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Chapter 2
Methods to improve pulmonary mucocilliary
clearance
Introduction
Efficient mucocilliary clearance and effective cough are the two basic
processes necessary for normal clearance of the airways. In abnormal
situations, this system may be dysfunctional and lead to mucus retention.
Recently both the ACCP (McCool FD and Rosen MJ, 2006) and the BTS
(Bott J et al., 2009) have published evidence-based guidelines reviewing
both pharmacological and non-pharmacological methods of augmenting
pulmonary clearance. Both guidelines are complete reviews on this topic. A
discussion of techniques aimed at enhancing airway clearance follows.
Augmentation of Mucociliary Clearance
Mucociliary clearance is one of the most important defense mechanisms of
the respiratory system. Mucociliary dysfunction is any defect in the cilliary
and secretory elements of mucocilliary interaction that disturbs the normal
defenses of the airway epithelium (Salathe M et al., 1996).
Mucociliary clearance may be ineffective because of depression of the
clearance mechanisms or oversecretion in the face of normal mucous
transport, or both. Mucus is ineffectively cleared and overproduced in
smokers with or without chronic bronchitis and in asthmatic patients (Kopec
SE, 2007).
It is also ineffectively cleared in the following situations: (a) in patients
with emphysema, bronchiectasis, and CF; (b) during and up to 4 to 6 weeks
after viral upper respiratory tract infections; (c) during and for an unknown
period after general anesthesia due to the inhalation of dry gas and cuffed
endotracheal tubes used during surgery; and (d) during prolonged endotracheal intubation due to the presence of the cuffed tube, administration of
elevated concentrations of inspired oxygen, and damage to the tracheobronchial tree from suctioning (Kopec SE, 2007).
PHARMACOLOGICAL AUGMENTATION
Numerous drugs with potential mucocilliary effect have been studied,
but only a few are clinically useful. Pharmaceutical therapy is frequently
used in conjunction with physical therapy.
Aerosol Therapy
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An aerosol is a stable suspension of solid or liquid particles dispersed in
air as a fine mist. Bland aerosols are generally used to humidify inspired
gases. Aerosol drug therapy represents the optimal modality for site-specific
delivery of pharmacologic agents to the lungs in the treatment of a number
of acute and chronic pulmonary diseases. Due to the cost and potential
hazards of aerosol therapy, use should be limited to aerosols whose clinical
value has been objectively shown (Brain J, 1990).
Bland Aerosols
Bland aerosols include sterile water or hypotonic, normotonic, and
hypertonic saline delivered with or without oxygen. These are typically
delivered via an ultrasonic nebulizer in an effort to decrease or aid in the
clearance of pulmonary secretions. The routine use of bland aerosols in the
treatment of some specific diseases has demonstrated mixed results. An
evidence-based recommendation for the use of bland aerosols has recently
been released by the British Thoracic Society (BTS) (Bott J et al., 2009).
The use of bland aerosols in the treatment of chronic obstructive
pulmonary disease (COPD) and croup appears not to be of any benefit
(Kopec SE, 2007).
The use of nebulized saline or sterile water may improve sputum clearance
in patients with non-CF bronchiectasis (Bott J et al., 2009).
Mist therapy, the delivery of a continuous aerosol of sterile water or saline,
is frequently used to treat upper airway infections in children, but has not
been shown to be more effective than air humidification (Kopec SE, 2007).
Humidity Therapy
Theoretic reasons for using humidified inspired gas are to prevent drying
of the upper and lower airways, hydrate dry mucosal surfaces in patients
with inflamed upper airways (vocal cords and above), enhance expectoration
of lower airway secretions, and induce sputum expectoration for diagnostic
purposes (Kopec SE, 2007).
Although adequate humidification is critical when dry medical gases are
administered through an artificial airway (endotracheal or tracheostomy
tube), there is little evidence to support the use of humidification in the non
intubated patient. Humidity therapy is water vapor and, at times, heat added
to inspired gas with the goal of achieving near-normal inspiratory conditions
when the gas enters the airway (Fink J, 2003).
Several external devices are available to artificially deliver heat and
moisture. Two such devices for mechanically ventilated patients are: (a) a
heated waterbath humidifier, which is an external active source of heat and
water, and (b) a heat and moisture exchanger filter (HMEF), which passively
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retains the heat and humidity, leaving the trachea during expiration and
recycles it during the next inspiration. HMEFs are also known as
hygroscopic condenser humidifiers or artificial noses. The HMEF is
designed to combine air-conditioning and bacterial filtration. In a
randomized controlled trial, both devices were shown to be equally safe
(Hurni J–M et al., 1997).
Cold-water devices such as bubble humidifiers are frequently used to add
humidity to supplemental oxygen administered to spontaneously breathing
patients. Due to a lack of objective evidence to support the practice, the
American College of Chest Physicians recommends elimination of the
routine use of humidification of oxygen at flow rates of 1 to 4 L per minute
when environmental humidity is sufficient (American College of Chest
Physicians, 1984), while the BTS does not recommend its use (Bott J et al.,
2009).
Patients requiring high flow rates of oxygen (> 10 L per minute)
frequently develop discomfort due to upper-airway dryness. There are
several devices available to deliver humidification via nasal cannulae at high
flow rates (high flow oxygen delivery), including Vapotherm (Vapotherm,
Annapolis, MD) and the Fisher & Paykel 850 (Fisher and Paykel Healthcare
Corp, Auckland, New Zealand). Although these devices have been shown to
improve patients' comfort (Chanques G et al., 2009).
Pharmacologically Active Aerosols
Inhaled therapy has several well-recognized advantages over other drug
delivery routes. The drug is delivered directly to its targeted site of action;
therefore, when compared to other routes of administration, a therapeutic
response usually requires fewer drugs, there are fewer side effects, and the
onset of action is generally faster (Robinson BR et al., 2009).
A broad range of drugs is available as aerosols to treat obstructive lung
diseases. These include β-adrenergic agonists, anticholinergics, antiinflammatory agents, and anti-infectives. Additionally, the inhaled route is
used to deliver drugs that are not effective when delivered by the oral route
(e.g., pentamidine) (Fink J, 2003).
