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© SUPPLEMENT TO JAPI • FEBRUARY 2012 • VOL. 60

Treatment of Acute Exacerbation of COPD

AG Ghoshal1, Raja Dhar2, Susmita Kundu3

C OPD exacerbation is a nightmare not only to all clinicians

but also for the patients themselves. Despite adequate
COPD control, patients experience episodes of exacerbation at
and several host factors including prior compliance to therapy.2
Bacterial etiology in AECOPD varies, one study from India
reporting Gram negative bacteria as the most common organism,
times with a huge impact on the overall health condition, both which may not reflect the entire scenario.3 Another study from
physically and mentally. Moreover, COPD exacerbation incurs a India stressed evidence of past pulmonary tuberculosis in 28.4%
huge cost and can cause significant dent in pulmonary function of patients and active tuberculosis in 5 patients with Type II
and the quality of life. It is therefore extremely important for diabetes mellitus (Table 1).4
practicing physicians to:
● Recognize the crisis early Symptoms
● Perform optimal management under appropriate settings Symptoms of COPD exacerbation include
● Escalate and de-escalate the therapy based on patient i. Increase in cough
response ii. Increase in breathlessness
● Bring back the patient to the initial baseline status iii. Increase in sputum volume and change in its colour(white
● Help the patient and family to cope with the situation with to green, yellow or blood streaked)
adequate support iv. Fever
● Discharge the patient in a stable clinical condition v. Chest pain
● Give necessary instruction about the proper follow up. vi. Increased tiredness
vii. Increase in oxygen requirement (for those on long-term
Definition1 oxygen therapy)
An exacerbation of COPD is an event in the natural course Usually patients present with varying combination of
of COPD characterised by an acute change in the patient’s these symptoms. During clinical assessment, further objective
baseline dyspnoea or breathing difficulty, cough and/or sputum evaluation is necessary. Several clinical elements must be
production beyond day-to-day variability sufficient to warrant considered when evaluating patients with exacerbations.
a change in management. These include the assessment of severity of underlying
Its cause can be infective or non-infective in nature. COPD, the presence of comorbidities and history of previous
exacerbation. The physical examination should evaluate the
Classification of exacerbations1 effect of the episode on hemodynamic and respiratory systems.
In the absence of a universal agreed criterion, the following The diagnostic procedures to perform such as chest radiology,
operational classification can help rank the clinical severity of sputum and blood examination and spirometry would depend
the episode and its outcome. on the clinical setting of evaluation.

• Level I : treated at home.

Where to treat5,6
• Level II : requires hospitalization.
The decision to treat a patient at home or hospital is based
• Level III: leads to respiratory failure. both on subjective evaluation as well as objective criteria. The
choice of the patient/patients` family should also be taken into
Causes account.
About 50% of COPD exacerbations are caused by lower Table 2 below offers a ready-reckoner
respiratory tract infections, while the remaining are caused by However it must be noted that there may be a sudden
exposure to indoor or outdoor air pollutants, changes in weather, deterioration of condition and the decision to treat at home or
Table 1: Precipitating factors for AECOPD at hospital can change rapidly.
Infectious Viral (Rhinovirus spp., influenza); Bacteria Table 3 shows the elements of the clinical evaluation and
process (Streptococcus pneumonia, Haemophilus influenzae, diagnostic procedures that are usually informative in patients
Moraxella catarrhalis, Enterobacteriaceae spp., with exacerbations according to the severity of the episode.7,8
Pseudomonas
spp.). Investigations
Environmental Sudden change in temperature and humidity, air
conditions pollution, exposure to tobacco smoke, noxious gases
Diagnosis of an exacerbation is primarily clinical and not so
or irritating chemicals much dependant on investigation results though they are useful
Host factors Patients with poor general heath condition, poor in assessing the severity and planning the optimum treatment.
nutritional status, immunocompromised status, The outline of the general investigation is provided in table 3.
lack of compliance with prescribed medical therapy. Primary care
1
Director,National Allergy Asthma Bronchitis Institute, Kolkata In patients with an exacerbation managed in primary care:
– 700017. 2Consultant Pulmonologist, Fortis Hospital, Kolkata. • Sending sputum samples for culture is not recommended
3
Associate Professor, Institute of Post Graduate Medical Education
in routine practice.8
and Research, Kolkata
© SUPPLEMENT TO JAPI • FEBRUARY 2012 • VOL. 60 39

