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Respiratory failure from severe asthma is a potentially
reversible, life-threatening condition. Poor outcome in this
setting is frequently a result of the development of
gas-trapping. This condition can arise in any mechanically
ventilated patient, but those with severe airflow limitation
have a predisposition. It is important that clinicians managing
these types of patients understand that the use of mechanical
ventilation can lead to or worsen gas-trapping. In this review
we discuss the development of this complication during
mechanical ventilation, techniques to measure it and strategies
to limit its severity. We hope that by understanding such
concepts clinicians will be able to reduce further the poor
outcomes occasionally related to severe asthma.
Introduction
Asthma
continues to inflict significant morbidity and mortality
worldwide. Despite advances in therapy and in our understanding
of its pathophysiology, the prevalence of asthma is increasing ,
although there is significant age and geographic variation.
While the prevalence of asthma has increased, outcomes of severe
asthma appear to be improving, with lower complication rates and
fewer in-hospital deaths. Nonetheless, it is estimated that
about 10% of individuals admitted to hospital for asthma go to
the intensive care unit, with 2% of all admitted patients being
intubated. Not surprisingly, admission to the intensive care
unit and need for mechanical ventilation are associated with
mortality. When death does occur it is most commonly a result of
one of the complications of severe gas-trapping. These
complications include barotrauma, hypotension and refractory
respiratory acidosis. If the morbidity and mortality associated
with severe asthma is to continue to decrease, then it is
imperative that clinicians caring for such patients have a clear
understanding of how gas-trapping can occur and of how it may be
recognized/measured and limited.
This
article reviews the principles of mechanical ventilation in
severe asthma, giving particular attention to the development of
gas-trapping as well as how to measure and limit it. Specific
details on pharmacological management and prevention of future
episodes of severe asthma are beyond the scope of this review
but can be found elsewhere.
Rationale for
mechanical ventilation in severe asthma
When a
patient with severe asthma does not respond adequately to
medical therapy, prompt intervention in an effort to provide
adequate oxygenation and ventilation by means of noninvasive
positive pressure ventilation (NPPV) or invasive positive
pressure mechanical ventilation is frequently life saving. Given
that these patients have a propensity to develop severe airflow
limitation, making it difficult to exhale all of their inspired
gas, gas-trapping (which leads to dynamic hyperinflation and is
also referred to as intrinsic positive end-expiratory pressure
[PEEP] and auto-PEEP) frequently occurs. As a result, one of the
most important principles of mechanical ventilation in this
setting is to utilize a strategy aimed at reducing the
likelihood that this complication will occur.
Noninvasive
positive pressure ventilation
It is
possible that in some patients with severe asthma NPPV may be
preferential to intubation. However, to date only two small,
prospective, randomized trials have been completed that
evaluated the use of NPPV in patients with severe asthma: one in
children and a pilot study in adults.
Both of those studies suggested that, in selected patients with
severe asthma, NPPV could improve lung function and possibly
reduce the need for hospitalization. There are also some
observational studies, which yielded consistent results. In
chronic obstructive pulmonary disease – another condition
frequently associated with severe airflow limitation – a number
of prospective randomized trials have shown that noninvasive
ventilation reduces the need for endotracheal intubation, length
of hospital stay and in-hospital mortality rate, and even that
it improves long-term survival. The degree to which these data
can be applied to the asthmatic population is debatable.
Even
though NPPV requires further investigation in severe asthma, it
is currently being used as an initial alternative to mechanical
ventilation in some centers. As is the case in other conditions,
the success of NPPV depends on a variety of factors including
clinician experience, patient selection and interfaces, and that
it is not used in patients with any known contraindications. It
is particularly important to be very cautious in using NPPV in
pediatric patients, in whom the margins of safety are narrow,
and a low threshold for intubation when required should be
maintained in these patients. The commonly accepted
contraindications to NPPV are as follows: cardiac/respiratory
arrest, severe encephalopathy, hemodynamic instability, facial
surgery/deformity, high risk for aspiration, non-respiratory
organ failure, severe upper gastrointestinal bleeding, unstable
arrhythmia, and upper airway obstruction.
