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com/content/10/3/R82

Research Open Access

Vol 10 No 3

Acute respiratory failure in the elderly: etiology, emergency

diagnosis and prognosis
Patrick Ray1, Sophie Birolleau2, Yannick Lefort2, Marie-Hélène Becquemin3, Catherine Beigelman4,
Richard Isnard5, Antonio Teixeira6, Martine Arthaud7, Bruno Riou1 and Jacques Boddaert8

1Department of Emergency Medicine and Surgery, Centre Hospitalo-Universitaire Pitié-Salpêtrière, Assistance Publique – Hôpitaux de Paris,
Université Pierre et Marie Curie-Paris 6 75651 Paris Cedex 13, France
2Department of Pneumology and Respiratory Intensive Care Unit, Centre Hospitalo-Universitaire Pitié-Salpêtrière, Assistance Publique – Hôpitaux de

Paris, Université Pierre et Marie Curie-Paris 6 75651 Paris Cedex 13, France
3Laboratory of Pulmonary Function Test and UPRES 2397, Centre Hospitalo-Universitaire Pitié-Salpêtrière, Assistance Publique – Hôpitaux de Paris,

Université Pierre et Marie Curie-Paris 6 75651 Paris Cedex 13, France

4Department of Radiology, Centre Hospitalo-Universitaire Pitié-Salpêtrière, Assistance Publique – Hôpitaux de Paris, Université Pierre et Marie Curie-

Paris 6 75651 Paris Cedex 13, France

5Department of Cardiology, Centre Hospitalo-Universitaire Pitié-Salpêtrière, Assistance Publique – Hôpitaux de Paris, Université Pierre et Marie

Curie-Paris 6 75651 Paris Cedex 13, France

6Department of Internal Medicine, Centre Hospitalo-Universitaire Pitié-Salpêtrière, Assistance Publique – Hôpitaux de Paris, Université Pierre et Marie

Curie-Paris 6 75651 Paris Cedex 13, France

7Laboratory of Emergency Biology, Centre Hospitalo-Universitaire Pitié-Salpêtrière, Assistance Publique – Hôpitaux de Paris, Université Pierre et

Marie Curie-Paris 6 75651 Paris Cedex 13, France

8Department of Geriatry, Centre Hospitalo-Universitaire Pitié-Salpêtrière, Assistance Publique – Hôpitaux de Paris, Université Pierre et Marie Curie-

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Paris 6 75651 Paris Cedex 13, France

Corresponding author: Patrick Ray, [email protected]

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Received: 3 Feb 2006 Revisions requested: 23 Feb 2006 Revisions received: 7 Apr 2006 Accepted: 24 Apr 2006 Published: 24 May 2006

Critical Care 2006, 10:R82 (doi:10.1186/cc4926)

This article is online at: http://ccforum.com/content/10/3/R82
© 2006 Ray et al.; licensee BioMed Central Ltd.
This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract
Introduction Our objectives were to determine the causes of acute asthma (3%); 47% had more than two diagnoses. In-
acute respiratory failure (ARF) in elderly patients and to assess hospital mortality was 16%. A missed diagnosis in the
the accuracy of the initial diagnosis by the emergency physician, emergency department was noted in 101 (20%) patients. The
and that of the prognosis. accuracy of the diagnosis of the emergency physician ranged
from 0.76 for cardiogenic pulmonary edema to 0.96 for asthma.
Method In this prospective observational study, patients were An inappropriate treatment occurred in 162 (32%) patients, and
included if they were admitted to our emergency department, lead to a higher mortality (25% versus 11%; p < 0.001). In a
aged 65 years or more with dyspnea, and fulfilled at least one of multivariate analysis, inappropriate initial treatment (odds ratio
the following criteria of ARF: respiratory rate at least 25 minute- 2.83, p < 0.002), hypercapnia > 45 mmHg (odds ratio 2.79, p
1; arterial partial pressure of oxygen (PaO ) 70 mmHg or less, or < 0.004), clearance of creatinine < 50 ml minute-1 (odds ratio
2
peripheral oxygen saturation 92% or less in breathing room air; 2.37, p < 0.013), elevated NT-pro-B-type natriuretic peptide or
arterial partial pressure of CO2 (PaCO2) ≥ 45 mmHg, with pH ≤ B-type natriuretic peptide (odds ratio 2.06, p < 0.046), and
7.35. The final diagnoses were determined by an expert panel clinical signs of acute ventilatory failure (odds ratio 1.98, p <
from the completed medical chart. 0.047) were predictive of death.

Results A total of 514 patients (aged (mean ± standard

deviation) 80 ± 9 years) were included. The main causes of ARF
were cardiogenic pulmonary edema (43%), community- Conclusion Inappropriate initial treatment in the emergency
acquired pneumonia (35%), acute exacerbation of chronic room was associated with increased mortality in elderly patients
respiratory disease (32%), pulmonary embolism (18%), and with ARF.

ARF = acute respiratory failure; BNP = B-type natriuretic peptide; CAP = community-acquired pneumonia; CI = confidence interval; COPD = chronic
obstructive pulmonary disease; CPE = cardiogenic pulmonary edema; CRD = chronic respiratory disease; CT = computed tomography; ED = emer-
gency department; HRCT = high-resolution computed tomography; ICU = intensive care unit; PaCO2 = arterial partial pressure of CO2; PaO2 = arte-
rial partial pressure of oxygen; PE = pulmonary embolism; PFT = pulmonary function test; ROC = receiver operating characteristic; SpO2 = peripheral
oxygen saturation.

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 Critical Care Vol 10 No 3 Ray et al.

