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Age and Ageing 2008; 37: 251–257  The Author 2008.

r 2008. Published by Oxford University Press on behalf of the British Geriatrics Society.
doi:10.1093/ageing/afn060 All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Published electronically 3 April 2008

REVIEW

Acute respiratory failure in the elderly: diagnosis


and prognosis
SAMUEL DELERME, PATRICK RAY
Emergency Department, CHU Pitié-Salpétriêre, 47-83 boulevard de l’hopital, 75013 Paris, Université Pierre et
Marie Curie-Paris 6, France
Address correspondence to: P. Ray. Tel: +33 1 42 17 72 42; Fax: +33 1 42 17 72 64. Email: patrick.ray@psl.aphp.fr

Abstract
Acute respiratory failure (ARF) in patients over 65 years is common in emergency departments (EDs) and is one of the key
symptoms of congestive heart failure (CHF) and respiratory disorders. Searches were conducted in MEDLINE for published
studies in the English language between January 1980 and August 2007, using ‘acute dyspnea’, ‘acute respiratory failure
(ARF)’, ‘heart failure’, ‘pneumonia’, ‘pulmonary embolism (PE)’ keywords and selecting articles concerning patients aged
65 or over. The age-related structural changes of the respiratory system, their consequences in clinical assessment and the
pathophysiology of ARF are reviewed. CHF is the most common cause of ARF in the elderly. Inappropriate diagnosis that is
frequent and inappropriate treatments in ED are associated with adverse outcomes. B-type natriuretic peptides (BNPs) help
to determine an accurate diagnosis of CHF. We should consider non-invasive ventilation (NIV) in elderly patients hospitalised
with CHF or acidotic chronic obstructive pulmonary disease (COPD) who do not improve with medical treatment. Further
studies on ARF in elderly patients are warranted.

Keywords: acute respiratory failure, elderly, pulmonary embolism, BNP, congestive heart failure

Introduction keywords and selecting articles concerning patients aged


65 or over.
Visits by older adults compose 12–21% of all emergency
Physiological changes according to age
department (ED) encounters [1]. Furthermore, studies
showed a progressive increase in the number of ED Several changes related to ageing need to be taken into
attendances and emergency admissions hospital of older account before discussing ARF.
patients in the last decade. Between 30 and 50% of all ED
visits by older patients result in a hospital admission. Lastly Pulmonary function
when admitted, older emergency patients are more likely to Chest wall compliance decreases progressively with age,
require an ICU (intensive care unit) bed [2]. Acute respiratory presumably related to structural changes within the rib
failure (ARF) is a common complaint of elderly patients in cage [4, 5].
ED, and the key clinical presentation of cardiac [congestive Total lung capacity does not change with age, but the
heart failure (CHF)] and respiratory disorders [3]. functional residual capacity and the residual volume both
This article will summarise the age-related structural increase. There is an increased tendency in airway closure
changes of the respiratory system and their consequences in at small volumes (senile emphysema) related to the loss
clinical practice. It will also overview the causes, difficulties of supporting tissues around the airways [4]. Because a
in diagnosis, treatment and the prognosis of ARF in elderly significant proportion of peripheral airways do not contribute
patients. to gas exchange (low V/Q ratio) zones, but also because of
Searches were conducted in MEDLINE for published a reduced alveolar area, ageing was classically thought to be
studies in the English language between January 1980 and accompanied by a progressive decline in arterial oxygen
August 2007, using ‘acute dyspnea’, ‘acute respiratory failure’, tension (PaO2 ). Actually, recent studies have found no
‘heart failure’, ‘pneumonia’, ‘pulmonary embolism (PE)’ significant correlation between PaO2 and age [6]. Because of