The decision
to intubate
The
decision to intubate should be based mainly on clinical
judgment. Markers of deterioration include rising carbon
dioxide levels (including normalization in a previously
hypocapnic patient), exhaustion, mental status depression,
hemodynamic instability and refractory hypoxemia. Clinical
judgment is crucial because many patients presenting with
hypercapnia do not require intubation, and thus the decision
should not be based solely on blood gases.
Development
of gas-trapping
Severe
airflow limitation is always associated with severe asthma
exacerbation and occurs as a result of broncho-constriction,
airway edema and/or mucous plugging. Consequently, the work of
breathing is significantly increased. Increased work occurs
because the normally passive process of expiration becomes
active in an attempt by the patient to force the inspired gas
out of their lungs. In addition, there is increased inspiratory
work caused by high airway resistance and hyperinflation. This
hyperinflation causes the lungs and chest wall to operate on a
suboptimal portion of their pressure–volume curves (i.e. they
are overstretched), resulting in increased work to stretch them
further in an attempt to ventilate adequately. Gas-trapping
occurs because the low expiratory flow rates mandate long
expiratory times if the entire inspired volume is to be exhaled.
If the next breath interrupts exhalation, then gas-trapping
results (Fig.
1). Because gas is
trapped in the lungs there is additional pressure at the end of
expiration (auto-PEEP or intrinsic PEEP) above applied PEEP,
which leads to dynamic hyperinflation. Auto-PEEP, intrinsic PEEP
and dynamic hyperinflation are terms that are frequently used
interchangeably.
Dynamic
hyperinflation has been defined as failure of the lung to return
to its relaxed volume or functional residual capacity at
end-exhalation. Of note, some refer to gas-trapping as the
component of hyperinflation that is due to airway occlusion, and
is therefore potentially less amenable to ventilator
manipulation (in some situations, the dominant component of
total hyperinflation in severe asthma).
Hyperinflation can be adaptive in that with higher lung volumes
the increase in airway diameter and elastic recoil pressure
enhances expiratory flow; however, excessive dynamic
hyperinflation has been shown to predict the development of
hypotension and barotrauma during mechanical ventilation of
severe asthma. These developments are the usual causes of excess
morbidity and mortality.
Measuring
gas-trapping
Gas-trapping
can be measured a variety of ways involving volume, pressure, or
flow of gas. Estimating gas-trapping using volume measures can
be done by collecting the total exhaled volume during 20–60 s of
apnea in a paralyzed patient. Tuxen and coworkers described
this volume as 'VEI', or the volume of gas at end-inspiration
above functional residual capacity (Fig.
2). Tuxen and Lane also
showed that a VEI above 20 ml/kg predicted complications of
hypotension and barotrauma in mechanically ventilated patients
with severe asthma. Prospective studies involving larger patient
numbers are needed to validate the predictive value of VEI.
Another way to estimate gas-trapping is to measure
end-expiratory pressure in the lungs. If the expiratory port of
the ventilator is occluded at end-expiration, then the proximal
airway pressure will equilibrate with alveolar pressure and
permit measurement of auto-PEEP (end-expiratory pressure above
applied PEEP) at the airway opening (Fig.
3). Expiratory muscle
contraction can elevate auto-PEEP without adding to dynamic
hyperinflation, and therefore for accurate measurement of
auto-PEEP the patient should be relaxed. Auto-PEEP measured in
this manner has not yet been shown to correlate with
complications. Another way to look for gas-trapping is to
observe the flow versus time graphics on the ventilator. If
inspiratory flow begins before expiratory flow ends, then gas
must be trapped in the lungs.
Each of the
measures of gas-trapping described thus far rely on the
assumption that the airways all remain in communication with the
proximal airway throughout expiration because pressure, flow, or
gas volume cannot be measured from a non-communicating airway.
