where only the FRC is filled. While theoretical advantages include improved oxygenation and recruitment of collapsed alveoli, clinical trials have shown no clear benefits over conventional ventilation and some increased risks. As a result, liquid ventilation is not currently recommended for routine clinical use.

1. PARTIAL LIQUID
VENTILATION
-DR. PRAPULLA CHANDRA

2. • INTRODUCTION
• HISTORY
• PERFLUOROCARBONS
• PHYSICAL PROPERTIES
• PHARMACOKINETICS
• TYPES & TECHNIQUE
• PHYSIOLOGY
• INDICATIONS
• ADVERSE EFFECTS
• CLINICAL OUTCOME
• SUMMARY &RECOMMENDATIONS

3. INTRODUCTION
• Liquid ventilation is a technique of mechanical
ventilation in which the lungs are insufflated with an
oxygenated perfluorochemical liquid rather than an
oxygen containing gas mixture.

4. HISTORY
• The use of fluids such as saline, silicone oils and perfluorocarbons
(PFC) for breathing has been under investigation for many decades.
• In 1963, Clark & Gollan first demonstrated that spontaneously
breathing mice could survive when submerged in PFC liquid.
• In 1970, Moskowitz, presented a demand regulated ventilator that used
PFC instead of gas.
• 1989 marked the first trial of liquid ventilation in preterm neonates.

5. • In 1991, Fuhrman et al. & Lachman et al. presented a new method of
using PFC at functional residual capacity (FRC) during conventional
mechanical ventilation.
• In 1993, Richmond et al., also showed improvements in gas exchange
and compliance with PFC liquids in an acute lung injury model using a
simple PFC lavage technique.

6. PERFLUOROCARBONS
• The ideal fluid for liquid ventilation (LV) should be non-toxic,
has a low surface tension, is capable of dissolving large
amounts of O2 & CO2, has minimal systemic absorption and
is chemically stable.

7. PHYSICAL PROPERTIES
• PFCs are derived from common organic compounds, such as
benzene, by replacing all the carbon bound hydrogen atoms
with fluorine atoms.
• PERFLUBRON (perfluorooctyl bromide) also called
Liquivent – only PFC accepted by FDA for use in human LV
trials.
• Perflubron contains one bromide atom, making it radiopaque.

9. • PFC fluids are clear, colourless, odourless and inert.
• Stable, insoluble in water, can be stored indefinitely at room
temperature, can be autoclaved.
• Oxygen, carbon dioxide and other gases are highly soluble
in PFCs.
• They can dissolve 15 times the amount of oxygen per given
volume as plasma.
• The O2 carrying capacity of PFCs can be more than 3 times
that of blood (35-70ml/dl at 250c) and that of CO2 is apprx
4times greater than that for O2(122-255 ml/dl)

10. • The PFC fluids have low surface tension (14-18dyne/cm) and
high density (1.7-1.9 mg/ml) which allows PFC to serve as
surfactant substitute.
• As PFC liquids are more dense and viscous than gas, assisted
mechanical ventilation is needed to support pulmonary gas
exchange when the lung is totally or partially filled with
medium.

12. • The ideal PFC for liquid ventilation should have :-
1. A high solubility for O2 & CO2 to maintain gas exchange.
2. A greater density than body fluids so that it descends to the
dependent parts of the lungs and re-opens the areas of
atelectasis,
3. A low surface tension to work like surfactant and improve lung
compliance,
4. Property of being inert and not metabolized and eliminated
intact by evaporation during exhalation or transportation
through the skin.
5. Sufficient volatility to allow elimination in an acceptable time.

13. PHARMACOKINETICS
• The main route of PFC elimination is through the lungs via
volatilization, and to a smaller extent through skin by
transportation.
• Very small amounts of PFCs diffuse into pulmonary capillary
blood.
• The rate of uptake in the blood depends upon the PFC vapour
pressure, permeability coefficients of blood vessels, solubility
of particular PFC used and the degree of ventilation/perfusion
matching.

14. • Perflubron blood concentrations are low, and persists for
atleast 8 days following administration of the last dose.
• It may persist in extrapulmonary tissues for years following
LV.

15. TYPES
• Two types –
-Total / Tidal liquid ventilation (TLV)
-Partial liquid ventilation (PLV)
-while TLV remains as an experimental technique,
PLV is under clinical trials for its effectiveness.

