Acute exacerbation of chronic obstructive pulmonary disease
Recommendations
Urgent
If COVID-19 infection is confirmed, manage the patient in line with your local COVID-19 guidelines. See Coronavirus disease 2019 (COVID-19).
Use systemic corticosteroids in COPD exacerbations according to the usual indications (see Initial pharmacological management below) whether or not there is evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. There is no evidence that this approach modifies the patient’s susceptibility to SARS-CoV-2 infection or worsens outcomes.[1]
Treat the patient with antibiotics according to the usual indications (see Treat the underlying cause below) whether or not there is evidence of SARS-COV-2 infection, particularly as patients with COPD who also have COVID-19 frequently develop bacterial or fungal co-infections.[1]
Immediately give a short-acting beta-2 agonist (at an increased dose or frequency from the patient’s usual baseline treatment), with or without a short-acting muscarinic antagonist.[1]
Stop any long-acting muscarinic antagonist the patient may already be on for maintenance therapy if a short-acting muscarinic antagonist is given.
Consider a systemic corticosteroid.[1][90]
Prescribe controlled oxygen for severe exacerbations in patients who are hypoxic.
Titrate controlled oxygen to a target saturation of 88% to 92% as COPD patients are considered at risk of hypercapnic (type 2) respiratory failure.[1][98]
Obtain arterial blood gas (ABG) and pulse oximetry measurements on presentation and repeat after 30-60 minutes.[1][98]
Monitor for signs of hypercapnic (type 2) respiratory failure with respiratory acidosis.
Acute respiratory failure is life-threatening when:[1]
Respiratory rate >30 breaths/minute
Patient using accessory respiratory muscles
Acute changes in mental status
Hypoxaemia does not improve with supplemental oxygen via Venturi mask or requiring fraction of inspired oxygen (FiO₂) >40%
Ensure that there is no evidence of hypercapnia before moving to higher concentrations of oxygen.
Carry out ongoing assessment with ABGs.
Document the FiO₂ or O₂ flow rate.
PaCO₂ increased compared with baseline or elevated approximately 8 kPa (>60 mmHg), or acidosis present.
In the community, refer the patient to hospital if they have:[1]
Sudden worsening of resting dyspnoea
High respiratory rate/acute respiratory failure (>30 breaths/minute)
Decreased oxygen saturation (SaO₂): SaO₂ <90% on air, or deteriorating SaO₂ in patients with known hypoxaemia (i.e., those on long-term oxygen therapy)[90]
Confusion or drowsiness
Acute respiratory failure
Change in or onset of new physical signs, such as cyanosis or worsening peripheral oedema[90]
Failure to respond to initial management
Serious comorbidities that would affect recovery or impact treatment, such as heart failure, atrial fibrillation, or other cardiorespiratory conditions
Insufficient support at home or in the community treatment setting.
Key Recommendations
Initial treatment for all patients
Give a short-acting beta-2 agonist (with or without a short-acting muscarinic antagonist) and consider a systemic corticosteroid.[1]
For the beta-2 agonist, use:
A nebuliser driven on air (not oxygen, due to the risk of hypercapnia) for a moderate to severe exacerbation[90]
During periods of high prevalence of COVID-19, seek advice from a respiratory specialist and consult local guidelines before using a nebuliser. There are currently differences of opinion between organisations in different countries on whether use of a nebuliser is an aerosol-generating procedure
A metered-dose inhaler (MDI) plus spacer for a mild exacerbation.
Add a short-acting muscarinic antagonist (e.g., ipratropium) administered via a nebuliser if the initial dose of the short-acting beta-2 agonist does not provide sufficient and prompt benefit.[1][129]
Stop any long-acting muscarinic antagonist the patient may already be on for maintenance therapy if a short-acting muscarinic antagonist is given.
Monitor the patient using an early warning score, such as the NEWS2 score:[92]
Respiration rate
Oxygen saturation (document FiO₂ or O₂ flow rate)
Systolic blood pressure
Pulse rate
Level of consciousness or new-onset confusion
Temperature.
Oxygen
Titrate controlled oxygen to a target saturation of 88% to 92%, as COPD patients are considered at risk for hypercapnic (type 2) respiratory failure.[1][98][102]
Use a Venturi mask to deliver 24% to 28% oxygen.[98]
Document the FiO₂ or O₂ flow rate.
Check blood gases to ensure satisfactory oxygenation and monitor for carbon dioxide retention and acidosis.
