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Pulmonary arterial embolism (PE) is not well characterized in elderly patients. In addition, unnecessary computed tomography pulmonary angiography (CTPA) examinations are often performed within this patient group, especially if the pretest probability is low.
Objective
To identify differences in clinical presentation in patients aged ≥80 years compared to patients <80 years and the effect of a BGA-optimized pretest probability to reduce unnecessary CTPAs according to age category.
Materials and methods
A retrospective analysis of patients with suspected PE and subsequent CTPA was performed, with evaluation of clinical data including capillary blood gas analysis (BGA) parameters (including standardized partial pressure of oxygen [sPaO2]) over a 5-year period. Subsequently, the clinical characteristics of patients with confirmed PE were compared between the two age groups. In addition, an age-adjusted analysis of a BGA-optimized algorithm was performed in patients with a low pretest probability (PTP) according to the Wells score to reduce unnecessary CTPAs.
Results
PE was confirmed in 433 of 1538 patients with suspected PE, of which n = 98 (22.6%) were ≥ 80 years of age. Elderly patients with PE were less frequently male (p < 0.001), had lower rates of tachycardia (p = 0.021), but higher rates of cardiovascular disease history (p = 0.001) and oxygen administration at admission (p = 0.006) compared to those < 80 years. Signs of right heart dysfunction (p = 0.047) and elevated cardiac biomarkers (troponin: p < 0.001; nt-pro-BNP: p = 0.026) were also more common in the elderly. Additionally, simplified Pulmonary Embolism Severity Index (sPESI, p < 0.001) and in-hospital or 30-day death risk (p < 0.001) were higher in the elderly. Using a BGA-optimized algorithm with sPaO2, unnecessary CTPA examinations were reduced by 33.2% in younger patients (75 of 226 without PE) and 23.5% in elderly patients (8 of 34 without PE).
Conclusions
Elderly patients with PE are characterized by higher clinical risk markers and elevated mortality rates compared to younger patients. In patients with suspected PE but low PTP, however, a significant number of unnecessary CTPAs could be avoided by using an BGA-optimized pretest algorithm in elderly patients.
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Introduction
As a result of demographic changes with increased life expectancy and further improvements in medical care, the average age of emergency care patients is expected to increase and people aged ≥ 80 years will represent an increasing proportion of patients [1]. Therefore, these patients should receive special consideration in studies. However, it is notable that older patients tend to be underrepresented in clinical trials [2].
The prevalence of pulmonary artery embolism (PE) correlates positively with age [3]. Hence, due to demographic changes, more patients with suspected PE are expected to present to the emergency department (ED). As part of the diagnostic process, it is recommended that a pretest probability (PTP) is determined prior to computed tomography pulmonary angiography (CTPA) with, for example, the Wells representing a well-established diagnostic tool, regardless of age [4]. Using the two-stage classification, PE can be expected in about 8.4% of cases in the “PE unlikely” category and in 34.4% in the “PE likely” category [5]. However, it is problematic that particularly in the group of patients with low PTP, only a few patients actually will have confirmed PE [6‐8], leading to frequent unnecessary CTPA in this patient group. Efforts should therefore be made to reduce unnecessary CTPA in primary assessment. In addition to the PTP, a blood gas analysis (BGA) is regularly performed in clinical practice, and although it does not have a specific role in determining PTP [4] it often influences further diagnostics. In a previous publication [9], we were able to show that a significant number of CTPA can be avoided by combining the Wells score with standardized PaO2 as a calculated product of the BGA even with increased D‑dimer threshold without missing a pulmonary artery embolism. However, as the physiological aspects of the lungs also change with increasing age [10], the effectiveness of this modified algorithm in elderly patients remains unclear. Therefore, the objective of this study was to evaluate the clinical presentations of patients with pulmonary artery embolism stratified by age, as well as to analyze blood gases and a BGA-optimized PTP in elderly patients with suspected pulmonary artery embolism.