Bronchodilators
There are two classes of inhaled bronchodilators: (a) β2-adrenergic
receptor agonists (short-acting and long-acting) and (b) anticholinergic
agents. Short-Acting β2-Adrenergic Receptor Agonists Although β1- and
β2-adrenergic receptors are present in the lungs, β2-adrenergic receptors
appear to be entirely responsible for bronchodilation. Therefore, β2adrenergic receptor agonists (e.g., albuterol, pirbuterol, and terbutaline) are
the agents commonly preferred for the relief of acute symptoms of
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bronchospasm. In addition to the bronchodilating properties of β2adrenergic receptor agonists, other actions include augmentation of
mucociliary clearance; enhancement of vascular integrity; metabolic
responses; and inhibition of mediator release from mast cells, basophils, and
possibly other cells (Kopec SE et al., 2007).
Inhalation of β2-selective agonists is considered first-line therapy for the
critically ill asthmatic (National Asthma Education and Prevention
Program, 2002) and COPD patient (GOLD Scientific Committee, 2005).
Although these agents can be administered orally, by inhalation, or
parenterally, the inhaled route is generally preferred because fewer side
effects occur for any degree of bronchodilation (Kopec SE et al., 2007).
For most patients experiencing acute asthma attacks, inhalation is at least
as effective as the parenteral route (Kopec SE et al., 2007).
Inhaled β2 agonists can be delivered as an aerosol from a jet or ultrasonic
nebulizer or from a metered-dose inhaler (MDI). The relative efficacies of
the nebulizer and MDI are dependent on the adequacy of technique.
Although it was formerly a standard practice to deliver bronchodilators by
nebulizer, several prospective, randomized controlled trials have challenged
this practice.
Delivering β2 agonists by MDI with a spacer device (holding chamber)
under the supervision of trained personnel is as effective in the emergency
setting as delivery by nebulizer for adults and children (Kopec SE et al.,
2007).
In hospitalized patients, β2 agonists delivered by MDI are as effective as
therapy with a nebulizer and can result in a considerable cost savings (Kopec
SE et al., 2007).
An analysis of 16 trials (686 children and 375 adults) to assess the effects
of MDIs with holding chambers compared to nebulizers for the
administration of β2 agonists for acute asthma concluded that MDI with a
holding chamber produced at least equivalent outcomes as nebulizer delivery
(Cates CJ et al., 2010).
Ideal frequency of administration and dosing of β2 agonists has not been
determined. For emergency department and hospital-based care of asthma,
the National Institutes of Health Expert Panel Report 2 (National Asthma
Education and Prevention Program, 2002) recommends up to three
treatments in the first hour. Subsequent treatments should be titrated to the
severity of symptoms and the occurrence of adverse side effects, ranging
from hourly treatments for moderate severity to hourly or continuous
treatments for severe exacerbations. Recommendations for initial treatment
of severe acute exacerbations of COPD are for the administration of short-4-
acting β2 agonists every 2 to 4 hours if tolerated (American Thoracic
Society, 1995).
When given by jet nebulizer, the usual adult dose of albuterol is 0.5 mL of
an 0.5% solution (2.5 mg) diluted in 2.5 mL of saline (or 3 mL of 0.083%
unit-dose nebulizer solution). The frequency of dosing varies depending on
the disease and the situation. It can range from every 4 to 6 hours in patients
with COPD and stable asthma to every 20 to 30 minutes for six doses in
patients with status asthmaticus (Kopec SE et al., 2007).
In this randomized controlled trial of spontaneously breathing patients
with FEV1 less than 40% predicted, continuous delivery of high-dose (7.5
mg per hour) or standard-dose (2.5 mg per hour) albuterol were both
superior to hourly intermittent treatments with 2.5 mg in increasing FEV1.
Although there was no difference in FEV1 improvement between the two
continuous doses, the standard dose had fewer side effects. Although the
usual dosage of bronchodilator by MDI is two puffs (90 μg per puff) every 4
to 6 hours in stable hospitalized and ambulatory adult patients, the dosage
must be increased up to six fold in acute severe asthma to achieve results
equivalent to those achieved with small-volume nebulizers (Kopec SE et al.,
2007).
In an emergency department treatment study of severe asthma, four puffs
of albuterol by MDI every 30 minutes for a total of six dosing intervals (24
puffs) was found to be safe and equivalent to 2.5 mg of albuterol diluted in 2
mL of saline given every 30 minutes for six doses (Kopec SE et al., 2007).
Others have treated acute episodes of asthma in the emergency department
in a dose-to-result fashion as follows: initially four puffs by MDI of
bronchodilator of choice, followed by one additional puff every minute until
the patient subjectively or objectively improved or side effects (e.g., tremor,
tachycardia, arrhythmia) occurred (Kopec SE et al., 2007).
Tremor is the principal side effect of β2 agonists, due to the direct
stimulation of β2-adrenergic receptors in skeletal muscle. Tachycardia and
palpitations are less frequent with the selective β2 agonists (e.g., albuterol)
than with nonselective β1-β2 agonists such as isoproterenol. Although
vasodilatation, reflex tachycardia, and direct stimulation of the heart can
occur even with the use of selective β2 agonists, cardiac adverse occurrences
are uncommon when usual doses of inhaled β2 agonists are administered. A
transient decrease in arterial oxygen tension may occur in patients with acute
severe asthma. This response is likely due to the relaxation of the
compensatory vasoconstriction in areas of decreased ventilation together
with increased blood flow due to increased cardiac output (Kopec SE et al.,
2007).
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Β2-adrenergic agonists can cause acute metabolic responses including
hyperglycemia, hypokalemia, and hypomagnesemia (Kopec SE et al., 2007).
Perinatal outcomes of 259 pregnant women with asthma who were treated
with β2-adrenergic agonists during pregnancy were compared to those of
101 women who were not treated with these agents, and 295 non-asthmatic
women (Kopec SE et al., 2007).