Avoid excessive oxygen use in patients with COPD as this can lead to worsening hypercapnia, acidosis, and respiratory failure and death.
This can develop rapidly (within the time of a hospital admission) even if the initial blood gas results were satisfactory.[98]
Beware that hypercapnic respiratory failure and death may occur as a consequence of high oxygen delivery in an ambulance when attempting hypoxaemia correction.[130]
Ventilation
Start non-invasive ventilation (NIV) for patients who have any of the following, despite optimal medical therapy, and have no contraindications to treatment:[1][102]
Respiratory acidosis
Acidaemia implies a severe exacerbation and predicts in-hospital and 30-day mortality.[103]
Consult local protocols for recommended thresholds to use as international guidelines differ:
Severe dyspnoea (as shown by use of respiratory accessory muscles, pursed lip breathing, paradoxical motion of the abdomen, or retraction of intercostal spaces)
Persistent hypoxaemia despite supplemental oxygen.
Consider the patient’s escalation policy and 'ceilings of care' before starting ventilation.
Follow your hospital’s protocol for initiation of NIV and subsequent management.
This will include recommendations on pressures, oxygen titrations, and frequency of ABGs.
In the UK, in line with recommendations from the British Thoracic Society, for patients who meet the criteria for acute NIV start treatment within:[93][104]
60 minutes of the blood gas result associated with the clinical decision to go ahead with treatment
120 minutes of hospital arrival for patients who present acutely.
Only consider invasive mechanical ventilation after careful consideration and discussion with the senior medical team. Bear in mind existing escalation strategies and any advance directives.[1]
Antibiotics
Give antibiotics to any patient who needs ventilation (invasive or non-invasive) or patients experiencing exacerbations with:[1]
Increase in sputum volume, plus
Increase in sputum purulence, and/or
Increase in dyspnoea.
Still give antibiotics if the patient has only two of the cardinal symptoms if increased sputum purulence is one of them.[1]
Choice of antibiotic should be based on local resistance patterns, any previous culture results for the individual patient, and local antibiotic guidelines.[1]
Duration of therapy should be 5-7 days, but consult your local guidelines.[1]
Give oral antibiotics first-line if possible and if the severity of the exacerbation does not require intravenous antibiotics.[1][97] If intravenous antibiotics are given, review them within 48 hours and consider stepping down to oral antibiotics where possible.[97]
Supplemental treatment for all patients
Monitor fluid balance.
Offer nicotine replacement therapy to all current smokers while in hospital and discuss smoking cessation options for after discharge.[90]
Treat any comorbidities.
Consider prophylaxis against thromboembolism.
Consider nutritional supplements.
There are no absolute criteria to determine the most appropriate treatment setting.
Consider the full clinical picture in the context of the patient’s usual state.
Consult senior colleagues if you are uncertain of the best treatment setting.
For specific advice on when to admit to hospital, see Diagnosis recommendations.
Inhaled bronchodilators
Give a short-acting beta-2 agonist (e.g., salbutamol) at an increased dose or frequency from the patient’s usual baseline treatment as first-line therapy.[1][90]
For a moderate to severe exacerbation, use a nebuliser driven on air (not oxygen).[90]
For a mild exacerbation, use an MDI plus spacer.
People with severe dyspnoea with low inspiratory flow rates may have difficulty achieving proper technique and medication delivery from the MDI; a nebuliser may be easier for these patients to use.
You may see benefit from this initial treatment within 30 minutes.
During periods of high prevalence of COVID-19, seek advice from a respiratory specialist and consult local guidelines before using a nebuliser.
There are currently differences of opinion between organisations in different countries on whether use of a nebuliser is an aerosol-generating procedure.
International guidelines from GOLD recommend minimal use of nebulisers, advising that inhalers should ideally be used for drug delivery instead. GOLD acknowledges that nebulisers may be needed in critically ill patients with COVID-19 receiving ventilatory support. GOLD recommends using a mesh nebuliser (to keep the circuit intact and prevent virus transmission) if absolutely necessary to do so (e.g., in ventilated patients).[1]
Practical tip
Observe patients while they use an MDI. It is common for patients to need advice and training on technique. If a patient is struggling to obtain the required dose, switch to a nebuliser.
Add a short-acting muscarinic antagonist (e.g., ipratropium) administered via a nebuliser if the initial dose of the short-acting beta-2 agonist does not provide sufficient and prompt benefit.[1][129]
Short-acting beta-2 agonists are typically favoured as a first-line option as they tend to have a more rapid effect than antimuscarinics.