• Pulse oximetry is useful if there are clinical features of a • A full blood count should be performed and urea and
severe exacerbation. electrolyte concentrations should be measured
Patients referred to hospital • If sputum is purulent, a sample should be sent for
In all patients with an exacerbation referred to hospital: microscopy and culture
• A chest radiograph should be obtained • Blood cultures should be taken if the patient has fever.
• Arterial blood gas tensions should be measured and the What should be the outpatient management for COPD
inspired oxygen concentration recorded Exacerbation?
• An ECG should be recorded to exclude cardiac co- The treatment of exacerbation has to be based on the clinical
morbidities presentation of the patient, as shown in table 3.
Level I: Outpatient treatment
Table 2 : Factors to consider where to treat AECOPD
Bronchodilators9,10
Factor Indication to Indication to
treat at home treat at hospital • Short-acting β2-agonist and/or ipratropium by metered dose
Able to cope at home Yes No
inhaler with spacer or nebuliser as needed.
Severity of breathlessness Mild Severe • Consider adding long-acting bronchodilator e.g., formoterol
General health condition Good/Satisfactory Poor/deteriorating (by MDI plus spacer or nebulised route) if patient is not
Level of activity Good Poor/confined to bed using it
Cyanosis No Yes Delivery systems for inhaled therapy during exacerbations
Worsening peripheral No Yes • Both nebulisers and hand-held inhalers can be used to
oedema administer inhaled therapy during exacerbations of COPD.
Level of consciousness Normal Impaired
• The choice of delivery system should reflect the dose of drug
Already receiving LTOT No Yes required, the ability of the patient to use the device and the
Social circumstances Good /adequate Living alone/not resources available to supervise the administration of the
support coping therapy.
Acute confusion/altered No Yes
mental status Corticosteroids11,12
Rapid rate of onset No Yes
In the absence of significant contraindications, oral
Significant co-morbidity No Yes corticosteroids should be considered in patients managed in the
(particularly
community who have an exacerbation with a significant increase
heart disease and insulin-
dependent in breathlessness which interferes with daily activities.
diabetes) • Oral prednisone 30–40 mg per day for 10 days
SaO2 < 90% No Yes • Consider using an inhaled corticosteroid 11
Changes on the chest No Present
radiograph Antibiotics13,14
Arterial pH level ≥7.35 <7.35 • May be initiated in patients with altered sputum
Arterial PaO2 ≥ 7kPa <7kPa characteristics.
Table 3: Stratification of AECOPD
Level I Level II Level III
(Treated at home) (Requires hospitalization) (Leads to respiratory failure)
Clinical history
Co-morbid conditions # + +++ +++
Frequent exacerbations + +++ +++
Severity of COPD Mild/Moderate Moderate/Severe Severe
Physical findings
Haemodynamics Stable Stable Stable/unstable
Use of accessory muscles while breathing/tachypnoea Not present ++ +++
Persistent symptoms after initial therapy No ++ +++
Diagnostic procedures
Oxygen saturation Yes Yes Yes
Arterial blood gases No Yes Yes
Chest radiograph No Yes Yes
Blood tests ǂ No Yes Yes
Serum drug concentration* If applicable If applicable If applicable
Sputum gram stain and culture $ No Yes Yes
Electrocardiogram No Yes Yes
Keys : + unlikely to be present; ++ likely to be present; +++ very likely to be resent; # the more common co-morbid conditions associated with poor
prognosis in exacerbations are congestive heart failure, coronary artery disease, diabetes mellitus, renal and liver failure; ǂ Blood test include complete
blood count, serum electrolytes, renal and lever function; * consider if patients are using theophylline, warfarin, carbamazepine, digoxin; $ consider
if patient has been recently on antibiotics
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Table 4 : Stratification of AECOPD with likely bacteriological profile and treatment
Group Microorganisms Oral Treatment Alternative Oral Treatment Parenteral Treatment
Group A • H.influenzae • Patient with only one cardinal • β-lactum/β-lactamase
Mild exacerbations : • S.pneumoniae symptom need not receive inhibitor (co-amoxyclav).
no risk factor for poor • M.catarrhalis antibiotics • Macrolides
outcome • Chlamydia pneumoniae • If indication then : (azithromycin,
• Viruses - β-lactum (penicillin, clarithromycin,
ampicillin/amoxicillin) roxithromycin).
- Doxycycline • Cephalosporins (2nd and
- Trimethoprim/ 3rd generations)
sulfamethoxazole. • Ketolides (telithromycin)
Group B • Group A plus presence • β-lactum/β-lactamase inhibitor • Fluoroquinolones • β-lactum/β-lactamase