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Materials and methods
Study design and patients
This study is a subanalysis of the previously published EMBOLISM study [9]. In brief, the aim of this single-center retrospective trial was to optimize PTP in the group of patients with a low PTP according to the Wells score (Wells score ≤ 4) using BGA. The hospital’s standard procedure for patients with suspected PE includes an assessment of the PTP using the Wells score and, if necessary, a D-dimer test (D-dimer Hemosil HS 500 with the ACL Analyser Top 750, Werfen, Germany), whereby an age-adjusted cut-off value was used for patients over 50 years of age. A total of 1538 patients were identified over a period of 5 years. All patients underwent a CTPA examination. Of these, 433 patients suffered a PE. Using a retrospectively calculated standardized PaO (standardized PaO2 = PaO2 − 1.66 × (40 − PaCO2)), a new algorithm was developed (Fig. 1), which allowed for raising the D‑dimer cut-off to < 1.5 mg/L. This resulted in an overall reduction of 31.9% of CTPA examinations without missing one PE [9]. The study was approved by the local ethical committee (reference number: 19-318A).
Fig. 1
Workflow for patients with suspected PE but low pretest probability and available capillary blood gas analysis. PE pulmonary embolism, standardized PaO2 partial pressure of oxygen standardized to a PaCO2 of 40 mm Hg [9]
In the current study, the cohort of patients with confirmed PE was divided into elderly patients defined as ≥ 80 years and patients < 80 years. Subsequently, both clinical and diagnostic variables of these patient groups were analyzed in patients with confirmed PE. In addition, an age-related analysis of the capillary blood gases was performed. Based on the original study, the effectiveness of the previously published algorithm was analyzed by age group. In this process, only patients with low PTP (≤ 4 points) according to the Wells criteria [11‐13] and capillary BGA were considered. In order to exclude the effect of oxygen therapy on the calculation of the standardized PaO2, patients with oxygen application were not included in the new algorithm.
CT pulmonary angiography
The CTPA was carried out using a 128-detector Siemens Somatom Definition AS+ and AS scanner (Siemens Healthineers, Erlangen, Germany). The scan covered the area from the clavicles to the diaphragm in the craniocaudal direction, with a detector scan area of up to 800 mm. A layer thickness of 1 mm was selected for the reconstruction, and the tube current and voltage were 100 mAs and 120 kV, respectively, with CARE Dose used for quality reference. A low osmolar nonionic contrast medium (100 ml) was injected through a peripheral venous catheter at a rate of 5 ml/s.
Statistical analysis
The statistical analysis was conducted using IBM SPSS Statistics 29.0 (Armonk, NY, USA), considering a two-sided p-value of less than 0.05 as statistically significant. Categorical variables were assessed with either the Chi-squared test or Fisher’s exact test, and their results are reported as numbers and percentages. Continuous variables were evaluated using the Mann–Whitney U test and are presented as medians with interquartile ranges (IQR). Baseline characteristics and BGA parameters were compared between patients < 80 years and those ≥ 80 years of age with confirmed PE. Scatter plots with linear regression graphs were used to display the results of the GBA.
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Results
Baseline characteristics of patients with confirmed PE
During the study period, PE was confirmed in 433 of 1538 patients, with n = 98 (22.6%) aged ≥ 80 years and n = 335 (77.4%) aged < 80 years. Table 1 shows the detailed baseline characteristics of the two subgroups. Patients aged ≥ 80 years were less frequently male (p < 0.001), had a lower prevalence of tachycardia (p = 0.021), and had more frequently a history of cardiovascular disease (p = 0.001). Moreover, more patients aged ≥ 80 years were more likely to received oxygen administration (p = 0.006) compared to patients aged < 80 years. Right heart dysfunction in CTPA or echocardiography (p = 0.047) and elevated troponin levels (p < 0.001) were more frequent in older patients. In addition, sPESI (p < 0.001) and an intermediate–high mortality risk (p = 0.004), as well as the risk of in-hospital death (p < 0.001), were higher in elderly patients, while a low risk of in-hospital or 30-day death was more frequent in patients aged < 80 years (p < 0.001).
