Acute COPD Exacerbation

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CHAPTER 4: MANAGEMENT OF EXACERBATIONS

KEY POINTS: • An exacerbation of COPD is defined as an event characterized by dyspnea and/or cough

and sputum that worsen over < 14 days. Exacerbations of COPD are often associated with increased local and systemic inflammation caused by airway infection, pollution, or other insults to the lungs.

• As the symptoms are not specific to COPD relevant differential diagnoses should be considered, particularly pneumonia, congestive heart failure and pulmonary embolism.

• The goals for treatment of COPD exacerbations are to minimize the negative impact of the current exacerbation and to prevent subsequent events.

• Short-acting inhaled beta2-agonists, with or without short-acting anticholinergics, are recommended as the initial bronchodilators to treat an exacerbation.

• Maintenance therapy with long-acting bronchodilators should be initiated as soon as possible. In patients with frequent exacerbations and elevated blood eosinophil levels addition of inhaled corticosteroids to the double bronchodilator regimen should be considered.

• In patients with severe exacerbations, systemic corticosteroids can improve lung function (FEV1), oxygenation and shorten recovery time including hospitalization duration. Duration of therapy should not normally be more than 5 days.

• Antibiotics, when indicated, can shorten recovery time, reduce the risk of early relapse, treatment failure, and hospitalization duration. Duration of therapy should be 5 days.

• Methylxanthines are not recommended due to increased side effect profiles.

• Non-invasive mechanical ventilation should be the first mode of ventilation used in COPD patients with acute respiratory failure who have no absolute contraindication because it improves gas exchange, reduces work of breathing and the need for intubation, decreases hospitalization duration and improves survival.

• Exacerbation recovery time varies, taking up to 4-6 weeks to recover, with some patients failing to return to the pre-exacerbation functional state. Following an exacerbation, appropriate measures for exacerbation prevention should be initiated (see Chapter 3).

DEFINITION

An exacerbation of chronic obstructive pulmonary disease (ECOPD) is defined as an event characterized by increased

dyspnea and/or cough and sputum that worsens in < 14 days which may be accompanied by tachypnea and/or

tachycardia and is often associated with increased local and systemic inflammation caused by infection, pollution, or

other insult to the airways.(304)

Considerations

Exacerbations of COPD are important events in the management of COPD because they negatively impact health

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status, rates of hospitalization and readmission, and disease progression.(435,436) COPD exacerbations are usually

associated with increased airway inflammation, increased mucus production and marked gas trapping. These changes

contribute to increased dyspnea that is the key symptom of an exacerbation. Other symptoms include increased

sputum purulence and volume, together with increased cough and wheeze.(1140,1141) Patients with COPD are at

increased risk of other acute events, particularly decompensated heart failure,(1142,1143) pneumonia,(1144,1145) pulmonary

embolism(1146,1147) that may also mimic or aggravate an ECOPD. Thus, while worsening of dyspnea, particularly if

associated with cough and, purulent sputum, and no other symptoms or signs in a patient with COPD may be diagnosed

as an ECOPD, other patients may have worsening of respiratory symptoms, particularly dyspnea without the classic

characteristics of ECOPD, that should prompt careful consideration and/or search of those potential confounders, or

contributors. In some patients one or more of these diagnoses may contribute to the clinical presentations and should

be addressed appropriately (Figure 4.1).

Currently, exacerbations are classified after the event has occurred as:

► Mild (treated with short acting bronchodilators only, SABDs)

► Moderate (treated with SABDs and oral corticosteroids ± antibiotics) or

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► Severe (patient requires hospitalization or visits the emergency room). Severe exacerbations may also be

associated with acute respiratory failure.

