Ultrasound-assessed diaphragmatic dysfunction as a predictor of weaning outcome in mechanically ventilated patients with sepsis in intensive care unit
Ain-Shams Journal of Anesthesiology volume 14, Article number: 18 (2022)
Weaning from mechanical ventilation is one of the most common challenges in the intensive care unit (ICU). Most of predictive indices of weaning from mechanical ventilation are often inaccurate. This study was performed to assess the accuracy of diaphragmatic ultrasonography for predicting weaning outcome in mechanically ventilated patients with sepsis in ICU.
Sixty patients with sepsis in medical ICU were prospectively enrolled. All patients were ventilated in pressure support. Patients underwent a spontaneous breathing trial (SBT) on T-piece when they met all the following criteria: FiO2 < 0.6, PEEP ≤5 cmH2O, PaO2/FiO2 > 200, respiratory rate <30 breaths per minute, absence of fever, alert and cooperative, hemodynamic stability without or with low-dose vasoactive therapy support, and rapid shallow breathing index (RSBI)<105. During the trial, the patient was instructed to perform deep breathing to total lung capacity (TLC) and then exhaling to residual volume (RV) and the diaphragm was visualized in the 8th or 9th intercostal space between anterior and mid-axillary lines using a 3–5-MHz curved ultrasound probe to measure diaphragmatic excursion (DE) and a 7–11-MHz linear ultrasound probe to measure diaphragmatic thickness (DT) at TLC and RV, and the diaphragmatic thickness fraction (DTF) was calculated as percentage from the following formula (thickness at end inspiration—thickness at end expiration)/thickness at end expiration. According to weaning outcome, patients were divided into 2 groups: successful weaning group and weaning failure group. Weaning failure was defined as the inability to maintain spontaneous breathing for at least 48 h, without any form of ventilatory support.
In the present study, right DTF of more than 37% and DE during deep breathing of more than 6.1 and 5.4 cm on the Rt and Lt side, respectively, were associated with successful weaning from MV. In the study, the sensitivities for right and left DE and DTF were 58.33, 62.5, and 58.33%, respectively, and the pooled specificities were 83.33, 83.33, and 100%, respectively, with p value = 0.032, 0.028, and 0.001, respectively. The area under curve (AUC) for Rt, Lt DE, and DTF were 0.701, 0.712, and 0.840, respectively. The present data indicate a satisfactory diagnostic accuracy in predicting extubation outcome.
Ultrasonography-based determination of diaphragm function by assessing DTF and DE can be used as predictor of weaning outcome in mechanically ventilated patients with sepsis.
Diaphragm is the primary muscle of respiration. Its dysfunction is characterized by decrease of diaphragm thickness and inadequate diaphragmatic contractility. From a clinical perspective, diaphragmatic dysfunction contributes to difficult weaning or even failure to wean from mechanical ventilation in ICU patients. Overall, data indicate that weaning failure may affect up to 25% of mechanically ventilated patients in ICU (McCool & Tzelepis, 2012).
Many factors contribute to this intriguing problem in ICU apart from inactivity by mechanical ventilation, including inflammation, malnutrition, the use of certain pharmacological agents, and the existence of neuromuscular syndromes prior to ICU admission have been reported to influence diaphragm dysfunction as well (Doorduin et al., 2013).
Limited previous literature suggests an association between sepsis and diaphragm dysfunction as a consequence of both functional and morphological damages. Sepsis is associated with preferential loss of diaphragm volume compared with the psoas muscle and associated with a lower diaphragm contractile force (Jung et al., 2014).
Bedside sonographic evaluation of the motion of the diaphragm dome (diaphragmatic excursion) has shown to be useful in predicting extubation outcomes; however, factors such as tidal volume, proximity of rib cage, and abdominal organs may affect diaphragm motion (Kim et al., 2011).
Recently, it has been suggested that ultrasound measurements of diaphragm muscle thickening in inspiration during weaning could provide an estimation of extubation success. This non-invasive, low-cost, and fast to perform technique seems to predict with a good accuracy the extubation failure (Zanforlin et al., 2014).
Aim of the present study is to assess whether the degree of diaphragm excursion and diaphragm thickness fraction measured by ultrasound during a weaning trial may be used to predict outcome of weaning from mechanical ventilation in patients with sepsis in intensive care units. Primary outcome is successful weaning from mechanical ventilation, and secondary outcomes are need for tracheostomy and mortality rate.
