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Luo et al. BMC Pulmonary Medicine (2017) 17:161 DOI 10.1186/s12890-017-0501-8 RESEARCH ARTICLE Open Access Different effects of cardiac and diaphragm function assessed by ultrasound on extubation outcomes in difficult-to-wean patients: a cohort study Ling Luo1,2, Yidan Li3, Xiukai Chen4, Bing Sun1, Wenxiong Li4, Wei Gu5, Shuo Wang5, Song Zhao4, Yanwei Lv 6, Mulei Chen7, Jingen Xia8, Feng Sui4, Xue Mei5, Huanzhong Shi1 and Zhaohui Tong1* Abstract Background: Ultrasound is a convenient tool to evaluate cardiac and diaphragm function. The ratio (E/Ea) of mitral Doppler inflow velocity to annular tissue Doppler wave velocity by transthoracic echocardiography (TTE) and diaphragmatic excursion (DE) by diaphragm ultrasound have been confirmed in predicting extubation outcomes independently, however their different roles in the weaning process have not been determined until now. Methods: We designed a cohort study to preform diaphragm ultrasound and TTE before and after the spontaneous breathing trial (SBT) in difficult-to-wean patients. Patients considered for enrollment should succeed on a SBT and have been extubated. They were followed up with the events of respiratory failure within 48 h, and divided into the respiratory failure and extubation success subgroups. Relevant risk factors predicting respiratory failure were analysed by a multivariate logistic regression model. Then, each subgroup was assessed with respect to re-intubation within 1 week, and divided into the re-intubation and non-intubation subgroups. Furthermore, relevant risk factors predicting re-intubation were also analysed in each subgroup. The area under the curve (AUC) and optimum cut-off value were identified by the receiver operating characteristic curve. Results: Among 60 patients, 29 cases developed respiratory failure within 48 h, and 14 cases were re-intubated or died within 1 week, respectively. Multivariate logistic regression analysis showed that E/Ea (average) after SBT [odds ratio (OR) 1.450, 95% confidence intervals (CI) 1.092-1.926, P = 0.01] and left ventricular ejection fraction were associated with respiratory failure. The AUC of E/Ea (average) after SBT was 0.789, and a cut-off value ≥ 12.5 showed the highest diagnostic accuracy with a sensitivity and specificity of 72.4% and 77.4%, respectively. Furthermore, in the respiratory failure subgroup only DE (average) after SBT was associated with re-intubation (OR 0.690, CI 0.499-0.953, P = 0.024). The AUC of DE (average) after SBT was 0.805, and a cut-off value ≤ 12.6 mm showed the highest diagnostic accuracy with a sensitivity and specificity of 80% and 68.4%, respectively. Conclusions: E/Ea (average) after SBT could help predict respiratory failure within 48 h. However, DE (average) after SBT could help predict re-intubation within 1 week in the respiratory failure subgroup. Keywords: Weaning, Extubation, Cardiac function, Echocardiography, Diaphragm function * Correspondence: tongzhaohuicy@sina.com 1 Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital, Capital Medical University, NO. 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing 100020, China Full list of author information is available at the end of the article © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Luo et al. BMC Pulmonary Medicine (2017) 17:161 Background Predictors of extubation outcomes are consistently difficult issues for patients with a high risk of difficult weaning. Common reasons for extubation failure include primary respiratory failure, cardiac dysfunction, ineffective cough, excess secretions, upper airway obstruction and other aetiologies [1, 2]. The ideal indicators would not only predict extubation failure, but would also confirm the reasons for such failures. Traditional indicators, such as respiratory rate (RR), minute ventilation, tidal volume (VT), and the rapid shallow breathing index (RSBI), can reflect patients’ integral conditions, but it is difficult to apply them in the analysis of the exact reasons for such failures. Some studies have reported that B-type natriuretic peptide (BNP) or N-terminal-pro-BNP (NT-pro-BNP) could help identify patients who failed to wean due to cardiac dysfunction. Nevertheless, it was difficult to confirm the cut-off values; because they were easily