16. TOTAL LIQUID VENTILATION
• In this, the entire lung is filled with an oxygenated PFC
liquid, and a liquid tidal volume of PFC is actively pumped
into and out of lungs.
• A specialized apparatus is required to deliver and remove the
relatively dense, viscous PFC and to extracorporeally
oxygenate and remove CO2 from the liquid.
• TLV is initiated by insufflating the desired volume of pre-
oxygenated PFC liquid ( FRC+TV) into the lungs using a
gravity assisted device.

17. • Optimum ventilation and oxygenation depend upon adequate
minute ventilation coupled with sufficient time for diffusion
of respiratory gases to and from the PFC liquid.
• During maintenance phase, a low respiratory rate (4-6
breaths/min) with an inspiratory-expiratory (I:E) ratio of 1:2
to 1:3.
• Tidal volumes and positive end expiratory pressures(PEEP)
are adjusted same as in gas ventilation.

19. WEANING FROM TLV
• The return to gas ventilation is done by a transition through a
period of partial liquid ventilation.
• PFC liquid is removed at the end of expiratory phase upto
FRC of lung, gas ventilation is begun and PFC liquid is not
replaced or augmented, as it is evaporated.
• Elimination from lung generally requires 1-7days.

20. PARTIAL LIQUID VENTILATION
• In PLV, the lungs are slowly filled with a volume of PFC
equivalent to FRC (functional residual capacity)
• The PFC within the lungs is oxygenated and CO2 is removed
by means of gas breaths by conventional ventilation.
• PLV is initiated by insufflating PFC (apprx 20-30ml/kg) into
the lungs using an intravenous syringe pump or by slowly
pushing the fluid over 15 min to 1hr period.
• The functional residual capacity is reached when a meniscus
of PFC is present within the ET tube at end expiration.

21. Illustration of PLV in a preterm infant. 1.
Thomas H. Shaffer et al. Pediatrics in Review 1999;20:e134-
e142
©1999 by American Academy of Pediatrics

23. • As the fluid evaporates out of lungs, it is intermittently and
gradually replaced with additional PFC at 2-8 ml/kg to
maintain a total liquid volume of FRC.
WEANING :
• PLV is discontinued by ceasing to replace the PFC that is lost
through evaporation.
• Most of the intrapulmonary liquid evaporates in 1-7days,
allowing a transition to gas ventilation.

25. Serial computerized tomography images of individual rabbits during partial liquid ventilation
with perflubron (left) or perfluorodecalin (right) 15 min (top) and 4 h (bottom) after
perfluorochemical (PFC) instillation.
Thomas F. Miller et al. J Appl Physiol 2001;90:839-849
©2001 by American Physiological Society

27. PHYSIOLOGY
• Liquid ventilation has many theoretical advantages over
conventional gas ventilation, including better gas exchange
and functional lung recovery by different mechanisms.
-Alveolar recruitment
-Better V/Q matching
-Lavage
-Anti inflammatory effects
-Temperature regulation

28. ALVEOLAR RECRUITMENT
• Filling of alveoli with liquid eliminates air-liquid interfaces
and greatly reduces surface tension forces.
• Collapsed alveoli may also be recruited and stabilized by
hydraulic forces.
• Alveolar expansion and stability is facilitated at much lower
airway pressures, reducing risk of barotrauma.
• As more alveoli are filled with PFC, effective diffusing
surface of the lung increases improvement in arterial
oxygenation and compliance.

29. V/Q MATCHING
• PFC fluids are denser than water, hence deposit in dependent
regions of the lungs.
• They improve V/Q matching by facilitating gas exchange in
lung units that were previously perfused but not ventilated.
• The weight of PFCs in dependent zones also redistribute
pulmonary blood flow to nondependent zones that were
previously ventilated but not perfused.

30. LAVAGE
• LV facilitates the removal of exudative material from the lung
but doesnot interfere with production or function of
surfactant.
• During TLV, the cyclical removal and replacement of fluid
may lavage the exudate while maintaining gas exchange.
• During PLV, exudative material in peripheral airways and
alveoli is lavaged into central airways and removed by
suctioning.

31. ANTI-INFLAMMATORY EFFECTS
• In the presence of PFCs, there is attenuation of neutrophil
adhesion, activation and migration.
• There is removal of inflammatory cells and mediators from
alveolar spaces.
• PFCs provide a mechanical barrier to intra alveolar exudation
and leukocyte translocation leading to reducing intensity of
inflammation and second lung injury.

32. TEMPERATURE REGULATION
• PFCs have a higher heat capacity than conventional gas
mixtures, and acts as a internal heat exchanger.
• They can be used to warm the lungs and increase core body
temperature.

