Use of ultrasonic left ventricular pressure-strain loops to predict weaning failure in critically ill patients: a pilot study

Introduction

Invasive mechanical ventilation (IMV) is an effective rescue measure for critically ill patients (1). However, delayed or premature weaning after IMV may lead to weaning failure, thereby prolonging the intensive care unit (ICU) stay and increasing the risk of death. Among patients who experienced weaning failure, some required re-intubation, with a mortality rate of 30–40% (2-4). The spontaneous breathing trial (SBT) is a standard test used to evaluate the patient’s ability to breathe spontaneously at a specified duration of time during the process of weaning; however, its assessment of left heart function is not comprehensive (5). The evaluation of left ventricular (LV) diastolic function in critically ill patients has important predictive value for successful weaning (6). However, it is not yet known whether LV systolic function affects weaning outcomes, as the traditional evaluation indicators of LV systolic function mainly include ejection fraction and the mitral valve early maximal ventricular filling velocity/atrial maximal ventricular filling velocity ratio, which are affected by LV afterload, and thus cannot be used to accurately evaluate weaning (7).

LV pressure-strain loops (PSLs) are a new method for evaluating LV systolic function. PSLs reflect the change in relationship between LV pressure and strain during a cardiac cycle. PSLs improve the accuracy of LV function measurement by improving the effect of afterload on myocardium (8,9). To date, the use of PSLs in the evaluating LV systolic function in IMV patients during weaning has not been examined. Thus, this study sought to use PSLs to evaluate the myocardial work performance of IMV patients during weaning, and to analyze the relationship between the myocardial work parameters and weaning outcomes. We present this article in accordance with the STROBE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-24-1351/rc).

Methods

Participants

The study included 70 patients who were hospitalized in the ICU of Zhangzhou Affiliated Hospital of Fujian Medical University from September 2022 to August 2023. The patients were divided into the weaning success group (n=41) and the weaning failed group (n=29). The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of Zhangzhou Affiliated Hospital of Fujian Medical University (No. 2024LWB251), and informed consent was obtained from all the participants.

The process for screening patients is shown in Figure 1. To be eligible for inclusion in the study, the patients had to meet the following inclusion criteria: (I) have received IMV more than 24 hours; and (II) have passed the SBT [i.e., fraction of inspired oxygen (FiO₂) <50%, partial pressure of oxygen (PaO₂)/FiO₂ >200 mmHg, respiratory rate ≤30 breaths/min, positive end-expiratory pressure ≤5 cmH₂O, and hemodynamic stability in the absence of vasopressors (10)]. Patients were excluded from the study if they met any of the following criteria (11): (I) were aged <18 years; (II) had previously failed the SBT or undergone accidental extubation; (III) had a history of severe chronic obstructive pulmonary disease; (IV) had severe arrhythmia; (V) had paraplegia above the T8 level; (VI) were pregnant; (VII) had a flail chest or rib fracture; (VIII) had severe ICU-acquired neuropathy; (IX) had used muscle relaxants within 48 hours prior to the study; (X) had poor-quality ultrasound images that could not be analyzed; and/or (XI) had incomplete ultrasound images.

Figure 1 Flowchart of the selection process for patients.

The weaning process began in the pressure-support ventilation mode, and was followed by SBT in T-piece oxygen inhalation at 5 L/min for 30 minutes. If all of the following criteria were satisfied, extubation was performed within 30 minutes: good tolerance to the SBT, oxygen saturation ≥90%, heart rate <120 beats/min or heart rate variability ≤20%, respiratory rate <35 breaths/min, 80 mmHg < systolic blood pressure <180 mmHg, or <20% change from baseline and an absence of increased breathing work or distress signs (10). When the patient passed the SBT, the LV systolic function was evaluated by PSLs, and extubation was performed offline.

Definition of extubation failure or success

Extubation failure was defined as the need for non-invasive positive-pressure ventilation, reintubation, or tracheostomy within 48 hours (12). Patients with failed extubation were allocated to the weaning failed group, while the others were allocated to the weaning success group.

Instruments and methods

The medical record system was used to obtain data on the patients’ age, gender, Sequential Organ Failure Assessment (SOFA) score [creatinine, mean arterial pressure, Glasgow Coma Scale (GCS) score, bilirubin, PaO₂/FiO₂], primary diseases, IMV duration, and brain natriuretic peptide (BNP), myoglobin, troponin I, partial pressure of carbon dioxide (PaCO₂), and PaO₂ levels.

For the ultrasound examination, the patient was placed in a 30° supine position. The ultrasound was performed by doctors with the same level of ultrasonic experience using the GE Vivid iq Color Doppler ultrasound diagnostic instrument (GE Healthcare, Chicago, IL, USA) coupled with a phased array probe (frequency: 1.5–4.6 MHz), which was equipped with Q-analysis software package, and an EchoPAC offline analysis workstation was used to evaluate the LV systolic function.