affected by age, renal function, weight, infection, etc. [3–5]. Bedside ultrasound is a convenient tool to evaluate cardiac function, diaphragm function, lung aeration, etc. Cardiac dysfunction is one of the important risk factors for extubation failure. Recent studies have indicated that the ratio (E/Ea) of mitral Doppler inflow velocity (E) to annular tissue Doppler wave velocity (Ea) by transthoracic echocardiography (TTE) could help identify the cardiac origin of weaning failure [6–9]. In addition to cardiac dysfunction, diaphragm dysfunction is another critical reason for extubation failure. Some studies have reported that diaphragmatic excursion (DE) or liver/spleen movements could predict extubation failure [10–12]. Although TTE and diaphragm ultrasound have been confirmed in independently assessing extubation outcomes, few studies have shown their different roles in the weaning process until now. This observational study was designed to test the ability of cardiac and diaphragm function assessed by bedside ultrasound to predict respiratory failure within 48 h and re-intubation within 1 week after extubation. Methods Patients This study was conducted in Beijing Chaoyang Hospital, which has a total of 58 beds in the 4 intensive care units (ICUs) (RICU, SICU, CCU and EICU), over a 16-month period (November 2012 to February 2014). The study was approved by an Institutional Review Board of Beijing Chaoyang Hospital on Sep 24th, 2012 (No.2012-ke-88). Consent forms were obtained from each patient’s immediate family members. All patients were assessed for readiness to wean by their attending physicians. Once the patients failed the spontaneous breathing trial (SBT) at least once and had Page 2 of 13 been intubated for more than 48 h, they were defined as difficult-to-wean patients [13]. Patients considered for enrollment should succeed on a SBT and have been extubated. The exclusion criteria were as follows: (a) pregnant women; (b) age < 18 years; (c) tracheostomy after the SBT; (d) severe mitral stenosis or prosthetic mitral valve; (e) a history of diaphragmatic palsy, cervical spine injury, or neuromuscular disease; (f) pneumothorax or pneumomediastinum; (g) use of muscle-paralyzing agents within 48 h before the study; (h) poor echocardiographic windows or difficult windows of diaphragmatic movement; (i) extubation failure definitely caused by upper airway obstruction; and (j) planned prophylactic noninvasive ventilation (NIV) after extubation. Study design All patients were connected to a ventilator with pressure support ventilation [pressure support 10-12 cmH2O, positive end expiratory pressure 5 cmH2O, and proper fraction of inspired oxygen (FiO2) ≤ 40%] before the SBT. They fulfilled the SBT through a T-piece over 30 min in a supine position (30°- 45°). It took 5 to 15 min to perform TTE and diaphragm ultrasound before and after the SBT. The attending physicians remained blinded to the TTE and diaphragm ultrasound results. All patients should be extubated within 24 h once the SBT has succeeded. Medications, NIV or reintubation could be performed in accordance with the patients’ conditions. Both TTE and diaphragm ultrasound were performed using a Vivid i (GE Medical Systems Israel Ltd) with a 3.0 MHz US probe. TTE was done after diaphragm ultrasound. Diaphragmatic movement was measured by specific ultrasound doctors with the US probe placed over one of the lower intercostal spaces in the right anterior axillary line for the right diaphragm and left midaxillary line for the left diaphragm. The liver or spleen was used as a window for each hemidiaphragm. A twodimensional mode was used to find the best approach and to select the exploration line for each hemidiaphragm. With the probe fixed on the chest wall during respiration, the ultrasound beam was directed to the hemidiaphragmatic domes at an angle of ≥70°; then, M-mode ultrasonography was used to display the motion of the anatomical structures along the selected line [11, 12, 14]. Unilateral diaphragmatic excursion (DE) equalled half of the sum of the values on the vertical axis of the tracing during the inspiration and expiration period, which were measured from baseline to the point of maximum height. DE (average) was equivalent to half of the sum of DE (right) and DE (left). Measurements were recorded at least six