Give ipratropium alone if the patient experiences adverse effects due to salbutamol (e.g., tremor, palpitations, headache, nausea, dizziness).
To avoid overdose, stop any long-acting muscarinic antagonist the patient may already be on for maintenance therapy (e.g., aclidinium, glycopyrronium, tiotropium, umeclidinium) while the short-acting muscarinic antagonist is given.
Continue the long-acting beta-2 agonist (the patient’s maintenance therapy) alongside the additional short-acting beta-2 agonist needed for recovery from the exacerbation.
Many patients are on a long-acting beta-2 agonist/long-acting muscarinic antagonist (with or without a corticosteroid) combination inhaler for maintenance therapy. If this is the case, stop the combination inhaler during the acute exacerbation.
Seek specialist advice on the optimal method of delivering bronchodilators (MDI or nebuliser) to adults with COPD exacerbation who are receiving mechanical ventilation via endotracheal tube.
There is insufficient evidence to recommend one route of delivery over the other.[131]
Systemic corticosteroids
Consider a systemic (oral or intravenous) corticosteroid.[1][90] Oral administration is preferred; however, some patients may require intravenous administration if they cannot tolerate oral therapy (e.g., if they are vomiting).
National Institute for Health and Care Excellence (NICE) and GOLD guidelines recommend a 5-day treatment course.[1][90]
Latest evidence shows no benefit from prolonged therapy.[132] [
]
Corticosteroids are associated with risk of pneumonia, sepsis, and death and should only be used in patients with significant exacerbations.[1]
Avoid use of a corticosteroid with a fluoroquinolone antibiotic, because co-administration could exacerbate fluoroquinolone-induced tendinitis and tendon rupture.[133]
Evidence: Corticosteroids
Evidence shows no benefit from prolonged therapy of corticosteroids.
A Cochrane review compared the efficacy of short-duration (7 or fewer days) and conventional longer-duration (longer than 7 days) systemic corticosteroid treatment of adults with acute exacerbations of COPD.[132]
Eight studies with 582 participants were included.
Corticosteroid treatment was given at equivalent daily doses for 3-7 days for short-duration treatment and for 10-15 days for longer-duration treatment.
Patients treated for 7 or fewer days did not have a higher rate of treatment failure.
Time in hospital and lung function at the end of treatment were not different.
No differences in side effects or death were noted between treatments.
The balance of risks and benefits of corticosteroids for people with milder exacerbations is uncertain.
Note that there may be guidance in future over which patients to prescribe corticosteroids to, in an effort to reduce their prescription.
At the moment there is no consensus owing to a lack of peer-reviewed data.
Recent studies suggest that systemic corticosteroids may be less effective in treating exacerbations in patients with lower levels of blood eosinophils.[58][112][113][114]
Eosinophil count may also become a useful indicator of likelihood of ongoing benefit from post-stabilisation inhaled corticosteroids.[1][112]
Evidence: The role of methylxanthines
The use of methylxanthines is not routinely recommended.
GOLD states that methylxanthines (theophylline or aminophylline) are not recommended due to their side-effect profile.[1]
NICE states that intravenous theophylline should only be used as an adjunct to exacerbation management if there is an inadequate response to nebulised bronchodilators, noting that there is potential for toxicity in patients already taking oral theophylline and that levels should be monitored.[90]
A meta-analysis of four randomised controlled trials found no consistent benefit from taking a methylxanthine to treat an exacerbation of COPD, but that they were associated with an increase in nausea and vomiting.[134]
The risks of nausea or vomiting were significantly higher for patients receiving a methylxanthine (OR 4.6, 95% CI 1.7 to 12.6) than for patients receiving placebo.[134]
In a trial to assess whether theophylline helps to prevent exacerbations, 1567 participants were randomised to receive low-dose theophylline or placebo.[135]
The main outcome measured was the number of participant-reported moderate or severe exacerbations treated with antibiotics, oral corticosteroids, or both over a 1-year treatment period.
It found that among adults with COPD at high risk of exacerbation treated with inhaled corticosteroids, the addition of low-dose theophylline, compared with placebo, did not reduce the number of COPD exacerbations over a 1-year period.
In total, there were 3430 exacerbations:
1727 in the theophylline group (mean exacerbations per year 2.24, 95% CI 2.10 to 2.38)
1703 in the placebo group (mean exacerbations per year 2.23, 95% CI 2.09 to 2.37).