This is a prospective observational study was held in medical intensive care unit and started from April 2021 till May 2021. Patient informed written consent from legal guardian, Local Ethical Committee approval (FMASU MD 44/2019) and Clinical Trial Registration (ClinicalTrials.gov ID: NCT04825509) were obtained before patient’s allocation.
Adult patients of both sexes, age between 18 and 60 years old, in sepsis according to the new sepsis definition in 2016 (life-threatening organ dysfunction due to a dysregulated host response to infection), hemodynamically stable without or with low-dose support till 0.05 μg/kg/min noradrenaline and on mechanical ventilation for at least 48 h and not more than 1 week.
Criteria for weaning protocol include fully conscious patients, on CPAP mode (PEEP 3–5 CmH2o, pressure support <15 CmH2O, FiO2 less than 60%, respiratory rate < 35 breath/min, PO2/FiO2 > 200, RSBI is < 105).
Patients who had any of these criteria were excluded from our study: patients with neuromuscular disorders, pregnant females in the second and third trimester, and patients with tense ascites or morbidly obese with body mass index more than 40 kg/m2.
When weaning criteria were reached, patients were disconnected from mechanical ventilation and a spontaneous breathing trial (SBT) on T-piece was attempted for 2 h administering supplemental oxygen to achieve peripheral oxygen saturation (SpO2) >94%. Then, diaphragmatic excursion (DE) was measured on both sides and diaphragmatic thickness (DT) was measured on right side during the SBT 30 min after patient was on T-piece. Diaphragmatic thickness fraction (DTF) was calculated as follow: thickness at end inspiration—thickness at end expiration)/thickness at end expiration. Clinicians in charge of the patient’s care were blinded to ultrasound measurements.
The SBT was considered successful when the patient succeeds to pass 120 min without the appearance of any of the following termination criteria: change in mental status, onset of discomfort, diaphoresis, respiratory rate (RR) >35 breaths/min, hemodynamic instability (heart rate >140, systolic blood pressure >180 or <90 mmHg), or signs of increased work of breathing. Failure of weaning was considered when patient needed MV during SBT and patient was reintubated and ventilated or needed non-invasive ventilation (NIV) within 48 h.
According to weaning outcomes, we had 2 groups, one group with successful weaning and the other group with weaning failure.
Transthoracic ultrasonography was performed at the bedside with a PHILIPS HD5 release 2.1 (distributed by PHILIPS healthcare, Bothell, WA, USA) @2011Koninklijke Philips N.V. All rights reserved.
Ultrasonography was done while patient was on T-piece during SBT 30 min after disconnecting mechanical ventilation. The examination was performed in both B- and M-modes. All examinations were carried out with patients in the supine position. The measurements were done by placing the transducer perpendicular to the chest wall or with angle not less than 70o according difficulty of the case, in the eighth or ninth intercostal space, between the anterior axillary and the midaxillary lines. The liver was identified as a window for right hemidiaphragm and the spleen was identified as a window for left hemidiaphragm. The ultrasound probe was placed in the direction in which the ultrasound beam reached the posterior third of the corresponding hemidiaphragm perpendicularly. In most of the cases this can be achieved by directing the US landmark medially, cranially, and dorsally.
The diaphragmatic excursion (DE) or displacement was measured in M-mode using a 1- to 5-MHz ultrasound curved transducer during maximal breathing (Fig. 1). During maximal inspiration, the normal diaphragm moved caudally toward the ultrasound transducer, which was recorded as an upward motion of the M-mode tracing. The amplitude of diaphragmatic excursion was measured as the point of maximal height of the diaphragm (white thick line covering the liver) in the M-mode tracing to the base line [the vertical distance expressed in cm]. We obtained diaphragmatic ultrasound values from three consecutive maximal breaths on the right side and three on the left side, and the average values on each side were used for analysis.