Frequently, all of the airways may not be in communication with
the proximal airway in severe asthma. For example, it has been
noted (perhaps as a result of complete airway closure) that
there may at times be 'unmeasured' or 'occult' auto-PEEP. This
occult auto-PEEP has all of the untoward effects of the
measurable auto-PEEP, but it cannot be quantified using the
usual approaches. As a result, exercising good clinical
judgment is important. When assessing dynamic
hyperinflation/gas-trapping in mechanically ventilated patients
with severe asthma, clinicians should question low auto-PEEP
measurements in clinical situations that suggest otherwise.
One such
clinical situation would be increasing plateau airway pressure (Pplat)
unexplained by decreases in respiratory system compliance during
volume-cycled ventilation. Pplat can be determined by stopping
flow at end-inspiration utilizing an end-inspiratory pause
(typically 0.4 s). During this pause, airway opening pressure
falls from peak pressure (the sum of static and resistive
pressures) to Pplat (static pressure alone) as resistive
pressure falls to zero (Fig.
4). Patients must be
paralyzed or heavily sedated to obtain reliable measurements.
Because alveolar pressure increases as lung volume increases,
measurement of Pplat should reflect gas-trapping (again assuming
that there is no other explanation, such as adjustments to the
ventilator or changes in respiratory system compliance). Some
have pointed out that if Pplat is kept at less than 30 cmH2O
then complications appear to be rare, although no studies have
yet shown Pplat to be a reliable predictor of complications.
Similarly, when using pressure cycled ventilation, decreasing
tidal volumes may indicate gas-trapping. Other situations in
which clinicians should suspect gas-trapping include increasing
chest wall girth, hyperinflation on chest imaging, reduced
efficiency of ventilation, increased patient effort, unexplained
patient agitation, development of barotrauma, hemodynamic
compromise and missed respiratory efforts (as patients attempt
to trigger the ventilator but cannot generate enough pressure to
overcome the auto-PEEP that has developed).
Limiting
gas-trapping
Because
gas-trapping is potentially associated with significant adverse
events in severe asthma, clinicians must be vigilant for its
development and employ strategies to limit it. Understanding how
gas-trapping occurs is the first step in developing such
strategies. These strategies include controlled hypoventilation
(reduced tidal volumes [less gas to exhale] and reduced
respiratory rates [longer expiratory time]), relieving
expiratory flow resistance (frequent airway suctioning if
necessary, bronchodilators, steroids, large-bore endotracheal
tube), reducing inspiratory time by increasing the inspiratory
flow rate or incorporating non-distensible tubing, and reducing
the need for high minute ventilation by decreasing carbon
dioxide production (e.g. sedation/paralysis, controlling
fever/pain). The application of external PEEP in severe asthma
remains a controversial topic. It could theoretically decrease
the work of breathing and hence carbon dioxide production, while
limiting gas-trapping by splinting the airways open; however, in
practice there are situations in which the application of
external PEEP may increase total PEEP and worsen gas-trapping.
Assuming that
appropriate medical therapy to alleviate airflow obstruction has
been administered (i.e. inhaled beta agonists, inhaled
ipratroprium bromide, steroids, with/without intravenous
magnesium sulphate, etc.), by far the most effective method of
decreasing dynamic hyperinflation/gas-trapping is to reduce the
minute ventilation. Reducing the minute ventilation by adjusting
the tidal volume, frequency, or set pressure on the ventilator
may result in carbon dioxide retention. In this setting the
controlled use of 'permissive hypercapnia' is generally
considered well tolerated. Permissive hypercapnia that maintains
a pH above 7.20 or an arterial carbon dioxide tension below 90
mmHg has gained widespread acceptance. Permissive hypercapnia
has been used successfully in mechanically ventilated patients
with status asthmaticus.