The findings do not support the use of low-dose theophylline as adjunctive therapy to inhaled corticosteroids for the prevention of COPD exacerbations.
Assess severity to determine where and how to treat the patient.[1][90]
Use pulse oximetry and ABG, acknowledging that values will need to be compared against the patient’s baseline.
Consider the patient's prior status and any changes to previous baseline investigation (based on symptoms, examination, and investigations).
Take into account frailty and comorbidities.
For specific advice on how to stratify exacerbations (into mild, moderate, and severe) and the impact of this on management, see Diagnosis recommendations.
Oxygen
Check arterial blood gas and pulse oximetry on presentation and then after 30-60 minutes to ensure satisfactory oxygenation and monitor for carbon dioxide retention and acidosis.[1][98]
Administer the oxygen in a controlled fashion via a Venturi mask to deliver 24% to 28% oxygen.[98]
Titrate controlled oxygen to a target saturation of 88% to 92% as COPD patients are considered at risk for hypercapnic (type 2) respiratory failure.[1][98][102]
Document the FiO₂ or O₂ flow rate.
Repeat ABG if the patient's clinical condition deteriorates or they fail to respond to initial therapy.
Avoid excessive oxygen use in patients with COPD due to the risk of hypercapnic (type 2) respiratory failure.
It is likely there are at least six mechanisms responsible for oxygen-induced hypercapnia:[98]
V/Q mismatch
Ventilatory drive
Haldane effect (the ability of deoxyhaemoglobin to carry more carbon dioxide than oxyhaemoglobin[136])
Absorption atelectasis
Higher density of oxygen compared with air
Rebreathing can occur if low oxygen flow rates are used through a face mask.
Risk factors for hypercapnic respiratory failure include:
The risk of respiratory acidosis in patients with hypercapnic respiratory failure is increased if the PaO₂ is above 10.0 kPa (75 mmHg) due to previous excessive oxygen use.[98]
Use a Venturi mask in preference to nasal prongs as they offer a more accurate delivery of oxygen.[1]
More evidence is needed on the use of high-flow oxygen therapy by nasal cannula in patients with acute exacerbations of COPD.[1]
Practical tip
Beware that hypercapnic respiratory failure may occur as a consequence of high oxygen delivery in an ambulance when attempting hypoxaemia correction.[130] Note that nasal prongs and standard Hudson masks do not deliver controlled oxygen.
Gradually reduce oxygen therapy as the patient recovers.[98]
Discontinue oxygen therapy once the patient can maintain their target oxygen saturation on room air.[98]
Bear in mind that some patients will be on long-term oxygen therapy as part of their usual treatment and this will need to be maintained.
Ventilation
Non-invasive ventilation (NIV)
Start NIV for patients with acute hypercapnic respiratory failure (respiratory acidosis) despite optimal medical therapy, who have no contraindications.[1][102] Consult local protocols for recommended thresholds to use; international guidelines differ:
The British Thoracic Society/Intensive Care Society define respiratory acidosis as pH <7.35 and PaCO2 >6.5 kPa[102]
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) defines respiratory acidosis as pH ≤7.35 and PaCO2 ≥6.0 kPa.[1]
Acidaemia implies a severe exacerbation and predicts in-hospital and 30-day mortality.[103] The evidence is less clear for patients with arterial pH ≤7.25. In these patients, NIV may be used as a 'ceiling of care' treatment for severe hypercapnic acidaemic ventilatory failure.
Also provide NIV to patients with:[1]
Severe dyspnoea (as shown by use of respiratory accessory muscles, paradoxical motion of the abdomen, or retraction of intercostal spaces) or
Persistent hypoxaemia despite supplemental oxygen.
NIV:[1][137]
[ ]
[Evidence B]
Improves survival
Improves gas exchange
Reduces the work of breathing
Reduces the need for intubation
Decreases length of hospital stay.
Follow your hospital’s protocol for initiation of NIV and subsequent management.
This should include recommendations on pressures, oxygen titrations, and frequency of ABGs.
In general:
Monitor oxygen saturations continuously[102]
Take intermittent measurements of PaCO₂ and pH[102]
Use ECG monitoring if the patient has a pulse rate >120 bpm or if there is dysrhythmia or possible cardiomyopathy[102]
Frequently assess the patient to monitor for any complications occurring.