Table 1
Baseline characteristics and risk stratification of patients with confirmed pulmonary embolism (PE)
< 80 years (n = 335)
≥ 80 years (n = 98)
p-value
Male
175 (52.2)
29 (29.6)
p≤0.001
Age
64 (52, 74)
84 (82, 87)
–
Central PE
155 (46.3)
49 (50.0)
p = 0.515
Segmental PE
141 (42.1)
42 (42.9)
p = 0.908
Subsegmental PE
39 (11.6)
7 (7.1)
p = 0.264
Chest pain
150 (44.8)
40 (40.8)
p = 0.491
Dyspnea
250 (74.6)
70 (71.4)
p = 0.601
Hemoptysis
14 (4.2)
2 (2.0)
p = 0.386
Syncope
36 (10.7)
16 (16.3)
p = 0.157
Clinical signs of deep vein thrombosis
90 (26.9)
27 (27.6)
P = 0.898
Tachycardia (>100bpm)
121 (36.1)
23 (23.5)
p=0.021
S1Q3 pattern
47 (14.0)
9 (9.2)
p = 0.235
T wave inversion in V1–V4
44 (13.1)
19 (19.4)
p = 0.142
Complete/incomplete RBBB
45 (13.4)
17 (17.3)
p = 0.412
History of cardiovascular disease
58 (17.3)
32 (32.7)
p=0.001
History of pulmonary disease
71 (21.2)
17 (17.3)
p = 0.476
History of renal disease
22 (6.6)
10 (10.2)
p = 0.217
Active cancer
67 (20.0)
13 (13.2)
p = 0.141
Previous PE or DVT
92 (27.5)
24 (24.5)
p = 0.606
D‑dimera, mg/L
4.46 (2.07, 9.55)
5.54 (2.81, 11.36)
p = 0.129
Administration of oxygenb
p=0.006
Unknow
23 (6.9)
2 (2.1)
Yes
73 (21.8)
35 (36.1)
No
239 (71.3)
60 (61.9)
Oxygen flow rate in liters per minutec
4 (2, 4)
4 (2, 8)
p = 0.148
Right heart dysfunction in CTPA or echocardiographyd
132 (39.6)
50 (51.5)
p=0.047
Elevated Troponin serum concentratione
172 (56.8)
78 (83.9)
p<0.001
Elevated NTpro-BNP serum concentrationf
84 (42.6)
35 (59.3)
p=0.026
sPESI
1 (0, 1)
1 (1, 2)
p<0.001
EMR: low riskg
95 (28.4)
2 (2.1)
p<0.001
EMR: intermediate low riskh
138 (41.3)
49 (50.0)
p = 0.133
EMR: intermediate high riskh
87 (26.0)
41 (41.8)
p=0.004
EMR: high riskh
12 (3.6)
6 (6.1)
p = 0.387
Confirmed DVTi
171 (54.3)
55 (61.1)
p = 0.280
In-hospital deathj
6 (1.8)
9 (9.2)
p=0.001
Data presented as n/N (%) or median (IQR). Numbers in bold type indicate a significant difference
PE pulmonary embolism, DVT deep vein thrombosis, RBBB right bundle branch block, BGA blood gas analysis, CTPA computed tomography pulmonary angiography, sPESI simplified PESI (Pulmonary Embolism Severity Index), EMR early mortality risk of in-hospital or 30-day death
an = 416, bn = 432, cn = 101, dn = 430, en = 396, fn = 256, gn = 430, hn = 431, in = 405, jn = 432
Blood gas analysis and pretest probability
For the evaluation of blood gases, all patients with possible or documented oxygen administration at admission (358 of 465 patients) and with an unknown extraction point of the BGA (62 of 465 patients), missing documentation (7 of 465 patients) or venous BGA (41 of 465 patients) were excluded. Based on these criteria, 1073 of 1538 patients could be considered for further analysis. Of these 1073 patients, a total of 278 patients were diagnosed with PE. Table 2 shows the results of the remaining 278 patients. Overall, 243 patients aged < 80 years and 35 patients aged ≥ 80 years could be analyzed with respect to BGA and PTP. There was only a statistically significant difference in the simplified revised Geneva score, which was slightly higher in elderly patients (p = 0.042). In addition, the changes in standardized PaO2 with increasing age were evaluated in patients with capillary BGA and without administration of oxygen within the entire cohort (n = 1073) and in patients with confirmed pulmonary artery embolism (n = 278). The results are shown in Fig. 2 and imply a decrease in the linear regression graphs with increasing age.