There were no differences in perinatal mortality rates, congenital
abnormalities, preterm delivery, low birth weights, mean birth weights, or
the number of small-for-gestational-age infants. In addition, there were no
differences in Apgar scores, labor or delivery complications, or postpartum
bleeding. Levalbuterol (Xopenex, Sepracor Inc, Marlborough, MA)
inhalation solution, the (R)-enantiomer of racemic albuterol, is a relatively
selective, third-generation β2-adrenergic receptor agonist approved for
treatment of bronchospasm in adults and children aged 12 years or older.
Levalbuterol appears to offer little benefit over albuterol in improving FEV1
in patients with asthma, and is not associated with any fewer systemic side
effects such as tachycardia and hypokalemia (Lotvall J et al., 2001).
Long-Acting Inhaled β2 Agonists
Long-acting inhaled β2 agonists (e.g., salmeterol and formoterol) are
currently not recommended for use in acute exacerbations of asthma (Expert
Panel Report 2) (National Asthma Education and Prevention Program,
2002) or COPD (American Thoracic Society, 1995). One prospective,
double-blind, randomized, placebo-controlled trial demonstrated a possible
role for salmeterol as an adjunct to conventional therapy for hospitalized
asthmatic patients (Peters J I et al., 2000).
Anticholinergics appear to have a role in acute asthma when combined
with sympathomimetic drugs (Kopec SE et al., 2007).
Mucolytics
N-Acetylcysteine
Theoretically, mucolytic agents facilitate expectoration of excessive lowerairway secretions and improve lung function (Kopec SE et al., 2007).
Although N-acetylcysteine (Mucomyst, Apothecon, Princeton, NJ), the
prototypic mucolytic agent, liquefies inspissated mucous plugs when
administered by direct intratracheal instillation (Irwin RS and Thomas HM
III, 1973), it is of questionable clinical use when administered as an aerosol
to nonintubated patients because very little of the drug is actually delivered
to the lower respiratory tract. Inhaled N-acetylcysteine failed to prevent
deterioration in lung function or exacerbations in patients with COPD
(Decramer M et al.,2005), and failed to demonstrate any benefit of
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nebulized N acetylcysteine in patients with CF (Duijvestijn YC and Brand
PL, 1999).
However, a small randomized trial suggested that nebulized Nacetylcysteine in combination with aerosolized heparin reduced the
incidence of acute lung injury (ALI) and decreased mortality in patients with
acute smoke inhalational injuries (Miller AC et al., 2009).
mucolytics should be administered to these patients in combination with a
bronchodilator (Kopec SE et al., 2007).
Recombinant Human DNase
Recombinant human DNase (Pulmozyme, Genentech, South San
Francisco, CA), when given as an aerosol in a dose of 2.5 mg once or twice
a day to patients with CF, led to a moderate but significant decrease in
dyspnea, a reduction in costs related to exacerbations of respiratory
symptoms, and a modest improvement in FEV1 after 3 months (Bott J et al.,
2009).
Other Mucolytics
Studies to determine the efficacy of other mucolytic agents, including
water, have produced conflicting results. Current evidence does not appear
to justify their use in clinical practice. Consensus guidelines for asthma
(National Asthma Education and Prevention Program, 2002) and COPD
(American Thoracic Society, 1995) do not recommend the use of mucolytic
agents in the treatment of acute exacerbations.
Anti-infectives
Aerosolization of antimicrobial solutions has been shown to be effective in
CF patients with tracheobronchial infections and colonization (Bott J et al.,
2009).
In addition, inhaled antibiotics have also been used to treat
tracheobronchial infections in patients with non-CF–related bronchiectasis,
to treat and prevent ventilator-associated pneumonia, to treat chronic
bronchitis in patients with COPD, to treat bronchiolitis in children, and to
treat patients with multidrug-resistant tuberculosis (MDR-Tb) and
mycobacterium avium complex (MAC) (Robinson BR et al., 2009).
However, unlike their use in treating patients with CF, the benefits of
using inhaled antibiotics for these other indications is less defined. Inhaled
tobramycin has been demonstrated to decrease sputum bacteria counts,
improve lung function, decrease the number of exacerbations, and improve
quality of life in patients with pulmonary infections or colonization from CF
(Fiel SB, 2008).
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For patients with non-CF–related bronchiectasis, inhaled antibiotics are
not as well studied, but may decrease sputum bacteria counts and decrease
the number of hospitalizations, but have no impact on lung function or
survival (LoBue PA, 2005).
Inhaled antibiotics have not been shown to provide any benefit in patients
with chronic bronchitis or COPD (MacIntyre N R and Rubin BK, 2007).
Prophylactic use of inhaled antibiotics to decrease the risk of developing
ventilator-associated pneumonia has not been shown to be of any benefit
(MacIntyre N R and Rubin BK, 2007).
In addition, inhaled antibiotics appear to have no benefit over systemic
antibiotics in treating ventilator-associated pneumonia (MacIntyre N R and
Rubin BK, 2007).
A few small studies suggest that inhaled amikacin and rifampicin may be
of some benefit in treating severe MDR-Tb and severe infections with MAC
(Mutti P et al., 2009).
Only tobramycin is currently FDA approved for inhalational use. Other
antibiotics occasionally administered via an aerosol include colistin,
amikacin, gentamicin, aztreonam, azithromycin, vancomycin, ceftazidime,
and imipenem. Inhaled colistin should be used with great caution. Colistin
decomposes into several toxic compounds that, if inhaled, can result in acute
lung injury and respiratory failure. Colistin suspension should be
administered within 6 hours after it is prepared (FDA MedWatch, 2007).
Inhaled tobramycin is approved for treatment of patients with CF who are
(a) at least 6 years of age, (b) have FEV1 greater than or equal to 25% and
less than or equal to 75% predicted, (c) are colonized with Pseudomonas
aeruginosa, and (d) are able to comply with the prescribed medical regimen
(Fiel SB, 2008).
Aerosolized ribavirin has been used for patients with RSV infection and
severe lower respiratory tract disease, or infants with chronic underlying
conditions such as cardiac disease, pulmonary disease, or a history of
prematurity (Kopec SE et al,. 2007).
However, proof of effectiveness in treating RSV infections is lacking. One
study failed to establish the efficacy of inhaled ribavirin in immunocompromised adults with RSV infections (Ebbert JO and Limper AH,
2005).