times and averaged for each hemidiaphragm. If the rhythm of respiration was not regular, measurements were needed at least ten times. Luo et al. BMC Pulmonary Medicine (2017) 17:161 All patients were followed up with the events of respiratory failure within 48 h, and they were divided into respiratory failure and extubation success subgroups, accordingly. Respiratory failure was defined by at least two of the following criteria: arterial pH < 7.35 with arterial carbon dioxide tension (PaCO2) > 45 mmHg or > 20% higher than baseline; RR > 30 breaths/min or ≥ 50% higher than baseline; arterial oxygen tension (PaO2) < 60 mmHg or percutaneous oxygen saturation (SpO2) < 90% at FiO2 ≥ 0.5; decreased consciousness (e.g., coma, stupor, delirium), agitation, or diaphoresis; and clinical signs suggestive of respiratory muscle fatigue or increased work of breathing, such as retraction of intercostal spaces, use of accessory respiratory muscles, or thoracic-abdominal paradoxical movement [13, 15–17]. Then, each subgroup was assessed with respect to reintubation within 1 week, and divided into re-intubation and non-intubation subgroups. The re-intubation should meet one of the following major criteria (a): respiratory or cardiac arrest, persistent severe hypoxemia (ratio of PaO2 to FiO2 ≤ 130 mmHg) despite NIV, haemodynamic instability with systolic blood pressure ≤ 85 mmHg despite adequate fluids and vasoactive drugs (dopamine or dobutamine ≥ 5 μg/kg/min or noradrenaline ≥ 0.05 μg/ kg/min), and severe cardiac arrhythmia; or (b) at least two of the following minor criteria: clinical signs of severe acute respiratory failure with respiratory rate persistently > 35 breaths/min, arterial pH ≤ 7.20, worsening of acute respiratory failure under NIV, clinical signs suggestive of severely decreased consciousness (e.g., coma, stupor, and delirium) under NIV, bronchial hypersecretion under NIV, and development of other organ failure [13]. The attending doctor decided whether to re-intubate in the end. The re-intubation subgroup included the patients who were re-intubated or died within 1 week after extubation. The criteria of readiness to wean and the SBT and NIV as well as, and the detailed methods for measuring E/Ea and left ventricular ejection fraction (LVEF) are described in Additional file 1. Records were taken on the patients’ characteristics, including age, sex, body mass index (BMI), Acute Physiology and Chronic Health Evaluation (APACHE) II score at the time of admission to the ICU, comorbidities, duration from onset to the first intubation, duration of the first intubation to extubation, VT and RSBI before the SBT, white blood cell count, haemoglobin, albumin, plasma creatinine and Glasgow coma scale (GCS) on the day of extubation. The data for DE, E, E/Ea and LVEF, arterial blood gas analysis, lactic acid and NT-pro-BNP were also collected. Statistical analysis Statistical analysis was performed with SPSS 17.0 (Inc., Chicago, IL, USA). Data were expressed as the means ± SD Page 3 of 13 or median quartile [first–third]. The Unpaired Student’s, Mann-Whitney, and the paired Wilcoxon tests were used to compare quantitative variables. Differences in the measurement data were compared with the one-way analysis of variance. Comparisons of proportions were performed with a Chi-square test or Fisher’s exact test. Risk factors predicting respiratory failure within 48 h or re-intubation within 1 week were selected by the backward-Wald method and analysed with a multivariate logistic regression model. The results were displayed in the last step. Meanwhile, the Hosmer-Lemeshow test was performed to verify the goodness of fit of the model. Then the area under the curve (AUC) and optimum cut-off value were identified by the receiver operating characteristic (ROC) curve. The level of significance was fixed at P ≤ 0.05. Results Figure 1 shows the flow-chart diagram of the study. Of the 75 patients who were screened, 60 patients (age range from 18 to 90 years -old) were enrolled. The reasons for intubation included severe pneumonia (n = 19), chronic obstructive airway disease (n = 10), cardiac events (n = 15), sepsis (n = 7), surgery (n = 8) and upper gastrointestinal haemorrhage (n = 1). The reasons for exclusion included severe mitral stenosis or prosthetic mitral valve (n = 2), poor echocardiography