Introduction pnea of less than two weeks' duration, a subjective criterion

In Western countries the population is getting older, and it is defined by the patient (the dyspnea was present if the patient
projected that the number of people between the age of 65 answered one of the following questions in the affirmative: Are
and 80 years will double by the year 2030 [1,2]. It is estimated you breathless? Do you feel short of breath? Do you experi-
that more than 10% of the population over the age of 80 years ence air hunger? Do you feel increased effort of breathing?);
have heart failure [1]. Acute respiratory failure (ARF) is one of and one of the following objective criteria of ARF: a respiratory
the major causes of consultation of elderly patients in emer- rate at least 25 minute-1, an arterial partial pressure of oxygen
gency departments (EDs) and is the key symptom of most car- (PaO2) of 70 mmHg or less, a peripheral oxygen saturation
diac and respiratory diseases, such as cardiogenic pulmonary (SpO2) of 92% or less while breathing room air, and an arterial
edema (CPE), and of exacerbation of chronic respiratory dis- partial pressure of CO2 (PaCO2) of 45 mmHg or more with an
ease (CRD) including chronic obstructive pulmonary disease arterial pH of 7.35 or less. There were no exclusion criteria.
(COPD), community-acquired pneumonia (CAP) and pulmo-
nary embolism (PE), which are associated with a high morbid- Routine clinical assessment
ity and mortality [3-8]. In elderly patients, differentiating CPE For every patient, standard medical care provided by the emer-
from respiratory causes is difficult for several reasons. Cardiac gency physician (resident or senior) in charge included the fol-
and respiratory diseases frequently coexist. Atypical clinical lowing: medical history, physical examination findings
presentation, such as wheezing in CPE (cardiac asthma) or including signs of acute ventilatory failure (use of accessory
lack of infectious signs in pneumonia, is confusing [5,7,8]. In respiratory muscles, paradoxical abdominal respiration), arte-

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the oldest patients, autopsy studies have demonstrated that rial blood gas analysis while breathing room air, 12-lead elec-
the main causes of death were CPE, CAP, and PE, which are trocardiogram, chest X-ray and the usual blood tests.

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frequently underestimated [9]. There is little knowledge of the Creatinine levels were measured, and creatinine clearance
presentation, clinical characteristics and outcomes of ARF in was estimated with the Cockcroft formula. Dependence and
elderly patients. Furthermore, two studies suggested that quality of life were assessed by the activity of daily living score
prognosis was improved when early diagnostic and treat- [12]. As usual, after the initial presentation in the emergency
ments were accurate [10,11]. room, all the patients were reviewed with one of the senior
staff members. Thus, depending on the suspected diagnoses,
The objectives of this study were therefore to determine the emergency treatment and admission were decided by the
causes of ARF in elderly patients, the accuracy of the initial emergency physician in accordance with normal practice and
diagnosis suspected by the emergency physician, the impact recommendations [4,7,13,14]. Usually, dyspneic patients stay
of initial diagnosis and treatment, and variables associated for less than eight hours in the emergency room before their
with in-hospital death. admission into another ward.

Methods In accordance with standard practice in our institution for ARF

Study design and setting in elderly patients, the performance of thoracic high-resolution
This epidemiological study of ARF in elderly patients was a sin- computed tomography (HRCT) without contrast iodine
gle-center prospective study performed from February 2001 medium, of transthoracic Doppler echocardiography with
to September 2002. It took place in the ED of an urban teach- emphasis on diastolic function, and of PFTs was encouraged
ing hospital (2,000 beds), in whom contrast-enhanced helicoi- whenever possible and as quickly as possible during hospital-
dal computed tomography (CT) scan and ultrasonography are ization. We did not conduct all examinations on every patient
available 24 hours a day. Conversely, Doppler echocardiogra- because the emergency physician decided whether they were
phy and other investigations (such as pulmonary function tests appropriate or not. Almost all thoracic HRCTs were performed
(PFTs) or lung scintigraphy) are not easily available in our ED. less than 12 hours after admission. Slices of 1 mm every 30
There is no cardiologist or pulmonologist assessment in the mm were performed on inspiration with lung and soft kernels,
emergency room. During the study period, 90,547 patients and read on lung and mediastinal windows respectively. All the
have consulted in our ED, of whom 10,156 (11%) were aged CT scans were interpreted again by a radiologist (CB) blinded
more than 65 years. This study was approved by our Ethical for any clinical information and medical chart (especially the
Committee, and waived informed consent was authorized results of echocardiography and PFTs), and only this interpre-
because routine care of the patient was not modified. tation was taken into account by the panel of experts. Tran-
sthoracic Doppler echocardiography included two-
Patients dimensional and M-mode examination, pulsed Doppler analy-
The criteria for inclusion in the study were the following: emer- sis of mitral flow, and continuous Doppler analysis of tricuspid
gency admission to our ED; age at least 65 years; acute dys- regurgitation. Systolic pulmonary arterial pressure was

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Figure 1

Effects of an appropriate medical care in the emergency department on prognosis.

prognosis Effects of an appropriate (full bars) or inappropriate (hatched
bars) diagnosis in the emergency department (a) or initial emergency treatment (b) on the number of hospital-free days within 1 month after admis-
sion (expressed as median), percentage of patients admitted to intensive care unit (ICU), or mortality. NS, not significant.