The current grading of the severity of an ECOPD, based on post facto use of healthcare resources, is a major limitation

of the current definition. Because of global variability in the available resources to treat patients and local customs

affecting the criteria for hospital visits and admissions, there is substantial variability in reported ECOPD outcomes.(1148)

Figure 4.2 shows a proposed clinical approach based on the current best available evidence.(304)

It has been proposed that these easy to obtain clinical variables can help define the severity of exacerbations on point

of contact (The ROME Proposal).(304) Using The ROME Proposal for exacerbations, hospitalized patients with acute

exacerbations can be further subclassified into mild, moderate and severe events with differences in mortality.(1149,1150)

Based on a thorough review of the available literature and using a Delphi approach to agree on the variable thresholds,

the severity classification is summarized in Figure 4.3.

In the primary care setting, where laboratories may not be available, severity can be determined with the easily

obtainable dyspnea intensity (using a VAS 0 to 10 dyspnea scale with zero being not short of breath at all and 10 the

worst shortness of breath you have ever experienced), respiratory rate, heart rate and oxygen saturation level. Where

available, blood C-reactive protein (CRP) level is recommended. To determine the need for ventilator support (usually

in the emergency room or hospital setting) arterial blood gases or equivalent should be measured. To move from a

mild to a moderate level, three of the variables need to exceed the established thresholds. It is hoped that prospective

validation will help better define exacerbations and their severity at point of contact, and that documented validation

may confirm or help modify the proposed thresholds of the variables now included. It is proposed that prospective

research can help determine a more specific marker of lung injury than the more generic CRP, as has been true for

other organs acute events.

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It is now recognized that many exacerbations are not reported to healthcare professionals for therapy and yet these

events, although often shorter in duration, also have a significant impact on health status.(1151,1152) Thus COPD patients

need to receive education about the importance of understanding exacerbation symptoms and when to seek

professional healthcare. The WHO has defined a minimum set of interventions for the management of

exacerbations.(742)

Exacerbations are mainly triggered by respiratory viral infections although bacterial infections and environmental

factors such as ambient air pollution and excess heat may also initiate and/or amplify these events.(1153,1154) Short-term

exposure to fine (PM2.5) and coarse (PM10) particulate matter is associated with increased hospitalizations, ER visits,

and outpatient visits,(1154) as well as increased mortality of COPD exacerbations.(1153,1155,1156) Another study also showed

that short-term exposure to ambient nitrogen dioxide and PM2.5 was associated with exacerbations in mild to

moderate COPD patients.(101) The most common viruses isolated are human rhinovirus (the cause of the common cold),

influenza, para-influenza and metapneumovirus which can be detected for up to a week after an exacerbation

onset.(1157,1158) When associated with viral infections, exacerbations are often more severe, last longer and precipitate

more hospitalizations, as seen during winter. Filamentous fungi, particularly Aspergillus species, may be identified in

sputum samples of patients during moderate or severe exacerbations(1159-1161) although their clinical relevance remains

unclear. Invasive pulmonary aspergillosis is rare (1.3%-3.9%)(1162) and more frequent in patients with more severe

baseline airflow obstruction, recent use of broad spectrum antibiotics or parenteral steroids, and

hypoalbuminemia.(1163) Aspergillus sensitization is also a marker of increased risk of exacerbations.(1164) The diagnostic

approach to invasive aspergillosis in this setting remains challenging.(1165)

Exacerbations can be associated with increased sputum production and, if purulent, they are most likely due to

bacterial infection(1141,1157,1166) There is reasonable evidence to support the concept that eosinophils are increased in

the airways, lung, and blood in a significant proportion of people with COPD.(1167-1169) The presence of sputum

eosinophilia has been related to susceptibility to viral infection.(1166) It has been suggested that exacerbations

associated with an increase in sputum or blood eosinophils may be more responsive to systemic steroids(1170) although

more prospective trials are needed to test this hypothesis.(1170)

During a COPD exacerbation, increased symptoms are usually present for 7 to 10 days, but some events may last

longer. At 8 weeks up to 20% of patients will not have recovered to their pre-exacerbation state.(1171) COPD

exacerbations contribute to disease progression,(1172) which is more likely if recovery from exacerbations is slow.(1173)

Exacerbations can also cluster in time and once they occur there is increased likelihood of another event(439,1174) (see

Chapter 2).