The British Thoracic Society sets out specific timeframes as measurable markers of good practice for the use of acute NIV in the UK.[93][104]
For patients who meet the criteria for acute NIV, start it within:
60 minutes of the blood gas result associated with the clinical decision to go ahead with NIV
120 minutes of hospital arrival for patients who present acutely.
Review the patient’s clinical progress within 4 hours of starting NIV.
This should be done by a healthcare professional with appropriate training and competence.
A consultant with training and competence in acute NIV should review the patient’s clinical progress within 14 hours of starting acute NIV.
If possible, perform a blood gas analysis within 30-60 minutes of starting acute NIV.
Although the British Thoracic Society (BTS) recommends performing blood gas analysis within 2 hours of starting acute NIV, in practice specialists recommend ideally waiting only 30-60 minutes to check for changes in PaCO2 and pH.[104]
Arrange review by a specialist healthcare professional with expertise in managing patients on NIV within 30 minutes if blood gas measurements fail to improve.
Plan with senior colleagues what to do if the patient deteriorates, including 'ceilings of care'.[90][102] Consider DNACPR (‘Do Not Attempt Cardiopulmonary Resuscitation’) for patients not suitable for escalation to an intensive care unit.
For specific advice on care planning, see Diagnosis recommendations.
Admit the patient to an intensive care unit if they have:[1]
Severe dyspnoea with a poor response to initial emergency therapy
Changes in mental status
Persistent or worsening hypoxaemia (PaO2 <40 mmHg or 5.3 kPa) and/or severe or worsening respiratory acidosis (pH <7.25) despite supplemental oxygen and non-invasive ventilation
Need for invasive mechanical ventilation
Haemodynamic instability (need for vasopressors).
Invasive mechanical ventilation
Only consider invasive ventilation after careful consideration and discussion with the senior medical team.[1]
This is not purely a clinical decision and there are no absolute numerical thresholds to adhere to. You will need to take many factors into account, including the patient’s own wishes regarding resuscitation.
Compare the patient’s functional status to their baseline and consider their overall fitness for ventilation.
Indications for invasive mechanical ventilation include:[1]
Unable to tolerate NIV
When NIV has failed
Post respiratory arrest or cardiac arrest
Diminished consciousness or inadequately controlled psychomotor agitation
Massive aspiration or persistent vomiting
Persistent respiratory secretions that cannot be removed
Severe haemodynamic instability, not successfully treated with fluid and drugs
Severe arrhythmias
Hypoxaemia and unable to tolerate NIV.
Complications associated with mechanical ventilation include:[1]
Ventilator-associated pneumonia
Barotrauma
Volutrauma
Respiratory weakness after prolonged ventilation (weaning and tracheostomy may be required to manage this).
Patient suitability
When assessing suitability for intubation and ventilation, take into account:[90]
Functional status
BMI
Need for oxygen when stable
Comorbidities
Previous admissions to intensive care units
Age
FEV₁.
Do not use age or FEV₁ in isolation when assessing suitability for intubation and ventilation.
How to insert a tracheal tube in an adult using a laryngoscope.
How to use bag-valve-mask apparatus to deliver ventilatory support to adults. Video demonstrates the two-person technique.
Give antibiotics to any patient who needs ventilation (invasive or non-invasive) or patients experiencing exacerbations with:[1]
Increase in sputum purulence, plus
Increase in sputum volume, and/or
Increased dyspnoea.
As well as the severity of symptoms, particularly sputum colour changes and increases in volume or thickness beyond the patient’s normal day-to-day variation, the National Institute for Health and Care Excellence (NICE) urges you to also consider:[97]
Whether the patient needs to go into hospital for treatment
Previous exacerbation and hospital admission history
Risk of developing complications
Previous sputum culture and susceptibility results
Risk of antimicrobial resistance with repeated courses of antibiotics.
Choose an antibiotic regimen based on local resistance patterns, any previous culture results for the individual patient, and local antibiotic guidelines.[1]
Duration of therapy will tend to be 5-7 days, but consult your local guidelines.[1]
More recent guidance from the American College of Physicians recommends limiting antibiotic treatment to 5 days in patients with COPD exacerbations and acute uncomplicated bronchitis.[141]
When used appropriately, antibiotics can:[1]
Shorten recovery time
Reduce the risk of early relapse and treatment failure
Shorten the length of hospital stay.
