Results
During the study period, 1218 patients (1371 admissions; age 61.8 ± 16.5 years; 492/40.4% female; APACHE II 22.7 ± 9.0) were treated in our ICU. We performed BCCE for 651 patients (709 admissions; age 61.0 ± 16.6 years; 251/38.6% female; APACHE II 24.0 ± 8.2). Although we did not collect information on the presence or absence of ARDS for patients who did not receive BCCE, these patients did not differ from the whole ICU population in terms of age (P = 0.973), gender (P = 0.448) and APACHE II score (P = 0.915).
Among patients who received BCCE, 234 patients fulfilled the Berlin Definition of ARDS (age 62.3 ± 14.3 years; 88/37.6% female; APACHE II 26.8 ± 8.3) (Table
1). Ninety-four patients (40.2%) had at least one major BCCE-detected abnormality. The more common major BCCE abnormality found was severe ACP (28.2%), followed by left ventricular ejection fraction < 40% (16.2%). Among our 66 patients with ACP, no patient had any clinical cor pulmonale at baseline. Additionally, of 42 (63.6% of 66) patients who had prior transthoracic echocardiography, no patient had moderate or severe right ventricular dysfunction noted, and only 3 (4.6% of 66) patients had mild right ventricular dysfunction noted. Hospital mortality was 20.5% (83 patients, 95% CI 12.4–30.8%) for mild ARDS, 33.3% (108 patients, 95% CI 24.6–43.1%) for moderate ARDS and 51.2% (43 patients, 95% CI 35.5–66.7%) for severe ARDS (Table
2).
Table 1
Patient characteristics and outcomes
Age (years) (mean ± SD) | 62.3 ± 14.3 | 62.0 ± 14.7 | 64.8 ± 12.9 | 0.180 |
Female sex (%) | 88 (37.6) | 65 (38.7) | 23 (34.9) | 0.654 |
APACHE II score (mean ± SD) | 26.8 ± 8.3 | 26.7 ± 8.1 | 27.3 ± 8.7 | 0.615 |
Arterial blood gas measurement |
PF ratio (mmHg) (mean ± SD) | 171 ± 67 | 172 ± 69 | 169 ± 63 | 0.801 |
pH (mean ± SD) | 7.33 ± 0.12 | 7.34 ± 0.11 | 7.31 ± 0.13 | 0.065 |
PaCO2 (mmHg) (mean ± SD) | 43 ± 14 | 42 ± 13 | 47 ± 16 | 0.001 |
ARDSa (%) |
Mild | 83 (35.5) | 59 (35.1) | 24 (36.4) | 0.892 |
Moderate | 108 (46.2) | 79 (47.0) | 29 (43.9) |
Severe | 43 (18.4) | 30 (17.9) | 13 (19.7) |
Primary diagnosis (%) |
Pneumonia | 208 (88.9) | 151 (89.9) | 57 (86.4) | 0.489 |
Non-pneumonia sepsis | 26 (11.1) | 17 (10.1) | 9 (13.6) |
Comorbidities (%) |
Diabetes mellitus | 81 (34.6) | 61 (36.3) | 20 (30.3) | 0.446 |
Hypertension | 115 (49.2) | 86 (51.2) | 29 (43.9) | 0.384 |
Ischaemic heart disease | 55 (23.5) | 43 (25.6) | 12 (18.2) | 0.304 |
Chronic heart failure | 9 (3.9) | 7 (4.2) | 2 (3.0) | 1.000 |
Asthma | 14 (6.0) | 10 (6.0) | 4 (6.1) | 1.000 |
COPD | 17 (7.3) | 13 (7.7) | 4 (6.1) | 0.785 |
Bronchiectasis | 10 (4.3) | 7 (4.2) | 3 (4.6) | 1.000 |
Chronic renal failure | 38 (16.2) | 27 (16.1) | 11 (16.7) | 1.000 |
Chronic liver disease | 10 (4.3) | 8 (4.8) | 2 (3.0) | 0.729 |