images or ultrasonic windows of diaphragm (n = 5), tracheotomy after SBT (n = 2), extubation failure caused by upper airway obstruction (n = 2) and planned prophylactic NIV (n = 4). Of 60 enrolled patients, 29 patients developed respiratory failure within 48 h after extubation, and 14 patients were re-intubated within 1 week. Predictors of respiratory failure within 48 h Among 60 patients, 29 cases (48%) developed respiratory failure within 48 h after extubation (respiratory failure subgroup, RF subgroup), and another 31 cases (52%) were successfully extubated (extubation success subgroup, ES subgroup). There were significant differences in some clinical characteristics between the RF and ES subgroups (Table 1). Partial differences were also seen in the laboratory and ultrasound data (Table 2). Multivariate logistic regression showed that E/Ea (average) after SBT [odds ratio (OR) 1.450, 95% confidence intervals (CI) 1.092-1.926, P = 0.01] and the LVEF (OR 0.904, CI 0.833-0.981, P = 0.015) were closely related to respiratory failure within 48 h. The P value for the Hosmer-Lemeshow test was 0.11. The AUC of E/Ea (average) after SBT was 0.789, and a cut-off value ≥12.5 showed the highest diagnostic accuracy with a sensitivity and specificity of 72.4% and 77.4%, respectively (Fig. 2). The results of logistic regression and the ROC curve in this study were summarized in Table 3. For example, compared with a case of extubation success (Fig. 3), Luo et al. BMC Pulmonary Medicine (2017) 17:161 Page 4 of 13 Fig. 1 Flow chart. ABG arterial blood gas analysis, DE diaphragmatic excursion, E/Ea the ratio of mitral Doppler inflow velocity (E) to annular tissue Doppler wave velocity (Ea), ES extubation success, NI non-intubation, NIV noninvasive ventilation, NT-pro-BNP N-terminal-pro-B-type natriuretic peptide, RF respiratory failure, RI re-intubation, SBT spontaneous breathing trial E/Ea (average) after SBT was high in a patient in the RF subgroup (Fig. 4). Meanwhile, NT-pro-BNP was analysed separately from the E/Ea and LVEF because of their significant correlations. Multivariate logistic regression analysis showed that the NT-pro-BNP level and PaCO2 after SBT, duration of the first intubation to extubation and haemoglobin were closely related to respiratory failure within 48 h (Additional file 1: Table S1). However, the OR value of NT-pro-BNP was very close to 1. Predictor of re-intubation within 1 week in the respiratory failure subgroup Among all patients, 29 cases developed postextubation respiratory failure within 48 h. These 29 cases received NIV, and 4 of them experienced re-intubation within 48 h. However, 6 of the remaining of 25 cases required re-intubation within 1 week. Of 10 cases with reintubation, 6 patients were re-intubated for heart failure and 4 patients for ineffective cough. One-way analysis of variance showed significant differences for DE (right) and DE (average) after SBT, the haemoglobin and BMI (Tables 4 and 5). However, multivariate logistic regression analysis showed that only DE (average) after SBT was associated with re-intubation within 1 week (OR 0.690, CI 0.499–0.953, P = 0.024) (Table 6). The P value for the Hosmer-Lemeshow test was 0.559. The AUC of DE (average) after SBT was 0.805, and the cut-off value ≤ 12.6 mm showed the highest diagnostic accuracy with a sensitivity and specificity of 80% and 68.4%, respectively (Fig. 5). Risk factors for re-intubation within 1 week in the extubation success subgroup Among 31 patients in the extubation success subgroup, 4 cases were re-intubated within 1 week after extubation (2 cases for abdominal infection, 1 case for ineffective cough and 1 case for heart failure). One-way analysis of variance showed significant differences for the duration from onset to the first intubation, PH after SBT, NTpro-BNP after SBT, and DE (average) before and after SBT (Tables 4 and 5). However, multivariate logistic regression analysis showed none of these factors were associated with re-intubation within 1 week (Additional file 1: Table S2). Discussion The most important findings in this study confirmed the different effects of cardiac and diaphragm function assessed by ultrasound on extubation outcomes in difficult-to-wean patients. Our results indicated that E/Ea (average) after SBT could predict respiratory failure