Aerosolized ribavirin has been suggested to be beneficial in treating
infections due to influenza A and B (Knight V and Gilbert BE, 1987).
Ribavirin, in combination with systemic corticosteroids, was used
empirically for the treatment of severe acute respiratory syndrome (SARS).
However, a review of 14 clinical reports failed to demonstrate that ribavirin
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decreased the need for mechanical ventilation, or mortality, in patients with
SARS (Fujii T et al., 2004).
There are several potential hazardous effects of aerosolized ribavirin. It
can cause nausea, headaches, and bronchospasm (Krilov L, 2002).
In addition, it poses potential risks to healthcare workers who administer
the medication. It has been shown to cause conjunctivitis as it can precipitate
on contact lenses, and bronchospasm in healthcare workers administering
the medication (Krilov L, 2002).
In addition, ribavirin is highly teratogenic. Although studies suggest that
absorption of ribavirin by healthcare workers administering the medication
is minimal (Kopec SE et al., 2007), the short-term and long-term risks to
women remain unknown. Therefore, conservative safety practices must be
followed (Krilov L, 2002).
At present, there is no indication for the use of inhaled corticosteroids in the
treatment of the critically ill with acute exacerbations of obstructive lung
disease. Systemic corticosteroids (oral or intravenous) are the recommended
first-line agents for the treatment of acute asthma (National Asthma
Education and Prevention Program, 2002) and COPD (American Thoracic
Society, 1995).
Racemic Epinephrine
Racemic epinephrine is effective in decreasing laryngeal edema by causing
vasoconstriction (Kopec SE et al., 2007).
The usual adult dose is 0.5 mL of a 2.25% solution diluted in 3 mL of
normal saline every 4 to 6 hours. Because rebound edema frequently occurs,
patients must be observed closely. Tachycardia is common during treatment
and may precipitate angina in patients with coronary artery disease Kopec
SE et al., 2007).
The role of racemic epinephrine aerosol in epiglottitis is not known.
Similarly, inhaled racemic epinephrine is used to treat postextubation
stridor, but this use has not been vigorously studied. Nebulized racemic
epinephrine appears to have no benefit over nebulized albuterol in the
management of bronchiolitis (Winterhalter M et al., 2008).
Aerosolized Vasodilators
Iloprost is an approved inhaled prostacyclin analog used for the chronic
treatment of primary pulmonary hypertension and pulmonary hypertension
due to use of appetite suppressants, portopulmonary syndrome, connective
tissue disease, and chronic thromboembolic disease. It has also been used in
patients with acute pulmonary hypertension after coronary bypass surgery,
and may be more effective than inhaled nitric oxide (Olschewski H et al.,
2002).
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It is currently FDA approved for patients with primary pulmonary
hypertension and New York Heart Association (NYHA) class III (symptoms
with minimal activity) and class IV (symptoms at rest) symptoms. Iloprost is
administered as 2.5 to 5 μg doses, six to nine times per day. It needs to be
delivered via a specialized nebulizer system, the Prodose AAD system
(Respironics, Murrysville, PA), to ensure proper dosing. A randomized
double-blind, placebo-controlled trial demonstrated that iloprost produced
improvements in 6- minute walk, hemodynamics, dyspnea, and quality of
life after 12 weeks of therapy (Olschewski H et al., 2002).
Inhaled Cyclosporin
A randomized double-blind, placebo-controlled trial demonstrated
improvement in survival and longer periods free of chronic rejection in lung
transplant patients treated with inhaled cyclosporin (Iacono AT et al, 2006).
Modes of Delivery
In the critical care setting, there are generally two types of aerosol delivery
devices in use: those that create and deliver wet particles (air-jet nebulizers)
and those that deliver preformed particles (pressurized MDIs) with or
without MDI auxiliary delivery systems (spacers).
Nebulizers
Air-jet nebulizers are a non propellant-based option for inhaled drug
delivery. Jet nebulizers rely on a high gas flow (provided by a portable
compressor, compressed gas cylinder, or 50-psi wall outlet), Venturi
orifices, and baffles to generate respirable particles, generally in the range of
1 to 5 μm diameter (Kopec SE et al., 2007).
Small-volume nebulizers, equipped with small fluid reservoirs, are used
for drug delivery (Kopec SE et al., 2007).
Metered-Dose Inhalers
An MDI is a pressurized canister that contains drug suspended in a
propellant and combined with a dispersing agent. The canister is inverted,
placed in a plastic actuator, and, when pressed, delivers a metered dose of
drug. The MDI is capable of delivering a more concentrated drug aerosol, as
a bolus, than the solutions commonly available for nebulizers (Kopec SE et
al., 2007).
Metered-Dose Inhaler Auxiliary Devices
To overcome problems such as incorrect administration, oropharyngeal
deposition, and inconsistent dosing associated with MDI aerosol delivery,
several auxiliary devices (i.e., spacer, holding chamber) were developed
(Kopec SE et al., 2007).
When used properly, these devices have the following advantages: (a) a
smaller, more therapeutic particle size is achieved; (b) oropharyngeal
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impaction is decreased; (c) fewer systemic side effects are experienced due
to less oropharyngeal deposition compared to MDI alone; and (d) the risk of
oral thrush associated with inhaled corticosteroids is decreased. It has been
shown that among patients who have difficulty with coordination particularly the elderly, handicapped, infants, and children younger than 5
years of age- spacer devices improve the efficacy of MDIs (Tinkelman DG
et al., 1991).
Choice of Delivery System
Since the development of the first MDI in the 1960s, there has been
continuing debate about which aerosol delivery system, nebulizers, or MDI
is superior. In 1997, Turner et al, (Turner MO et al., 1997) published a
meta-analysis of 12 studies that compared bronchodilator delivery via
nebulizer to delivery via MDI. Studies included in the review were all
randomized clinical trials of adults with acute asthma or COPD who were
treated in the emergency department or hospital and measured FEV1 or peak
expiratory flow rate. In all but two of the trials, spacers were used with
MDIs. Based on the results of these studies, the authors concluded that there
was no difference in effectiveness between the two delivery methods.