Moderate of resistant organisms (co-amoxyclav). (gemifloxacin, inhibitor (co-amoxyclav,
exacerbations with (β-lactamase producing, levofloxacin, ampicillin/salbactum).
risk factors for poor penicillin resistant S. moxifloxacin) • Cephelosporins (2nd and
outcome pneumoniae) 3rd generations)
• Enterobacteriace (K. • Fluoroquinolones
pneumoniae, E. coli, (levofloxacin,
Proteus, Enterobacter, moxifloxacin)
etc)
Group C • Group B plus • In patients at risk for • Fluoroquinolones
Severe exacerbations P.aeruginosa pseudomonas infections : (ciprofloxacin,
with risk factors for P. - Fluoroquinolones levofloxacin- high dose) or
aeruginosa infection (ciprofloxacin, levofloxacin- • β-lactum with P.
high dose) aeruginosa activity
• Choice should be based on local bacterial resistance patterns, • If a patient is hypercapnic or acidotic, the nebuliser
if available. should be driven by compressed air, not oxygen (to
• As the severity of COPD exacerbation is an important avoid worsening hypercapnia). If oxygen therapy is
determinant of the type of microorganism, empirical needed it should be administered simultaneously by
antibiotics need to be guided accordingly. Options are : nasal cannulae.
• If the patient has failed prior antibiotic therapy, antibiotics • The driving gas for nebulised therapy should always
for group B may be initiated. However, there is a growing be specified in the prescription.
concern about undiagnosed tuberculosis and overuse of
Systemic Corticosteroids
fluoroquinolones in India (Table 4).
• Inhaled corticosteroids by MDI or hand-held nebuliser
Patient education
should be considered.
• Check inhalation technique
• In the absence of significant contraindications, oral
• Consider use of spacer devices corticosteroids should be used in conjunction with other
What should be the Inpatient management of COPD therapies in all patients admitted to hospital with an
Exacerbation?15 exacerbation of COPD.
Level II andIII: Inpatient treatment • Prednisolone 30 mg orally should be prescribed for 7 to 14
As mentioned earlier, the decision to admit a patient is days.
derived from subjective interpretation of clinical features, such • If patient cannot tolerate oral intake, consider equivalent
as the severity of dyspnoea, determination of respiratory failure, dose i.v. for up to 14 days (20 mg hydrocortisone is
short-term response to emergency room therapy, degree of cor- equivalent to 5 mg prednisolone,4 mg methyl- prednisolone
pulmonale and the presence of complicating features, such as and 0.75 mg dexamethasone) .
severe bronchitis, pneumonia or other co-morbid conditions. • It is recommended that a course of corticosteroid treatment
Other factors that identify “high-risk” patients include a previous should not be longer than 14 days as there is no advantage
emergency room visit within 7 days, the number of doses in prolonged therapy.
of nebulised bronchodilators, use of home oxygen, previous
• Osteoporosis prophylaxis should be considered in patients
relapse rate, administration of aminophylline, and the use of
requiring frequent courses of oral corticosteroids.
corticosteroids and antibiotics at the time of previous emergency
room discharge.5,6 Antibiotics (as discussed above)
What is the ideal pharmacologic management for these • Antibiotics should be started for patients with history of
patients? producing purulent sputum.
Pharmacologic management remains the mainstay of COPD • Any change in sputum characteristics like colour,
exacerbation along with other supportive measures. consistency and volume should also prompt the initiation.
Bronchodilators • Antibiotics need not be started for patients having
exacerbations without increase in sputum purulence,
• Short acting inhaled β2-agonist (salbutamol 100-200 mcg
unless there are signs of consolidation on chest
inhaler/levosalbutamol) and/or
radiograph or clinical symptoms of pneumonia.
• Ipratropium MDI(20, 40mcg) with spacer or nebuliser as
• Antibiotic choice should be based on local bacteria
needed.
resistance patterns, if available.
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Oximeters.
Exacerbation of COPD
Requiring Ventilatory Support • Even if oximeter is not available for any reason, oxygen
should be given to all patients with an exacerbation of
COPD who are breathless. But careful monitoring of the
patient condition is essential to prevent excessive CO 2
Contraindication washout and cause respiratory depression since CO2 acts
for NPPV?
as the respiratory drive for many COPD patients.
• It is important to note that prevention of tissue hypoxia
yes no
supersedes CO2 retention issue.
Intubate NPPV with • The principal delivery device for oxygen comprises of