Stroke | 16 (6.8) | 13 (7.7) | 3 (4.6) | 0.566 |
Cancer | 39 (16.7) | 31 (18.5) | 8 (12.1) | 0.330 |
Actual body weight (kg) (mean ± SD) | 63.3 ± 17.2 | 63.4 ± 16.6 | 62.9 ± 18.6 | 0.840 |
Ventilation modes (%) |
Nil ventilation | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0.942 |
CPAP | 17 (7.3) | 13 (7.7) | 4 (6.1) |
NIV | 10 (4.3) | 7 (4.2) | 3 (4.6) |
Invasive | 207 (88.5) | 148 (88.1) | 59 (89.4) |
Respiratory parameters at time of BCCE |
Respiratory rate (breaths/min) (mean ± SD) | 24 ± 3 | 24 ± 4 | 24 ± 2 | 0.274 |
Tidal volume (ml) (mean ± SD) | 408 ± 113 | 409 ± 113 | 407 ± 112 | 0.931 |
Tidal volume (ml/kg IBW) (mean ± SD) | 7 ± 2 | 7 ± 2 | 7 ± 3 | 0.276 |
PEEP (cm H2O) (mean ± SD) | 7 ± 3 | 6 ± 3 | 7 ± 3 | 0.089 |
Plateau pressureb (cm H2O) (mean ± SD) | 21 ± 3 | 21 ± 2 | 21 ± 5 | 0.507 |
Complianceb (ml/cm H2O) (mean ± SD) | 31 ± 14 | 29 ± 12 | 34 ± 18 | 0.047 |
On vasoactive agents (%) |
Any agentc
| 77 (32.9) | 55 (32.7) | 22 (33.3) | 1.000 |
Dopamine | 4 (1.7) | 2 (1.2) | 2 (3.0) | 0.316 |
Noradrenaline | 73 (31.2) | 52 (31.0) | 21 (31.8) | 1.000 |
Dobutamine | 2 (0.9) | 2 (1.2) | 0 (0.0) | 1.000 |
Vasopressin | 1 (0.4) | 1 (0.6) | 0 (0.0) | 1.000 |
BCCE-detected major abnormalities (%) |
Left ventricular ejection fraction < 40% | 38 (16.2) | 28 (16.7) | 10 (15.2) | 0.846 |
Severe acute cor pulmonale | 66 (28.2) | 0 (0.0) | 66 (100.0) | < 0.001 |
Any major abnormalities | 94 (40.2) | 28 (16.7) | 66 (100.0) | < 0.001 |
LOS, ICU (days), median (IQR) | 7 (4–12) | 7 (4–12) | 7 (3–13) | 0.931 |
LOS, hospital (days), median (IQR) | 17.5 (9–28) | 18 (9–26) | 17 (8–31) | 0.837 |
Mortality, ICU (%) | 62 (26.5) | 37 (22.0) | 25 (37.9) | 0.021 |
Mortality, hospital (%) | 75 (32.1) | 47 (28.0) | 28 (42.4) | 0.043 |
Table 2
Hospital mortality of patients with acute respiratory distress syndrome, with or without severe acute cor pulmonale
Severity of ARDSa (%, CI) |
Mild | 17/83 (20.5, 12.4–30.8) | 10/59 (17.0, 8.4–29.0) | 7/24 (29.2, 12.6–51.1) | 0.239 |
Moderate | 36/108 (33.3, 24.6–43.1) | 22/79 (27.9, 18.3–39.1) | 14/29 (48.3, 29.4–67.5) | 0.065 |
Severe | 22/43 (51.2, 35.5–66.7) | 15/30 (50.0, 31.3–68.7) | 7/13 (53.8, 25.1–80.8) | 1.000 |
Overall cohort (%, CI) | 75/234 (32.1, 26.1–38.4) | 47/168 (28.0, 21.3–35.4) | 28/66 (42.4, 30.3–55.2) | 0.043* |
On multivariate analysis, among the major BCCE abnormalities, only severe ACP was associated with ICU and hospital mortality (Table
3). No associations between major BCCE abnormalities and ICU/hospital length of stay existed (Table
4). Hospital mortality for mild, moderate and severe ARDS was 17.0, 27.9 and 50.0%, respectively (without severe ACP), and was 29.2, 48.3 and 53.8%, respectively (with severe ACP) (Table
2).