Some patients are susceptible to frequent exacerbations (defined as two or more exacerbations per year), and these

patients have worse health status and morbidity than patients with less frequent exacerbations.(436) The exact reason

for an individual’s increased susceptibility to exacerbation symptoms remains largely unknown. However, the

perception of breathlessness is greater in frequent exacerbators than infrequent exacerbators,(489) suggesting that a

perception of breathing difficulty may contribute to precipitating the respiratory symptoms rather than solely

physiological, or causative factors. The strongest predictor of a patient’s future exacerbation frequency remains the

number of exacerbations they have had in the prior year.(439) It is recognized that these patients form a moderately

stable phenotype, although some studies have shown that a significant proportion of patients change their

exacerbation frequency especially with worsening FEV1.(1175)

Other factors that have been associated with an increased risk of acute exacerbations and/or severity of exacerbations

include an increase in the ratio of the pulmonary artery to aorta cross sectional dimension (i.e., ratio > 1),(301) a greater

percentage of emphysema or airway wall thickness(1176) measured by chest CT imaging and the presence of chronic

bronchitis.(169,1177)

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Vitamin D has an immune-modulating role and has been implicated in the pathophysiology of exacerbations. As with

many chronic diseases vitamin D levels are lower in COPD than in health. Some, but not all studies have shown that

supplementation in people with severe deficiency results in a 50% reduction in episodes and hospital

admission.(896,1178) Therefore it is recommended that all patients hospitalized for exacerbations should be assessed and

investigated for severe deficiency (< 10 ng/ml or < 25 nM) followed by supplementation if required.

TREATMENT OPTIONS

Treatment setting

The goals of treatment for COPD exacerbations are to minimize the negative impact of the current exacerbation and

prevent the development of subsequent events.(1179) Depending on the severity of an exacerbation and/or the severity

of the underlying disease, an exacerbation can be managed in either the outpatient or inpatient setting. More than

80% of exacerbations are managed on an outpatient basis with pharmacological therapies including bronchodilators,

corticosteroids, and antibiotics.(439,740,1180)

The indications for assessing the need for hospitalization during a COPD exacerbation are shown in Figure 4.4. When

patients with a COPD exacerbation come to the emergency department, if hypoxemic they should be provided with

supplemental oxygen and undergo assessment to determine whether the exacerbation is life-threatening and if

increased work of breathing or impaired gas exchange requires consideration for non-invasive ventilation. If so,

healthcare providers should consider admission to an area where proper monitoring and care can be provided. In less

severe cases, the patient may be managed in the emergency department or hospital ward unit. In addition to

pharmacological therapy, hospital management of exacerbations includes respiratory support (oxygen therapy,

ventilation). The management of severe, but not life threatening, exacerbations is outlined in Figure 4.5.

The clinical presentation of COPD exacerbation is heterogeneous, thus we recommend that in hospitalized patients

the severity of the exacerbation should be based on the patient’s clinical signs and recommend the following

classification:(1181)

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No respiratory failure: Respiratory rate: ≤ 24 breaths per minute; heart rate < 95 beats per minute, no use of

accessory respiratory muscles; no changes in mental status; hypoxemia improved with supplemental oxygen given via

Venturi mask 24-35% inspired oxygen (FiO2); no increase in PaCO2.

Acute respiratory failure – non-life-threatening: Respiratory rate: > 24 breaths per minute; using accessory

respiratory muscles; no change in mental status; hypoxemia improved with supplemental oxygen via Venturi mask

> 35% FiO2; hypercarbia i.e., PaCO2 increased compared with baseline or elevated 50-60 mmHg.