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calculated from the velocity of tricuspid or pulmonary regurgi- reached by a third expert. The main final proposed diagnoses
tation, when present. The left ventricular ejection fraction was were CPE including left heart failure, CAP, acute exacerbation

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estimated by visual inspection. PFTs included the measure- of CRD, PE, acute asthma, bronchitis, and other main diag-
ment of lung volumes and flow-volume loop. In some cases, noses not listed above, and lack of any diagnosis. The use of
spirometry was performed at the bedside (n = 14) with a vali- validated criteria, response to diuretic or vasodilator, results of
dated portable spirometer (Easyone™; Dyn'air, Muret, France) echocardiography Doppler, and BNP and NT-proBNP levels
[15]. All PFTs were interpreted again by a pulmonologist performed at admission in the emergency room, and other car-
(MHB) blinded for any clinical information and medical chart, diac tests were specifically analyzed for CPE [5,13,17].
and only this interpretation was taken account by the panel of Results from PFT or bedside spirometry, thoracic HRCT and
experts. Results from various other investigations decided by response to bronchodilator or steroids or antibiotics were spe-
the physician in charge (in the emergency room or in another cifically analyzed for respiratory disorders [7,18]. Results of
medical ward) were also recorded, such as ultrasonography of ultrasonography, contrast-enhanced helical CT scan and per-
the lower limbs, contrast-enhanced thoracic CT scan, pulmo- fusion/ventilation nuclear lung scan were specifically analyzed
nary arterial catheter in intensive care unit (ICU), and other rel- for PE, as recommended [14].
evant results. During this study, levels of B-type natriuretic
peptide (BNP) (Triage BNP; Biosite, San Diego, CA, USA) Emergency physicians were asked for their diagnosis just
and NT-proBNP (Elecsys 2010 analyse; Roche Diagnostics, before the patient was leaving the emergency room for either
Meylan, France) were evaluated in separate studies [16], and the observation unit of our ED or another ward, including the
the emergency physicians were not aware of the results. As ICU. According to the final diagnosis made by the experts, an
we demonstrated previously in an elderly population, the cutoff inaccurate emergency physician diagnosis was recorded only
values of 250 pg ml-1 for BNP and 1,500 pg ml-1 for NT- if one of the following diagnoses was missed: PE, CPE, CAP,
proBNP were used in the analysis [16]. The length of hospital- and acute asthma. This was because all these causes of ARF
ization, admission to the ICU in the first 24 hours, the number are thought to be linked to increased mortality when initial early
of hospital-free days within one month after admission, and the treatment is inappropriate, thus requiring early diagnosis. The
in-hospital mortality during a short stay were also recorded. emergency diagnosis was recorded before thoracic CT scan,
The final diagnosis of ARF was then determined by two inde- Doppler echocardiography or PFT was performed.
pendent senior experts (pulmonologist, cardiologist, general-
medicine internist, intensivist, geriatric or emergency physi- The initial specific treatment was defined as that administered
cian) from an examination of the complete medical chart when the patient was still in the emergency room. In the same
including all initial clinical findings, emergency laboratory tests, manner, an inaccurate initial treatment was recorded when PE
X-ray chest data, and the results of thoracic HRCT, transtho- was diagnosed by the experts without initial anticoagulation,
racic Doppler echocardiography, PFT (or bedside spirometry), when CPE was diagnosed without initial administration of
and BNP and/or NT-proBNP levels when available. In cases of nitrate and/or diuretics, when CAP was diagnosed without ini-
disagreement between the two experts, a consensus was tial antibiotics, and when acute asthma was diagnosed without

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 Critical Care Vol 10 No 3 Ray et al.

Table 1

Patient characteristics

Variable Men (n = 253) Women (n = 261) All patients (n = 514)

Age (years) 78 ± 8 82 ± 9a 80 ± 9
Age ≥ 70 years 157 (62) 201 (77)a 358 (70)
Weight (kg) 72 ± 17 62 ± 19a 67 ± 9
Body mass index (m2.kg-1) 25 ± 6 25 ± 8 25 ± 7
Living in an institution 19 (8) 26 (10) 45 (9)
Activity of daily living score 6 [6-6] 6 [6-6] 6 [6-6]
Medical history
Previous cardiac disease 107 (42) 123 (47) 230 (45)
Coronary artery disease 62 58 120
Valvular disease 13 11 24
Others 38 55 93
Previous cardiac insufficiency 53 (21) 57 (22) 110 (21)

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Hypertension 122 (48) 151 (58)a 275 (53)
Chronic respiratory disease 93 (37) 40 (15)a 133 (26)

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Obstructive 84 13 97
Restrictive 3 6 9
Mixed or others 6 21 27
COPD 104 (41) 21 (8)a 125 (24)
Asthma 9 (4) 21 (8)a 30 (6)
Diabetes 47 (19) 34 (13) 81 (16)
Chronic renal insufficiency 7 (3) 9 (3) 16 (3)
Cancer 48 (19) 28 (11)a 76 (15)
Remission 16 14 30
Stable 7 3 10
In progress 25 11 36
MacCabe score 3 113 (45) 63 (24)a 176 (34)
Previous neurological disease 46 (18) 44 (17) 90 (18)
Cerebrovascular disease 18 15 33
Parkinson's disease 9 15 24
Dementia 11 10 21
Others 8 4 12
Clinical signs
Respiratory rate (minute-1) 27 ± 6 29 ± 6a 28 ± 6
Cardiac rate (minute-1) 94 ± 20 92 ± 20 93 ± 20
Systolic arterial pressure (mmHg) 140 ± 30 145 ± 32a 142 + 31
Diastolic arterial pressure (mmHg) 76 ± 17 76 ± 19 76 + 18
Temperature (°C) 37.5 ± 1.0 37.3 ± 1.2 37.4 ± 1.1
Blood gas analysis (n = 490)

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Table 1 (Continued)

Patient characteristics

pH 7.43 ± 0.07 7.43 ± 0.08 7.43 ± 0.07

PaO2 (mmHg) 65 ± 18 65 ± 21 65 ± 20
PaCO2 (mmHg) 41 ± 12 41 ± 14 41 ± 13
Bicarbonates (mmol l-1) 26.7 ± 5.3 26.7 ± 5.7 26.7 ± 5.5

