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Airway pressure-release ventilation (APRV) is a mechanical ventilation strategy that is usually time-
triggered but can be patient-triggered, pressure-limited, and time-cycled. APRV provides 2 levels of
airway pressure (Phigh and Plow) during 2 time periods (Thig and Tlow), both set by the clinician. APRV
usually involves a long Thigh and a short Tlow. APRV uses an active exhalation valve that allows
spontaneous breathing during both Thigh and Tlow. APRV typically generates a higher mean airway
pressure with a lower tidal volume (VT) and lower positive end-expiratory pressure than comparable
levels of other ventilation strategies, so APRV may provide better alveolar recruitment at a lower end-
inflation pressure and therefore (1) decrease the risk of barotrauma and alveolar damage in patients
with acute lung injury or acute respiratory distress syndrome (ALI/ARDS), and (2) provide better
ventilation-perfusion matching, cardiac filling, and patient comfort than modes that do not allow
spontaneous breaths. However, if the patient makes a spontaneous breath during Thigh, the VT
generated could be much larger than the clinician-set target VT, which could cause the end-inflation
transpulmonary pressure and alveolar stretch to be much larger than intended or produced in other
ventilation strategies. It is unknown whether a patient͛s inspiratory effort (and consequent larger VT)
can damage alveoli in the way that mechanically delivered, positive-pressure breaths can damage alveoli
in ALI/ARDS. Other ventilation modes also promote spontaneous breaths, but at overall lower end-
inflation transpulmonary pressure. There is a dearth of data on what would be the optimal APRV
inspiratory-expiratory ratio, positive end-expiratory pressure, or weaning strategy. The few clinical trials
to date indicate that APRV provides adequate gas exchange, but none of the data indicate that APRV
confers better clinical outcomes than other ventilation strategies.

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Much of the rationale for APRV is based on the ͞open lung͟ concept, which is a mechanical ventilation
approach designed to maximize and maintain alveolar recruitment throughout the ventilatory cycle.
With APRV this is accomplished by setting Phigh well above the closing pressure of recruitable alveoli.

Thus, the majority of the ventilatory cycle is spent at a pressure and volume well above the lower
inflection point of the pressure-volume curve. The set Thigh generally maintains this pressure (and thus
alveolar recruitment) for several seconds, while the set Tlow is of duration adequate to assist in CO2
removal but not be so long as to permit substantial de-recruitment.

Put another way, during the long inflation phase, recruitment is maintained, whereas during the brief
release, inherent lung recoil properties facilitate ventilation and the slower-emptying alveolar
compartments remain expanded through intrinsic PEEP.
This ͞reverse͟ concept form of ventilation thus provides an alternative way to assist ventilation and
maximize and maintain alveolar recruitment (and thereby maximize oxygenation) with substantial mean
airway pressure.

(SOURCE):http://www.rcjournal.com/contents/04.07/04.07.0452.pdf

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In adults, lung injury may complicate a wide range of serious medical and surgical conditions, only some of which
involve a direct pulmonary insult. The most extreme form of acute lung injury, adult respiratory distress syndrome
1
(ARDS), was first described formally 35 years ago by Ashbaugh et al. The overall incidence of ARDS remains
2
unclear, but many studies suggest a rate of two to eight cases per 100,000 people per year. The American-
3
European Consensus Conference members agreed that the diagnostic criteria for ARDS should include acute onset,
bilateral infiltrates visible in chest radiographs, a pulmonary-artery±occlusion pressure of less than 18 mm Hg or a
lack of evidence of left ventricular failure, and impaired oxygenation.

4
Recent data have demonstrated that ARDS is clearly a heterogeneous lung injury marked by consolidation, normal
lung tissue, and markedly overdistended lung units. CT scans have shown infiltration that is generally more dense in
the dependent regions of the lung, along with signs of atelectasis caused by the hydrostatic effect of edema fluid
interspersed with normal-appearing lung tissue. The pathological picture of ARDS is characterized by diffuse alveolar
5
damage, marked by the replacement of alveolar type I cells by proliferating alveolar type II cells. Gattinoni et al have
referred to the lungs of patients with ARDS as baby lungs to emphasize that there is a considerable loss of lung units;
approaches to ventilatory management should focus on this fact.