Acute respiratory failure – life-threatening: Respiratory rate: > 24 breaths per minute; using accessory

respiratory muscles; acute changes in mental status; hypoxemia not improved with supplemental oxygen via Venturi

mask or requiring FiO2 > 40%; hypercarbia i.e., PaCO2 increased compared with baseline or elevated > 60 mmHg or the

presence of acidosis (pH ≤ 7.25).

Long-term prognosis following hospitalization for COPD exacerbation is poor, with a five-year mortality rate of about

50%.(1182) Factors independently associated with poor outcome include older age, lower BMI, comorbidities (e.g.,

cardiovascular disease or lung cancer), previous hospitalizations for COPD exacerbations, clinical severity of the index

exacerbation and need for long-term oxygen therapy at discharge.(1183-1185) Patients characterized by a higher

prevalence and severity of respiratory symptoms, poorer quality of life, worse lung function, lower exercise capacity,

lower lung density and thickened bronchial walls on CT-scan are also at increased risk for a higher mortality following

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an acute COPD exacerbation.(1186) Mortality risk may be heightened during spells of cold weather.(1187)

An updated Cochrane review concluded that the use of COPD exacerbation action plans with a single short educational

component, in conjunction with ongoing support, reduced in-hospital healthcare utilization. Such educational

interventions were also found to increase the treatment of COPD exacerbations with corticosteroids and

antibiotics.(1188)

Key points for the management of all exacerbations are given in Figure 4.6.

Pharmacological treatment

The three classes of medications most commonly used for COPD exacerbations are bronchodilators, corticosteroids,

and antibiotics.

Bronchodilators

Although there is no high-quality evidence from RCTs, it is recommended that short-acting inhaled beta2-agonists, with

or without short-acting anticholinergics, are the initial bronchodilators for acute treatment of a COPD

exacerbation.(1135,1189) A systematic review of the route of delivery of short-acting bronchodilators found no significant

differences in FEV1 between using metered dose inhalers (MDI) (with or without a spacer device) or nebulizers to

deliver the agent,(527,1190) although the latter may be an easier delivery method for sicker patients. It is recommended

that patients do not receive continuous nebulization but use the MDI inhaler one or two puffs every one hour for two

or three doses and then every 2-4 hours based on the patient’s response. Although, there are no clinical studies that

have evaluated the use of inhaled long-acting bronchodilators (either beta2-agonists or anticholinergics or

combinations) with or without ICS during an exacerbation, we recommend continuing these treatments during the

exacerbation or to start these medications as soon as possible before hospital discharge. Intravenous methylxanthines

(theophylline or aminophylline) are not recommended to use in these patients due to significant side effects.(1191,1192)

If a nebulizer is chosen to deliver the bronchodilator agent, air-driven bronchodilator nebulization is preferable to

oxygen-driven in acute exacerbations of COPD in order to avoid the potential risk of increasing the PaCO2 associated

with oxygen-driven bronchodilator administration.(1193)

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Glucocorticoids

Data from studies (mostly hospital based) indicate that systemic glucocorticoids in COPD exacerbations shorten

recovery time and improve lung function (FEV1). They also improve oxygenation,(1194-1197) the risk of early relapse,

treatment failure,(1198) and the length of hospitalization.(1194,1196,1199) A dose of 40 mg prednisone-equivalent per day

for 5 days is recommended.(1200) One observational study suggests that longer courses of oral corticosteroids for COPD

exacerbations are associated with an increased risk of pneumonia and mortality.(1201) Therapy with oral prednisolone

is equally effective to intravenous administration.(1202) Nebulized budesonide alone may be a suitable alternative for

treatment of exacerbations in some patients,(1195,1203,1204) and provides similar benefits to intravenous

methylprednisolone, although the choice between these options may depend on local cost issues.(1205,1206) Even short

bursts of corticosteroids are associated with subsequent increased risk of pneumonia, sepsis and death(1207) and use

should be confined to patients with significant exacerbations. Recent studies suggest that glucocorticoids may be less

efficacious to treat acute COPD exacerbations in patients with lower levels of blood eosinophils(439,1167,1170,1208) and

more trials of steroid-sparing treatment regimens are required.