within Luo et al. BMC Pulmonary Medicine (2017) 17:161 Page 5 of 13 Table 1 Clinical characteristics Table 2 Laboratory and ultrasonic data before and after SBT Respiratory failure within 48 h Respiratory failure within 48 h Variables RF subgroup ES subgroup Variables RF subgroup ES subgroup N (cases) 29 31 N (cases) 29 31 Age (yrs) 70.8 ± 15.6 62.3 ± 22.2 PH 7.45 ± 0.06 7.46 ± 0.05 Male 18 (62) 17 (55) PaCO2 (mmHg) 46.4 ± 13 39.1 ± 5.1* BMI (kg/m2) 24.4 ± 5.3 24.3 ± 4.3 PaO2/FiO2 277 ± 83 281 ± 80 Lactic acid (mmol/l) 1.2 ± 0.6 1.1 ± 0.4 Chronic respiratory diseasesa 19 (66) 7 (23)* NT-pro-BNP(pg/ml) 6519 ± 9162 1578 ± 1843* Demographic factors: Before SBT Comorbidities: Coronary heart disease 16 (55) 7 (23)* Pleural effusion 22 (76) 24 (77) Myocardial infarction 11 (38) 6 (19) LVEF (%) 57 ± 14 64 ± 9* Hypertension 17 (59) 19 (61) E (cm/s) 92.9 ± 25.6 78.2 ± 18.4* Atrial fibrillation 8 (28) 3 (32) E/Ea (septal) 18.2 ± 8.1 13 ± 3.8* Diabetes 11 (38) 12 (39) E/Ea (lateral) 12.8 ± 5.1 8.4 ± 2.7† Renal dysfunction 10 (29) 5 (16) E/Ea (average) 14.7 ± 5.6 10.1 ± 2.8† Cerebral vascular diseasesb 6 (21) 4 (13) Clinical characteristics: APACHE II 23.9 ± 4.7 20 ± 6.4* Duration from onset to the first intubation (d) 6.3 [1.5–9] 3.6 [1–6]* Duration of the first intubation to extubation (d) 10.4 ± 6.9 7.2 ± 4.7* RR (breaths/min) 21.6 ± 4.3 DE (right) (mm) 11.2 ± 4.7 10.1 ± 4.7 DE (left) (mm) 11.6 ± 6.3 10.8 ± 5.5 DE (average) (mm) 11.4 ± 4.5 10.5 ± 3.4 After SBT PH 7.43 ± 0.05 7.47 ± 0.05* PaCO2 (mmHg) 48 ± 11.7 38.7 ± 5.5† 21.5 ± 4.7 PaO2/FiO2 291 ± 103 275 ± 79 1.1 ± 0.5 1.1 ± 0.5 VT (l) 0.43 ± 0.12 0.41 ± 0.09 Lactic acid (mmol/l) RSBI 55.8 ± 22.2 55.9 ± 22.1 NT-pro-BNP(pg/ml) 6518 [421-10,477] 1471[176-1575]* E (cm/s) 99.7 ± 24.3 85.1 ± 18.2* GCS 13.4 [13–15] 13.8 [13–15] WBC (×109/l) 9.8 ± 3.9 10.9 ± 5.6 E/Ea (septal) 18.6 ± 6.5 13.4 ± 4.4* 14.4 ± 7.3 9.0 ± 3.0* Hemoglobin (g/l) 103 ± 23 89 ± 14* E/Ea (lateral) Albumin (g/l) 28.8 ± 4.2 27.7 ± 3.9 E/Ea (average) 15.8 ± 6.2 10.6 ± 3.2† Plasma creatinine (micromole/l) 121 ± 74 115 ± 80 DE (right) (mm) 13.7 ± 6 11 ± 4.4 DE (left) (mm) 13.8 ± 6.4 13 ± 5.4 DE (average) (mm) 13.7 ± 5.4 12 ± 3.4 Data are presented as median ± SD or median (IQR) or n (%). APACHE II Acute Physiology and Chronic Health Evaluation II, BMI body mass index, ES extubation success, GCS Glasgow coma scale, RF respiratory failure, RR respiratory rate, RSBI rapid shallow breathing index, VT tidal volume, WBC white blood cell. aAsthma, obsolete tuberculosis, chronic obstructive pulmonary disease, bronchiectasis and interstitial lung disease are included. bCerebral infarction, cerebral hemorrhage and subarachnoid hemorrhage are included. * Significant at p < 0.05 48 h, and DE (average) after SBT might predict reintubation within 1 week in the respiratory failure subgroup. These results supported that cardiac diastolic function occurred in the short term after extubation, and diaphragm dysfunction persisted in the long term after extubation. On the one hand, during abrupt transfer from mechanical ventilation to spontaneous breathing, decreases in intrathoracic pressures would augment venous return and intrathoracic blood volume, increasing the cardiac preload. Furthermore, increased left ventricular transmural pressures would augment cardiac afterload during the process. Otherwise, the increase in the breathing Data are presented as median ± SD or median (IQR) or n (%). DE diaphragmatic excursion, E mitral Doppler early peak diastolic velocity, E/Ea the ratio of mitral Doppler inflow velocity to annular tissue Doppler wave velocity, ES extubation success, LVEF left ventricular ejection fraction, NT-pro-BNP N-terminal-pro-B-type natriuretic peptide, PaCO2 arterial carbon dioxide tension, PaO2/FiO2 the ratio of arterial oxygen tension to fraction of inspired oxygen, RF respiratory failure, SBT spontaneous breathing trial. * Significant at p < 0.05, and † significant at p < 0.001 work and discharge of catecholamine might increase the cardiac work and myocardial oxygen demand [18]. Therefore, cardiac diastolic function would become worse and could lead to postextubation respiratory failure quickly. On the other hand, diaphragm dysfunction usually occurred with chronic respiratory diseases or abdominal diseases, which were often accompanied with refractory respiratory