Patients with acute cardiogenic pulmonary edema (APE) may some times experience severe acute respiratory failure that can lead to the application of controlled mechanical ventilation in the Intensive Care Unit (ICU). In these cases, discontinuation of ventilatory support is a challenging task and involves a careful weighting of the benefits of early extubation and the risks of premature spontaneous breathing trial (SBT). Both unnecessary delay and premature weaning may have adverse effects on patients' outcome, prolonging mechanical ventilation and length of ICU stay [¹]. As a consequence, critical care physicians need accurate prediction tools for the early assessment of patients' ability to perform a successful SBT.

Doppler-echocardiography is increasingly used in the ICU for the estimation of both systolic and diastolic function of the left ventricle (LV) [^2-5]. Recently, the combination of tissue Doppler imaging (TDI) and pulsed Doppler transmitral flow has been proven to reliably diagnose acute pulmonary edema as a cause of weaning failure in a mixed-population of critically ill patients without pre-existing heart disease [⁶]. However, prediction of successful liberation from the ventilator with echocardiography, before weaning is attempted has not been studied yet.

Therefore, in this observational study we tried to investigate a possible relation between different echo-derived indices obtained at admission and length of the weaning process, in a homogeneous group of patients with acute pulmonary edema, who were under controlled mechanical ventilation. The main question was if looking at the right ventricle (RV) through the estimation of simple and reproducible indices, such as tricuspid annular plane systolic excursion (TAPSE) and RV TDI velocities, could predict duration of weaning. For that reason, we also decided to correlate these measures with different echocardiographic indices of LV function, in order to estimate their accuracy in discriminating patients with more or less severe LV heart failure. In this case, changes of the right side of the heart could reliably reflect left sided findings, early in the course of liberating patients from the ventilator and therefore, identify a unique value of such analysis.

In this study we demonstrated that TAPSE and RV TDI velocities obtained by 2D echocardiography were significantly correlated with ?/e', LVEF and length of ventilatory support in a cohort of mechanically ventilated patients with acute pulmonary edema. Furthermore, these indices were proven to discriminate successfully patients with different duration of weaning.

Liberation from mechanical ventilation can impose a significant load upon the cardiovascular system, especially in patients with heart disease. The shift from positive to negative intrathoracic pressure can augment venous return and central blood volume, increasing left ventricular preload and afterload. Moreover, high levels of catecholamines may reduce supply of oxygen to the heart due to tachycardia and decrease cardiac output due to increased pulmonary and vascular resistance [^21-23].

Different studies in mechanically ventilated patients have confirmed that increased pulmonary artery systolic and occlusion pressure (PAOP) during the weaning trial are associated with weaning failure [²¹,²⁴] whereas only one study using echocardiography investigated the relation between the echo-derived index ?/e' and PAOP during liberation from the ventilator, in patients without pre-existing heart diseases [⁶]. However, baseline filling pressures have not been proven to successfully predict weaning outcome [²¹,²⁵], whereas early assessment of weaning readiness with echocardiography during the course of mechanical ventilatory support has not been studied yet. In a recent study, high levels of B-type natriuretic peptide (BNP) just before the performance of weaning trial in a mixed population of patients were identified as independent risk factors for weaning failure [²⁶].

In our study, we decided to investigate the prognostic impact of different RV echo-derived indices upon duration of weaning, which have been proven to be easily reproduced and obtained [^15-17], without suffering technical limitations of LV derived measures, such as LVEF [¹⁰]. We also used the ?/e' lateral ratios as an indirect measure of LV filling pressures, since this index is highly reproducible [¹⁸,¹⁹], whereas a threshold value more than 9.5 has been proven to predict PAOP values higher than 18 mmHg [¹⁹]. We finally hypothesized that looking early at the right side of the heart might be more easy and accurate than estimating different load dependent variables of the left side, in case that significant correlations were found between each other.

Numerous studies have documented TAPSE is linearly related to right ejection fraction in different clinical scenarios such as ischemia, congestive heart failure and pulmonary hypertension, whereas its measurement has been proven to be highly reproducible and easy to obtain [¹⁵,^27-30]. Its value in the ICU setting was explored in a recent investigation by Lamia et al, who studied for the first time the relation of TAPSE with both LV and RV function in critically ill patients with cardiovascular and respiratory failure and found a significant correlation between TAPSE and LVEF [³⁰].

Tissue Doppler imaging (TDI) techniques measure velocities of cardiac tissue and reflect directly myocardial function. Meluzin et al has found that systolic velocities Sm correlate with RVFAC and prognosis of patients with LV heart failure [³¹,³²]. Dokainish has shown that Sm detected mild degrees of RV dysfunction not yet apparent from visual assessment and found that Sm was an independent predictor of cardiac death or rehospitalization in patients with LV heart failure [³³].