33. INDICATIONS
NEONATAL :
-Respiratory distress syndrome
-Meconium aspiration
-Persistant pulmonary hypertension of newborn
-Congenital diaphragmatic hernia
-Temperature control
-Lung protection during cardiopulmonary bypass

34. RESPIRATORY DISTRESS SYNDROME
• Exogenous surfactant therapy for hyaline membrane disease
is limited by unequal delivery and distribution within the
injured or premature lung.
• LV may facilitate more uniform endogenous surfactant
distribution and may be of use in surfactant unresponsive pts.
• It can reduce surface tension, thereby reducing inflation
pressure and barotrauma and may stimulate surfactant
synthesis.

35. • MECONIUM ASPIRATION:
-Lavage with TLV and PLV may remove meconium from airways
more effectively than conventional measures.
• PERSISTANT PULMONARY HYPERTENSION :
-LV provides uniform delivery of oxygen to distal regions of the
lungs, improving V/Q matching and facilitating pulmonary vasodilation.
• TEMPERATURE CONTROL :
-The heat exchange may help to maintain normothermia in premature
infants.

36. ADULT INDICATIONS :
• -Acute respiratory distress syndrome
• -Pneumonia
• -Cancer therapy
• -Drug delivery
• -Donor lung preservation

37. • ARDS:
-LV can improve gas exchange in ARDS by recruiting the
atelectatic, consolidated, dependent regions of the lungs.
-Pulmonary blood flow is also redistributed to less
severely injured regions of the lungs, thus improving V/Q
matching.
• PNEUMONIA :
-Lavage with LV removes infectious and inflammatory
debris from the airways.

38. • CANCER THERAPY :
-LV may augment antineoplastic effects of RT &CT by
inducing localized hyperthermia or hyperoxia.
-Concentrated chemotherapeutic agents can also be
delivered through PFC.

39. ADVERSE EFFECTS
• The toxicity of PFCs is not fully known. Other complications are -
-Mucous plug formation
-Pneumothorax
-Bleeding complications
-Hypoxia
-Hypotension
-Bradycardia
• But it is still unclear whether these adverse effects were due to
PLV or the underlying disease.

40. • LV can complicate the supportive and general care of the patients.
-PFC is almost twice as dense as saline, hence patient weights
should not be the sole index of fluid balance in ICU care.
-PFCs are radio-opaque and will eliminate much of the diagnostic
utility of chest radiography.
-No audible breath sounds are heard during TLV.
-The impact of LV upon the development of nosocomial
pneumonia is uncertain.
-Use of liquid ventilation is unpleasant for the patient, therefore,
deep sedation and paralysis are necessary.

41. CLINICAL OUTCOMES

43. • The study included 13 premature infants with severe
respiratory distress syndrome in whom conventional
treatment had failed.
• The outcome of this study is, 8 out of the 13 infants survived
to a corrected gestational age of 36 weeks.

45. Conclusions of the study:
• Partial Liquid Ventilation leads to clinical
improvement and survival in some infants with severe
respiratory distress syndrome who are not predicted to
survive.

47. • This is a 2013 meta-analysis review of two randomized
controlled trials that compared PLV with CMV in the
treatment of acute lung injury with or without ARDS.
• The two RCTs are :
-Kacmarck trial (2006) – 311 patients
-Hirschl trial (2002) -90 patients

48. • Out of 401 participants,
170 – high dose PLV (mean dose of 20 ml/kg)
99 – low dose PLV (dose of 10 ml/kg)
132 – conventional mechanical ventilation

52. • The conclusion of this study is,
-No evidence of benefit for the use of Partial Liquid
Ventilation and some evidence suggests PLV may be
associated with increased risk of adverse effects.

53. SUMMARY & RECOMMENDATIONS
• LV is a technique of mechanical ventilation in which the lungs are
insufflated with oxygenated perfluorocarbon fluid rather than gas.
• PFCs are stable and nontoxic with minimal systemic absorption. They
dissolve large amounts of O2 & CO2 ; thus ideal for gas exchange.
• Two techniques of PFC based liquid ventilation : total & partial liquid
ventilation.
• Theoretical advantages of LV over conventional MV include
recruitment and stabilization of alveoli, improvement in V/Q
matching, removal of exudative material from the lung, anti-
inflammatory effects and temperature regulation.

54. • In theory, LV may be of benefit for numerous neonatal and adult
diseases. But, clinical trials have shown little improvement in
important clinical outcomes.
• As a result, liquid ventilation cannot be recommended in routine
clinical care.
• Adverse effects include mucous plug formation, pneumothorax,
bleeding disorders, although it is unclear whether these are due to LV
or the underlying disease.