Data are means ± SD, or number (%). ap < 0.05 compared with men. COPD, chronic obstructive pulmonary disease; PaO2, arterial partial
pressure of oxygen; PaCO2, arterial partial pressure of CO2; Mac Cabe score 3 : death expected in 1 year.
β2-agonist administration. Oxygen was considered as a symp- bles in the univariate analysis (p value of entry < 0.10), except
tomatic treatment not a specific treatment (for example, initial for some variables that were thought to be prognostic or had
anticoagulation for PE). When patients had two or more been demonstrated to be prognostic in previous studies (Mac-
causes of ARF, they required treatment for both (for example, Cabe score 3 (death expected in one year) elevated troponin
diuresis and antibiotics for a patient with congestive heart fail- value, elevated natriuretic peptides and clinical signs of acute
ure and acute pneumonia) to be considered appropriate. ventilatory failure). Interactions were not tested. The receiver
operating characteristic (ROC) curve was used to determine
At the time of the study, non-invasive ventilation or continuous the best threshold for continuous variables to predict death.
positive airway pressure was not performed in the elderly in The best threshold was the one that minimized the distance to
the ED, but they were performed in the ICU when the patients the ideal point (sensitivity = specificity = 1) on the ROC curve.
were transferred. The Spearman coefficient matrix correlation was used to iden-

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tify significant collinearity (more than 0.70) between variables.
Statistical analysis Odds ratios and their 95% confidence interval of variables

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The data were collected by three research assistants and ver- selected by the logistic model were calculated. The discrimi-
ified by one of us (PR). Consistency checks between data nation of the model was assessed with the ROC curve and the
entered in the database and searches for erroneous values calculation of the area under the ROC curve [20]. The per-
were performed by one of us (BR) before closing the database centage of patients correctly classified by the logistic model
and performing statistical analysis. Data are expressed as was calculated by using the best threshold determined by the
means ± SD or medians and 95% confidence intervals (CIs) ROC curve. Calibration of the model was assessed with Hos-
for non-Gaussian variables (Kolmogorov-Smirnov test). Com- mer-Lemeshow statistics [21].
parison of two means was performed with Student's t test,
comparison of two medians with the Mann-Whitney test, and All statistical tests were two-sided, and p < 0.05 was required
comparison of two proportions with Fisher's exact method. to reject the null hypothesis. Statistical analysis was performed
with NCSS 2001 software (Statistical Solutions Ltd, Cork,
Assessment of the diagnostic performances of the emergency Ireland).
physicians was performed by calculating the sensitivity, specif-
icity, positive and negative predictive values, and accuracy Results
(defined as the sum of concordant cells divided by the sum of We included 514 patients with ARF; their main characteristics
all cells in the 2 × 2 table) and their 95% CIs were calculated. are summarized in Table 1. In our ED, the prevalence of acute
The reference diagnosis was that of the experts. dyspnea in patients older than 65 years who consulted at our
ED was 5%. All the patients experienced an ED visit and acute
To enable us to compare the length of hospitalization in a short dyspnea, and 80% of them had a respiratory rate of at least 25
stay in different groups while taking mortality into account, we minute-1. Table 2 summarizes the additional inclusion criteria
calculated the number of hospital-free days within one month and the clinical severity criteria. Previous medications included
after admission, as reported previously [19]. Because some of diuretics in 167 patients (33%), nitrates in 127 (25%), calcium
our elderly patients were sent to chronic care before returning channel blockers in 130 (25%), inhaled bronchodilatators in
home, we considered only hospitalization into an acute care 120 (23%), beta-blockers in 72 (14%), angiotensin-convert-
setting for this calculation, and all dead patients were scored ing enzyme inhibitors in 136 (26%), anticoagulation in 53
0 hospital-free days. (10%), and oral corticosteroids in 21 (4%); 23 patients (4%)
received home oxygen. A cough was noted in 222 patients
We performed a multivariate analysis to assess variables asso- (43%), expectoration in 91 (18%), chest pain in 33 (6%), and
ciated with missed diagnosis. We also performed a multiple hemoptysis in 6 (1%) patients. Most of the patients had a nor-
backward logistic regression to assess variables associated mal Glasgow coma scale (n = 481 (94%)). The mean serum
with death. To avoid overfitting, we used a conservative creatinine was 110 ± 75 µmol l-1 (n = 484), with an estimated
approach and included only the significant preoperative varia- creatinine clearance of 52 ± 24 ml minute-1, 239 of 484

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Table 2

Additional inclusion criteria and severity of acute respiratory failure

Criterion Number of patients (%), or value (mean ± SD) Number of additional criteria Number of patients
(%)

Additional
Ventilatory rate ≥ 25 minute-1 413 (80) None 0
Ventilatory rate (mm-1) 30 ± 6 1 criterion 162 (31)
PaO2 ≤ 70 mmHg 342 (67) 2 criteria 189 (37)
PaO2 (mmHg) 57 ± 9 3 or more 163 (32)
PaCO2≥ 45 mmHg and pH ≤ 7.35 44 (9)
PaCO2 (mmHg) 67 ± 19
pH 7.28 ± 0.09
SpO2 ≤ 92% 241 (47)
SpO2 (%) 83 ± 9

Criteria of clinical severity Number of criteria of clinical Number of patients

severity (%)

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Heart rate ≥ 120 minute-1 52 (10) None 139 (27)
Heart rate (mm-1) 129 ± 14 1 criterion 114 (22)