Diaphragmatic thickness (DT) was subsequently measured at the zone of apposition (ZOA), which is the area of the diaphragm attached to the rib cage, at both end of maximal inspiration or total lung capacity (TLC) and end of maximal expiration or residual volume (RV) using a high frequency 7–11 MHz ultrasound linear transducer in M-mode (Fig. 2). The diaphragm in the ZOA presents itself as a hypoechoic layer between two hyperechoic bright and parallel lines, which represent the pleural and peritoneal membranes. The ZOA is located 0.5–2 cm below the costophrenic sinus. The costophrenic sinus can be seen as a transition zone between the lungs cranially, identified by specific artifacts (A lines if well aerated), and the liver or the spleen caudally. We obtained diaphragmatic ultrasound values from six consecutive maximal breaths, and the average values were used for analysis. On each frozen M-mode image, the diaphragm thickness was measured from the middle of the pleural line to the middle of the peritoneal line. Then, the diaphragmatic thickening fraction (DTF) was calculated as percentage from the following formula:
[Thickness at end inspiration − thickness at end expiration]/thickness at end expiration
Sixty-six patients were included in our study. Sample size was calculated using SATA program, setting the type-1 error (alpha) at 0.05 and the power (1beta) at 0.8. Results from previous study (Fayed et al., 2016) showed that diaphragmatic excursion by US had sensitivity of 83.3% and a specificity of 85.4% in prediction of successful weaning in about 70% of cases. Calculation according to these values produced minimal sample size of 50 cases.
Data were collected using Epi Info statistical software (Centers for Disease Control and Prevention, Atlanta, GA, USA) and analyzed using R version 2.15.0 (R Development Core Team: http://www.R-project.org). Data were presented as mean (SD) or median [interquartile range] when appropriate. Descriptive statistics are shown for both the whole cohort and the subgroups of interest. Differences of continuous variables between the subgroups for the independent variable were assessed by non-parametric tests. The χ2 test, with Fisher’s correction when appropriate, was used for comparisons among categorical variables. Receiver operating characteristic (ROC) curve analysis was performed to assess DE and DTF ability to discriminate between patients who succeeded weaning and those who failed. The Spearman coefficient was used to evaluate correlations. A two-tailed p value of less than 0.05 was taken to indicate statistical significance.
During the study period, 66 patients were planned to be included in the study. Two patients had unplanned extubation and four patients had SBT on a mode other than T-piece. The remaining 60 patients were analyzed. Of these, 48 had a successful weaning while the remaining 12 failed weaning from MV within 48 h from SBT (Fig. 3).
Table 1 summarizes the main clinical-demographic characteristics of the population enrolled in the study. Ultrasound examination was feasible in all patients, including those with body mass index >30. On occasion, the presence of pleural effusion or parenchymal lung consolidation did not affect the quality of ultrasound studies targeted to diaphragm evaluation.
There was no statistically significant difference between the two groups regarding age and sex while there was statistically significant increase in BMI, qSOFA score on admission and days of mechanical ventilation in weaning failure group than successful weaning group.
A significant difference in DTF was observed between successful weaning and weaning failure groups (Fig. 4). A ROC curve was used to assess the diagnostic accuracy of DTF (Fig. 5) and DE (Fig. 6) in predicting weaning success. As regards DTF, cutoff value >37% was associated with a successful spontaneous breathing test with a sensitivity of 58.33%, specificity of 100.0%, and area under curve (AUC) of 84.0%.
As regards DE, the best cutoff point for Lt DE to differentiate between successful and failure weaning was > 5.4 with sensitivity of 62.5%, specificity of 83.33%, and area under curve (AUC) of 71.2% while for Rt DE the best cutoff point for Lt DE to differentiate between successful and failure weaning was > 6.1 with sensitivity of 58.33%, specificity of 83.33%, and AUC of 70.1%.
In continuation of many previous studies on the usefulness of the US assessment of the diaphragm as a tool to predict weaning from mechanical ventilation, this study was done for patients with sepsis requiring mechanical ventilation who were planned for discontinuation of mechanical ventilation. The study was conducted upon 60 mechanically ventilated patients (18 females and 42 males), mean age of 46.73 years and mean of BMI 25.80 kg/m2, were admitted to the MICU with sepsis.
In the present study, as regards successful weaning group, the number of patients with successful weaning from mechanical ventilation was 48 out of 60 patients (80%), while the number of patients with failure of weaning from mechanical ventilation was 12 out of 60 patients (20%). This is consistent with (Osman & Hashim, 2017), Esteban and his colleagues (Esteban et al., 1995), Saeed and his colleagues (Saeed et al., 2016), and Baess and his colleagues (Baess et al., 2016), who showed failure rate about 26.5%, 27%, 26.7%, and 23.3%, respectively. This is in contrast with Ferrari and his colleagues (Ferrari et al., 2014) who reported 63% failure rate. This is explained by different causes for mechanical ventilation as well as different ventilation periods before starting weaning process; in addition to the selected population with Ferrari as he did the study with different population.
