Liquid ventilation-two techniques
Total liquid ventilation (TLV)
The lungs are filled with perfluorocarbon to a
volume equivalent to the functional residual
capacity (FRC, approximately 30 mL/kg) and a "liquid
ventilator" is used to generate tidal breathing with
perfluorocarbon. Optimal CO2 clearance is
achieved when ventilation is performed at a rate of
4-5 breaths/minute. Typical tidal volumes are in the
15-20 ml/kg range. One of the advantages of TLV is
that exudate may be lavaged from the airways in the
setting of respiratory failure. In addition, the
distribution of perfluorocarbon within the lungs may
be more uniform during TLV.
Partial liquid ventilation (PLV)
During PLV, gas ventilation of the
perfluorocarbon-filled lungs is performed using a
standard gas mechanical ventilator. This is a
relatively simple technique which does not require
use of a specialized device. The adequacy of
perfluorocarbon dose is assessed during PLV by
visually identifying a meniscus of perfluorocarbon
within the endotracheal tube at end-expiration. A
typical initial dose of perfluorocarbon during PLV
is equivalent to FRC or approximately 30 ml/kg.
In the 30 years since the landmark studies by
Kylstra and Clark, numerous studies have evaluated
the efficacy of liquid ventilation with
perfluorocarbon fluids to improve gas exchange and
pulmonary function in animal models of respiratory
failure. Many of the initial studies were performed
in premature, surfactant-deficient animal models of
respiratory insufficiency. One important property of
perfluorocarbons is that they have a low surface
tension of approximately 18 to 19 dynes/cm which
allows perfluorocarbons to serve as "surfactant
substitutes". Studies in early pre-term animals
clearly demonstrated improvement in compliance, gas
exchange, and survival during liquid ventilation
when compared to gas ventilation. Subsequent
research has revealed marked improvements in
parameters of gas exchange and pulmonary function
during total and partial liquid ventilation, when
compared to gas ventilation, in full term newborn,
pediatric, and adult animal models of respiratory
failure. One other finding, is a reduction in the
degree of lung injury and inflammatory infiltrate
observed during liquid ventilation when compared to
gas ventilation in these models of respiratory
failure.
Mechanisms of Liquid ventilation
In preterm newborns, gas exchange may be enhanced
during liquid ventilation because of a reduction in
the alveolar surface tension which is associated
with ventilation of the liquid-filled lung. The
mechanical lavage associated with total liquid
ventilation may have a salutary effect in the
setting of ARDS, pneumonia, or meconium aspiration
since exudate may be evacuated from the lungs.
Perfluorocarbons also enhance alveolar recruitment
in the setting of atelectasis. Cross-sectional
imaging has revealed that there is homogenous
distribution of the ventilating medium during liquid
ventilation when compared to gas ventilation.
Specifically, the atelectatic, consolidated,
dependent regions of the lungs, which contribute
greatly to the associated physiologic shunt observed
during gas ventilation in the setting of ARDS, are
re-inflated during liquid ventilation. It appears
that perfluorocarbons enhance recruitment of alveoli
in the setting of atelectasis and, because they are
relatively dense, have a predilection for the
dependent zones of the lungs. This results in
re-inflation of dependent, atelectatic segments and
more homogenous ventilation of the lungs.
A second effect of the relatively dense
perfluorocarbons may be to redistribute blood flow
from the dependent to the non-dependent regions of
the lung. In so doing, pulmonary blood flow may be
redistributed to less severely injured/atelectatic
areas of the lungs with associated improvement in
ventilation/perfusion matching.
In 1990, the first clinical evaluation of liquid
ventilation was reported in three premature,
moribund newborns who underwent pulmonary lavage
with perfluorocarbons. The response was varied, but
the majority of patients demonstrated improvement in
gas exchange and pulmonary compliance. A number of
centres are currently evaluating the efficacy of
liquid ventilation in the setting of respiratory
failure in premature newborns, full-term newborns,
children, and adults. It is clear that partial
liquid ventilation is at an early stage in its
clinical evolution, although substantial progress
has been made in the development and evaluation of
this new method of ventilation. Prospective,
randomized, controlled studies which will allow
accurate assessment of the safety, efficacy, and
relative cost of this technique in adults, children,
and premature neonates are underway. It is likely
that total liquid ventilation will enter the
clinical arena in the near future as some of the
technical aspects of device design are refined. The
preliminary pre-clinical and clinical experience
would suggest that both techniques of liquid
ventilation have the potential to play a significant
role in enhancing the management and outcome of
patients with respiratory failure.
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Artificial Blood
The first real success in fluid breathing
came in 1966, with Dr. Leland Clark's
"liquid-breathing-mouse" experiment. Dr.
Clark (inventor of the Clark electrode)
realized that oxygen and carbon dioxide were
very soluble in fluorocarbon liquids (like
freon). Assuming that the alveoli of the
lungs should be capable of drawing oxygen
out of the fluid and replacing it with
carbon dioxide, Clark suggested that these
fluorocarbons should support respiration of
animals. Performing the first tests on
anaesthetized mice, Dr. Clark temporarily
paralyzed each intubated animal, inflating a
cuff inside the trachea to provide a seal
and ensure that no air entered the lungs,
and no solution leaked out.
After bubbling oxygen through the
fluorocarbon, the oxygenated fluid was
pumped into the animals' lungs, and
recirculated (about 6 cycles of inhalation
and exhalation per minute). Most of the
animals who were kept in the fluid for up to
an hour survived for several weeks after
their removal, before eventually succumbing
to pulmonary damage. Autopsies uniformly
revealed that the lungs appeared congested
when collapsed but normal when inflated.
Some of the early problems Clark encountered
seemed to be due to the size of the animals'
airway. The tiny size physically limited the
amount of fluid that could get into the
lungs. For that and other reasons, carbon
dioxide tended to build up in the system: it
simply couldn't be removed fast enough.
This photograph demonstrates a living mouse
breathing in the liquid, while a goldfish
inhabits the water floating on top.
Dr. Clark discovered that the length of time
the mice could survive in the fluid was
directly related to the fluorocarbon's
temperature: the colder the fluid, the lower
the respiration rate which in turn prevented
carbon dioxide buildup. He therefore induced
hypothermia in the animals. This technique
seemed to give the most success, as one
animal survived over 20 hours breathing
fluid at 18oC.
Purified hemoglobin
This is produced from expired red blood
cells, for example diaspirin cross-linked
hemoglobin.
Recombinant hemoglobin
 This
is a modified human hemoglobin tetramer
cross-linked with a glycine bridge between
the alpha subunits. It is produced from
Escherichia Coli or yeast. The
cross-links prevent renal excretion.
The
hemoglobin solutions must be free of
red cell debris to avoid renal damage. Other
effects include impairment of macrophage
activity. These products are hyperosmotic
and are quickly broken down in the blood.
The oxygen dissociation curve is shifted to
the left with use of these products. Bovine
hemoglobin has also been used.
Perfluorocarbons
These are inert chemicals with oxygen
solubility 20X that of plasma. They exist as
a 10% solution. These solutions carry
dissolved oxygen in an amount directly
proportional to its partial pressure. its
accumulation in the reticulo-endothelial
system is at present, of unknown
significance.
Adapted from
Anaesthesia UK : FRCA Home Page for
Anesthetists in training for postgraduate exams
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