The severe hypoxemia that is both a hallmark and a diagnostic criterion for ARDS is caused by the presence of
intrapulmonary shunting or areas having very low ratios of ventilation to perfusion. The shunting is presumably due to
edema and atelectasis. Normocapnia (or even hypocapnia) is common during the early stages of ARDS. Later,
carbon dioxide retention is caused by an increase in dead space that results from the formation of bullae, fibrosis,
and vascular obliteration.

Recently, experiments6 and clinical evidence have suggested that ARDS may represent an inflammatory response in
the lung that may also be present in other organs, accounting for their dysfunction or failure. Considerable attention
7
has focused on neutrophils and their aggregation by complement. A recent study using bronchoalveolar lavage has
shown increased amounts of concretions of neutrophils in patients with ARDS, along with the presence of
inflammatory cytokines.

Management of patients with ARDS should be aimed at revealing the underlying diseases associated with the
condition and preventing iatrogenic lung injuries associated with supportive care. Ventilator-induced lung trauma,
pneumonia, and impaired cardiac output decrease the likelihood of a positive outcome. Until recently, the fatality rate
8
for ARDS was considered to be around 50%. Mortality is higher in patients aged 60 or more years and in those with
marked sepsis, but new ventilatory strategies and innovations are aimed at reducing that percentage and preventing
ventilator-induced trauma.

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High-frequency ventilation (HFV) is defined as mechanical ventilatory support using respiratory rates that are higher
than normal. Usually, the respiratory rate for HFV is set at more than 300 breaths per minute. When high frequencies
are used, tidal volume (Vt) is usually smaller than normal and airway-pressure swings are consequently smaller.
   




     

There are two main reasons for considering HFV in ARDS. First, the smaller pressure swings, coupled with
appropriate baseline pressure elevations, create an ideal lung-protective strategy. The combination of applied and
intrinsic positive end-expiratory pressure (PEEP) promotes alveolar recruitment and the smaller pressure swings
prevent overdistention. Ventilation occurs between the upper and lower inflection points, maintaining alveolar inflation
and preventing lung injury due to overinflation. Second, in addition to better alveolar recruitment, the rapid flow
pattern may enhance gas mixing and improve ventilation-perfusion matching.

Delivery of HFV can employ either a high-frequency oscillator (HFO) or a high-frequency percussive ventilator
(HFPV). HFOs operate using a to-and-fro application of pressure to the airway opening by either pistons or
microprocessor gas controllers. Fresh gas is supplied within the ventilator circuit as a bias flow, and mean airway
pressure is adjusted according to the relationship between fresh gas inflow and any positive or negative pressure
placed on the gas outflow from the bias flow circuit. The clinician has the ability to set oscillator frequency, oscillator
displacement (volume), inspiratory-to-expiratory ratio, and bias flow.

Several mechanisms of gas transport are involved in oscillatory ventilation. Bulk flow from subtidal volume delivery,
coaxial flow, Taylor dispersion, molecular diffusion, and pendelluft all contribute to ventilation and oxygenation during
oscillatory ventilation.9 Currently, trials are being conducted comparing oscillatory ventilation with conventional
ventilatory management.

In an attempt to combine the beneficial effects of HFV and conventional ventilation, an HFPV ventilator delivers a
small Vt and percussion, along with a bulk distribution of gas similar to that of a pressure-limited conventional breath.
This allows for gas stacking and provides alveolar recruitment at lower peak inspiratory and mean airway pressures.
10,11
In contrast to the exhalation seen in HFO support, exhalation is passive. Several small studies and case
scenarios have demonstrated positive outcomes in ARDS patients. In addition, HFPV may have a role in the care of
head-injury patients who develop ARDS. By providing internal mucokinesis, head-injured patients are not subject to
elevated intercerebral pressures often associated with conventional secretion-removal procedures.



      


Airway±pressure-release ventilation (APRV) can be described as consisting of two levels of PEEP that are applied for
set periods of time, allowing spontaneous breathing to occur at both levels. Alveolar recruitment is maintained by the
baseline pressure application, while ventilatory support is provided through two mechanisms. First, periodic, brief
deflations lasting less than 1 second provide some level of bulk gas distribution. Second, spontaneous ventilation is
provided through use of a dynamic or floating exhalation valve. APRV is often referred to as inverse-pressure
ventilation with spontaneous ventilation or as invasive bilevel positive airway pressure.