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S. Delerme and P. Ray

a decline in tests of forced expiration (i.e. increasing airway functions, i.e. oxygenation (PaO2 <60 mmHg) of and/or
resistance), an obstructive pattern could exist even in women elimination of carbon dioxide (arterial carbon dioxide tension
who are non-smokers. Furthermore, studies suggest that (PaCO2 ) >45 mmHg) [11]. Both cut-off values simply serve
the ß-adrenoceptor dysfunction explains a less response to as a general guide in combination with the history and
bronchodilation in older asthmatic patients [7]. clinical assessment of the patient. Thus, ARF could also be
Other common important changes include loss of suspected by ‘simple’ clinical criteria: polypnea >30 per min,
diaphragmatic mass and strength with age [8]. Finally, as contraction of the accessory inspiratory muscles, abdominal
a consequence of poor nutritional status, decreased T-cell respiration, orthopnea cyanosis, and asterixis. Orthopnea is
function, decline in mucociliary clearance, poor dentition frequently associated with all causes of ARF, and is neither a
with oropharyngeal colonisation, and swallowing dysfunction sensible nor specific predictor of CHF [3].
(Parkinson’s disease, Alzheimer’s disease and stroke), The four pathophysiological mechanisms related to
community-acquired (CAP) and aspiration pneumonia is hypoxaemic ARF (1) ventilation/perfusion inequality which
exceedingly common in elderly patients [9]. is the main mechanisms in an emergency setting (CHF or
Furthermore, decreased sensitivity of respiratory centres pneumonia), (2) increased shunt (acute respiratory distress
to hypoxaemia, hypercapnia, or added resistive loads will syndrome), (3) alveolar hypoventilation [chronic obstructive
result in a diminished ventilatory response in cases of ARF; pulmonary disease (COPD)], and (4) diffusion impairment
and could delay diagnosis because of the poor perception of (pulmonary fibrosis) [11].
the respiratory insults [4]. Failure of the pump (or ventilatory failure) results in
alveolar hypoventilation with an increase in PaCO2 (Table 1).
Cardiovascular changes Mechanisms responsible are decreasing minute ventilation
The physiological cardiovascular changes involve the and increasing dead space. In elderly patients, the major
decrease of myocyte number, intrinsic contractility, coronary cause is severe hyperinflation, with flattened diaphragm and
flow reserve, ventricular compliance and ß-adrenoceptor- reduced mechanical action of the inspiratory muscles (COPD
mediated modulation of inotropy. exacerbation) [4].
The ageing heart increases cardiac output by increasing Actually, hypoxaemic ARF is a situation accompanied by
stroke volume rather than increasing heart rate. However, increased work of breathing. However, energy availability is
this compensatory mechanism is dependent on the effective reduced due to hypoxaemia, resulting in muscle fatigue and
atrial contribution to late diastolic filling (>30% in the elderly
patient) [10]. This explains the frequency of CHF caused by
rapid atrial fibrillation in the elderly. Table 1. Principal causes of acute respiratory failure
Cardiac and respiratory systems are dependent. For (adapted from [11])
example, (1) a bout of pneumonia is sufficient to trigger
Decreased central drive
an acute exacerbation of heart failure, (2) a reduction in
Morphine (or other drugs: sedatives)
cardiac output accompanying septic shock is a cause of Central nervous system diseases (encephalitis, stroke, trauma)
ARF caused by diaphragm hypoperfusion leading to alveolar Altered neural and neuromuscular transmission
hypoventilation, and respiratory arrest. Spinal cord trauma, transverse myelitis, tetanus, amyotrophic lateral
sclerosis, poliomyelitis, Guillain–Barre’ syndrome
Other relevant changes Myasthenia gravis, botulism
Muscle abnormalities
Decrease in glomerular filtration rate (approximately 45% Muscular dystrophy, disuse atrophy
by the age of 80) with ageing has important implications in Chest wall and pleural abnormalities
terms of drug dosing, as most drugs are renally excreted [2]. Kyphoscoliosis
Chest wall trauma (flail chest, diaphragmatic rupture)
Most studies have shown an imbalance between
Lung and airways diseases
procoagulant/antifibrinolytic and anticoagulant factors, Acute asthma
which could contribute to an increased incidence of PE. Acute exacerbation of chronic obstructive pulmonary disease
Congestive heart failure and non-cardiogenic pulmonary oedema
Definition and pathophysiology of acute (acute respiratory distress syndrome)
Pneumonia, tuberculosis
respiratory failure Upper airways obstruction
Lung cancer, pulmonary fibrosis
The respiratory system consists of two parts: the lung, i.e. Pneumothorax, pleural effusion
the gas-exchanging organ, and the pump [11]. The pump Bronchiectasis
consists of the chest wall, including the respiratory muscles Vascular diseases
(essentially the diaphragm), the respiratory controllers in Pulmonary embolism
the central nervous system and the pathways that connect Severe haemoptysis
the central controllers with the respiratory muscles (spinal Other
Severe sepsis or septic shock, other shock
and peripheral nerves). ARF is a condition in which the
respiratory system fails in one or both of its gas exchange The main causes of ARF in elderly patients are in bold.