A Cochrane Library meta-analysis by Cates et al. (Cates CJ et al., 2010)
compared the clinical outcomes of adults and children with acute asthma
who received β2 agonists by nebulizer or MDI with spacer. In this review
that included 16 randomized controlled trials, the authors concluded that the
outcomes (hospital admission, length of stay in the emergency department,
respiratory rate, heart rate, arterial blood gases, tremor and lung function) of
both groups were equivalent. In the United States, MDIs are underused in
the acute care setting (Kopec SE et al., 2007).
Barriers to selection of these devices include reimbursement issues and
the misconception of clinicians regarding efficacy. Many third-party payors
reimburse for the nebulizer/drug package but not for the MDI. In the critical
care setting, selection of an aerosol delivery system for the spontaneously
breathing patients should be based on several factors. In general, because the
MDI with or without spacer is the most convenient and cost-effective
method of delivery, it should be chosen whenever possible. Its use may be
limited by factors such as the patient's ability to actuate and coordinate the
device, either of which can affect aerosol deposition to the lungs; patient
preference; practice situations; and economic evaluations. Additionally,
parenchymal dosing with drugs such as pentamidine and ribavirin requires
the use of a nebulizer (Kopec SE et al., 2007) .
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The cost of a disposable nebulizer system in a hospital setting may be
lower than the cost of a MDI and spacer device if patients are discharged
with a second spacer device (Cates CJ et al., 2010).
Aerosols can be delivered to intubated and mechanically ventilated
patients with small-volume side-stream nebulizers connected to the
inspiratory tubing or MDIs with an aerosol holding chamber. Although both
delivery systems are effective in delivering aerosolized medications to the
ventilated patient (Kopec SE et al., 2007), drug delivery can be significantly
reduced if proper technique in setting up and using both devices is not
followed.
MECHANICAL AUGMENTATION
Chest physiotherapy
Positioning
Postural drainage
Percussion
Vibration
High frequency chest compression
Rotational therapy
Forced expiration
Augmentation of Cough Effectiveness
Mechanical insufflation and exsufflation
Bronchoscopy
Chest physiotherapy:
Chest physical therapy is used in the intensive care unit (ICU) to minimize
pulmonary secretion retention, to maximize oxygenation, and to re-expand
atelectatic lung segments. This article reviews how chest physical therapy is
used with patients who are critically ill. A brief historical review of the
literature is presented. Chest physical therapy treatments applicable to
patients in the ICU are discussed. Postural drainage, percussion, vibration,
breathing exercises, cough stimulation techniques, and airway suctioning are
described in detail, with current references. The importance of patient
mobilization is emphasized. The advantages of chest physical therapy over
therapeutic bronchoscopy also are discussed. Two patient examples are used
to demonstrate the beneficial effects that may be obtained with chest
physical therapy. Following the removal of retained secretions, arterial
oxygenation and partial pressure of arterial oxygen/fraction of inspired
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oxygen concentration ratios improved, and atelectasis resolved without the
negative hemodynamic side effects of therapeutic bronchoscopy. Physical
therapists trained in the ICU can safely perform chest physical therapy with
the majority of patients who are critically ill (Ciesla ND, 1996).
Efficacy of Chest Physical Therapy in the Intensive Care Unit
The efficacy of chest physical therapy can be determined by a reduction in
the incidence of pulmonary infection or an improvement in pulmonary
function. The mortality rate from nosoconmial pneumonia remains high and
ranges from 30% to 60% (Light RB et al., 1992), (Ruiz-Santana S et al.,
1987).
The diagnosis of pneumonia in the critical care setting is difficult. The
clinical criteria used to diagnose pneumonia include the presence of fever,
purulent sputum expectoration, and leukocytosis, a Gram stain showing
many polymorphonuclear cells and a single morphologically distinct
organism, and a new pulmonary infiltrate on chest radiograph (Stevens RM
et al., 1974).
For some patients in the ICU, the response to chest physical therapy can
differentiate the diagnosis of atelectasis from pneumonia and can be used to
determine which patients require antimicrobial therapy (Light KB et al.,
1992).
Indications for Treatment
Many authors have described the inappropriate use of chest physical therapy.
For example, the American Association of Respiratory Care's clinical
practice guideline for postural drainage (American Association of
Respiratory Care, 1991) considers recent spinal surgery, rib fractures, and
bronchopleural fistulas to be contraindications for postural drainage. This
approach may be a result of prescribing therapy without a clear-cut
indication for treatment (Tab. 1) or of the health care provider not having the
training to position the patient with neurologic and orthopedic injuries or the
skills to assess the patient's breath sounds, vital signs, and ability to cough.
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Chest Physical Therapy Components
Mucociliary activity and an effective cough are needed for normal airway
clearance (Leith DE, 1985; Mossberg B and Cramer P, 1980).
Viscous secretions, the presence of a cuffed tracheal tube, dehydration,
hypoxemia, immobility, and poor humidification of gases impede
mucocilliary clearance, causing secretion retention (Newhouse MT, 1973).
Neurologic conditions and pharmacologically induced paralysis affecting
the innervation of the glottis or intercostal and abdominal muscles may
diminish airflow, resulting in an ineffective cough (Siebens AA et al., 1974).
Positioning
The benefits of positioning versus postural drainage are often difficult to
discern. Changes in ventilation- perfusion relationships with positional
changes have been documented (Clauss RH et al., 1968; Douglas WW et
al., 1977).
Side-to-side turning decreases postoperative fever and improves
oxygenation (Chulay M et al., 1982).
Improvements in arterial oxygenation after patient positioning, including
in patients with adult respiratory distress syndrome (ARDS), have been
shown (Remolina C et al., 1981; Langer M et al., 1988; Arborelius M et
al., 1974; Pappert D et al., 1994).
Positioning patients for chest physical therapy with the "good lung down"
is associated with improved ventilation-perfusion ratios and oxygenation
(Zack MB et al., 1974).
Prone positioning
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Prone positioning has been shown to increase the PaO2 in many patients
with acute lung injury and acute respiratory distress syndrome (Chatte G et
al., 1997).