The direct correlations that were found in our study between low TAPSE and RV TDI velocities with LVEF reflect systolic ventricular interdependence, while the inverse correlations between the RV function parameters and ?/e' indicate that LV filling pressures comprise an important part of RV afterload in the context of acute pulmonary edema [³⁴]. Consistent with prior studies, the measurements of TAPSE Sm, Em/Am and ?/e' were highly reproducible with acceptable interobserver and intraobserver agreement. On the contrary, RVFAC and LVEF measurements' reproducibility was moderate, since the variability of these metrics reflects inaccurate endocardial visualization and dependence upon mathematical assessment [¹⁴,²⁹].

The fact that ten patients from the whole study group did not have pulmonary hypertension was peculiar; however, this cohort consisted of subjects without a history of CHF. In addition, the 12 patients who experienced prolonged weaning had increased PASP and included mostly patients with decompensated chronic heart disease. Moreover, technical reasons concerning PASP estimation cannot be excluded since, different levels of tidal volume (TV) and positive end-expiratory pressure (PEEP) may alter inferior vena cava (IVC) diameter. Right atrial pressure depends not only on RV preload but also on pleural pressures transmitted to the right atrium, leading to differences between intravascular and transmural pressures under mechanical ventilation. For that reason, measurement of distensibility index (dIVC) of IVC has been proposed for RAP estimation in ventilated patients [³⁵]. However, we did not apply this method in our study. Finally, different effects and time onset of therapy (both ventilation and drug administration) before performance of echo measurements could be another reason of low PASP values in some of our patients.

Since PAOP estimation loses prognostic value with time from initial diagnosis due to rapid change in response to treatment, ?/e' ratio could not accurately discriminate patients according to different length of weaning. On the contrary, significantly increased AUC values of TAPSE, RV TDI velocities, RVFAC and LVEF possibly reflect a biventricular failure with a more severe effect of increased LV filling pressures upon RV performance, in the subgroup of patients with prolonged separation from the ventilator.

The above associations between TAPSE and RV TDI velocities with length of weaning may have limited validity due to the study design. First, the combination of a small sample size with multiple comparisons between different subgroups might have predisposed to both false positive and false negative results. Second, we did not use pulmonary artery catheter (PAC) for estimating PASP, RV and LV function. As it has been suggested, assessment of RV and LV filling pressures with PAC seems to be inaccurate, especially during mechanical ventilation [³⁶].

Third, the associations being found do not imply causality. More studies with bigger sample size are needed to confirm possible significance of our results, whereas other echocardiographic indices could also be tested or even compared with those used in our study for early prediction of weaning outcome.

In conclusion, we suggest that reduced TAPSE and tricuspid annular TDI systolic and diastolic velocities are associated with increased duration of weaning in critically ill patients with pulmonary edema, reflecting a more severe LV heart failure. These measurements are fast and easily reproducible, can accurately estimate LV performance even by less experienced operators in the ICU setting, whereas their adoption for weaning outcome assessment in different groups of patients merits further investigation. A comparison with other indices of cardiac function, like BNP serum levels and an associated change with different treatment protocols could also be investigated in future studies.

APE: acute pulmonary edema; BNP: B-type natriuretic peptide; BSA: body surface area; CHF: chronic heart failure; CW: continuous wave; ICU: Intensive Care Unit; IVC: inferior vena cava; LVEF: left ventricular ejection fraction; LV: left ventricle; PAOP: pulmonary artery occlusion pressure; PASP: pulmonary artery systolic pressure; PEEP: positive-end expiratory pressure; PW: pulsed-wave; RAP: right atrial pressure; RV: right ventricle; RVFAC: right ventricular fractional area change; SBP: systolic blood pressure; SBT: spontaneous breathing trial; TAPSE: tricuspid annular plane systolic excursion; TDI: tissue Doppler imaging; TR: tricuspid regurgitation; TV: tidal volume.

The authors declare that they have no competing interests.

All authors have read and approved the final manuscript. VP: Was the principal investigator who designed the study, made echo calculations, statistical analyses and wrote the manuscript. DS: Was associate investigator who also performed echo calculations and chequed the first author's echo-derived measurements. CD: Helped with data gathering and statistical analysis. IP: He reviewed the manuscript and helped in final submission format.

The pre-publication history for this paper can be accessed here:

http://www.biomedcentral.com/1471-2261/10/20/prepub