failure or ineffective cough. These were two important reasons for re-intubation. Therefore, diaphragm dysfunction could be associated with re-intubation. Furthermore, other accessory respiratory muscles or NIV Luo et al. BMC Pulmonary Medicine (2017) 17:161 Page 6 of 13 Fig. 2 The ROC curve for E/Ea (average) after SBT predicting respiratory failure within 48 h. The AUC of E/Ea was 0.789 (P < 0.001). A cut-off value ≥ 12.5 of E/Ea (average) after SBT showed the highest diagnostic accuracy with a sensitivity and specificity of 72.4 and 77.4%, respectively. AUC area under curve, E/Ea the ratio of mitral Doppler inflow velocity (E) to annular tissue Doppler wave velocity (Ea), ROC receiver operating characteristic curve, SBT spontaneous breathing trial could partially compensate for diaphragm dysfunction. As a result, re-intubation often occurred in the long term, compared to postextubation respiratory failure. In this study, we demonstrated that E/Ea (average) after SBT could predict respiratory failure within 48 h, and that a cut-off value ≥12.5 had the highest predictive value. These conclusions were partially in line with the results of early case studies [6–9]. However, three issues should be addressed. First, E/Ea (average) but not E/Ea (septal or lateral) after SBT was identified as an ideal predictor in this study; because 17 cases (28%) were diagnosed with myocardial infarction in this study. E/Ea (average) instead of E/Ea (septal or lateral) was recommended to reflect cardiac diastolic function in the presence of regional dysfunction by the Guidelines [19]. Second, the NT-pro-BNP level was higher in the respiratory failure subgroup, but further analysis showed that the OR value was very close to 1, which limited its predictive value. As the NT-pro-BNP was easily affected by multiple factors, it might be more suitable for E/Ea (average) to accurately reflect cardiac diastolic dysfunction related to extubation. Finally, there were no differences in DE between the respiratory failure and extubation success subgroups, indicating that diaphragm dysfunction did not play an important role in respiratory failure within 48 h. Other accessary respiratory muscles could partially compensate for diaphragm dysfunction. Therefore, it often took a long time for diaphragm dysfunction to cause respiratory failure, compared to cardiac dysfunction. A study by Carrie et al. showed that DE could predict weaning failure with a low sensitivity and specificity of 59% and 71%, respectively [20]. Weaning failure was defined as SBT failure, respiratory failure or death within 48 h after extubation. Although there were partial differences between the criteria for weaning failure and those for postextubation respiratory failure, DE seemed not to be significantly associated with respiratory failure within 48 h. In the respiratory failure subgroup, DE (average) after SBT was the only protective factor associated with reintubation within 1 week, which was a significant finding. The cut-off value ≤12.6 mm showed the highest diagnostic accuracy. As the diaphragm serves as a main part in the formation of the cough reflex arc, its function can partly reflect the ability to cough and discharge sputum. Many studies have indicated that cough strength is a good predictor of extubation failure [21–24]. Diaphragm dysfunction was closely related to ineffective cough and primary respiratory failure, which were considered two important reasons for re-intubation. Therefore, diaphragm dysfunction could help predict reintubation. Jiang JR et al. reported that the movements of the liver and spleen during SBT could predict extubation success within 72 h, and that the cut-off value of 1.1 cm had the greatest sensitivity (84.4%) and specificity (82.6%) [10]. Kim WY et al. demonstrated that patients Table 3 The parameters of the ROC curve of the predictors of respiratory failure within 48 h Variables OR 95% CI P-value Cut-off value AUC Sensitivity Specificity Chronic respiratory diseases 5.013 0.738–34.067 0.099 NA NA NA NA Duration from onset to the first intubation 1.269 0.989–1.627 0.061 NA NA NA NA PH after SBT < 0.001 0–3.322 0.066 NA NA NA NA PaCO2 after SBT 1.146 0.980–1.340 0.088 NA NA NA NA LVEF 0.904 0.833–0.981 0.015 ≤ 52 0.646 34.5% 96.8% E/Ea (average) after SBT 1.450 1.092–1.926 0.010 ≥ 12.5 0.789 72.4% 