However, recent studies reporting no survival benefit for the use of prone
positioning in acute respiratory distress syndrome have dampened
enthusiasm for this technique (Guerin C et al., 2004).
Semi-Recumbent Position
Several studies using radiolabeled enteral feeding solutions in
mechanically ventilated patients have reported that aspiration of gastric
contents occurs to a greater degree when patients are in the supine position,
compared with the semi-recumbent position (Orozco-Levi M et al., 1995).
Ibanez et al (Ibanez J et al., 1992) randomized orally intubated patients to
supine or semi-recumbent position.
Postural Drainage
Postural drainage refers to placing the body in a position that allows
gravity to assist drainage of mucus from the lung periphery to the segmental
bronchus and upper airway (Wong JW et al., 1977).
Postural drainage enhances peripheral lung clearance, increases functional
residual capacity, and accelerates mucus clearance (Bateman J et al., 198;
Sutton PP et al., 1983).
Postural drainage in conjunction with mechanical ventilation and PEEP is
thought to increase transpulmonary pressure, improve ventilation-perfusion
ratios, increase lung/thorax compliance of the non- dependent hemithorax,
and reduce collateral airway resistance (Mackenzie CF, 1989).
Percussion and Vibration
Percussion and vibration are the techniques most frequently recommended
for the patient who is intubated and mechanically ventilated and for patients
with impaired cognition or poor coughing ability (Imle PC, 1989).
Percussion and vibration are used to enhance mucocilliary clearance from
both central and peripheral airways (Imle PC, 1989).
The exact mechanism of action of chest percussion is unknown, but there
is some evidence from animal models that physical stimulation alters airflow
and is associated with the release of pulmonary chemical mediators,
mediators that may improve cilliary transport speed by as much as 340%
(King M et al., 1983).
This is particularly important for patients in the ICU who have periods of
hemodynamic instability and require multiple diagnostic and therapeutic
procedures. Both techniques are used with postural drainage.
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Manual techniques should be applied only over the lung that approximates
the chest wall with full inspiration (Seidel HM et al., 1995).
Percussion:
Percussion is used during both the inspiratory and expiratory phases of
respiration. The therapist's hand should create an air cushion, and the energy
wave created by that hand is transmitted through the chest wall and is
thought to dislodge secretions from the bronchial walls (Brimoulle S et al.,
1988).
Once the secretions are removed by coughing or suctioning, breath sounds
improve (Ciesla ND, 1989).
When bronchospasm persists as a result of percussion, appropriate
intervention should be implemented. The optimal frequency and force of
chest percussion are not known. Frequencies of 100 to 480 cycles per
minute, producing 2 to 4 ft-lb (2.7-5.4 Nsm) and 58 to 65 N of force 011 the
chest wall have been reported (Imle PC, 1989).
Differences in technique may account for discrepancies in therapy
advocated in different parts of the United state (Kigin C:M, 1984).
For patients with rib and sternal fractures, controlled mechanical
ventilation may even stabilize the fracture site by minimizing negative
intrathoracic pressure (Imle PC, 1989).
Vibration
Vibration is a more forceful technique than percussion. At 12 to 20 HZ,
vibration is similar to the normal beat frequencies of human cilia (Dulfano
MJ et al., 1981).
The rib cage is "shaken" during the expiratory phase of respiration. Some
clinicians define vigorous vibration as "rib shaking" or "rib springing.
Vibration is used with both patients who are spontaneously breathing and
patients who are mechanically ventilated. Secretions move into the upper
airway's when vibration is performed during bronchoscopy (Kigin C: M,
1984).
Mechanical devices: Mechanical percussors and vibrators were introduced
in the late 1960s to permit patients with cystic fibrosis more independence
with therapy. For adult patients in the ICU, use of these devices increases
cost, does not reduce staffing requirements, and introduces the risk of crossinfection, without documented benefit over manual techniques. Although
Radford and colleagues (Radford G et al., 1982) advocate mechanical
percussion at 25 to 35 Hz, their research using an animal model has not been
extended to human subjects. Mechanical devices, used with patients who
have chronic pulmonary disease, offer no benefit over forced-expiration
techniques combined with postural drainage (Hammon WE, 1978).
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Breathing Exercises
Once extubated, alert, and cooperative, the patient in the ICU may benefit
from breathing exercises to increase tidal volume, improve thoracic cage
mobility, increase inspiratory capacity, enhance cough efficacy, and assist in
removal of secretions. Breathing exercises are indicated in the ICU setting
for patients with neuromuscular disease or injury affecting the respiratory
muscles.Breathing exercises also is used when thoracic excursion is
decreased as a result of retained secretions or pain or when a patient is
immobile following surgery.
Breathing exercises are not indicated during mechanical ventilation but
may be used during weaning from mechanical ventilation. There are several
types of breathing exercises. Diaphragmatic breathing and lateral costal and
segmental costal expansion exercises are used most often postoperatively.
Use of a flutter valve, the forced-expiration technique- more recently
referred to as the active cycle of breathing (huffing at various lung volumes
interspersed with diaphragmatic breathing)-and autogenic drainage
(Using a sequence of breathing maneuvers at various lung volumes to
optimize airflow within multiple generations of bronchi) are beneficial in
patients with cystic fibrosis, although the efficacy of these procedures after
surgery has not been determined. Inspiratory muscle training and resistive
diaphragmatic breathing exercises may be beneficial while weaning the
patient with quadriplegia or chronic obstructive pulmonary disease from the
ventilator.
High-frequency chest compression (HFCC)
High-frequency chest compression (HFCC) has recently gained popularity
as a means of enhancing mucus clearance in patients with cystic fibrosis
(Hansen LG et al., 1994).
Tracheal Suctioning
Tracheal suctioning is an integral component of chest physical therapy for
the patient who is intubated. Deep suctioning is necessary for patients who
cannot mobilize secretions to the proximal portion of the tracheal tube by
coughing or huffing. Withholding suctioning may result in airway occlusion
and hypoxemia (Stone KS and Turner B, 1989).
Occupational Safety and Health Administration guidelines (Goodner B,
1993) for exposure to blood and body fluids, therefore, must be followed.