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ARF in the elderly: diagnosis and prognosis

ventilatory failure through imbalance between demand and Outcomes


supply [11].
The mortality rate associated with ARF in the elderly varies
ARF in elderly patients according to the etiology. In a study, the crude mortality
of CAP requiring hospitalisation was 26%, and age by itself
Etiology of ARF was not a significant factor related to prognosis [14]. CHF
The EPIDASA study prospectively evaluated ARF in 514 has an in-hospital mortality, ranging from 13 to 29%, with
patients (mean age of 80 years), presenting to the ED. a rate of early re-hospitalisation from 29 to 47% within
CHF (43%), pneumonia (35%), COPD exacerbation (32%), 3–6 months of the initial discharge, and a 1 year survival of
and PE (18%) were the main causes [3]. Half of the 50% [3, 16, 25, 26]. In the EPIDASA study, 29% of patients
patients had more than two diagnoses (CHF and CAP were admitted to an ICU, and 16% died in hospital. The
in 17%). Pneumothorax, lung cancer, severe sepsis and five variables associated to death were: inappropriate initial
acute asthma were less frequent (<5%). An autopsy study treatment, hypercapnia >45 mmHg, creatinine clearance
of 234 elderly patients confirmed that the most common <50 ml/min, elevated B-type natriuretic peptides (BNP
causes of death were CAP and CHF, both frequently and NT-proBNP), and clinical signs of ARF. Age was not
underestimated [12]. Ely et al. reported the causes of being significantly associated with mortality.
mechanically ventilated: CHF (16%), CAP (16%), COPD
(14%), and sepsis (10%) [13]. Prognosis of elderly admitted in an ICU
Difficult diagnosis of ARF in the elderly Age is included in several scores of severity such as the
APACHE II, Fine’s score for CAP [27], and Aujesky’s
Ray et al. found that the sensitivity of the emergency physician
score for PE [2, 28]. However, the large majority of the
was 86% for pneumonia, 75% for PE, and 71% for CHF [3].
studies indicate that acute physiology disturbances and
In this study, the variables associated to a missed diagnosis
diagnosis have larger relative contributions to prognosis
were a final diagnosis of CHF, CAP or PE, highlighting the
than age [2]. Kaarlola et al. reported that the cumulative 3-
fact that frequent causes of ARF are very challenging to diag-
year mortality rate among the elderly patients was lower than
nose in the ED. Riquelme et al. demonstrated that the definite
that among the controls (40% versus 57%). However, 88%
diagnosis of CAP was delayed for more than 72 h in 62% of
of the elderly survivors assessed their present health state as
patients [14]. The association of dyspnea, cough, and fever,
satisfactory [29].
was observed in only 32% of patients with CAP, and delirium
at admission was very common (45%) [9, 14]. Atypical signs
Ethical considerations
of CHF are frequent (confusion or leg swelling, or wheezing),
and confusing [15, 16, 17]. Unfortunately, an inappropriate The decision to admit a patient to the ICU from the ED
diagnosis is associated with an increased mortality (Figure 1a is challenging, as physicians must decide in a short time.
and b) [3, 18]. The difficulties of diagnosing CHF and When a patient potentially requiring ICU care is admitted to
PE [19, 20, 21, 22, 23, 24] are reported in Appendix 1 and the ED, emergency physicians take the first decision as to
Appendix 2 in the supplementary data on the journal’s web- whether to propose the patient to the ICU. Thus, intensivists
site http://www.ageing.oxfordjournals.org (Figure 2 and see are involved only if an ICU admission is requested for
Appendix 4 in the supplementary data on the journal’s the patient. Age over 85 years seems to be an independent
website http://www.ageing.oxfordjournals.org). predictor of ICU refusal [30]. Actually, the decision to admit

Emergency Diagnosis Emergency Treatment


20 50 20 50
P<0.001 P<0.001
P<0.001
40 40
15
Percent of patients

15
Percent of patients
Number of Days

Number of Days

NS
P<0.001 30
30
P<0.001
10 10
20 20

5 5
10 10

0 0 0 0
Hospital ICU Death Hospital ICU Death
A Free Days B Free Days
Figure 1. (a) Effects of an appropriate (black bars) or inappropriate (white bars) initial diagnosis in the emergency department on
prognosis (used with permission from Ray P. [3]). (b) Effects of an appropriate (black bars) or inappropriate (white bars) initial
treatments in the emergency department on prognosis (used with permission from Ray P. [3]).