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Orthopnea 255 (50) 2 criteria 89 (17)
Abdominal respiration 77 (15) 3 or more 172 (34)
Use of accessory muscles 146 (28)
Cyanosis 56 (11)
Ventilatory rate ≥ 30 minute-1 100 (19)
Encephalopathy 13 (3)
Mottling 37 (7)
Clinical signs of right heart failurea 288 (56)

All patients fulfilled the other inclusion criteria (namely admission to the emergency department, acute dyspnea, and age ≥ 65 years). Data are
number (%) and means ± SD for the numeric variables in patients who fulfilled the given criteria. aAbdominal jugular reflux and/or jugular venous
pulse. PaO2, arterial partial pressure of oxygen; PaCO2, arterial partial pressure of CO2; SpO2, peripheral oxygen saturation.
patients (49%) had an estimated creatinine clearance of 50 ml = 11), tense ascitis (n = 5), pneumothorax (n = 4), neurologic
minute-1 or less. An elevated troponin Ic level was observed in diseases (n = 2), and various other medical diagnoses (n =
83 of 356 patients (23%). 11). The main causes of CPE that were clearly determined
were concomitant exacerbation of COPD in 55 cases, rapid
Thoracic HRCT was performed in 275 patients (54%). Tran- atrial fibrillation in 43, acute coronary syndrome (including 2
sthoracic Doppler echocardiography was performed in 230 with ST-segment elevated myocardial infarction) in 40, CAP in
patients (45%), and was performed in 152 of the 212 patients 38, anemia in 20, and associated PE in 11.
with final diagnostic of CPE PFTs or spirometry was per-
formed in 180 patients (35%), of whom 164 were patients All patients except two were admitted to the hospital; 289
with exacerbation of CRD. Measurements of NT-proBNP or patients (56%) were initially admitted to the observation unit of
BNP levels were performed in 375 patients (73%). our ED before they were hospitalized in a medical ward, and
74 were admitted directly to a medical ward (14%). During the
There was good agreement between experts for the diagnosis first 24 hours, 151 patients were admitted to an ICU (29%).
of CPE (82%), CAP (87%), PE (91%), acute exacerbation of The median length of stay in the hospital was 12 days (95%
CRD (83%), and acute asthma (98%). The final diagnoses CI 11 to 13) (range 0 to 87). Eighty patients (16%) died in
defined by the experts and their mortality are reported in Table hospital (95% CI 13 to 19). The mortality of patients with two
3; 244 patients (47%) had more than two diagnoses of ARF. or more final diagnoses was not significantly different from that
Other diagnoses included severe sepsis other than acute of patients with only one final diagnosis (18% versus 14%, p
pneumonia (n = 30), malignancy (n = 15), pleural effusion (n = 0.11).

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Table 3

Diagnosis of causes of acute respiratory failure by experts, and mortality

Diagnosis Number of patients (%) Mortalitya, %

Cardiogenic Pulmonary Edema 219 (43) 21 [16–27]

Community-acquired pneumonia 181 (35) 17 [12–23]
Exacerbation of chronic respiratory disease 164 (32) 12 [8–18]
Pulmonary embolism 93 (18) 15 [9–24]
Bronchitis 23 (4) 4 [0–21]
Acute asthma 15 (3) 0 [0–20]
Others 78 (15) 24 [16–34]
No diagnosis 8 (2) 0 [0–32]

Ranges in square brackets are 95% confidence intervals. Because several causes could occur in the same patient, the percentages do not total
100%. aPercentages represent mortality in each diagnostic category.

Table 4

Assessment of the diagnostic performance of the emergency physicians (n = 514)

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Diagnosis Sensitivity Specificity Positive predictive Negative predictive Accuracy
value value

CPE 0.71 [0.65–0.77] 0.80 [0.75–0.84] 0.74 [0.70–0.87] 0.78 [0.72–0.82] 0.76 [0.72–0.80]

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CAP 0.86 [0.80–0.90]a 0.76 [0.71–0.80] 0.66 [0.59–0.71]a 0.91 [0.87–0.93]a 0.79 [0.75–0.82]
Acute exacerbation of CRD 0.71 [0.64–0.78] 0.83 [0.79–0.87] 0.66 [0.59–0.73]a 0.86 [0.82–0.89]a 0.81 [0.78–0.84]a
Pulmonary embolism 0.75 [0.66–0.83] 0.78 [0.74–0.82] 0.43 [0.36–0.51]a 0.93 [0.90–0.96]a 0.78 [0.74–0.81]
Asthma 0.67 [0.42–0.85] 0.97 [0.95–0.98]a 0.42 [0.24–0.61]a 0.99 [0.98–1.00]a 0.96 [0.94–0.98]a

Data are value [95% confidence interval]; ap < 0.05 compared with CPE. CPE, cardiogenic pulmonary edema; CAP, community-acquired
pneumonia; CRD, chronic respiratory disease.