Give oral antibiotics first-line if the patient is able to tolerate oral medications, and if the severity of the exacerbation does not require intravenous antibiotics.[1][97]
If a patient is started on intravenous antibiotics, review them by 48 hours and consider stepping down to oral therapy where possible.[97]
NICE recommends amoxicillin, doxycycline, or clarithromycin as suitable first-line oral options. Alternative oral options include amoxicillin/clavulanate, levofloxacin, and trimethoprim/sulfamethoxazole. Suitable first-line intravenous options include amoxicillin, amoxicillin/clavulanate, clarithromycin, trimethoprim/sulfamethoxazole, or piperacillin/tazobactam.[97]
It is worth noting that you must not prescribe fluoroquinolones (e.g., levofloxacin) for mild to moderate acute exacerbation of COPD unless other antibiotics are considered inappropriate. This is due to reports of disabling, long-lasting, or potentially irreversible adverse reactions affecting the musculoskeletal and nervous systems.[133][142] Avoid fluoroquinolones in patients who have previously had serious adverse effects with a fluoroquinolone antibiotic. Avoid use of a corticosteroid with a fluoroquinolone, because co-administration could exacerbate fluoroquinolone-induced tendinitis and tendon rupture.[133]
Look for improvements in dyspnoea and sputum purulence to measure success of antibiotic treatment.[1]
Additional considerations in the community
Give the patient/their family specific advice about when to seek further medical help, in particular:[97]
If symptoms worsen rapidly or significantly
If symptoms do not start to improve within an agreed time (e.g., 2-3 days if taking antibiotics)
If the patient becomes systemically very unwell.
Give advice on possible adverse effects of antibiotics (particularly diarrhoea).[97]
Explain that their respiratory symptoms may not be fully resolved when the course has been completed.[97]
Reassess the patient if their symptoms worsen rapidly or significantly. In particular:
Beware symptoms and signs of:
Pneumonia
Cardiorespiratory failure
Sepsis.
Refer the patient to hospital if you suspect a more serious illness (e.g., sepsis or cardiorespiratory failure).
Consider antibiotic-resistant bacteria and send a sputum sample for microscopy, culture, and Gram stain if symptoms have not improved following antibiotic treatment and these tests have not been done already.[97]
Only request sputum microscopy, culture, and Gram stain in severe disease and if hospitalisation is being considered. This is not a routine investigation in primary care.[90]
Seek specialist advice for patients:[97]
Whose symptoms do not improve after repeated courses of antibiotics
With a bacterial infection resistant to oral antibiotics
Who cannot take oral medications.
Other options may be to give intravenous antibiotics at home or in the community, rather than in hospital, where appropriate.
Some patients will keep antibiotics at home for use in an exacerbation as part of their existing action plan.
Evidence: Efficacy of antibiotics
Antibiotics offer a large and consistent beneficial effect across outcomes of patients admitted to an intensive care unit (ICU), but for inpatients and outpatients the effects are inconsistent.
A Cochrane review of 19 trials with 2663 participants looked at the effects of antibiotics in the management of acute COPD exacerbations on:[143]
Treatment failure (observed 7 days to 1 month after treatment initiation)
Mortality
Length of hospital stay.
In the study:
Three groups of patients were considered:
Outpatients (mild to moderate exacerbation)
Inpatients (severe exacerbation)
ICU patients (very severe exacerbation)
In outpatients, there was low-quality evidence that antibiotics do significantly reduce the risk for treatment failure between 7 days and 1 month after treatment initiation (RR 0.72, 95% CI 0.56 to 0.94).
In inpatients (excluding ICU), moderate-quality evidence does not show that antibiotics significantly reduce the risk of treatment failure in inpatients with severe exacerbations (RR 0.65, 95% CI 0.38 to 1.12).
In ICU patients:
A trial of 93 patients showed a large and statistically significant effect of antibiotics on treatment failure (RR 0.19, 95% CI 0.08 to 0.45)
Antibiotics significantly reduced length of hospital stay (mean difference ‐9.60 days, 95% CI ‐12.84 to ‐6.36 days).
Length of hospital stay (in days) was similar in the antibiotic and placebo groups for inpatients.
The authors conclude that there is beneficial effect across outcomes of patients admitted to an ICU, but that for inpatients and outpatients the effects of antibiotics are inconsistent.[143]
Evidence: Choice of antibiotic
Many antibiotics have been found to be effective for the treatment of an acute exacerbation of COPD.