Eye protection, a mask for protection from bloody or mucus secretions and
sterile gloves should be worn. As part of the initial assessment, the therapist
should evaluate the patient's need for and response to suctioning. Airway
suctioning frequently improves breath sounds and may lower airway
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pressures. When no segmental or lobar pathology is present, suctioning may
be adequate and postural drainage with manual techniques may not be
indicated. Patients who are intubated and who have a poor cough usually
require tracheal suctioning. As with all physical therapy in the ICU, the
patient's vital signs should be assessed before, during, and after the
procedure. Table 2 lists the most frequently cited complications associated
with tracheal suctioning and the recommended interventions to minimize
side effects.
Table 2
Precautions and contraindications:
For patients who have retained secretions, are unable to cough effectively,
and have difficulty tolerating suctioning, suctioning should be timed with
chest physical therapy to minimize the risk of hypoxemia.
Nasotracheal suctioning (suctioning through the nose into the trachea
without an artificial airway in place) is contraindicated in the presence of
stridor because of the increased risk of mechanical trauma to an edematous
airway (Peruzzi W and, Shapiro BA, 1996).
Because the catheter may enter the brain, nasotracheal suctioning with
basilar skull fracture, facial fractures, and known or suspected cerebrospinal
fluid leaks is also contraindicated (Peruzzi W and, Shapiro BA, 1996).
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Nasotracheal suctioning may result in apnea, laryngospasm,
bronchospasm, and severe cardiac arrhythmia (Stone KS and Turner B,
1989).
Systems:
Suctioning can be performed using either an open or closed system. When
using an open system, the patient is disconnected from the mechanical
ventilator and suctioned using a conventional catheter. The patient remains
on the mechanical ventilator for closed- system suctioning. Closed-system
suctioning is accomplished by using either a "port adapter" or the more
recently introduced in-line suctioning (Bodai BI, 1982).
The recommended features of suction catheters are listed in Table 3.
Prior to suctioning a patient who is mechanically ventilated, the therapist
should be aware of the washout time (the time necessary for the gas volume
in the ventilator circuit to be replaced with gases at the higher FIO,) of the
ventilator in use (Benson MS and Pierson DJ, 1990).
Table 3
Interventions for minimizing hypoxemia:
The harmful effects of tracheal suctioning include hypoxia, cardiac
arrhythmias, and death (Stone KS and Turner B, 1989).
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Accepted methods for minimizing suction-induced oxygen desaturation
include use of a port adapter, lung hyperinflation, preoxygenation, and inline suctioning. Placing a valve or port adapter over the end of the
endotracheal or tracheal tube allows ventilation during the procedure,
maintains PEEP, and preserves functional residual capacity. The result is
improved oxygenation during suctioning (Kulmar A et al., 1970).
Wsing the adapter may minimize the need for preoxygenation, therefore
eliminating the potential hazards of exposure to 100% oxygen (Jung RE
and Newman J,1982).
A port adapter is recommended for patients who are mechanically
ventilated patients and require a PEEP of > 10 cm H20 and for patients who
are at high risk for suction-induced arrhythmias and hypokalemia (Brown
SE et al., 1983).
Proponents of in-line suctioning report less oxygen desaturation than with
an open system; however, the same results have been achieved by using a
port adapter (Noll IML et al., 1990).
Clinical impressions of in-line suctioning that need to be substantiated
with further research include the following: (1) The catheter is more difficult
to maneuver, (2) the additional weight of the catheter may increase tracheal
damage, (3) higher inspiratory flow rates may be required, and (4) airway
pressure may drop as a result with suctioning and intermittent mandatory
ventilation (IMV) (Noll IML et al., 1990).
Preoxygenation is the most commonly used method for preventing oxygen
desaturation (Taggart JA et al., 1988).
The mechanical ventilator or an MRB is used to inflate the lungs and
increase the inspired oxygen concentration prior to suctioning. For patients
who are mechanically ventilated, the ventilator is preferred over the MRB.
Minute ventilation, PEEP, and FIO, are all controlled, and there are no
variations in lung volume, flow rates, and pressure based on the clinician's
bagging technique (Stone KS et al., 1991).
When using the ventilator, the second clinician who may be required when
using an MRB is not needed. When using an MRB, the FIO, varies from
33% to loo%, depending on flow rate, minute ventilation, and whether the
bag has a reservoir (Chulzy M, 1987).
Saline installation:
Saline instillation is commonly used before and during tracheal suctioning
to "loosen" secretions. Saline instilled through a tracheal or endotracheal
tube is not likely to reach the peripheral airways, where secretions are most
prevalent. To be effective, the saline must pass through several generations
of segmental bronchi and reach the terminal bronchioles and alveoli..
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Patient Mobilization
Mobilizing the patient in the ICU is important, but the patient's medical
condition usually prohibits independent ambulation and vigorous activity.
The severity of injury or disease and life-sustaining paraphernalia also
usually limit mobilization of patients who are mechanically ventilated to
dependent or stand-pivot transfers and active- and passive-range of motion
exercises. Upright positioning of patients is encouraged to improve coughing
and lung volumes, including functional residual capacity, and lung
compliance. Patients who are difficult to wean from the ventilator frequently
benefit from transfer training and ambulation with portable ventilator.
Rehabilitative techniques are used while monitoring vital signs to note any
alterations from baseline. The details of mobilizing the patient in the ICU are
beyond the scope of this article but are described elsewhere
Rotational Therapy
Normal persons, even during sleep, change their position approximately
every 12 min, which Keane5 called the minimum physiologic mobility
requirement. In contrast, critically ill patients are often cared for in the
supine position for extended periods of time. In the supine position, the
functional residual capacity is decreased because of alveolar closure in
dependent lung zones. Immobility may impair mucocilliary clearance, with
the accumulation of mucus in dependent lung regions. This can lead to
atelectasis and infection of dependent lung zones. As standard practice,
patients in the ICU are usually turned every 2 hours by the nursing staff.