Antibiotics

Although the infectious agents in COPD exacerbations can be viral or bacterial,(1158,1209) the use of antibiotics in

exacerbations remains controversial.(326,1210,1211) The uncertainties originate from studies that did not differentiate

between bronchitis (acute or chronic) and COPD exacerbations, studies without placebo-control, and/or studies

without chest X-rays that do not exclude that patients may have had underlying pneumonia. There is evidence

supporting the use of antibiotics in exacerbations when patients have clinical signs of a bacterial infection e.g.,

increased sputum purulence.(326,1211) Indeed the use of observed sputum color can safely modulate antibiotic therapy

with no adverse effects if sputum is white or clear in color. On the other hand observed sputum purulence has 94.4%

sensitivity and 52% specificity for high bacterial load, indicative of a causative relationship.(326)

A systematic review of placebo-controlled studies has shown that antibiotics reduce the risk of short-term mortality

by 77%, treatment failure by 53% and sputum purulence by 44%.(1212) The review provides evidence to treat

moderately or severely ill patients with COPD exacerbations and increased cough and sputum purulence with

antibiotics.(1212,1213) These data are supported by more RCTs in patients with diagnoses of moderate COPD.(1214) In an

RCT, the addition of doxycycline to oral corticosteroid an outpatient setting did not prolong time to next

exacerbation.(1215) In the outpatient setting, sputum cultures are not feasible as they take at least two days and

frequently do not give reliable results for technical reasons. Several biomarkers of airway infection are being studied

in exacerbations of COPD that have a better diagnostic profile. Earlier studies of C-reactive protein (CRP) have reported

contradictory findings.(1216,1217) A randomized trial found a marked reduction in antibiotic prescriptions without

impaired outcomes in UK primary care outpatients with ECOPD in whom antibiotics prescriptions were guided by

point-of-care CRP testing.(1218) Another trial in patients hospitalized for exacerbations of COPD in The Netherlands

found similar results (reduced antibiotic use with no increase in treatment failure). These findings need confirmation

in other settings before a recommendation to generalize this approach. However, data has indicated that antibiotic

usage can be safely reduced from 77.4% to 47.7% when CRP is low.(1219)

Procalcitonin is an acute phase reactant that increases in response to inflammation and infection and has been studied

to determine the use of antibiotics in COPD exacerbations.(1220) The efficacy of this biomarker is controversial. Several

studies, mainly done in the outpatient setting, suggested that procalcitonin-guided antibiotic treatment reduces

antibiotic exposure and side effects with the same clinical efficacy.(1221-1223) A systematic review and meta-analysis on

the use of procalcitonin in hospitalized patients with a COPD exacerbation found no significant reduction in overall

antibiotic exposure.(1224) In patients with COPD exacerbations treated in an ICU setting, the use of a procalcitonin-

based algorithm for initiating or stopping antibiotics was associated with a higher mortality rate when compared to

those receiving standard antibiotic regimens.(1225) Based on these conflicting results we cannot recommend at this

time the use of procalcitonin-based protocols to make the decision on using antibiotics in patient with COPD

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exacerbations; however, confirmatory trials with rigorous methodology are required.

In summary, antibiotics should be given to patients with exacerbations of COPD who have three cardinal symptoms:

increase in dyspnea, sputum volume, and sputum purulence; have two of the cardinal symptoms, if increased

purulence of sputum is one of the two symptoms; or require mechanical ventilation (invasive or noninvasive).(1141,1158)

A metanalysis demonstrated that ≤ 5 days of antibiotic treatment had the same clinical and bacteriological efficacy to

longer conventional treatment in outpatients with COPD exacerbations. Furthermore, shorter exposure to antibiotics

may decrease the risk developing antimicrobial resistance and complications associated with this therapy. The

recommended length of antibiotic therapy is 5-7 days.(1226) We recommend a duration of ≤ 5 days of antibiotic

treatment for outpatient treatment of COPD exacerbations.(1225,1227)