A review of 19 randomised controlled trials (RCTs) found that macrolides, fluoroquinolones, and amoxicillin/clavulanate may be considered equivalent for the treatment of patients with an acute bacterial exacerbation of chronic bronchitis in short-term effectiveness.[144]
Treatment success was lower for macrolides compared with fluoroquinolones (OR 0.47, 95% CI 0.31 to 0.69).
Fewer fluoroquinolone recipients experienced a recurrence of acute exacerbation after resolution of the initial episode, compared with macrolide recipients, during the 26-week period following therapy.
Amoxicillin/clavulanate was associated with more adverse effects (mainly diarrhoea) than fluoroquinolones (OR 1.36, 95% CI 1.01 to 1.85).
An analysis of five RCTs involving 287 patients found that there were no differences between patients with acute exacerbation of chronic bronchitis receiving semisynthetic penicillins (e.g., amoxicillin, ampicillin) and those receiving trimethoprim-based regimens (e.g., trimethoprim, trimethoprim/sulfamethoxazole, trimethoprim/sulfadiazine) in:[145]
Treatment success (intention-to-treat patients: n = 262; OR 1.68, 95% CI 0.91 to 3.09; clinically evaluable patients: n = 246; OR 1.59, 95% CI 0.79 to 3.20)
Number of drug-related adverse events in general (n = 186 patients; OR 0.37, 95% CI 0.11 to 1.24).
Choose an antibiotic regimen based on local resistance patterns, any previous culture results for the individual patient, and local antibiotic guidelines.[1]
Monitor fluid balance.
This may be particularly important in patients with comorbidities, such as heart failure.
Depending on the patient’s clinical condition, you may need to:[1]
Treat any comorbidities
Comorbidities, such as lung cancer, cardiovascular disease, osteoporosis, and depression, are common in patients with COPD
Consider any other drugs the patient is taking
Administer prophylaxis against thromboembolism, if needed
Give nutritional supplements
Patients with COPD who are undernourished are at an increased risk of exacerbations.[146]
Monitor recovery
Regularly assess symptoms and observe the patient’s functional status.[90]
Use intermittent ABG measurements to monitor the recovery of people with respiratory failure who are hypercapnic or acidotic, until they are stable with a normalised pH.[90]
Use pulse oximetry to monitor the recovery of people with non-hypercapnic, non-acidotic respiratory failure.[90]
Do not use daily monitoring of peak expiratory flow or FEV₁ to monitor recovery from an exacerbation, because the magnitude of change is small compared with the variability of the measurement.[90]
Practical tip
Change drug delivery from a nebuliser to an MDI once the patient has stabilised. This may allow an earlier discharge from hospital.
Discharge planning
You (along with the patient and family) should be confident that the patient can manage their symptoms at home before they are discharged.
If the patient smokes, reinforce the advice to the patient that they must stop smoking (including electronic cigarettes) and provide information on how to access the services that help with this.[147]
Offer a 'harm reduction' approach, such as reducing the number of cigarettes smoked or temporary abstinence. This may be a practical step for patients struggling to quit.[147]
Review the patient’s long-term medication.
Re-establish people on their optimal maintenance bronchodilator therapy before discharge.[90]
Some patients may benefit from inhaled corticosteroids once the exacerbation has been stabilised.[1] At the moment there is no consensus owing to a lack of peer-reviewed data although the eosinophil count may become a useful indicator of likelihood of benefit. For patients with one exacerbation per year, a peripheral blood count ≥300 eosinophils/microlitre may identify those who are more likely to respond to inhaled corticosteroids in combination with a long-acting beta-2 agonist.[1] For patients with two or more exacerbations per year, or at least one exacerbation severe enough to require hospitalisation, inhaled corticosteroids in combination with a long-acting beta-2 agonist can be considered at blood eosinophil counts ≥100 cells/microlitre. However these thresholds should be regarded as estimates, rather than precise cut-off values, that can predict different probabilities of treatment benefit.[1]
Provide vitamin D supplementation, if required. Supplementation of patients with severe deficiency results in a reduction in exacerbations and hospitalisation.[1]
Consider a hospital-at-home or assisted discharge scheme, where available, once the patient is stable.[90][148][149] [
]
The decision over which patients are suitable for such schemes will need a team approach, as will the implementation of such schemes. Take patient factors and preferences into account.[90] Consider using a validated prognostic score, such as the DECAF (Dyspnoea, Eosinopenia, Consolidation, Acidaemia, and atrial Fibrillation) score, to determine which patients are suitable for this approach.[148]
Be aware that patients who have suffered from a significant exacerbation of COPD may not always recover back to their pre-illness functional status. Discuss this as needed with the patient and their family, so that their expectations of the duration and extent of recovery are realistic.