253
S. Delerme and P. Ray

Medical History, physical findings,


CXR, ABG, EKG

Unknown diagnoses Obvious diagnosis


Previous cardiac or lung disease CHF, CAP, ACS …

Suspected CHF

BNP
or NT-proBNP

BNP < 100 pg/mL 100 < BNP < 500 BNP > 500 pg/mL

CHF very likely2


CHF unlikely Possible CHF1
Respiratory disorders ? Nitrate IV bolus, diuretics,
Doppler-echocardiography
ACEi, NIV, Doppler-EC

Further investigations
CT chest with parenchymal
windows, then protocole PE
or lung ultrasonography

Figure 2. Diagnostic strategy based on B-type natriuretic peptide levels in elderly patients admitted for ARF in the emergency
department. 1 In the grey zone (BNP between 100 and 500 pg/ml), which represents less than a quarter of patients, further
investigations are needed, and ER physicians should consider massive PE, CHE, severe exacerbation of COPD or severe
pneumonia as possible diagnoses. 2 Physicians should keep in mind that half of elderly patients with ARF has more than one
diagnosis, i.e. a BNP greater than 500 pg/ml strongly suggests CHF, but other diagnosis that could have precipitated CHF.
CXR: chest X-ray; EKG: electrocardiogram; ABG: arterial blood gas analysis; CHF: congestive heart failure; ACS: acute coronary
syndrome; CT: computed tomography; IV: intravenous; NIV: non-invasive ventilation including continuous positive airway
pressure; ACEi: angiotensin converting enzyme inhibitor; EC: echocardiography.

an elderly patient to an ICU should be based on the patients’ 1 in the supplementary data on the journal’s website
co-morbidities, acuity of illness, pre-hospital functional status http://www.ageing.oxfordjournals.org) [35].
and the patient’s preferences [2].

How could we improve outcomes of ARF Role of B-type natriuretic peptides


in elderly patients?
Studies suggested that an inappropriate diagnosis and BNP is a polypeptide, released by ventricular myocytes
treatment were associated with an increased mortality rate directly proportional to wall tension, for lowering renin-
[Figure 1(b)] [3, 18]. Usual tools used to differentiate CHF angiotensin-aldosterone activation. In the blood, the
from respiratory disorders are not very accurate, even the cleavage of a precursor protein produces BNP and the
chest X-ray (CXR) in CHF [31] or the classical hypocapnia in biologically inactive NT-proBNP. For diagnosing CHF,
PE [32]. Thus valid diagnostic tools for differentiating CHF both BNP and NT-proBNP have similar accuracy [36, 37]
from other etiologies of ARF could aid clinicians. (see Appendix 1 in the supplementary data on the journal’s
website http://www.ageing.oxfordjournals.org). However,
Usefulness of transthoracic echocardiography threshold values are higher than in middle-aged population.
Echocardiography (EC) should be encouraged because A study demonstrated that the use of BNP in patients
the diagnosis of systolic CHF can be easily confirmed >70 years early in the ED reduced the time to discharge,
by the emergency physician [33, 34]. However non-systolic total treatment cost, and 30-day mortality. Figure 2 shows a
CHF is more difficult to evaluate by EC, and needs diagnostic strategy based on BNP in elderly patients admitted
Doppler and myocardial tissue imaging (see Appendix for ARF in the ED [38, 39]