The diagnostic performance of the emergency physicians is Oxygen was given in 444 patients (86%) in the ED, but was
reported in 4. A missed diagnosis of CPE (n = 56), CAP (n = considered a symptomatic rather than a specific treatment.
26), PE (n = 23) or asthma (n = 5) in the ED was noted in 101 Inappropriate initial treatment of CPE (n = 93), CAP (n = 56),
(20%) patients. The number of hospital-free days within one PE (n = 36), or asthma (n = 0) was noted in 162 patients
month after admission was significantly lower and mortality (32%). Seventy-nine patients (15%) with a missed diagnosis
was significantly higher in patients with a missed diagnosis had also an inappropriate treatment in the emergency room.
(Figure 1a). Patients with a missed diagnosis were not differ- The number of hospital-free days within one month after
ent from patients with appropriate diagnosis performed in the admission was significantly lower, and the rates of admission
emergency ward, in terms of medical past history, clinical into ICU and mortality (25% versus 11%, p < 0.001) were sig-
signs, and results of laboratory tests. In the multivariate analy- nificantly higher, in patients with an inappropriate initial treat-
sis, three variables were significantly associated with a missed ment (Figure 1b). Most of the difference in mortality occurred
diagnosis: final diagnosis of CPE, final diagnosis of PE, and within few days after admission (Figure 2). The following vari-
final diagnosis of CAP (5). Conversely, systemic arterial hyper- ables were considered in the logistic model to predict death:
tension was associated with fewer missed diagnoses. The previous cancer, McCabe score less than one year, any previ-
Hosmer-Lemeshow statistic was 7.38 (p = 0.39), indicating ous cardiac disease, hypotension (systolic arterial pressure
appropriate calibration. The area under the ROC curve was less than 90 mmHg), acidosis (pH less than 7.35), hypercap-
0.775 ± 0.027 (p < 0.05); the accuracy of the logistic model nia (PaCO2 more than 45 mmHg), peripheral hypoxia (SpO2
was 0.80 (95% CI 0.72 to 0.82). BNP and NT-proBNP levels less than 92%), elevated serum creatinine (more than 120
were significantly higher in the group of patients with a missed µmol l-1), low estimated creatinine clearance (less than 50 ml
diagnosis, namely 143 pgml-1 (95% CI 101 to 171) versus minute-1), elevated troponin Ic, elevated NT-proBMP or BNP,
403 pg ml-1 (95% CI 337 to 503; p < 0.001) and 1,181 pg ml- hyperkalemia (more than 5 mmol l-1), mottling, ventilatory rate
1 (95% CI 781 to 1,700) versus 3,555 pg ml-1 (95% CI 1,735 more than 30 minute-1, clinical signs of ventilatory failure (the
to 6,330; p = 0.01), respectively. use of accessory respiratory muscles and/or abdominal para-
doxical respiration), missed diagnosis, and inappropriate treat-

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 Critical Care Vol 10 No 3 Ray et al.

Table 5

Variables associated with missed diagnosis in the emergency department

Variable Appropriate diagnosis (n = 413) Missed diagnosis (n = 101) Adjusted odds ratio p

History of arterial 288 (55) 45 (45) 0.59 [0.36–0.98] 0.04

hypertension
Final diagnosis of CAP 152 (37) 67 (66) 4.85 [2.73–8.61] <0.001
Final diagnosis of CPE 135 (33) 46 (46) 9.35 [5.16–16.14] <0.001
Final diagnosis of PE 60 (15) 33 (33) 9.27 [4.72–18.22] <0.001

Data are numbers of patients (%) or medians [95% confidence intervals]. All differences between survivors and dead patients in the univariate
analysis were significant (p < 0.05). CAP, community-acquired pneumonia; CPE, cardiogenic pulmonary edema; PE, pulmonary embolism.
Table 6

Variables associated with in-hospital death

Variables Alive (n = 434) Dead (n = 80) Adjusted odds ratio p

Inappropriate treatment in the ED 73/434 (17) 28/80 (35) 2.83 [1.48–5.41] 0.002
PaCO2 ≥ 45 mmHg 90/414 (21) 29/73 (40) 0.004
PaCO2 (mmHg) 41 ± 13 (n = 414) 44 ± 14 (n = 73) 2.79 [1.39–5.58]

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Creatinine clearance ≤ 50 ml minute-1 191/410 (47) 48/74 (65) 0.013
Creatinine clearance (ml minute-1) 54 ± 26 (n = 410) 43 ± 18 (n = 74) 2.37 [1.20–4.71]

proibida venda
Elevated natriuretic peptide 148/317 (47) 43/58 (74) 2.06 [1.01–4.18] 0.046
BNP (pg ml-1) 148 [102–178] (n = 275) 371 [237–503] (n = 54)
ProBNP (pg ml-1) 1,172 [748–1,700] (n = 208) 4,084 [1,317–7,887] (n = 38)
Clinical signs of acute ventilatory failure 91/434 (21) 36/80 (45) 1.98 [1.01–3.90] 0.047

Data are numbers/totals of patients (%), means ± SD for the numeric variables in patients who fulfilled the given criteria, or medians [95%
confidence intervals]. All differences between survivors and dead patients in the univariate analysis were significant (p < 0.05), including
continuous variables. The logistic model was finally applied in 347 patients. Clinical signs of acute ventilatory failure included the use of accessory
respiratory muscles and abdominal paradoxical respiration. ED, emergency department; PaCO2, arterial partial pressure of CO2; BNP, B-type
natriuretic peptide.