Refer for a pulmonary rehabilitation programme, as required, to improve exercise tolerance, physical ability, and quality of life.[150]
Pulmonary rehabilitation is a multidisciplinary programme of care that involves physical rehabilitation as well as guidance on disease management, nutrition, and other lifestyle issues (e.g., smoking cessation, medicine compliance and inhaler technique, supplemental oxygen, and maintenance of physical activity).[151]
Review all clinical data and test results: identify and manage any abnormalities.
Measure (or review previous) spirometry in all patients.[93] During periods of high prevalence of COVID-19 in the community, spirometry should be restricted to patients requiring urgent or essential tests for the diagnosis of COPD, and/or to assess lung function status for interventional procedures or surgery.[1][99] Performing spirometry and pulmonary function testing may lead to SARS-CoV-2 transmission as a result of droplet and aerosol formation during the tests, especially with coughing.
Ensure satisfactory oximetry or ABG results in patients who have had an episode of respiratory failure.
Assess the need for continuing oxygen therapy.
Check the patient’s understanding of the withdrawal of their acute medications and their re-established maintenance therapy.
Give appropriate information on the correct use of medications and oxygen.
Reassess inhaler technique.
Provide a management plan for comorbidities.
Make arrangements for follow-up and home care.
Practical tip
Although there are insufficient data that specific 'care bundles' at hospital discharge reduce readmission rates, improve mortality, or are cost-effective, the general principles are all worth considering as part of discharge and follow-up:[1]
Education
Optimisation of medication
Supervision and correction of inhaler technique
Assessment and management of comorbidities
Early rehabilitation
Telemonitoring
Continuing patient contact.
Evidence: Pulmonary rehabilitation
Pulmonary rehabilitation was found to be a safe intervention to improve quality of life and exercise capacity for patients with COPD after an exacerbation. It may reduce mortality and re-hospitalisations in this context, although data are limited.
The 2023 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guideline cites a systematic review and meta-analysis (updated search to October 2017) including 13 randomised controlled trials (RCTs) comparing early supervised pulmonary rehabilitation (started during or within 4 weeks after hospitalisation) following an exacerbation of COPD with usual care or no pulmonary rehabilitation programme.[1][152]
The review found moderate-quality evidence that pulmonary rehabilitation reduced mortality at the end of treatment (four studies), although the difference was not statistically significant at longest follow-up (three studies).
Moderate-quality evidence (six studies) found that readmissions due to exacerbation were significantly reduced with pulmonary rehabilitation at the longest follow-up.
Improvements in health-related quality of life and exercise capacity appeared to be maintained for at least 12 months.
These results have been corroborated by real world evidence from a retrospective cohort study of 197,376 adults aged >65 years (Medicare beneficiaries in the US) who were hospitalised with COPD during 2014. It found that pulmonary rehabilitation within 90 days of discharge was significantly associated with a lower risk of mortality and fewer re-hospitalisations at 1 year.[1][153] The GOLD guideline mentions one RCT that reported that survival may be compromised if pulmonary rehabilitation is started too early, but the mechanism was unexplained.[1][154]
Improvements in quality of life and exercise capacity with pulmonary rehabilitation after an exacerbation of COPD compared with usual care were also found by a Cochrane review.[150]
The review included 20 studies involving 1477 participants.
Quality of life was measured using questionnaires and exercise capacity was measured using walking tests, such as the 6-minute walk test.
Eight studies that used the St George’s Respiratory Questionnaire reported a statistically significant effect on total score with pulmonary rehabilitation (high-quality evidence).
Thirteen studies (819 participants) used the 6-minute walk test. The 6-minute walk distance improved, on average, by 62 metres with pulmonary rehabilitation (high-quality evidence).
Moderate-quality evidence from eight studies (810 participants) showed that pulmonary rehabilitation reduced hospital readmission. However, four of these studies showed large and statistically significant reductions in the risk of hospital admission associated with pulmonary rehabilitation, and four showed no effect.
Low-quality evidence from six studies (670 participants) showed no statistically significant effects of rehabilitation on mortality.
Data on adverse effects was available from five studies (278 participants). Even though no adverse events were reported in four of these studies, one reported a serious event.
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