Table 2
Capillary BGA and PTP scores of patients with confirmed PE
< 80 years (n = 243)
≥ 80 years (n = 35)
p-value
Wells score
1.5 (0, 1.5)
1.5 (0, 3)
p = 0.309
Simplified Wells score
1 (0, 1)
1 (0, 1)
p = 0.758
Original revised Geneva score
3 (2, 5)
4 (1, 6)
p = 0.721
Simplified revised Geneva score
2 (1, 2)
2 (1, 3)
p=0.042
BGA pH
7.46 (7.44, 7.49)
7.48 (7.45, 7.53)
p = 0.087
BGA PaCO2
34 (29, 37)
32 (28, 36)
p = 0.226
BGA PaO2
68 (58, 78)
72 (55, 79)
p = 0.766
BGA HCO3−a
23.95 (21.8, 26.08)
23.9 (21.5, 26.1)
p = 0.676
BGA BEa
0.9 (−0.65, 2.55)
1.1 (−1.05, 3.48)
p = 0.686
BGA lactateb
1.0 (0.8, 1.6)
1.1 (0.9, 1.5)
p = 0.298
BGA saturationc
96.00 (93.35, 97.78)
96 (92.7, 97.2)
p = 0.950
PaO2stand
57.38 (48.34, 67.06)
53.04 (42.40, 63.36)
p = 0.254
Data presented as median (IQR). Numbers in bold type indicate a significant difference
PE pulmonary embolism, PTP pretest probability, BGA blood gas analysis, PaCO2 arterial carbon dioxide tension, PaO2 arterial oxygen tension, HCO3− bicarbonate, BE base excess, PaO2stand standardized to a PaCO2 of 40 mm Hg [24]
an = 271, bn = 272, cn = 253
Fig. 2
The upper scatter plots illustrate the trends in standardized PaO2 in capillary blood gas analysis across the age spectrum in the entire cohort of patients with suspected PE (n = 1073). The lower scatter plots demonstrate the standardized PaO2 in capillary blood gas analysis with increasing age in the cohort of patients with confirmed PE who met all criteria of the new algorithm (n = 278). PE pulmonary arterial embolism
In a next step, we performed an age-stratified analysis of the previously published algorithm with BGA-optimized PTP. Therefore, we focused on patients with a low PTP (defined by a Wells score ≤ 4), available capillary BGA and (age-adjusted) increased D‑dimers with an upper limit of < 1.5 mg/L. A total of 278 patients met these criteria, and PE was detected in a total of 6.5% (n = 18) of these patients (elderly patients: 1 of 35 patients; younger patients: 17 of 243 patients). With application of our new algorithm using a standardized PaO2 of 65 mm Hg (Fig. 1), the number of unnecessary CTPA examinations could be reduced by 33.2% in younger patients (75 of 226 patients without PE) and 23.5% in elderly patients (8 of 24 patients without PE, Fig. 3).