MV monitoring nasal canula and venturi mask. Alternative delivery
devices include nonrebreather mask, reservoir cannula, or
Weaning transtracheal catheter .
Improvement • The aim of oxygen therapy during exacerbation of COPD
pH; PaCO2;
Clinical status
is to maintain adequate level of oxygen (SaO2 >90%)
without worsening or precipitating respiratory acidosis or
worsening hypercapnia. If pH falls below 7.35 (acidaemia),
yes no consider mechanical ventilation.
Management of AECOPD in critical care18, 19
Continue Intubate
NPPV MV x 48 hrs The decision to shift/admit a patient to the Critical Care
Unit largely depends on subjective assessment and clinician’s
judgment, although various diagnostic parameters help in
2 hr T-tube trial
decision making.
success fail Presence of the following features merits consideration for
Wean to complete
disconnection
shifting to IRCU-
Discontinue MV NPPV
• Persistent respiratory distress despite standard management
Fig. 1 : Flow chart for ventilation in AECOPD. • Inability to maintain oxygen level above 90% despite
oxygen therapy by high-flow mask
• When sputum has been sent for culture, the sensitivity to
antibiotics should be checked to ensure appropriate therapy. • Persistent hypercapnia
• If Pseudomonas spp. and/or other Enterobacterecaes • Abnormal blood gas parameters (PaO2< 60 mm of Hg
spp. are suspected, consider combination therapy [e.g.- and/or PaCO2>60 mm of Hg)
Piperacillin/tazobactam (3.375 g q4h IV) or imipenem (500 • Alteration of mental status, acute confusion, drowsiness
mg q6h IV) or meropenem (1 g q8h IV) plus Amikacin (7.5 • Increased signs of infection (pyrexia, increased sputum
mg/kg q12h or 15 mg/kg q24h IV) or Levofloxacin (500mg purulence/volume etc)
daily) for 10-14 days].
• Significant abnormal changes in chest radiograph
Theophylline and other methylxanthines
• Clinical deterioration
• Intravenous theophylline should only be used as an adjunct
to the management of exacerbations of COPD if there is an
inadequate response to nebulised bronchodilators.
Assisted Ventilation
Despite optimal pharmacologic management, severe cases of
• Care should be taken when using intravenous theophylline
exacerbation necessitates ventilatory support, when the patient
because of interactions with other drugs (e.g.-ciprofloxacin,
is unable to maintain the breathing function and/or unable to
clarithromycin, allopurinol, phenytoin etc.) and potential
maintain sufficient gaseous exchange for normal physiologic
toxicity if the patient has been on oral theophylline.
function (Figure 1).
Respiratory stimulants16 Ventilatory support can be of two types –
It is recommended that doxapram is used only when i. Non-invasive ventilation given through
non-invasive ventilation is either unavailable or considered • nasal or face masks
inappropriate.
• negative pressure ventilation (e.g. iron lung)- not
Oxygen Therapy17 practiced now
• The goal is to prevent tissue hypoxia by maintaining arterial ii. Invasive ventilation
oxygen saturation (SaO2) at >90%. Mechanical ventilation, either “invasive” or “noninvasive”,
• All patients with COPD exacerbation should have their is not a therapy but is a form of life support until the cause of
arterial oxygen tension (PaO2), arterial carbon dioxide underlying acute respiratory failure is reversed with medical
tension (PaCO2) and pH measured upon admission, during therapy.
the course of treatment and whenever there is any change Non invasive Positive Pressure Ventilation (NIPPV)20, 21
in patient’s clinical condition.
NIPPV is an option for patients who have respiratory failure
• In case of unavailability of arterial blood gas measurement and can no longer breathe on their own. It provides ventilatory
facility, oxygen saturation should be measured by Pulse support to a patient through the upper airways. It enhances
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Bronchospasm; Mucus
What are the parameters for judging the success of NPPV?
Buildup; Airway Inflammation
NPPV can be called successful if
Arterial blood gases and pH improve
Air Increaseed Dyspnoea is relieved
Trapping Raw
The acute episode resolves without the need of endotracheal
intubation
Mechanical ventilation can be discontinued
Increased Increased
Diaphragm
flattening
intrinsic
PEEP
Elastic
recoil
The patient improves steadily and can be discharged from
the hospital.
It is important to note that the one-year mortality was
Increased
reported to be lower in patients receiving NPPV for exacerbations
Muscle Increased
weakness Dyspnea Work of of COPD, compared to both optimal medical therapy alone and
Breathing
conventional mechanical ventilation.
Mechanical Ventilation (MV)23
IPPB
Rx
PE AP