ment in the emergency room. No significant collinearity was Discussion

noted between these variables. Missing values were observed In this large prospective study, which evaluated ARF in elderly
for natriuretic peptides values (n = 139 (27%)), estimated cre- patients, the in-hospital mortality was 16%. We observed that
atinine clearance (n = 30 (6%)), and hypercapnia and acidosis predictive variables of mortality were the following: initial inap-
(n = 24 (5%)). Thus, the final logistic model was performed in propriate treatment, hypercapnia at least 45 mmHg, clearance
347 (68%) patients. In the multivariate analysis, five variables of creatinine 50 ml minute-1 or less, clinical signs of acute ven-
were significantly associated with mortality: inappropriate ini- tilatory failure, and elevated BNP or NT-proBNP levels. Inap-
tial treatment in the emergency room, hypercapnia, low esti- propriate initial treatment occurred in one-third of cases, and
mated clearance of creatinine, elevated NT-proBNP or BNP, the in-hospital mortality was double that of patients with appro-
and clinical signs of ventilatory failure (6). The Hosmer-Leme- priate treatment.
show statistic was 2.22 (p = 0.99), indicating appropriate cal-
ibration. The area under the ROC curve was 0.767 ± 0.040 (p Both the incidence and prevalence of heart failure, COPD,
< 0.05). The best threshold for the probability of death was CAP, and PE are increasing with age [1,7]. Previous studies
0.21 with a sensitivity of 0.68 (95% CI 0.42 to 0.68), a specif- have reported that CPE is one of the main causes of hospital-
icity of 0.80 (95% CI 0.75 to 0.84). The accuracy of the logis- ization in elderly patients and has a high mortality rate [1,4-
tic model was 0.76 (95% CI 0.71 to 0.80). Figure 3 6,22]. This was confirmed in our study. However, we also
represents the mortality according to the number of variables showed that almost half of the patients had more than two
previously associated with death in the multivariate analysis. causes of ARF. Landahl and colleagues [23] reported that the
The in-hospital mortality varied from 5% when patients had main causes of dyspnea in 70-year-old people were heart fail-
less than two of these variables (n = 151) to 52% when ure, bronchitis, and emphysema. However, this phone-call
patients had four or more variables associated with death (n = study evaluated stable dyspnea. In a recent study that evalu-
27) (Figure 3). ated the usefulness of BNP in acute dyspnea, heart failure was

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 Available online http://ccforum.com/content/10/3/R82

the main cause, followed by exacerbation of COPD [10]. All Figure 2

studies that evaluated the accuracy of physical examination in
diagnosing causes of dyspnea have also demonstrated that
CPE, acute exacerbation of CRD, or respiratory infection were
the primary causes of dyspnea [24-30]. In contrast with a
younger population, the rate of acute asthma and bronchitis
were low [24]. Nevertheless it should noted that all these pre-
vious studies had several differences from our study or various
biases, namely: various settings (ED, pulmonary clinic, com-
munity cohort population sample); middle aged population
studied; the number of patients; the numbers of patients
excluded from the analysis; the absence of standardized meth-
odology to determine the final diagnosis of acute dyspnea; low
mortality; difference in inclusion criteria between isolated dys-
pnea and ARF; and no emphasis on risk factors of deaths.
Kaplan-Meier
received in theestimates
emergencyof survival
department
according to the initial treatment
Our study demonstrated an in-hospital mortality of 16% (95% received in the emergency department. Inappropriate treatment was
CI 13 to 19), with a higher mortality in patients with CPE noted in 162 (32%) of the 514 patients. The log-rank test was used to
(21%). These results are similar to previous studies that dem- calculate p.
onstrated a mortality of severe CPE from 13 to 29%
[10,22,31,32]. In a multivariate analysis, we observed that congestive heart failure (15%), and PE (8%). Furthermore, the

t.me/medicinalivre2
three predictive variables of mortality were easily evaluated in highest diagnostic error rate was in the underdiagnosis of PE
emergency room: hypercapnia at least 45 mmHg, clearance of (39% ante-mortem accuracy rate only). Conversely, systemic

proibida venda
creatinine 50 ml minute-1 or less, and clinical signs of acute arterial hypertension was significantly associated with fewer
ventilatory failure. Thus, physicians should focus more on missed diagnoses, suggesting that emergency physicians
these criteria to evaluate the severity of illness in elderly more frequently evoked the diagnosis of CPE in patients with
patients with ARF. We also confirmed that elevated BNP or ARF and known hypertension. A missed diagnosis in the emer-
NT-proBNP levels should also be considered prognostic vari- gency room was noted in 20% of patients, leading to a smaller
ables [16,33]. Thus, their measurement should be developed number of hospital-free days within one month after admission
in the emergency room, because rapid measurement of BNP and to higher mortality. Interestingly, age over 75 years,
in the ED improved the evaluation and treatment of patients dementia, previous quality of life, fatal disease, and clinical
with dyspnea, especially in the elderly [10,32]. presentation were not significantly associated with missed
diagnosis. The higher level of BNP and NT-proBNP in the
In our study, the sensitivity of the diagnostic performance of group of patients with a missed diagnosis is probably
the emergency physician varied from 0.67 for acute asthma to explained by the fact that CPE represented more than half of
0.86 for CAP, and the accuracy of the diagnosis of CPE (0.76) the missed diagnoses. Wuerz and Meador [11] suggested in
was quite similar to that in another study [33]. Several reasons a retrospective pre-hospital study that mortality was reduced
explain the difficulties in assessing causes of ARF in elderly in treated patients with CPE in comparison with untreated
patients. For CPE, atypical presenting symptoms are frequent, patients (odds ratio for survival, 2.51 (95% CI 1.37 to 4.55)).
such as cardiac asthma presenting as obstructive airways dis- We confirmed that undertreatment of the causes of ARF was
ease or fatigue or leg swelling [5]. Furthermore, classical associated with higher morbidity and mortality (Figure 1b) with
radiological signs of CPE are sometimes confusing. In cases a close odds ratio for improved survival (2.83 (95% CI 1.48 to
of CAP, up to 50% of elderly patients had attenuated respira- 5.41), p < 0.002). Again, age, sex, previous quality of life, res-
tory symptoms and non-respiratory symptoms such as confu- piratory rate, initial severity of hypoxemia, and admission to
sion or falls, and over one-third had no systemic signs of ICU were not significantly associated with mortality.
infection [7,8].
Our study has several limitations. We included patients aged
We wished to estimate the diagnostic accuracy of the emer- more than 65 years although some geriatric physicians now
gency physician and to test whether missed diagnosis and/or define elderly patients as being more than 75 years. Neverthe-
inappropriate treatment could be of any prognostic value. In less, the median age was 80 years and most of our patients
our study three variables were significantly associated with were aged more than 70 years. Our study was monocentric
missed diagnosis: a final diagnosis of CPE, PE, or CAP. This but included consecutively a large cohort of elderly dyspneic
result confirms a previous autopsy study [9] that analyzed the patients. Our results, especially the diagnostic performance of
clinical and autopsy records of 234 elderly patients: the most emergency physicians and outcomes, could have been modi-
common causes of death included bronchopneumonia (33%), fied if the study had taken place in other medical department

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 Critical Care Vol 10 No 3 Ray et al.