In this study, DT at TLC and at RV were not significant as weaning predictors—this is mostly because the diaphragm is heterogeneous across its surface (Poole et al., 1997); accordingly, the placement of the probe must be standardized to minimize to measurement variability. We tried to overcome this problem by standardization of measurements through carrying out the US examination for all patients in supine position and placing the transducer perpendicular to the chest wall or with angle not less than 70o in the eighth or ninth intercostal space between the anterior axillary and the mid-axillary lines and get the measurements at the zone of opposition.
The present study found that a right DTF of more than 37% had better accuracy for predicting weaning successfulness. This result is consistent with the studies from (Ferrari et al., 2014; DiNino et al., 2014), and (Dube et al., 2017) which demonstrated that right DTFs of more than 36, 30, and 29%, respectively, were associated with weaning success and better ICU outcomes.
There were no studies measuring DE during deep breath to assess successful weaning from MV. All studies we found were measuring DE during tidal breath, of these studies, Ali and Mohamad (2016), Baess et al. (2016), and Saeed et al. (2016), which demonstrated that DE during tidal breathing of more than 1.5, 1, and 1.1 cm, respectively, were associated with successful weaning from MV. However, many studies were done to measure DE during deep breath in healthy population to diagnose diaphragmatic dysfunction, of these studies, Kantarci et al. (2004) and Scarlata et al. (2018), which demonstrated that DE during deep breathing of less than 4.2 and 5.47 cm were associated with diaphragmatic dysfunction. In our study, DE during deep breathing of more than 6.1 and 5.4 cm on the Rt and Lt side respectively were associated with successful weaning from MV.
In the present study, the sensitivities for right and left DE and DTF were 58.33, 62.5, and 58.33%, respectively, and the pooled specificities were 83.33, 83.33, and 100%, respectively. The ROC curve and the AUC were used to assess the overall diagnostic performance. The AUC for Rt, Lt DE, and DTF were 0.701, 0.712, and 0.840, respectively. Our data indicate a satisfactory diagnostic accuracy in predicting extubation outcome.
In agreement with other studies, the duration of mechanical ventilation before weaning was statistically significant with DE, DTF, and weaning outcome (Table 2), meaning, the longer duration of mechanical ventilation days, the less DE and DTF, the more probability of weaning failure, the more probability of need for tracheostomy and mortality (Kim et al., 2011; Jiang et al., 2004).
In conclusion, ultrasonography-based determination of diaphragm function by assessing diaphragmatic thickness fraction and diaphragmatic excursion can be used as a predictor of weaning outcome in mechanically ventilated patients with sepsis. It is a useful, feasible, non-invasive, bed side technique for ruling out severe diaphragmatic dysfunction.
Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Intensive care unit
Spontaneous breathing trial
- FiO2 :
Fraction of inspired oxygen
Positive-end expiratory pressure
- PaO2 :
Partial arterial oxygen tension
Rapid shallow breathing index
Total lung capacity
Diaphragm thickness fraction
Area under curve
- SPO2 :
Peripheral oxygen saturation
Zone of apposition
Receiver operation characteristic curve
Body mass index
Positive predictive value
Negative predictive value
Ali ER, Mohamad AM (2016) Diaphragm ultrasound as a new functional and morphological index of outcome, prognosis and discontinuation from mechanical ventilation in critically ill patients and evaluating the possible protective indices against VIDD. Egypt J Chest Dis Tuberc 66(2):339–351. https://doi.org/10.1016/j.ejcdt.2016.10.006
Baess A, Abdallah TH, Emara DM (2016) Diaphragmatic ultrasound as a predictor of successful extubation from mechanical ventilation thickness, displacement, or both. Egypt J Bronchol 10(2):162–166. https://doi.org/10.4103/1687-8426.184370
DiNino E, Gartman EJ, Sethi JM, McCool FD (2014) Diaphragm ultrasound as a predictor of successful extubation from mechanical ventilation. Thorax 69(5):423–427. https://doi.org/10.1136/thoraxjnl-2013-204111
Doorduin J, van Hees HW, van der Hoeven JG, Heunks LM. Monitoring of the respiratory muscles in the critically ill. Am J Respir Crit Care Med. 2013;187(1):20–7. https://doi.org/10.1164/rccm.201206-1117CP.