Table 3
Association of basic critical care echocardiography screening-derived abnormalities with mortality in patients with acute respiratory distress syndrome
Screened patients with acute respiratory distress syndrome (Berlin Definition) |
Left ventricular ejection fraction < 40% | 2.37 (1.15–4.89)* | 2.10 (0.99–4.43) | 2.19 (1.08–4.45)* | 2.00 (0.95–4.18) |
Severe acute cor pulmonale | 2.16 (1.17–4.00)* | 2.14 (1.13–4.04)* | 1.90 (1.05–3.43)* | 1.89 (1.02–3.50)* |
Table 4
Association of basic critical care echocardiography screening-derived abnormalities with log(length of stay) in patients with acute respiratory distress syndrome
Screened patients with acute respiratory distress syndrome (Berlin Definition) |
Left ventricular ejection fraction < 40% | 1.00 (0.75–1.33) | 1.00 (0.74–1.34) | 0.84 (0.62–1.15) | 0.86 (0.63–1.17) |
Severe acute cor pulmonale | 1.07 (0.84–1.36) | 1.10 (0.87–1.39) | 1.04 (0.81–1.34) | 1.06 (0.82–1.37) |
Discussion
The main findings of our study are as follows: firstly, BCCE abnormalities in ARDS patients were common, affecting 40% of the patients. Secondly, the presence of severe ACP—but not moderate/severe left ventricular dysfunction—within 48 h of ICU admission identified patients who were at increased risk of ICU and hospital mortality. Thirdly, both the BCCE-detected major abnormalities were not associated with ICU or hospital length of stay. Finally, the presence of severe ACP appears to upstage ARDS severity by one level.
Our study provided new information on the relative frequency of two major BCCE abnormalities in ARDS patients. We found that the more common abnormality was severe ACP, at 28.2%, which was around the same frequency demonstrated in another smaller study [
18] and in a separate study focusing on severe H1N1 infection [
19]. Nonetheless, this frequency was higher than the prevalence of severe ACP of 7% found in a prior multicentre study by Mekontso-Dessap and colleagues [
3], which could be due to our non-adoption of strategies such as prone positioning to off-load the right ventricle and a higher proportion (89 vs. 40%) of pneumonia (pneumonia being a risk factor for ACP) in our cohort [
5]. Across the ARDS severity gradient, ACP was fairly consistently found in 28.9, 26.9 and 30.2% of mild, moderate and severe ARDS cases. This would imply that, in our setting of high pneumonia prevalence, there was little interaction between ACP and ARDS severity. It is possible that ACP may be more a consequence of treatment strategies than disease manifestation, which would then make ACP potentially modifiable. Interestingly, among patients with ARDS, patients with ACP had slightly better respiratory system compliance compared to patients without ACP. This could reflect the lung recruitment effect of slightly higher positive end-expiratory pressure applied in cases of ACP.
Moderate/severe left ventricular dysfunction was less common in our study population, occurring in 16.2% of patients. Although previously published ARDS-specific data are not available, the frequency of left ventricular dysfunction in our cohort is consistent with prior data derived from patients with septic shock [
20]. Similarly, our finding that left ventricular dysfunction had no association with mortality is also consistent with the lack of association in septic patients [
21‐
23]. Given that we saw no increased mortality even though we only used inotropic medications very sparingly, our findings do not support the need to treat isolated left ventricular dysfunction in ARDS.
In contrast to left ventricular dysfunction, we found the presence of severe ACP to be particularly important for predicting mortality [
3,
4,
11,
12]. Our definition of severe ACP involved a right-to-left ventricular size ratio ≥ 1 on transthoracic echocardiography, which corresponds to the definition of severe ACP on trans
esophageal echocardiography in a recent study [
3]. The latter study also found that less severe ACP (i.e. right-to-left ventricular size ratio > 0.6 and < 1) was conversely
not associated with mortality. The increased mortality engendered by severe ACP may be due to an increased incidence of circulatory failure in ARDS patients [
4]. In our experience, such patients are harmed by fluid administration and often require moderate-to-high doses of noradrenaline support [
5]. Separately, the absence of any relationship between BCCE findings and ICU/hospital length of stay is in line with prior data for ACP [
4] and with our earlier study [
9], which implies that length of stay may be more influenced by non-cardiac factors. Moreover, although ACP could be contributed by volume overload, we feel that this would be partially mitigated by our ICU’s fluid management protocol, which we had established since 2011 [
13]. Also, although we cannot completely exclude a cardiac contribution to ACP, the overlap between left ventricular ejection fraction < 40% and ACP was only 10 patients, which was 15.2% of the 66 patients with ACP. We also did a sensitivity analysis for the presence or absence of left ventricular ejection fraction < 40%, using logistic regression with respect to ICU and hospital mortality, adjusted for age and APACHE II score. Including patients with left ventricular ejection fraction < 40%, ACP was associated with ICU and hospital mortality with an adjusted odds ratio of 2.14 (95% CI 1.13–4.04) and 1.89 (1.02–3.50), respectively. Excluding patients with left ventricular ejection fraction < 40%, ACP was associated with ICU and hospital mortality with an adjusted odds ratio of 2.38 (95% CI 1.17–4.84) and 1.88 (0.95–3.71), respectively. Therefore, the presence of left ventricular ejection fraction < 40% did not substantially alter the conclusions of our study.