The advantage of APRV is that the prolonged baseline pressure (which lasts more than 4 seconds) maintains
alveolar recruitment without imposing additional peak inspiratory pressures that could lead to barotrauma. Clinical
12
studies have shown that oxygenation and ventilation can be maintained at lower pressures with APRV than with
conventional ventilatory management. Because the patient is allowed to breathe spontaneously, there are fewer
cardiac side effects, and the negative consequences of paralytic drugs are avoided.13 Typical ventilatory settings
would be a high PEEP of 25 to 30 cm H2O with an inspiratory time of 4 to 5 seconds and a low PEEP of 0 to 3 cm
H2O for 0.5 to 1 second. As the high PEEP is lowered, the inspiratory time is increased in order to maintain a high
mean airway pressure. Several newer ventilators have this mode available.


 

! 
" 
14
Recently, the ARDS network founded by the National Heart, Lung, and Blood Institute published a study indicating
22% lower mortality among ARDS patients for whom a low-Vt strategy was used. The network¶s protocol reduces Vt
to 4 to 6 mL/kg to limit plateau pressures to less than 30 cm H2O. During the acute phase, patients are managed
using volume-targeted assist-control mechanical ventilation. The continuous mechanical ventilation portion of the
protocol contains five interdependent algorithm components that control Vt, plateau pressure, arterial pH,
oxygenation, and respiratory rate. The goal of the protocol is to provide adequate oxygenation with the minimal
amount of alveolar distending pressure. Weaning is based on daily spontaneous breathing trials. Several major
medical centers are currently using this ventilatory strategy.

Monotonous Vt can lead to lung collapse. It has been postulated that periodic hyperinflation can prevent the alveolar
derecruitment associated with edema. Evidence of alveolar inflation can be seen as variation in inflection points along
the pressure-volume curve. Selected intervals that increase PEEP to more than 35 cm H2O have been studied in
 15
animals and have shown alveolar recruitment. Typically, a high level of PEEP is maintained for 2-minute intervals
and the best PEEP is determined after lung units have been reinflated and the pressure-volume curve has been
reexamined for evidence of reinflation. Currently, clinical trials are under way to examine the effectiveness of these
maneuvers in ARDS patients.


! 


Liquid ventilation uses fluorinated organic liquids (perfluorocarbons) as respiratory media. Perfluorocarbons are an
attractive choice, both for the high solubility of respiratory gases in them and for their low surface tensions.16 Partial
liquid ventilation uses a conventional ventilator to supply a gas Vt to lungs filled partially with a perfluorocarbon. The
liquid is allowed to trickle in slowly or is administered using a buretrol-regulating setup that uses the side port of an
endotracheal connector. Filling the functional residual capacity (FRC) requires approximately 20 mL/kg of the
perfluorocarbon; filling is confirmed through the observation of a fluid meniscus in the endotracheal tube when the
patient is receiving no PEEP. Up to 5 days of redosing may be performed to maintain a liquid-filled FRC. A ventilator-
management algorithm is used to reduce the chance of ventilator-induced trauma. The perfluorocarbon acts as a
liquid form of PEEP, holding open previously collapsed lung units and reducing edema and exudative
debris.17 Perfluorocarbon use can reexpand closed lung units, increase lung volume, improve oxygenation in a dose-
dependent manner, improve lung compliance, and prevent or reduce the lung impairment that might otherwise occur
18
due to the high airway pressures that characterize conventional mechanical ventilation. The low miscibility of
perfluorocarbons makes them very effective at washing unwanted debris from the lungs in a form of alveolar lavage.
Exudative debris and aspirated materials tend to float on top of the perfluorocarbon all the way to the airways, where
they can be removed using suction.

In clinical and animal studies, liquid ventilation has improved oxygenation and shown a possible lung-protective
mechanism. A reduction in neutrophils was observed during lung lavage following the administration of liquid
ventilation. Currently, the results of a large, multicenter randomized trial are being examined to determine the impact
of liquid ventilation on ventilator-free days and mortality.