Fig. 3
Number of examined patients with low pretest probability analyzed separately according to standard algorithm and novel algorithm. *n = 243, **n = 35. PE was detected in a total of 18 patients (< 80 years: n = 17 of 243 patients, ≥ 80 years: n = 1 of 35 patients). Using the new algorithm, 33.2% (75 of 226 patients) of all patients < 80 years and 23.5% (8 of 34 patients) of all patients ≥ 80 years would not have been classified as suspected PE. PE pulmonary embolism
With this study we can make an important contribution to an optimized ED management of patients aged ≥ 80 years with suspected or confirmed PE who are currently underrepresented in clinical trials [2]. First, we characterize clinical findings and prognostic parameters in octogenarians with confirmed PE compared to younger patients. Overall, elderly patients with PE are characterized by higher clinical risk markers and elevated mortality rates compared to younger patients. Moreover, to our knowledge, this is the first study to investigate a BGA-optimized Wells score in elderly patients using a standardized PaO2 in order to reduce the number of unnecessary CTPAs. With this study, we were able to demonstrate that in patients with suspected PE but low PTP a significant number of unnecessary CTPAs could be avoided by using an BGA-optimized pretest algorithm even in elderly patients.
The comparison of all baseline characteristics reveals that patients aged ≥ 80 years are significantly more likely to be female. This is likely due to the longer life expectancy of female patients, a finding consistent with other studies of very old patients with PE [14]. Gómez et al. [14] found similar results irrespective of the PTP. However, the study also found significant differences in dyspnea, chest pain and hemoptysis, which could not be confirmed by the analysis of our cohort. Nevertheless, these results do not contradict our findings, but rather emphasize the heterogeneity of the clinical presentation of patients with PE [15]. Our trial data also showed that older patients had less tachycardia, more cardiovascular comorbidity and more oxygen administration. This appears plausible in the context of the increasing number of comorbidities with advancing age [16] and the higher number of medications in this patient cohort [17]. Additional documentation of medication upon admission was not conducted in this retrospective study, which would have further strengthened the validity of the results. However, it is not uncommon for elderly patients ≥ 65 years of age to be prescribed β‑blockers [17], which could explain the reduced heart rate observed in older patients compared to younger ones. Furthermore, elderly patients also have a higher risk profile. Patients ≥ 80 years of age were significantly more likely to have signs of right heart dysfunction in CTPA or echocardiography, elevated cardiac markers (troponin and nt-pro-BNP) and a higher sPESI and were, therefore, assigned to a higher risk class. Accordingly, the in-hospital mortality was also significantly higher in these patients, although the significantly different cohort size and the lack of documentation of the cause of death must also be considered when analyzing the data. Study data also show similar or even higher mortality rates within 30 days in elderly patients ≥ 80 years, even after pulmonary artery embolism has been excluded [18]. Overall, these results are consistent with previous studies showing that elderly patients with acute pulmonary embolism have higher in-hospital mortality than younger patients [19].
There is limited data available on very elderly patients with PE. A cut-off of 65 years is often used as a definition for elderly [15, 20], but this threshold needs to be reconsidered in the context of demographic changes [21] and the continuously improving medical care. Additionally, diagnostics are challenging regardless of age [14]. The lack of significant differences in diagnostic and clinical findings between older and younger patients with confirmed PE further emphasizes these difficulties. For example, there was no significant difference in chest pain, dyspnea or ECG documentation when comparing the two age cohorts. Therefore, other parameters like blood gases should be considered. Notably, there was no significant difference in BGA separated by age cohorts. A number of factors appear to be involved in this process. First of all, the group of patients aged ≥ 80 years is relatively small, which must be taken into account during statistical evaluation. Additionally, the age-associated decline in standardized PaO2, although not statistically significant, is noticeable. This trend is also illustrated by linear regression slopes in the scatter plot, indicating an impact on the effectiveness of the blood gas-optimized algorithm. Follow-up studies with larger cohorts are necessary to verify this trend.