Rotational therapy, which includes kinetic therapy and continuous lateral
rotation therapy (CLRT), emerged in the 1980s for patients with prolonged
immobilization. Kinetic therapy is the continuous turning of a patient to at
least 40 degrees on each side. The entire kinetic bed frame rotates the patient
from side to side at a speed of about half a degree per second. Oscillating
beds, or air-loss beds, accomplish turning by inflating and deflating
compartments in the mattress of the bed, and the bed frame does not rotate.
With CLRT, the degree of turn to each side is less than 40 degrees. The
degree of turning and the length of time the patient spends on each side are
programmable; kinetic beds can provide percussion and vibration therapy,
and they allow for elevation of the head of the bed.
Augmentation of Cough Effectiveness
Although mucocilliary transport is the major method of clearing the airway
in healthy subjects, cough is an important reserve mechanism, especially in
lung disease (Kopec SE et al., 2007).
Pathophysiology of Ineffective Cough
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The effectiveness of cough in clearing an airway theoretically depends on
the presence of secretions of sufficient thickness to be affected by twophase, gas-liquid flow and the linear velocity of air moving through its
lumen (Kopec SE et al., 2007).
The ineffectiveness of voluntary coughing in normal subjects to clear
tagged aerosol particles in the lower airways is probably due to the inability
of the moving airstream to interact appropriately with the normally thin
mucus layer on which the particles were deposited (Kopec SE et al., 2007).
All conditions that may lead to an ineffective cough interfere with the
inspiratory or expiratory phases of cough; most conditions affect both.
Cough effectiveness is likely to be most impaired in patients with respiratory
muscle weakness because their ability to take in a deep breath in (flow rates
are highest at high lung volumes) and to compress their airways dynamically
during expiration are impaired, placing them at double liability. The muscles
of expiration appear to be the most important determinant in producing
elevated intrathoracic pressures, and they are capable of doing so even with
an endotracheal tube in place (Kopec SE et al., 2007).
Protussive Therapy
When cough is useful yet inadequate, protussive therapy is indicated (e.g.,
bronchiectasis, CF, pneumonia, postoperative atelectasis) (Kopec SE et al.,
2007).
The goal of protussive therapy is to increase cough effectiveness with or
without increasing cough frequency. It can be of a pharmaceutical or
mechanical nature. Only a small number of pharmacologic agents have been
adequately evaluated as protussive agents (Irwin RS et al., 1993).
Of these, aerosolized hypertonic saline in patients with chronic bronchitis
and amiloride aerosol in patients with CF have been shown to improve
cough clearance (Donaldson SH et al., 2006).
Although aerosolized ipratropium bromide diminished the effectiveness of
cough for clearing radiolabeled particles from the airways in COPD,
aerosolized terbutaline after CPT significantly increased cough clearance in
patients with bronchiectasis [(Kopec SE et al., 2007).
The conflicting results with these two types of bronchodilators suggest that
terbutaline achieved its favorable effect by increasing hydration of mucus or
enhancing cilliary beating, and these overcame any negative effects that
bronchodilation had on cough clearance. If bronchodilators result in too
much smooth muscle relaxation of large airways, flow rates can actually
decrease even in healthy individuals result in too much smooth muscle
relaxation of large airways, flow rates can actually decrease even in healthy
individuals when more compliant large airways narrow too much because
- 22 -
they cannot withstand dynamic compression during forced expirations
(Kopec SE et al., 2007).
Expiratory Muscle Training
Because expiratory muscle weakness diminishes cough, strengthening the
muscles may improve cough effectiveness. In quadriplegic subjects, there
was a 46% increase in expiratory reserve volume after a 6-week period of
isometric training to increase the clavicular portion of the pectoralis major
(Estenne M et al., 1989).
This technique may improve cough by allowing patients with
neuromuscular weakness to generate higher intrathoracic pressures (Kopec
SE et al., 2007).
Mechanical Measures
A variety of mechanical measures have been advocated as possible
therapies to improve cough effectiveness (Kopec SE et al., 2007), including
(a) positive mechanical insufflation, followed by (b) manual compression of
the lower thorax and abdomen in quadriparetic patients (an abdominal push
maneuver that assists expiratory efforts in patients with spinal cord injuries),
(c) mechanical insufflation–exsufflation, (d) abdominal binding and muscle
training of the clavicular portion of the pectoralis major in tetraplegic
patients, and (e) CPT in patients with chronic bronchitis. The usefulness of
the first four measures in improving clinical outcomes has yet to be studied,
and in patients with CF, one technique does not appear to be superior to the
others (Kopec SE et al., 2007).
Mechanical insufflation-exsufflation
Mechanical insufflation-exsufflation is a therapy in which the device (the
Cough Assist In-Exsufflation is the only currently marketed insufflationexsufflation device) gradually inflates the lungs (insufflation), followed by
an immediate and abrupt change to negative pressure, which produces a
rapid exhalation (exsufflation), which simulates a cough and thus moves
secretions cephalad. Mechanical insufflation-exsufflation is used with
patients with neuromuscular disease and muscle weakness due to central
nervous system injury. Insufflation-exsufflation decreases episodes of
respiratory failure, particularly during upper-respiratory-tract infection, and
provides greater success in weaning from mechanical ventilation than do
conventional methods. Alternatives to insufflation-exsufflation that can
produce sufficient peak cough flow for airway clearance include (1)
insufflation to maximum insufflation capacity (via breath-stacking with a
bag and mask, a volume ventilator, or glossopharyngeal breathing) followed
by a spontaneous cough, and (2) manually assisted cough with an abdominal
thrust. The effectiveness of insufflation-exsufflation in patients with
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obstructive lung disease, such as chronic obstructive pulmonary disease or
asthma, and in pediatric patients, is less clear (Davidson. 2007).
Bronchoscopy in the ICU
As a recent review highlighted, (Kreider ME and Lipson DA, 2003)
bronchoscopy is a moderately effective technique for the treatment of
atelectasis in the critically ill patient, with success rates ranging from 19% to
89% depending on the extent of atelectasis (lobar atelectasis responds better
than subsegmental atelectasis). When compared with aggressive multimodal
chest physiotherapy in the only randomized trial, no difference in the rate
of resolution was seen between the two methods (Marini JJ et al.,
1979).
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