#
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ARDS is often characterized by neutrophilic inflammation and increased permeability of the pulmonary
21
vasculature. Neutrophil elastase is a mediator released by the neutrophil that is responsible for endothelial injury
and increased vascular leakage into the lung. It has also been shown to induce mucus hypersecretion, to reduce
ciliary beating frequency, to induce respiratory metaplasia, and to induce pulmonary endothelial-cell detachment.22 In
a clinical study,6 neutrophils have been found to be the predominant inflammatory cell in the bronchoalveolar fluid of
subjects with ARDS. Furthermore, both neutrophil counts and concentrations of total neutrophil elastase have been
found to correlate with the severity of lung injury in ARDS patients.

Sivelestat is a therapeutic agent that is a potent, low±molecular-weight inhibitor of human elastase. It is administered
as a continuous intravenous infusion. The duration of infusion depends on the length of mechanical ventilation;
sivelestat can be administered for a maximum of 14 days. A phase II clinical study is now under way to determine the
effectiveness of sivelestat in reducing ventilator days and mortality in patients with ARDS.

Despite the technological innovations of the past 30 years, ARDS still has a significant mortality rate. Ventilator
strategy has shifted from curative to lung protective. Today¶s clinicians have a great arsenal from which to select in
managing ARDS. New ventilatory modes, ventilator types, pharmacological agents, and protective lung strategies are
available to help promote more positive outcomes. The quest for more and better weapons in this fight continues to
be the goal of clinicians who manage ARDS patients.

(SOURCE):http://www.rtmagazine.com/issues/articles/2002-04_05.asp
`
 

  
 

 

Thomas L. Petty, MD
From the Center for Health Sciences Education, HealthOne, Denver, Colo.


An expanding number of techniques that can provide adequate oxygenation and carbon dioxide elimination in
acute respiratory distress syndrome (ARDS) are available for the critical care expert. These include mechanical
ventilation with positive end-expiratory pressure (PEEP)1 and newer modifications of the ventilator's pressure
waveforms. 2 In addition, extracorporeal life support (ECLS) using a membrane oxygenator can nearly match the
success rate achieved by mechanical ventilation using inverse ratio mechanical ventilation and PEEP in ARDS.
These observations were obtained in a randomized controlled clinical trial3; the survival rate was 35% to 40% in
ARDS patients who, by previous entry criteria, had only a 10% salvage rate. 4

A new innovation in supportive care, partial liquid ventilation using a perfluorocarbon (PFC) instilled directly
into the trachea until airways and alveolar units were partially "flooded," appears to be another alternative that
can be applied if any one

(SOURCE):http://jama.ama-assn.org/content/275/5/404.short

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The ARDS Network is conducting several additional studies. As noted above, we are comparing high and low
PEEP values (the ALVEOLI study) combined with low-tidal volume (6 mL/kg) ventilation. We are comparing
pulmonary artery catheters with central venous catheters, and a liberal fluid strategy with a conservative fluid
strategy (FACTT). And in yet another study -- the Late ARDS Steroid Rescue Study (LASRS) --we are
investigating the value of giving corticosteroids to patients with late-stage ARDS. The reason for the last study
is suggestive data generated by previous trials indicating that corticosteroids may hasten recovery from late-
stage, fibroproliferative ARDS. Although high doses of corticosteroids given early in the disease process have
shown very little benefit for patients with septic shock, ARDS, or multiple organ system failure, there is
evidence that lower doses of corticosteroids given later in the disease process may be useful.

A study by a French research group has shown that for patients with refractory septic shock, low doses of a
corticosteroid (hydrocortisone, 50 mg/kg, q6h) reduced mortality by approximately 30%.5 Similar findings were
derived from a study of patients with ARDS who had entered the fibroproliferative phase.6 This study has
gained remarkable popularity, but the data must be acknowledged as limited. Just 24 patients were included,
and half of the patients in the placebo group crossed over to the corticosteroid group, leaving only 4 patients
who were truly unexposed to corticosteroids. So from a statistical point of view, it is difficult to say whether the
late administration of corticosteroids is beneficial. The ARDS Network study examining corticosteroids hopes to
reach its second interim analysis of 240 patients in late summer of 2001, at which time there may be more
answers.