On the other hand, the absence of a statistical difference in PaO2 should be recognized as an indicator for this parameter’s limitations, as it does not account for potential hypocapnic hyperventilation. This limitation is overcome by the use of standardized PaO2, i.e., the value of paO2 adjusted for partial pressure of carbon dioxide. Standardized PaO2 better reflects the respiratory efforts in hypoxemic conditions and may have greater diagnostic significance in the assessment of suspected PE. The reduction in CTPA examinations by using our BGA-optimized algorithm published previously was lower in the present subanalysis. Given that the current PaO2 is used to calculate the standardized PaO2, and this value declines with increasing age due to physiological changes [22, 23], the significance of using standardized PaO2 within our algorithm is diminished. Nonetheless, 23.5% of CTPAs could still be avoided in patients over 80 years, compared to 33.2% in those younger than 80 years. Thus, younger patients particularly benefit from reduced exposure to unnecessary X‑rays. However, avoiding nearly one in four CTPA examinations in this elderly patient cohort still represents a relevant resource-efficient reduction of overall CTPA examination.
Limitations
Several aspects should be considered when interpreting our results. For example, the retrospective data were only obtained from single center and, therefore, cannot be generalized. In addition, the group of patients over 80 years of age is comparatively small, especially when looking at BGAs. Although this analysis is based on a large and well-characterized cohort of patients with suspected PE, larger prospective studies are needed to validate our proposed score in patients with suspected PE and low PTP. In addition, the cause of death during hospitalization was not recorded. Therefore, it remains unclear whether this was related to PE or another cause. Moreover, patients with lung disease were also included in our study (table S1). These study data, therefore, represent a clinically relevant but also heterogeneous patient population. However, an influence of the pulmonary diseases on the results cannot be excluded with certainty. Further studies with larger numbers of patients are necessary to investigate this aspect. The present study also represents a significant improvement in the management of patients with suspected pulmonary embolism. However, it is important to recognize the potential for selection bias due to the retrospective nature of the data analysis and the initial exclusion process.
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Conclusion
The present study shows that elderly patients with confirmed pulmonary embolism (PE) have a higher clinical risk profile and higher all-cause in-hospital mortality compared to the respective younger cohort. It also demonstrates the additional benefit of a blood gas analysis (BGA)-optimized algorithm including standardized PaO2 to improve pretest probability (PTP) assessment even in elderly patients with suspected PE and, thus, reduce the number of computed tomography pulmonary angiography (CTPA) examinations. We therefore suggest implementing the following ideas:
Routine implementation of a capillary BGA,
Calculation of the standardized PaO2,
Implementation BGA results in the decision on further diagnostics in combination with the two-level Wells score for suspected PE, and
Increased awareness for elderly patients with pulmonary artery embolism
Declarations
Conflict of interest
T. Pätz, K. Gruber, S. Kupp, G.-M. Schmidtke, A. Fürschke, F. Sayk, T. Stiermaier, I. Eitel, S. Wolfrum and M. Meusel declare that they have no competing interests.
The study was approved by the local ethical committee (reference number: 19-318A).
The supplement containing this article is not sponsored by industry.
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Auf mögliche kardiale Auswirkungen postoperativer Schmerzen weist die Subgruppenanalyse des randomisierten kontrollierten HIP-ATTACK-Trials hin. Bei ausgeprägten Schmerzen im Zusammenhang mit einer Hüftoperation stiegen die Troponinspiegel signifikant an – ein Kausalzusammenhang ist damit allerdings noch nicht belegt.
Laut einer Querschnittstudie leiden rund 7% der in Deutschland lebenden über 16-Jährigen unter chronischen Schmerzen, die ihren Alltag stark beeinträchtigen. Außer biologischen scheinen auch psychische und soziale Faktoren mit sogenanntem High-Impact Chronic Pain assoziiert zu sein.
Ob nun Sonogerät, Praxiscomputer oder gar TI-Konnektor: Einfach zum nächsten Wertstoffhof sollten Praxisteams ausgediente Elektrogeräte nicht bringen. Was bei der Entsorgung zu beachten ist. Und wie die Teams sicher sensible Daten auf PC-Festplatte, externem Datenspeicher und TI-Komponenten löschen.
Im Fall einer Sepsis ist eine Körpertemperatur unter 36 °C bei älteren Menschen ein Warnsignal. In einer Studie aus Dänemark war bei Hypothermie, nicht aber bei Fieber das Mortalitätsrisiko deutlich erhöht.
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