Dynamic images of the apical four-, three-, and two-chamber heart were obtained for 5–8 consecutive cardiac cycles by adjusting the frame rate at 50–80 frames/s for offline processing. Then LV end-diastolic volume, LV end-systolic volume, and left ventricular ejection fraction (LVEF) were measured using the biplanar Simpson method. The dynamic images of the apical four-, three-, and two-chamber heart were imported into the EchoPAC offline analysis workstation, which was used to detect the LV global longitudinal strain (GLS) on the section of the apical four-, three-, and two-chamber heart. Next, blood pressure was input to obtain the PSL curve, and finally the LV myocardial work results, including the global work index (GWI), global constructive work (GCW), global waste work (GWW), and global work efficiency (GWE), were obtained (Figure 2). All the analyses were performed in a double-blinded manner by two doctors with the same level of ultrasonic experience.

Figure 2 The myocardial work conditions of the (A) weaning failure group and (B) weaning success group. In (A) and (B), the upper left quadrants represent the pressure-strain loops. The area of the pressure-strain loops represents the GWI. The y-axis of the left-bottom graph represents the values of the GCW and GWW. The upper right quadrant shows the efficiency of myocardial work for each segment of the left ventricle. The right-bottom quadrant represents the various myocardial work parameters. (A) Weaning failure group: GLS: −11%, GWI: 1,436 mmHg%, GCW: 1,942 mmHg%, GWW: 398 mmHg%, and GWE: 81%. (B) Weaning success group: GLS: −20%, GWI: 1,317 mmHg%, GCW: 2,144 mmHg%, GWW: 118 mmHg%, and GWE: 94%. BP, blood pressure; GCW, global constructive work; GLS, global longitudinal strain; GWE, global work efficiency; GWI, global work index; GWW, global waste work; LVP, left ventricular pressure.

A total of 20 patients were randomly selected using the random number table method. A consistency analysis of GLS, GWE, GWI, GCW, GWW was performed by the two doctors with the same level of ultrasonic experience, and an image analysis of the same sample was re-performed by one of the doctors after a week’s interval. The interobserver and intraobserver consistency of the measurements was evaluated using the intraclass correlation coefficient (ICC).

Statistical analysis

All the statistical analyses were performed using R version 4.3.1 (https://posit.co/downloads/). The normally distributed measurement data are expressed as the mean ± standard deviation. The skewed distributed data are presented as the median (25th, 75th percentile). The enumeration data are presented as the percentage and frequency. For comparisons between the two groups of patients, the independent sample t-test was used to compare the continuous variables, the Mann-Whitney test was used to compare the non-parametric data, and the Chi-squared test was used to compare the enumeration data.

The statistically significant (P<0.05) ultrasound features and clinical data from the univariate analysis were included in the multivariate logistic regression analysis. The odds ratio (OR), 95% confidence interval (CI), and the beta coefficient (β) were obtained. A Spearman correlation analysis was used to analyze the correlation between the variables and extubation failure. The diagnostic efficacy of the independent risk factors was evaluated using the area under the curve (AUC), which was computed by the receiver operating characteristic (ROC) curve. ICCs were calculated to detect interobserver and intraobserver agreement. A P value <0.05 was considered statistically significant.

Results

The clinical characteristics of the patients and ultrasound features are shown in Table 1. Except for IMV duration, there were no significant differences between the two groups in terms of age, gender, primary disease, SOFA score, GCS score, and BNP, myoglobin, troponin I, PaCO₂, and PaO₂ levels. The main causes of intubation in the two groups were pneumonia and myocardial infarction. In the weaning success group, 17 patients had pneumonia and 10 patients had myocardial infarction. In the weaning failure group, 19 patients had pneumonia and 6 patients had myocardial infarction. Patients with pneumonia and myocardial infarction accounted for 74% of all cases. The other 26% of patients were intubated after traumatic hemorrhagic shock, septic shock after inflammation, or complications related to malignant tumors.

Both the intraobserver and interobserver consistency of the myocardial work parameters were strong; all the ICC values were above or equal to 0.8 (Table 2).

In the univariate analysis, IMV duration, GLS, GWI, GCW, GWW, GWE, and LVEF were significant factors affecting weaning failure, while in the multivariate logistic regression analysis only GWE (OR =6.599, P=0.029) and IMV duration (OR =0.407, P=0.039) were independent factors affecting weaning failure. IMV duration, GLS, GWW, GWE, and LVEF were significantly correlated with weaning failure (Table 3). Our results showed that the GWE was lower in the weaning failed group than the weaning success group, while IMV duration was significantly longer in the weaning failed group.