Figure 3 ficiently large to encompass all causes of ARF that cannot be

reduced to those associated with hypoxemia below 60 mmHg.
Furthermore, the rate of patients with clinical severity criteria
(73%) and ICU admission (29%) observed in our cohort was
relatively high, and the mortality was similar to that of elderly
patients requiring treatment in the ICU for CAP or for CPE,
indicating that we did indeed select a critically ill population
[7,22].

The method used in our study to diagnose the cause of ARF

requires comment. As in most EDs, Doppler echocardiogra-
phy is not immediately available and in any case is rarely per-
formed on elderly patients in clinical practice [5,31,34]. Thus,
we encouraged, as soon as possible after hospitalization, the
use of several non-invasive investigations including HRCT
without contrast iodine medium, Doppler echocardiography,
and PFTs. Furthermore, to determine the final diagnosis, the
experts also had the results of BNP or NT-proBNP levels per-
formed blind at admission, within the framework of a published
study [16]. For an evident ethical reason, these investigations
Mortality
death in the
(%)multivariate
according toanalysis
the five variables (X axis) associated with were not performed on all patients. In fact, almost all the

t.me/medicinalivre2
death in the multivariate analysis. patients had one of these investigations. Because the agree-
ment between experts was above 85%, we suggest that the

proibida venda
(a respiratory unit or ICU, for example) or in another country final diagnoses by experts were appropriate. Unfortunately,
where the medical care of patient is different, whether with because it is rarely feasible in our country we did not perform
cardiologists and pulmonologists in the assessment of the an autopsy, which should be considered as the definitive diag-
patients in the ED and hospital admission, or if Doppler nostic test in deceased patients [9]. In our study, the rate of
echocardiography or natriuretic peptides levels were available patients with an initial inappropriate treatment (32%) was
24 hours a day, or if non-invasive ventilation was performed in higher than the rate of patients with an initial missed diagnosis
the ED. As one of the inclusion criteria was acute dyspnea (a (14%). It should be noted that we recorded the initial treat-
subjective symptom), it means that patients should have ment administered during the first hours in the emergency
expressed their shortness of breath, which might have room, whereas the diagnosis of the emergency physician was
excluded some patients with severe neurological diseases but recorded when the patient left the ED. A noticeable delay
who had ARF. This might explain the good health-related qual- occurred between these two records, particularly in patients
ity of life and the relatively low rate of institutionalized patients admitted into our observation unit before being sent to another
in our study population. Nevertheless, the incidences of neu- department, usually within less than 24 hours. Although inap-
rological diseases and other coexisting non-cardiovascular propriate treatment in the ED was the main factor associated
diseases in our patients were similar to those observed previ- with increasing mortality, we cannot demonstrate a link of cau-
ously [10,21,31,32]. sality between inappropriate initial treatment and outcomes.
Thus, because our study was observational, we can only sug-
Some argue that ARF is usually identified by a PaO2 below 60 gest that early appropriate treatments could improve progno-
mmHg and/or a PaCO2 above 45 mmHg (irrespective of the sis, and that further studies are merited to confirm that
degree of respiratory acidosis), and we agree that these usual hypothesis. Nevertheless, a prospective randomized control-
criteria are stricter than ours. Thus, we used a different cut off led study in elderly patients suggested that rapid measure-
point to select ARF from that which is usually considered, with ment of BNP in the ED reduced the time to discharge and the
mild hypoxemia (70 mmHg or less). However, some previous total treatment cost, and seemed to reduce 30-day mortality
studies have already used other criteria in selecting patients [32].
for randomized clinical trials in non-invasive ventilation [22],
with the use of clinical inclusion criteria (such as polypnea at Conclusion
least 25 per minute or contraction of the accessory muscles of We have demonstrated in a large sample of elderly patients
respiration), not only gas exchange impairment. Moreover, it with ARF that mortality of patients with inappropriate treatment
should be noted that we studied elderly patients in whom the in the ED was double that of patients with appropriate treat-
capacity to face a respiratory distress is markedly reduced ment. To evaluate the severity of illness of elderly patients with
because of the ageing process and/or frequently associated ARF, physicians should focus more on easily available criteria
chronic disease. In fact, we believe that our definition was suf- associated with higher mortality: hypercapnia, a creatinine

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 Available online http://ccforum.com/content/10/3/R82

clearance of 50 ml minute-1 or less, elevated levels of BNP or 4. Komajda M, Follath F, Swedberg K, Cleland J, Aguilar JC, Cohen-
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PR, SB, YL and JB were responsible for study concept and mittee to revise the 1995 Guidelines for the Evaluation and
design, acquisition of subjects and/or data, interpretation of Management of Heart Failure). J Am Coll Cardiol 2001,
38:2101-2113.
data, and preparation of the manuscript. 14. Task Force on Pulmonary Embolism European Society of Cardiol-
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M-HB, MA, CB, AT, and RI were responsible for acquisition of 21:1301-1336.
subjects and/or data, and interpretation of data. BR was 15. Barr RG, Taveras B, Basner RC: Reproducibility and validity of a
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approved the final manuscript. B: Comparison of brain natriuretic peptide and pro-brain natri-
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