254
ARF in the elderly: diagnosis and prognosis

Inflammatory markers Management of pneumonia in the elderly


Diagnosing CAP is difficult and urgent because it requires Previous studies showed the important role of silent
prompt antibiotics [40]. Thus, biological markers such as C- aspiration and the low prevalence of Legionella sp., Chlamydia
reactive protein (CRP) and procalcitonin (PCT) may be useful and Mycoplasma pneumoniae in CAP [9] Streptococcus pneumoniae
to suggest bacterial infection [41]. PCT seems to be more is the most common cause of CAP in the elderly.
sensitive and specific than CRP, with an additional prognostic Conversely, gram-negative bacilli (Klebsiella, Proteus sp,
value [42]. Several studies suggested that, in a middle-aged Escherichia coli, and others) account for half of all the
population with suspected CAP or COPD exacerbation, PCT culture-diagnosed pneumonias in nursing-home acquired
guidance of antibiotherapy reduced antibiotic use without pneumonia. Recommendations for anti-microbial drug
adverse effect [43]. However, in elderly patients Strucker use depend on the suspected specific organism, and
et al. have found that it had a low sensitivity (24%) for guidelines [54, 55]. The main objective is to start antibiotics
infection [44]. as early as possible since antibiotic administration within
4 h of hospital arrival is associated with a lower 30-day
mortality [56]. Recently, it was suggested that the SOAR
Potential usefulness of thoracic imaging
score (based on systolic blood pressure, oxygenation, age
When PE is suspected, throcacic computed tomography and respiratory rate) was an alternative criteria for a
(CT) is now one of the first line investigations (see Appendix better identification of severe CAP in advanced age where
2 in the supplementary data on the journal’s website both raised urea level above 7 mmol/l and confusion are
http://www.ageing.oxfordjournals.org, Figure 2) [45]. Fur- common [57].
thermore, thoracic CT is useful in determining alternate
diagnoses (pneumonia or CHF missed on CXR). In case of Pharmalogical treatment of CHF
unknown ARF, we recommend to begin with parenchymal Classically, medical treatments of CHF consisted of diuretics,
windows to diagnose obvious CHF or pneumonia, following and morphine, based on the ‘inappropriate’ concept that
by contrast injection to rule in PE if the parenchymal win- CHF is caused by fluid accumulation rather than fluid
dows do not explain the clinical picture [46, 47]. However, redistribution. Nitrate conveys both venodilatation (reducing
physicians should be aware of the risks taken in performing right and left ventricular preload and reducing pulmonary
helical CT scan. [48]. venous pressure directly) and arteriodilatation (reducing
Lung ultrasound could also be useful, but needs further the afterload mismatch and therefore increasing cardac
evaluation [49, 50]. index). Cotter et al. [58] demonstrated that boluses of high-
dose isosorbide dinitrate improved outcome compared to
Treatment of ARF repeated high-doses furosemide [58]. Sacchetti et al. [59]
demonstrated that morphine sulfate use in the ED was
Medical and social aspect associated with an increased ICU admission and endotracheal
Most emergency physicians do not have the expertise to intubation, whereas captopril sublingual use was associated
comprehensively address the myriad of needs of elderly with a decreased ICU admissions, and a decreased need for
patients with complex chronic illnesses (for example, in the endotracheal intubation. Considering the fact that 50% of
EPIDASA study, 45% of the patients had previous cardiac the elderly with CHF have preserved systolic function [60]
disease and 26% chronic respiratory disease [3]) and daily and that nearly two thirds present with hypertension, nitrate
treatments (in one study, the average number of drugs taken should be preferred [61]. Rapid determination of whether
by elderly patient was 4.2 [51]). Furthermore, polymedication there is a systolic or non-systolic CHF is important because
the etiologies and pharmalogical treatment are different (see
may affect the respiratory and cardiac systems (for example,
Appendix 1 in the supplementary data on the journal’s
ß-blockers prescribed for hypertension have an effect on
website http://www.ageing.oxfordjournals.org) [62].
lung function). A multi-disciplinary care model, involving
emergency physicians, gerontologist physicians, nurses,
Potential role of non-invasive ventilation by a face
clinicial pharmacist, social worker, family doctor should
mask
be encouraged [26].
In acute COPD exacerbations, non-invasive positive-
pressure ventilation (NPPV) decreases PaCO2 by unloading
Oxygen therapy
the respiratory muscles and supplementing alveolar venti-
Hypoxaemic patients with ARF need oxygen supplemen- lation. Several trials and meta-analysis support the use of
tation as the first stage of treatment. However, studies NPPV by reducing ventilator associated pneumonia, intuba-
suggested that injudicious use of oxygen therapy is asso- tion, duration of ICU stay, and mortality [13]. The few studies
ciated with increased hypercapnia in COPD patients [52]. on NPPV suggest that the response of middle-aged patients
Thus, it is important that, emergency physicians aim at pro- with acidotic COPD exacerbations to NPPV may extend to
viding an oxygen saturation >90%, and check blood gases the geriatric population. In CHF, NPPV improves oxygena-
30 min after starting oxygen in COPD patients [53]. tion, reduces work of breathing, and may prevent intubation,

255
S. Delerme and P. Ray

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