The choice of the antibiotic should be based on the local bacterial resistance pattern. Usually, initial empirical

treatment is an aminopenicillin with clavulanic acid, macrolide, tetracycline or, in selected patients, quinolone. In

patients with frequent exacerbations, severe airflow obstruction,(1228,1229) and/or exacerbations requiring mechanical

ventilation,(1230) cultures from sputum or other materials from the lung should be performed, as gram-negative

bacteria (e.g., Pseudomonas species) or resistant pathogens that are not sensitive to the above-mentioned antibiotics

may be present. The route of administration (oral or intravenous) depends on the patient’s ability to eat and the

pharmacokinetics of the antibiotic, although it is preferable that antibiotics be given orally. Improvements in dyspnea

and sputum purulence suggest clinical success.

Adjunct therapies

Depending on the clinical condition of the patient, an appropriate fluid balance, use of diuretics when clinically

indicated, anticoagulants, treatment of comorbidities and nutritional aspects should be considered. Among COPD

patients hospitalized with a suspected exacerbation, up to 5.9% were found to have pulmonary embolism.(1146)

Hospitalized patients with COPD are at an increased risk of deep vein thrombosis and pulmonary embolism(1231,1232)

and prophylactic measures for thromboembolism should be instituted.(1233,1234) At all times, healthcare providers

should strongly enforce the need for smoking cessation.

Respiratory support

Oxygen therapy

This is a key component of hospital treatment of an exacerbation. Supplemental oxygen should be titrated to improve

the patient’s hypoxemia with a target saturation of 88-92%.(1235) Once oxygen is started, blood gases should be checked

frequently, or as clinically indicated, to ensure satisfactory oxygenation without carbon dioxide retention and/or

worsening acidosis. Pulse oximetry is not as accurate as arterial blood gas(488) and in particular, may overestimate

blood oxygen content among individuals with darker skin tones.(1236) A study demonstrated that venous blood gas to

assess bicarbonate levels and pH is accurate when compared with arterial blood gas assessment.(1237) Additional data

are needed to clarify the utility of venous blood gas sampling to make clinical decisions in scenarios of acute respiratory

failure; most patients included had a pH > 7.30 on presentation, PCO2 levels were dissimilar when measured by venous

compared to arterial blood samples and the severity of airflow obstruction was not reported.(1237) Venturi masks offer

more accurate and controlled delivery of oxygen than do nasal prongs.(1135)

High-flow nasal therapy

High-flow nasal therapy (HFNT) delivers heated and humidified air-oxygen blends via special devices (e.g.,

Vapotherm®, Comfort Flo®, or Optiflow®) at rates up to 8 L/min in infants and up to 60 L/min in adults.(1238) HFNT has

been associated with decreased respiratory rate and effort, decreased work of breathing, improved gas exchange,

improved lung volume and dynamic compliance, transpulmonary pressures and homogeneity.(1239,1240) These

physiologic benefits positively improve oxygenation and clinical outcomes in patients with acute hypoxemic

respiratory failure.(1239-1242) HFNT has been reported to improve oxygenation and ventilation, decrease hypercarbia and

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improve health-related quality of life in patients with acute hypercapnia during an acute exacerbation, and also in

select patients with stable hypercapnic COPD.(1239,1243-1245) However, the small sample sizes, heterogeneity of the

patient populations and short duration of follow-up are current limitations in the interpretation of the value of HFNT

for the COPD patient population at large.(1246) A meta-analysis, based on poor quality studies, showed no clear

benefit.(1247) HFNT has been reported to improve oxygenation and ventilation, decrease hypercarbia, prolong the time

to next moderate exacerbation and improve health-related quality of life scores in patients with acute hypercapnia

during an exacerbation or in select patients with stable hypercapnic COPD receiving long term oxygen therapy.(1248)

HFNT did not prevent intubation in a RCT conducted in patients hospitalized with an acute exacerbation.(1249) It should

be noted that European Respiratory Society (ERS) Clinical Practice Guidelines recommend trialling NIV prior to use of

HFNT in patients with COPD and hypercapnic ARF.(1250) There is a need for well-designed, prospective, randomized and

controlled multicenter trials to study the effects of HFNT in people with COPD experiencing episodes of either acute

or chronic hypercapnic respiratory failure.