Dube BP, Dres M, Mayaux J, Demiri S, Similowski T, Demoule A (2017) Ultrasound evaluation of diaphragm function in mechanically ventilated patients: comparison to phrenic stimulation and prognostic implications. Thorax 72(9):811–818. https://doi.org/10.1136/thoraxjnl-2016-209459
Esteban A, Frutos F, Tobin MJ, Alía I, Solsona JF, Valverdú I, Fernández R, de la Cal MA, Benito S, Tomás R, et al. A comparison of four methods of weaning patients from mechanical ventilation. Spanish Lung Failure Collaborative Group. N Engl J Med. 1995;332(6):345–50. https://doi.org/10.1056/NEJM199502093320601
Fayed AM, Barakat MS, Zakaria EM (2016) Diaphragmatic dysfunction evaluation using ultrasonography as a predictor of weaning for patients with acute exacerbation of chronic obstructive pulmonary disease from mechanical ventilation. JMSCR 4(6):10950–10956. https://doi.org/10.18535/jmscr/v4i6.44
Ferrari G, De Filippi G, Elia F, Panero F, Volpicelli G, Apra F (2014) Diaphragm ultrasound as a new index of discontinuation from mechanical ventilation. Crit Ultrasound J 6(1):8–9. https://doi.org/10.1186/2036-7902-6-8
Jiang J-R, Tsai T-H, Jerng J-S, Yu C-J, Wu H-D, Yang P-C (2004) Ultrasonographic evaluation of liver/spleen movements and extubation outcome. Chest 126(1):179–185. https://doi.org/10.1016/S0012-3692(15)32912-3
Jung B, Nougaret S, Conseil M (2014) Sepsis is associated with a preferential diaphragmatic atrophy: a critically ill patient study using tridimensional computed tomography. Anesthesiology 120(5):1182–1191. https://doi.org/10.1097/ALN.0000000000000201
Kantarci F, Mihmanli I, Demirel MK, Harmanci K, Akman C, Aydogan F (2004) Normal diaphragmatic motion and the effects of body composition: determination with Mmode sonography. J Ultrasound Med 23(2):255–260. https://doi.org/10.7863/jum.2004.23.2.255
Kim WY, Suh HJ, Hong SB, Koh Y, Lim CM (2011) Diaphragm dysfunction assessed by ultrasonography: influence on weaning from mechanical ventilation. Crit Care Med 39(12):262–730. https://doi.org/10.1097/CCM.0b013e3182266408
McCool FD, Tzelepis GE (2012) Dysfunction of the diaphragm. N Engl J Med 366(10):932–942. https://doi.org/10.1056/NEJMra1007236
Osman A, Hashim R (2017) Diaphragmatic and lung ultrasound application as new predictive indices for the weaning process in ICU patients. Egypt J Radiol Nuclear Med 48(1):61–66. https://doi.org/10.1016/j.ejrnm.2017.01.005
Poole DC, Sexton WL, Farkas GA (1997) Diaphragm structure and function in health and disease. Med Sci Sports Exerc 29(6):738–754. https://doi.org/10.1097/00005768-199706000-00003
Saeed A, El Assal G, Ali T (2016) Role of ultrasound in assessment of diaphragmatic function in chronic obstructive pulmonary disease patients during weaning from mechanical ventilation. Egypt J Bronchol 10(2):167–172. https://doi.org/10.4103/1687-8426.184363
Scarlata S, Mancini D, Laudisio A, Benigni A, Antonelli Incalzi R (2018) Reproducibility and clinical correlates of supine diaphragmatic motion measured by M-mode ultrasonography in healthy volunteers. Respiration 96(3):259–266. https://doi.org/10.1159/000489229
Zanforlin A, Bezzi M, Carlucci A, DI Marco F. Clinical applications of diaphragm ultrasound: moving forward. Minerva Med. 2014;105(5 Suppl 1):1–5.
Ethics approval and consent to participate
Approval of research ethical committee of Faculty of Medicine, Ain-Shams University, was obtained (code number: FMASU M D 44/2019) and written informed consent from all the participants’ guardians was obtained.
Consent for publication
Prof Ahmed Nagah El-Shaer is a co-author of this study and the Executive Editor for the journal. He declares a competing interest for this submission. He has not handled this manuscript. The rest of the authors have no conflict of interest to declare.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Saad, M.A., Nashed, S.W., El-Shaer, A.N. et al. Ultrasound-assessed diaphragmatic dysfunction as a predictor of weaning outcome in mechanically ventilated patients with sepsis in intensive care unit. Ain-Shams J Anesthesiol 14, 18 (2022). https://doi.org/10.1186/s42077-022-00211-8