Expiratory
time can be lengthened by using higher inspiratory flow settings
(70–100 l/min) during volume cycled ventilation, using a shorter
inspiratory time fraction, reducing respiratory rate, and
eliminating any inspiratory pause. Prolongation of expiratory
time has been shown to decrease dynamic hyperinflation in
patients with severe asthma, as is evident by decreased plateau
pressures. The magnitude of this effect becomes relatively
modest when the baseline minute ventilation is 10 l/min or less
and when the baseline respiratory rate is low. It should be
emphasized that while modifying the I/E ratio is important in
fine tuning the amount of gas-trapping, the single most
effective way is by reducing minute ventilation.
Applying
adequate sedation and analgesia is a fundamental step in
lowering the production of carbon dioxide and subsequently
ventilatory requirements. Sedation and/or paralysis may also
allow the clinician to avoid patient–ventilator dysynchrony and
facilitate strategies to limit gas-trapping in the most severe
of cases. It is beyond the scope of this review to recommend
which agents or protocols are best for this. The use of
neuromuscular blocking agents should be limited to short periods
of time and only when absolutely necessary in patients with
severe asthma who are not achieving synchrony with other agents.
Although neuromuscular blocking agents effectively promote
synchrony, lower the risk for barotrauma, reduce lactate
accumulation and reduce oxygen consumption and carbon dioxide
production, their prolonged use, particularly when combined with
steroids, can lead to prolonged paralysis and/or myopathy.
The
addition of extrinsic PEEP in the setting of auto-PEEP may
reduce work of breathing and possibly even prevent gas-trapping
by splinting the airways open. In terms of reducing the work of
breathing, the addition of extrinsic PEEP in patients with
dynamic hyperinflation would theoretically reduce the
inspiratory muscle effort required to overcome auto-PEEP and
initiate an inspiration. It has been demonstrated that in
patients with chronic obstructive pulmonary disease more than
40% of inspiratory muscle effort can be expended to overcome
auto-PEEP, and that adding extrinsic PEEP can attenuate the
inspiratory muscle effort needed to trigger inspiration and
improve patient–ventilator interaction. In these patients
extrinsic PEEP must be titrated individually, with an average of
80% of the auto-PEEP being tolerated before the plateau
pressures and total PEEP begin to increase. Such an approach is
only useful in those patients who are breathing spontaneously
and capable of triggering the ventilator. In addition, extrinsic
PEEP may prevent airway collapse (which could lead to occult
auto-PEEP) by splinting the airways open. If this is the case
then extrinsic PEEP would be most useful only in the most severe
of cases, including those patients who are not spontaneously
breathing. It should be noted that extrinsic PEEP has also been
shown to be effective at preventing ventilator-induced lung
injury in other forms of lung injury and hence may be of added
benefit in this situation. In practice, however, adding
extrinsic PEEP in some patients with severe asthma has been
shown to worsen auto-PEEP. As mentioned above, it is
occasionally difficult to measure auto-PEEP reliably, and if the
extrinsic PEEP is greater than the auto-PEEP then gas-trapping
will likely worsen. This has led some to recommend minimizing
the use of extrinsic PEEP or not using it at all in the
ventilation of patients with severe asthma. If extrinsic PEEP is
to be used, then careful bedside observation with a clear
understanding of how the benefits (reductions in auto-PEEP) and
adverse effects (worsening gas-trapping) would manifest is
mandatory.
Considerations for initial ventilator settings in patients with
severe asthma
There have
been a number of review articles recommending initial ventilator
settings and algorithmic approaches to mechanical ventilation in
severe asthma. The fine details of the ventilator settings are
not as crucial as close attention to the basic principles of
ventilating patients with severe asthma: employ low tidal
volumes and respiratory rate; prolong expiratory time as much as
possible; shorten inspiratory time as much as possible; and
monitor for the development of dynamic hyperinflation.