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² Use of surfactant. While earlier studies have shown no benefit, newer formulations of surfactant may
prove different.

² Neutrophil elastase inhibitor to block neutrophil-mediated lung damage

² High-frequency oscillatory ventilation

What is clear even now is that a more conservative, low-tidal volume approach to ventilation in ARDS
patients² with calculations based on   body weight² produces a more favorable clinical outcome.

(SOURCE): http://www.medscape.org/viewarticle/413116_1

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X !"#$% http://davidkirkpatrick.wordpress.com/2010/09/12/stem-cell-therapy-potential-here-comes-
the-science/

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Cell-based therapies with embryonic or adult stem cells, including induced pluripotent stem cells, have emerged as
potential novel approaches for several devastating and otherwise incurable lung diseases, including emphysema,
pulmonary fibrosis, pulmonary hypertension, and the acute respiratory distress syndrome. Although initial studies
suggested engraftment of exogenously administered stem cells in lung, this is now generally felt to be a rare
occurrence of uncertain physiologic significance. However, more recent studies have demonstrated paracrine effects
of administered cells, including stimulation of angiogenesis and modulation of local inflammatory and immune
responses in mouse lung disease models. Based on these studies and on safety and initial efficacy data from trials of
adult stem cells in other diseases, groundbreaking clinical trials of cell-based therapy have been initiated for
pulmonary hypertension and for chronic obstructive pulmonary disease. In parallel, the identity and role of
endogenous lung progenitor cells in development and in repair from injury and potential contribution as lung cancer
stem cells continue to be elucidated. Most recently, novel bioengineering approaches have been applied to develop
functional lung tissue ex vivo. Advances in each of these areas will be described in this review with particular
reference to animal models.

(SOURCE): http://www.ncbi.nlm.nih.gov/pubmed/20801416
Prone ventilation in ARDS
February 4, 2011 by Cliff
Filed under All Updates, ICU

Prone ventilation can improve refractory hypoxaemia in ARDS but its effects on mortality have not been impressive in
some studies which may be underpowered or include patients with less severe hypoxaemia. An updated meta-
analysis showed significantly reduced ICU mortality in the four recent studies that enrolled only patients with ARDS,
as opposed to ARDS/ALI (odds ratio = 0.71; 95% confidence interval = 0.5 to 0.99; P = 0.048; number needed to
treat = 11). There may also be benefit from a greater duration of prone positioning.

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Critical Care 2011, 15:R6 Full text
Tags: ARDS, critical care, outcome, ventilation
Newborn mask ventilation
December 25, 2010 by Cliff
Filed under All Updates, Sick Kids, Tips

Seventy doctors and nurses from neonatal units administered positive pressure ventilation to a term newborn manikin
using a Neopuff T-piece device. Recordings were made (1) before training, (2) after training in mask handling and (3)
3 weeks later. Leak and obstruction were calculated.
Median (IQR) leak was 71% (32±95%) before training, 10% (5±37%) directly after training and 15% (4±33%) 3 weeks
later (p<0.001). When leak was minimal, gas flow obstruction was observed before, directly after training and 3 weeks
later in 46%, 42% and 37% of inflations, respectively.
The training provided included the following demonstrated mask technique:

1. Place the manikin¶s head in a neutral position and gently roll the mask upwards onto the face from the tip of
the chin.
2. Hold the mask with the two-point-top hold where the thumb and index finger apply balanced pressure to the
top flat portion of the mask where the silicone is thickest.
3. The stem is not held and the fingers should not encroach onto the skirt of the mask.
4. The thumb and index finger apply an even pressure on top of the mask.
5. The third, fourth and fifth fingers perform a chin lift with the same pressure upwards as applied by the thumb
and index finger downwards.
In this technique the mask is squeezed onto the face, between the downward thrust of the fingers and upward pull of
the chin lift.
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Arch Dis Child Fetal Neonatal Ed 2010;95:F398-F402
Even with the right technique, adequacy of ventilation can be hard to assess. Principles to bear in mind are:
V International guidelines recommend that infants with inadequate breathing or bradycardia be given positive
pressure ventilation (PPV) via a face mask with a self-inflating bag, flow-inflating bag or T-piece device.
V Adequacy of ventilation is then judged by assessing the heart rate.
V However, if the heart rate does not increase, chest wall movements should be assessed to gauge adequacy of
ventilation.
V A human observational study reported a mean VT of 6.5 ml/kg in spontaneous breathing preterm infants in the
first minutes of life.
V When assisted ventilation is required, a peak inflating pressure (PIP) is chosen with the assumption that this will
deliver an appropriate VT.
V However, lung compliance and therefore the PIP required to deliver an appropriate VT vary in the minutes after
birth.
V It is likely that there are even greater differences between infants as the mechanical properties of the lung vary
with gestational age and disease states.
V In addition, many infants breathe during PPV adding to the inconsistency of VT delivered with a set PIP.
Therefore, relying on a fixed PIP and subjective assessment of chest wall movement may result in either under-
or over-ventilation.
V Animal studies have shown that PPV with VT >8 ml/kg or inflations with large VTs can damage the lungs.
In an observational study of actual newborn resuscitations in Melbourne, researchers measured inflating pressures
and VT delivered using a respiratory function monitor, and calculated face mask leak. After 60 seconds of PPV,
resuscitators were asked to estimate VT and face mask leak. These estimates were compared with measurements
taken during the previous 30 s.
In 20 infants, the median (IQR) expired tidal volume (VTe) delivered was 8.7 ml/kg (5.3±11.3). VTe and mask leak
varied widely during each resuscitation and between resuscitators, who were also poor at estimating VT and mask
leak.

(SOURCE): http://www.resusme.em.extrememember.com/?tag=ventilation
˜


  
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All of us may be able to breathe a little easier now that scientists from Pennsylvania have found a new
therapeutic target for controlling dangerous inflammation in the lungs. A new research report in the
January 2011 issue of the l 
  !  "  (http://www.jleukbio.org) suggests that blocking the
activation of an enzyme called delta-protein kinase C (delta-PKC) could protect the lungs from neutrophil-
mediated damage, which can result in out of control inflammation. In an animal model of acute respiratory
distress syndrome (ARDS), inhibiting delta-PKC in the lungs showed dramatically reduced inflammation,
thereby protecting the lungs from further damage.
"ARDS is a major public health problem and one of the leading causes of death in intensive care units. It
is characterized by excessive pulmonary inflammation and neutrophil infiltrations of the lung," said Laurie
E. Kilpatrick, Ph.D., co author of the study from the Center for Inflammation, Translational and Clinical
Lung Research and Department of Physiology at Temple University School of Medicine in Philadelphia.
"While no specific pharmacologic therapeutics are available to treat this disease, control of delta-PKC
activity may offer a unique therapeutic target for the treatment of ARDS and prevent the significant
morbidity and mortality associated with sepsis and trauma."

To make this discovery, Kilpatrick and colleagues used a rat model of severe inflammation or sepsis that
produces lung injury. The animals were divided into two groups; one group received the inhibitor directly
into the lungs and the other group received a placebo. After 24 hours, the placebo group showed signs of
lung injury and illness, lung tissue damage and breathing problems. In contrast, the group that received
the delta-PKC inhibitor had markedly reduced evidence of lung injury and distress. These results suggest
that delta-PKC is an important regulator of inflammation in the lung and that targeted inhibition of this
enzyme may protect the lungs from the damage associated with severe infection.

"ARDS and acute lung inflammation can be very dangerous for patients, can progress rapidly and can be
difficult for doctors to treat," said John Wherry, Ph.D., Deputy Editor of the l 
  !  "  .
"This study is important not only because it offers some potential clues about how to treat and control
acute lung inflammation, but also because it points to the mechanistic pathways involved that might be
targeted to prevent this dangerous inflammatory situation in the first place."

According to the National Heart, Lung and Blood Institute of the U.S. National Institutes of Health, ARDS
leads to low oxygen levels in the blood and can be life threatening. ARDS usually occurs in very ill people
who have another disease or who have major injuries. Most people are already in the hospital when they
develop ARDS. Some people who survive ARDS may recover completely, while other may have lasting
damage to their lungs and other related health problems.

(SOURCE): http://www.chem.info/News/Feeds/2011/01/topics-material-handling-scientists-discover-
that-a-specific-enzyme-inhibit/