The ROC curves for GWE, IMV duration, and their combination are shown in Figure 3. The AUC values for GWE, IMV duration, and their combination were 0.845, 0.742, and 0.859, respectively, and these factors were able to predict weaning failure accurately.

Figure 3 ROC curves of IMV duration, GWE and their combination. AUC, area under the curve; GWE, global work efficiency; IMV, invasive mechanical ventilation; ROC, receiver operating characteristic.

The diagnostic cut-off value, Youden’s Index, sensitivity, and specificity of GWE, IMV duration, and their combination are shown in Table 4. The specificity and AUC value of the combination of GWE and IMV duration were higher than those of any single index. When a patient has an IMV duration >5.5 days and a GWE <0.835, IMV weaning may fail.

Discussion

LV diastolic dysfunction is closely associated with weaning failure in IMV patients, but it is not yet known whether LV systolic dysfunction as assessed by LVEF is associated with weaning failure (13,14). The increase of pleural pressure during the weaning process would result in increased LV afterload, which in turn affects LVEF; thus, it is impossible to accurately evaluate LV systolic dysfunction during the weaning process (7,14). PSLs overcome the influence of afterload on the myocardium, and thus can accurately evaluate LV systolic function.

Pneumonia is a systemic disease that is prone to cardiovascular complications, such as acute myocardial infarction, arrhythmia, and heart failure. Cardiovascular complications may cause sudden exacerbation or death. Therefore, the early evaluation of cardiac function is of great importance (15). In our study, 74% of the patients had pneumonia or myocardial infarction, while the other 26% had circulatory-related conditions; thus, the results of our study only apply to diseases related to the cardiovascular and pulmonary circulatory systems.

The results of this study showed that the GWE of the weaning failed group was significantly lower than that of the weaning success group; thus, GWE could be used as an independent factor for evaluating weaning failure. However, GCW and GWW were not found to be independent factors for weaning failure. It may be that when IMV changes to spontaneous respiration during the weaning process, the negative pressure in the chest and the venous return blood flow increases, which in turn increases the pre-load and afterload. At the same time, there is an increase in sympathetic nerve excitation, peripheral vascular resistance, and afterload. Because of the heart and lung interaction, myocardial oxygen consumption and myocardial work increases (16). GWE is an important parameter of cardiac ejection function, which refers to the proportion of GCW in the sum of GCW and GWW, and represents the proportion of effective work done in the process of myocardial work. GCW contributes to the work done by the LV ejection, while GWW refers to the work done against LV ejection (17,18). There may be a mutual relationship between the GCW and GWW. In the multivariate logistic regression, only GWE was found to be an independent risk factor for predicting weaning outcomes. However, the mechanism of myocardial work during weaning is still unclear, and needs to be further examined in large, multicenter studies.

The longer the IMV duration, the more likely the occurrence of ventilator-related complications, such as diaphragmatic atrophy and ventilator-associated pneumonia, which can result in ventilator dependence, and lead to weaning failure (19). Our results showed that IMV duration is an independent risk factor for weaning failure, which is consistent with the results of Baptistella et al. (20).

Limitations

This study had many limitations. First, it was a single-center retrospective study and lacked external validation. Second, only 70 patients were enrolled in this study; thus, large sample-size studies are needed for verification. Third, PSLs have a high requirement in terms of image quality, and the quality of some of images was poor due to the influence of the body position of the IMV patients and the gas in the precardiac area. Fourth, we did not include clinical prediction indicators such as Pimax and frequency/tidal volume in the study. In future studies, we intend to include relevant indicators for analysis and comparison. Despite these limitations, the sample size conformed to the empirical criteria for sample-size estimation in a logistic regression analysis (21), the consistency of the measurements was good, and this was an exploratory study; thus, the results of our study have a certain reliability.

PSLs were used in this study to evaluate LV systolic function during the weaning of IMV patients, and to explore the relationship between myocardial work parameters and weaning outcomes. Our findings provide evidence for clinical practice on the relationship between LV systolic dysfunction and weaning outcomes.

Conclusions

PSLs are significantly related to weaning outcomes, and GWE could serve as an independent risk factor for predicting weaning outcomes, and thus has real-time and dynamic predictive value for the clinic.

Acknowledgments

We would like to thank all the patients and their families who participated in this study.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-24-1351/rc

Funding: This work was supported by the Start-up Fund for Scientific Research, Fujian Medical University (No. 2021QH1267) and the Natural Science Foundation of Fujian Province, China (No. 2022J011485).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-1351/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of Zhangzhou Affiliated Hospital of Fujian Medical University (No. 2024LWB251), and informed consent was obtained from all the participants.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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