77.4% AUC area under curve, CI confidence interval, E/Ea the ratio of mitral Doppler inflow velocity to annular tissue Doppler wave velocity, LVEF left ventricular ejection fraction, NA not available, PaCO2 arterial carbon dioxide tension, OR odds ratio, ROC receiver operating characteristic curve, SBT spontaneous breathing trial Luo et al. BMC Pulmonary Medicine (2017) 17:161 Page 7 of 13 Fig. 3 The measurements of E/Ea and DE before and after SBT in a patient of extubation success. a, b, c, d, e represented the results before SBT, and f, g, h, i, j represented the results after SBT. a DE (right) was 1 mm. b DE (left) was 26 mm. c E was 64 cm/s. d Ea (septal) was 6 cm/s. e Ea (lateral) was 8 cm/s. f DE (right) was 12 mm. g DE(left) was 22 mm. h E was 76 cm/s. i Ea (septal) was 6 cm/s. j Ea (lateral) was 11 cm/s. Before SBT, DE (average) was 13.5 mm, and E/Ea (average) was 9.1. After SBT, DE (average) was 17 mm, and E/Ea (average) was 8.9. After extubation, the patient did not develop respiratory failure within 48 h. The patient did not require re-intubation within 1 week. DE diaphragmatic excursion, E/Ea the ratio of mitral Doppler inflow velocity (E) to annular tissue Doppler wave velocity (Ea), SBT spontaneous breathing trial Luo et al. BMC Pulmonary Medicine (2017) 17:161 Fig. 4 (See legend on next page.) Page 8 of 13 Luo et al. BMC Pulmonary Medicine (2017) 17:161 Page 9 of 13 (See figure on previous page.) Fig. 4 The measurements of E/Ea and DE before and after SBT in a patient of respiratory failure within 48 h. a, b, c, d, e represented the results before SBT, and f, g, h, i, j represented the results after SBT. a DE (right) was 7 mm. b DE (left) was 10 mm. c E was 68 cm/s. d Ea (septal) was 5 cm/s. e Ea (lateral) was 7 cm/s. f DE (right) was 9 mm. g DE (left) was 17 mm. h E was 94 cm/s. i Ea (septal) was 5 cm/s. j Ea (lateral) was 7 cm/s. Before SBT, DE (average) was 8.5 mm, and E/Ea (average) was 11.3. After SBT, DE (average) was 13 mm, and E/Ea (average) was 15.7. After extubation, respiratory failure occurred within 48 h and then NIV was used. The patient was not re-intubated within 1 week and free of NIV in the end. DE diaphragmatic excursion, E/Ea the ratio of mitral Doppler inflow velocity (E) to annular tissue Doppler wave velocity (Ea), NIV noninvasive ventilation, SBT spontaneous breathing trial with diaphragm dysfunction, defined as DE < 10 mm or paradoxical movements during SBT, had higher rates of primary weaning failure and secondary weaning failure [11]. Our conclusions were partially consistent with these studies. However, three problems should be highlighted. First, DE (average) after SBT instead of DE (right) after SBT was identified as an ideal predictor in this study. In fact, the discrepancy of bilateral diaphragmatic movement was very common in this study, which was similar to another study mentioned above [11]. Unilateral diaphragm dysfunction could be compensated by the reverse side. Therefore, DE (average) could more accurately reflect the overall diaphragm function. Second, all patients received NIV in this subgroup, but 10 cases Table 4 Clinical characteristics in the respiratory failure and extubation success subgroups Respiratory failure subgroup Extubation success subgroup Variables RI subgroup NI subgroup RI subgroup NI subgroup N (cases) 10 19 4 27 Age (yrs) 70.1 ± 21.5 71.2 ± 12.2 70.0 ± 11.5 61.2 ± 23.3 Male 6 (60) 12 (63) 4 (100) 13 (48) BMI (kg/m2) 21.6 ± 4.1 25.9 ± 5.4* 23.9 ± 1.1 24.4 ± 4.5 7 (70) 12 (63) 1 (25) 6 (22) Demographic factors: Comorbidities: Chronic respiratory diseasesa Coronary heart disease 5 (50) 11 (58) 1 (25) 6 (22) Myocardial infarction 2 (20) 9 (47) 1 (25) 5 (19) Hypertension 5 (50) 12 (63) 3 (75) 16 (59) Atrial fibrillation 4 (40) 4 (21) 0 (0) 3 (11) Diabetes 2 (20) 6 (32) 2 (50) 8 (30) Renal dysfunction 6 (60) 5 (26) 3 (75) 9 (33) 4 (40) 2 (11) 1 (25) 3 (11) b Cerebral vascular diseases Clinical characteristics: APACHE II 26.2 ± 6.4 22.7 ± 3.0 24.0 ± 5.0 19.3 ± 6.4 Duration from onset to the first intubation (d) 9.0 ± 7.0 5.0 ± 3.4 1.0 ± 0.8 4.0 ± 4.0* Duration of the first intubation to extubation (d) 13.6 ± 9.6 8.7 ± 4.4 5.8 ± 3.0 7.4 ± 4.9 RR (breaths/min) 22.5 ± 5.6 21.2 ± 3.5 23 ± 6.7 21.3 ± 4.4 VT (l) 0.40 ± 0.12 0.44 ± 0.12 0.38 ± 0.09 0.41 ± 0.09 RSBI 63.9 ± 33.1 51.6 ± 12.8 63.9 ± 29.0 54.8 ± 21.3 GCS 12.4 ± 3.6 14.0 ± 1.0 13.5 [13-14] 13.9 [13-15] WBC (×109/l) 8.5 ± 4.1 10.6 ± 3.6 8.8 ± 3.7 11.3 ± 5.8 Hemoglobin (g/l) 87.2 ± 12.0 111.5 ± 23.3* 81.0 ± 16.8 90.6 ± 14.0 Albumin (g/l) 28.9 ± 5.1 28.8 ± 3.9 25.3 ± 3.3 28.0 ± 3.9 Plasma creatinine (micromole/l) 134.9 ± 83.0 113.0 ± 70.7 155.4 ± 90.5 109.4 ± 79.0 Data are in median ± SD or median (IQR) or n (%). APACHE II Acute Physiology and Chronic Health Evaluation II, BMI body mass index, GCS Glasgow coma scale, NI non-intubation, RI re-intubation, RR respiratory rate, RSBI rapid shallow breathing index, VT tidal volume, WBC white blood cell. aAsthma, obsolete tuberculosis, chronic obstructive pulmonary disease, bronchiectasis and interstitial lung disease. bCerebral infarction, cerebral hemorrhage and subarachnoid hemorrhage. *p < 0.05 Luo et al. BMC Pulmonary Medicine (2017) 17:161 Page 10 of 13 Table 5 Laboratory and ultrasonic data in the respiratory failure and extubation success subgroups before and after SBT Respiratory failure subgroup Extubation success subgroup Variables RI subgroup NI subgroup RI subgroup NI subgroup N (cases) 10 19 4 27 7.44 ± 0.06 7.46 ± 0.06 7.47 ± 0.05 7.46 ± 0.05 Before SBT PH PaCO2 (mmHg) 51.1 ± 15.3 44.2 ± 11.6 38.8 ± 9.5 39.1 ± 4.4 PaO2/FiO2 311 ± 88 261 ± 77 304 ± 99 278 ± 78 Lactic acid (mmol/l) 1.2 ± 0.6 1.1 ± 0.7 1.1 ± 0.8 1.1 ± 0.3 NT-pro-BNP (pg/ml) 8907 ± 10,180 5262 ± 8597 3043 ± 2014 1344 ± 1744 Pleural effusion 7 (70) 15 (79) 4 (100) 20 (74) LVEF (%) 58 ± 16 57 ± 14 58.5 ± 7.9 65.3 ± 8.9 E (cm/s) 97.0 ± 24.6 90.7 ± 26.4 82.1 ± 28.6 77.6 ± 17.2 E/Ea (septal) 17.2 ± 11.0 18.7 ± 6.4 12.8 ± 5.9 13.0 ± 3.6 E/Ea (lateral) 11.7 ± 6.0 13.4 ± 4.6 6.6 ± 3.0 8.7 ± 2.6 E/Ea (average) 13.5 ± 6.7 15.4 ± 5.1 8.6 ± 3.9 10.3 ± 2.6 DE (right) (mm) 9.6 ± 4.4 12.1 ± 4.8 6.0 ± 1.4 10.7 ± 4.7 DE (left) (mm) 10.4 ± 5.1 12.3 ± 6.9 8.3 ± 3.7 11.2 ± 5.6 DE (average) (mm) 10.0 ± 3.4 12.2 ± 4.9 7.2 ± 2.3 11.0 ± 3.2* PH 7.43 ± 0.05 7.44 ± 0.06 7.42 ± 0.05 7.47 ± 0.04* PaCO2 (mmHg) 51.5 ± 14.2 46.1 ± 10.1 39.3 ± 7.0 38.6 ± 5.4 After SBT PaO2/FiO2 317 ± 107 278 ± 101 307 ± 59 271 ± 81 Lactic acid (mmol/l) 1.1 ± 0.5 1.1 ± 0.6 1.5 ± 1.0 1.0 ± 0.3 NT-pro-BNP (pg/ml) 8778 ± 11,082 5329 ± 8654 3631 ± 3273 1138 ± 1517* E (cm/s) 99.2 ± 27.3 99.9 ± 23.3 83.5 ± 23.5 85.3 ± 17.8 E/Ea (septal) 17.8 ± 7.8 19.0 ± 5.8 12.6 ± 5.3 13.5 ± 4.4 E/Ea (lateral) 13.2 ± 8.0 15.0 ± 7.0 7.2 ± 2.5 9.2 ± 3.0 E/Ea (average) 14.6 ± 7.0 16.4 ± 5.9 9.1 ± 3.4 10.8 ± 3.1 DE (right) (mm) 8.9 ± 4.6 16.2 ± 5.1* 8.2 ± 2.4 11.5 ± 4.5 DE (left) (mm) 10.7 ± 5.3 15.5 ± 6.4 9.6 ± 2.4 13.5 ± 5.5 DE (average) (mm) 9.8 ± 3.6 15.8 ± 5.1* 8.9 ± 1.9 12.5 ± 3.4* Data are in median ± SD or median (IQR) or n (%). DE diaphragmatic excursion, E mitral Doppler early peak diastolic velocity, E/Ea the ratio of mitral Doppler inflow velocity to annular tissue Doppler wave velocity, LVEF left ventricular ejection fraction, NI non-intubation, NT-pro-BNP N-terminal-pro-B-type natriuretic peptide, PaCO2 arterial carbon dioxide tension, PaO2/FiO2 the ratio of arterial oxygen tension to fraction of inspired oxygen, RI re-intubation, SBT spontaneous breathing trial. *p < 0.05 (34%) required re-intubation within 1 week. Currently, NIV as an early weaning technique from mechanical ventilation is controversial [13]. NIV can be used to partially improve respiratory muscular fatigue and cardiac dysfunction, but it remains a challenge to correct ineffective cough. Diaphragm function can partially reflect the ability of cough. Therefore, diaphragm ultrasound could partially help identify patients with a high risk for re-intubation. Finally, Spadaro S et al. demonstrated that the diaphragmatic-rapid shallow breathing index (DRSBI) could predict weaning failure with a high sensitivity of 94.1% and a specificity of 64.7%, and the AUC was 0.89 [25]. D-RSBI was a good comprehensive index that could reflect both the diaphragm function and presence Table 6 The parameters of the ROC curve of the predictor of re-intubation within 1 week in the respiratory failure subgroup Variables OR 95% CI P-value Cut-off value AUC Sensitivity Specificity DE (average) after SBT 0.690 0.499-0.953 0.024 ≤ 12.6 0.805 80% 68.4% AUC area under curve, CI confidence interval, DE diaphragmatic excursion, OR odds ratio, ROC receiver operating characteristic curve, SBT spontaneous breathing trial