Ventilatory support

Some patients need immediate admission to the respiratory care or intensive care unit (ICU) (Figure 4.7). Admission

of patients with severe exacerbations to intermediate or special respiratory care units may be appropriate if adequate

personnel skills and equipment exist to identify and manage acute respiratory failure. Ventilatory support in an

exacerbation can be provided by either noninvasive (nasal or facial mask) or invasive (oro-tracheal tube or

tracheostomy) ventilation. Respiratory stimulants are not recommended for acute respiratory failure.(1189)

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Noninvasive mechanical ventilation

The use of noninvasive mechanical ventilation (NIV) is preferred over invasive ventilation (intubation and positive

pressure ventilation) as the initial mode of ventilation to treat acute respiratory failure in patients hospitalized for

acute exacerbations of COPD. NIV has been studied in RCTs showing a success rate of 80-85%.(641,1251-1254) NIV has been

shown to improve oxygenation and acute respiratory acidosis i.e., NIV increases pH and decreases PaCO2. NIV also

decreases respiratory rate, work of breathing and the severity of breathlessness but also decreases complications such

as ventilator associated pneumonia, and length of hospital stay. More importantly, mortality and intubation rates are

reduced by this intervention.(1252,1255-1257) Once patients improve and can tolerate at least 4 hours of unassisted

breathing, NIV can be directly discontinued without any need for a “weaning” period.(1258) The indications for NIV(1254)

are summarized in Figure 4.8.

Invasive mechanical ventilation

The indications for initiating invasive mechanical ventilation during an exacerbation are shown in Figure 4.9, and

include failure of an initial trial of NIV.(1259) As experience is gained with the generalized clinical use of NIV in COPD, a

number of indications for invasive mechanical ventilation are being successfully treated with NIV, thus eliminating

invasive mechanical ventilation as first line treatment of acute respiratory failure during hospitalization for COPD

exacerbation.(1259) In patients who fail non-invasive ventilation as initial therapy and receive invasive ventilation as

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subsequent rescue therapy, morbidity, hospital length of stay and mortality are greater.(641) The use of invasive

ventilation in patients with very severe COPD is influenced by the likely reversibility of the precipitating event, the

patient’s wishes, and the availability of intensive care facilities.(641) When possible, a clear statement of the patient’s

own treatment wishes, such as an advance directive or “living will”, makes these difficult decisions easier to resolve.

Major hazards include the risk of ventilator-acquired pneumonia (especially when multi-resistant organisms are

prevalent), barotrauma and volutrauma, and the risk of tracheostomy and consequential prolonged ventilation.

Acute mortality among COPD patients with respiratory failure is lower than mortality among patients ventilated for

non-COPD causes.(1260) Despite this, there is evidence that patients who might otherwise survive are frequently denied

admission to intensive care for intubation because of unwarranted prognostic pessimism.(1261) A large study of COPD

patients with acute respiratory failure reported in-hospital mortality of 17-49%.(1262) Further deaths were reported

over the next 12 months, particularly among those patients who had poor lung function before invasive ventilation

(FEV1 < 30% predicted), had a non-respiratory comorbidity, or were housebound. Patients who did not have a

previously diagnosed comorbidity, had respiratory failure due to a potentially reversible cause (such as an infection),

or were relatively mobile and not using long-term oxygen, did well after ventilator support.