As a
starting point for ventilating patients with severe asthma, we
recommend that the ventilator initially be used in pressure
control mode, setting the pressure to achieve a tidal volume of
6–8 ml/kg, respiratory rate of 11–14 breaths/min and PEEP at 0–5
cmH2O. We use these settings with a goal of obtaining
a pH, in general, above 7.2 and a Pplat under 30 cmH2O.
If a Pplat under 30 cmH2O cannot be maintained, then
the patient must be evaluated for causes of decreased
respiratory system compliance (i.e. pneumothorax, misplaced
endotracheal tube, pulmonary edema, etc.) beyond the
development of dynamic hyperinflation. If no such causes are
evident then efforts to limit gas-trapping further must be
considered. If permissive hypercapnia results in a pH below 7.2,
then the same type of evaluation needs to occur, including
consideration of increased sedation/paralysis and methods of
decreasing carbon dioxide production (i.e. reducing fever,
preventing over-feeding, decreasing patient effort, etc.). In
addition to these examples, administration of sodium bicarbonate
to maintain a pH of 7.2 during controlled hypoventilation has
been investigated in patients with status asthmaticus; however,
no studies have demonstrated any benefit associated with
bicarbonate infusion. Decisions regarding ongoing ventilator
management must be based on the principles outlined in this
review.
Adjuncts to
mechanical ventilation
A large
variety of unproven therapies that clinicians may need to
consider in an emergent situation have been proposed, including
intravenous magnesium sulphate, general anesthesia,
bronchoscopic lavage, heliox and extracorporeal membrane
oxygenation.
Intravenous
magnesium sulphate has bronchodilating properties and has been
shown in limited studies to improve pulmonary function in
patients with severe asthma, at least in the short term. Several
inhalation anesthetic agents have intrinsic bronchodilator
properties and there are reports of successful use of these
agents in refractory status asthmaticus. The special equipment
and personnel needed for inhalation anesthesia and the
significant hemodynamic complications associated with these
agents make their use problematic. Ketamine is an intravenous
agent that has analgesic and bronchodilating properties. There
are limited clinical data available regarding the use of
ketamine in status asthmaticus, and its side effects of
tachycardia, hypertension, delirium and lowering the seizure
threshold should always be taken into account.
In patients
with status asthmaticus and severe mucous impaction, it has been
suggested that bronchoscopic examination of the airways and
removal of secretions may be beneficial. As the presence of the
bronchoscope may worsen lung hyperinflation and increase the
risk for pneumothorax, we do not recommend this technique.
Heliox is a
blend of helium and oxygen (usually at a 70 : 30 ratio), which
is less dense than air, theoretically permitting higher flow
rates through a given airway segment for the same driving
pressure, thereby alleviating dynamic hyperinflation. Several
small studies have shown heliox to reduce peak inspiratory
pressure and arterial carbon dioxide tension, and to improve
oxygenation in mechanically ventilated patients. That heliox is
expensive, has a limited concentration of oxygen and has
conflicting results in the literature make it a somewhat
controversial therapy, and at this time we cannot recommend it
for routine use in severe asthma.
Extracorporeal membrane oxygenation is another expensive
modality that has been successfully used in patients with severe
refractory asthma. The use of these second-line therapies should
be on a case-by-case basis, carefully weighing the risks and
benefits.
Conclusion
Severe asthma exacerbation causing respiratory failure
has not yet been eliminated, and remains a potentially
reversible, life-threatening condition that imposes
significant morbidity and mortality. When mechanical
ventilation is required in severe asthma, it is
important that clinicians managing these patients
understand why gas-trapping occurs, how to measure it
and how to limit its severity. We hope that by
understanding such concepts clinicians will be able to
reduce further the number of poor outcomes that are
occasionally associated with severe asthma.
Abbreviations
NPPV
= noninvasive positive pressure ventilation; PEEP =
positive end-expiratory pressure; Pplat = plateau airway
pressure; VEI = volume of gas at end-inspiration above
functional residual capacity.
From
Clinical review: Mechanical ventilation in severe asthma
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