Mechanical ventilation is a mode of assisted or controlled

EP
CP
Rx

ventilation through intubation using mechanical devices that

Ventilatory Decreased Increased
muscle Ventilation PaCO2 cycle automatically to generate airway pressure.
failure
Indications of mechanical ventilation
Fig. 2 : Pathophysiological rationale for combined application of Intubation should be considered in patients with the following:
CPAP and PSV.
Keys: CPAP: Continuous positive airway pressure; PSV: Pressure • NPPV failure: worsening of arterial blood gases and or pH
support ventilation; Raw: Airway resistance; PEEP: Positive in 1–2 h; lack of improvement in arterial blood gases and
end-expiratory pressure; IPPV: Intermittent positive pressure or pH after 4 h.
ventilation; Pa,CO2: Arterial carbon dioxide tension.
• Severe acidosis (pH <7.25) and hypercapnia (Pa, CO2 >8
the breathing process by giving the patient a mixture of air and kPa (60 mmHg)).
oxygen from a flow generator through a tightly fitted facial or
• Life-threatening hypoxaemia.
nasal mask. Also known as just Noninvasive Ventilation (NIV),
it assists the patient in taking a full breath and helps to maintain • Tachypnoea >35 breaths/min.
an adequate oxygen supply to the body. • Impaired mental status.
NIPPV is by far the most popular mode of providing
noninvasive ventilation with a combination of continuous Indication for discharge
positive airway pressure (CPAP 4–8 cmH2O) plus pressure Discharge should be planned when:
support ventilation (PSV 10–15 cmH2O) (Figure 2). There is significant improvement in the clinical status of the
It improves the gas exchange by improving the alveolar patient.
ventilation, without causing significant modifications in the Significant improvement of symptoms like breathlessness,
alveolar ventilation/perfusion mismatching and gas exchange cough, remission or steady improvement in infection symptoms
in the lungs .The application of the combination of CPAP and (reduction in sputum volume, non-pyrexial status, non-
PSV offers a better outcome than either alone because CPAP purulence of sputum as confirmed by culture)
counterbalances the intrinsic positive end expiratory pressure.
Ability to maintain blood gas at acceptable range.
NIV should be offered to patients with exacerbations when,
after optimal medical therapy and oxygenation, hypercapnia Ability and inclination to perform day to day activities, even
with some degree of assistance.
(PaCO2>50 mm of Hg), respiratory acidosis (pH <7.35) and/
or excessive breathlessness persist. All patients considered Planning of Discharge:
for mechanical ventilation should have arterial blood gases • Spirometry measurement is a must for all patients before
measured. discharge (though daily monitoring of PEF or FEV1 does
• If pH <7.30, NIPPV should be delivered under controlled not help during the exacerbation).
environments such as intermediate intensive care units • Patients should be re-established on their optimal
(ICUs) and/or high-dependency units. If pH <7.25, NPPV maintenance bronchodilators.
should be administered in the ICU and intubation should • Patients and/or home carers must be given the necessary
be readily available. information so that they fully understand the correct usage
• Indian recommendations insist use of NIPPV even in of medication including oxygen ( if applicable).
absence of ABG and/or ICU facilities.22 • It is useful to hand over a written plan on daily self care,
• NIV may also be considered for patients who are slow in medication management, emergency action plan during
weaning from ventilator. exacerbation to all patients/carers before discharge, with
• When put on NIV, there should be a well-defined plan for adequate explanation.
every patient on course of action on deterioration as well • Vaccination: Influenza (annual) and Pneumococcal (once in
clear indicators of the limits of such deterioration, when the a lifetime).
next action is to be taken.
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