Knowledge of the presence of ACP may be key to improving the survival of ARDS patients [
5,
24]. To this end, Mekontso-Dessap and colleagues found that four variables could be used to risk-stratify ARDS patients for the presence of ACP (as determined by transesophageal echocardiography within three days of ARDS diagnosis): pneumonia as a cause of ARDS, driving pressure ≥ 18 cm H2O, PF ratio < 150 mmHg and arterial carbon dioxide partial pressure ≥ 48 mmHg [
3]. Among our patients (Table
1), arterial carbon dioxide partial pressure was indeed significantly higher in patients with severe ACP, though we did not detect significant differences in PF ratio, pneumonia diagnosis or driving pressure. Nonetheless, to use this four-variable risk stratification method, arterial blood gases must be drawn and that patients had to be well sedated or even paralyzed for accurate measurement of driving pressure. Furthermore, after risk stratification, confirmation by echocardiography would still be required. Based on our study, we suggest an alternative approach of directly screening
all ARDS patients with BCCE, which we believe can be done quickly at the bedside.
In addition, we found that the presence of severe ACP can significantly add to the Berlin Definition for ARDS, and should not be taken as a mere marker of ARDS severity. Previously, the ARDS Definition Task Force reported that using the Berlin Definition, mild, moderate and severe ARDS were associated with hospital or 90-day mortality of 27% (95% CI 24–30%), 32% (95% CI 29–34%) and 45% (95% CI 42–48%), respectively [
17]. In our cohort of patients with ARDS, the presence of severe ACP appears to upstage ARDS severity by one level—this may have implications on treatment thresholds and patient recruitment for future studies.
Our results suggest that screening of patients on admission, rather than waiting for clinical deterioration, would be preferable for early identification and treatment of abnormalities. For instance, the detection of severe ACP in ARDS patients should prompt strategies to protect the right ventricle. Such strategies include targeting plateau pressures below 27 cm H
2O, maintaining adequate oxygenation and avoiding hypercarbia beyond 60 mmHg [
2,
5]. Prone positioning to off-load the right ventricle and extracorporeal carbon dioxide removal to allow tidal volume (and hence plateau pressure) reduction could also be considered [
5,
6]. However, while we encourage BCCE, it should only be done if frontline physicians are competent in its use and interpretation [
25]. Moreover, it is a complementary modality and does not replace good clinical acumen and practice.
We acknowledge limitations for our study. Firstly, we performed a single-centre observational study, and our results require external validation. Secondly, due to resource limitations, we only managed to screen patients once within 48 h of admission and do not know whether a narrower screening interval (e.g. within 24 h of admission) or repeated screening after that would yield further information. Thirdly, we did not utilize transesophageal echocardiography as our ICU physicians have not acquired this level of expertise, and transesophageal echocardiography may improve the detection of severe ACP compared to using transthoracic echocardiography. Fourthly, although we checked that no patient had any pre-existing cor pulmonale clinically or on prior echocardiography (which was available for 63.6% of ACP cases), some patients might have developed subclinical cor pulmonale after their last echocardiography. Fifthly, we concede that determination of both LVEF and ACP may be imperfect. Nonetheless, in our experience, accuracy of visual LVEF grading and visual estimation of RV/LV size ratio were fairly good, even for trainees when compared with an experienced supervisor (correct grading achieved in 85% of cases for visual LVEF and in 92.5% of cases for visual estimation of RV/LV size ratio, after performing 30 echo examinations) [
9]. Finally, we did not mask BCCE findings from clinicians, which meant that BCCE could have changed management. We did not study specific treatments administered, but should they improve survival, the association of BCCE-detected abnormalities with mortality would then be biased towards the null.
In conclusion, severe ACP—but not left ventricular dysfunction—may help identify ARDS patients at elevated risk of ICU and hospital mortality. BCCE, when used as a screening tool, can then alert the treating physician to the presence of ACP, allowing prompt institution of measures that may alter ARDS outcomes. While further validation is required, we believe that our study should encourage ICU physicians to incorporate BCCE into routine screening of ARDS patients admitted to ICU.
Authors’ contributions
KCS, JN, WTS, VO and JP jointly conceived the study and prepared the manuscript; KCS, JN, WTS and VO performed the data extraction; KCS performed the data analysis; JP supervised the analysis and edited the manuscript. All authors read and approved the final manuscript.