Hospital discharge and follow-up

The cause, severity, impact, treatment and time course of exacerbations varies from patient to patient and facilities in

the community, and healthcare systems, differ from country to country. Accordingly, there are no standards that can

be applied to the timing and nature of discharge. However, it is recognized that recurrent exacerbations leading to

short-term readmission and increased all-cause mortality are associated with the initial hospitalization for an acute

episode of deterioration.(1263)

When features related to re-hospitalization and mortality have been studied, defects in perceived optimal

management have been identified including spirometric assessment and arterial blood gas analysis.(1264) A systematic

review has shown that comorbidities, previous exacerbations and hospitalization, and increased length of stay were

significant risk factors for 30- and 90-day all-cause readmission after an index hospitalization with an exacerbation of

COPD.(1265) Mortality relates to patient age, the presence of acidotic respiratory failure, the need for ventilatory

support and comorbidities including anxiety and depression.(1266)

The introduction of care bundles at hospital discharge to include education, optimization of medication, supervision

and correction of inhaler technique, assessment and optimal management of comorbidities, early rehabilitation,

telemonitoring and continued patient contact have all been investigated to address these issues (Figure 4.10).(1267)

While these measures all seem sensible there is insufficient data that they influence either readmission rates or short-

term mortality(1264,1266,1268,1269) and there is little evidence of cost-effectiveness.(1266) One RCT showed that

telemonitoring did not change hospitalization or exacerbation rates in people with COPD.(1270) Nevertheless, it remains

good clinical practice to cover these issues before discharge and their effectiveness on health status and readmission

rates may be increased if they are delivered with an approach that includes motivational interview-based health

coaching.(964)

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The only possible exception is early rehabilitation as there is some evidence that this factor is associated with increased

mortality, although the reasons remain unknown.(1269) However, other data suggest that early rehabilitation post

hospital discharge (i.e., < 4 weeks) may be associated with improved survival.(702)

Early follow-up (within one month) following discharge should be undertaken when possible and has been related to

less exacerbation-related readmissions.(1271) There are many patient issues that prevent early follow-up; those not

attending early follow-up have increased 90-day mortality. This may reflect both patient compliance, limited access to

medical care, poor social support, and/or the presence of more severe disease. Nevertheless, early follow-up permits

a careful review of discharge therapy and an opportunity to make any needed changes in therapy.

Additional follow-up at three months is recommended to ensure return to a stable clinical state and permit a review

of the patient’s symptoms, lung function (by spirometry), and where possible the assessment of prognosis using

multiple scoring systems such as BODE.(1272) In addition, arterial oxygen saturation and blood gas assessment will

determine the need for long-term oxygen therapy more accurately at prolonged follow-up compared to shortly after

discharge.(1273)

CT assessment to determine the presence of bronchiectasis and emphysema should be done in patients with recurrent

exacerbations and/or hospitalizations.(483,1274) A further detailed assessment of the presence and management of

comorbidities should also be undertaken (Figure 4.10).(1274)

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Be sure to read and understand the paragraph entitled Important Purpose & Liability Disclaimer 113

Prevention of exacerbations

After an acute exacerbation, appropriate measures for prevention of further exacerbations should be initiated (Figure

4.6 and Figure 4.11). For the following treatment modalities significant effects on exacerbation risk/frequency could

be shown in clinical trials. For details refer to Chapter 3.

Based on findings from observational studies in various countries(1275-1278) there was a major decrease in hospital

admissions for COPD exacerbations during the COVID-19 epidemic. It was hypothesized that this phenomenon may be

a consequence of shielding measures (e.g., wearing masks, avoiding social contact, regular hand washing etc). An

alternative explanation is that patients may not have been seeking medical assistance during an exacerbation due to

concern about becoming infected with the SARS-CoV-2 virus. If this was the case, then a corresponding increase in

COPD related mortality would be expected. However, two major studies from the US and the UK(1275,1279) did not report

increased COPD associated mortality during the pandemic. Accordingly, shielding measures could be considered

during the winter months (on top of established pharmacological and non-pharmacological measures) in patients at

risk of exacerbation.

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