European Journal of Cardiovascular Medicine

Global initiative for chronic obstructive lung disease 2023 defines chronic obstructive pulmonary disease (COPD) as a heterogeneous lung condition characterized by chronic respiratory symptoms as dyspnoea, cough, expectoration, and exacerbations, due to abnormalities of the airways (bronchitis, bronchiolitis) and/or alveoli (emphysema) that cause persistent, often progressive, airflow obstruction.^1,2 Chronic obstructive pulmonary disease (COPD), a common chronic respiratory disease, has become the third leading cause of death and is one of the most serious public health problems worldwide.^{3, 4} Recent research indicates that dynamic pulmonary hyperinflation and intrinsic positive end-expiratory pressure are the most crucial mechanical respiratory alterations observed in COPD patients experiencing respiratory failure.^{5, 6}

In individuals with acute exacerbations of COPD (AECOPD), these two mechanical respiratory abnormalities become even more pronounced, leading to a notable increase in oxygen consumption and the respiratory workload on patients, surpassing the effective compensatory ability of respiratory muscles like the diaphragm.^7,8 This situation can result in varying degrees of hypoxemia and hypercapnia, ultimately culminating in type II respiratory failure.^{9, 10} Therefore, evaluating diaphragm functionality is essential for the diagnosis and management of AECOPD.^{11, 12} If it is not addressed promptly respiratory failure poses a significant threat to the patient's life.

Currently, beyond standard treatments such as infection control, antispasmodic medications, cough relief, and mucus clearance, adequate respiratory support is a critical component of AECOPD therapy.¹³

Mechanical ventilation establishes a pressure difference between the airway opening and the alveoli to keep the airway open, thereby improving oxygenation and reversing hypoxia and carbon dioxide retention in the body. Mechanical ventilation is two types: Invasive ventilation & non-invasive ventilation. Invasive ventilation can rapidly correct hypoxemia and hypercapnia, but it may also have unavoidable complications, such as ventilator-associated pneumonia and pneumatic injuries, and will bring a huge economic burden to the patients.^{14, 15} Non-invasive ventilation can provide patients with double-level pressure support and reduce the work of breathing. Meanwhile, it can avoid lung injury and infection caused by invasive ventilation to the greatest extent.

However, in clinical application 20% of patients cannot tolerate the treatment due to the occurrence of adverse reactions such as man-machine incordination, poor sputum drainage, suppressed fear, flatulence, and facial pressure sores.^{16 Patients} with severe hypoxia requiring non-invasive ventilation (NIV) are at risk of diaphragmatic impairment, which can negatively impact outcomes, potentially leading to the need for invasive mechanical ventilation.

Ultra-sonography (USG) has been widely used in various studies to assess the functionality of the diaphragm and assist in predicting outcomes for patients with NIV.^{14, 15}

Recent studies have indicated that utilizing USG to assess the diaphragm-related rapid shallow breathing index for guiding the weaning process of ICU patients from ventilators has yielded significant findings. It can serve as an early indicator for the necessity of discontinuing non-invasive ventilators in cases of AECOPD and also in  evaluating  patient prognosis to help prevent or mitigate the advancement of the condition.¹⁷ However, there is very few literature discussing the predictive value of USG indicators concerning mechanical ventilation therapy; thus, we have taken  this study to observe  how ultrasound-assessed diaphragmatic impairment (DI) can predict the need for invasive mechanical ventilation (IMV) in patients undergoing treatment with non-invasive ventilation (NIV) and also its impact on duration of IMV days, length of ICU stay and outcome.

This prospective observational study was approved by the Institutional Ethical committee, B.L.D.E university (BLDE (DU)/IEC/949/2023-24). Written informed consent was taken from all patients before recruitment into the study. The study was conducted from April 2023 to November 2024 in the ICU at Shri B.M. Patil medical college, Hospital and Research Centre. It included patients of either gender admitted to the ICU with acute exacerbation of chronic obstructive pulmonary disease and excluded the patients with neuromuscular diseases, chest wall deformities, diaphragmatic palsy and contraindications to NIV.

Patients admitted to ICU with suspected Acute exacerbation of COPD, were assessed for enrolment in the study. Clinical assessment and Arterial blood gases (ABGs) were performed on admission and then hourly or earlier until stabilization or worsening clinical parameters.

Ultra-sound assessment of the diaphragm was performed after starting NIV under the guidance of critical care physician. Motility of the diaphragm were assessed using a Sonosite with a 7-13MHz linear probe to assess the diaphragm at the zone of apposition, between the 8th and 10th intercostal space in the mid-axillary or anterior axillary line, 0.5–2 cm below the costophrenic sinus. Measurements were performed with the patient in supine position at an average inclination of 45 degrees. Two parallel echogenic layers identified at a depth of 1.5–3 cm, the superficial one being parietal pleura and the deeper layer being peritoneum.

The diaphragm is the less echogenic structure in between these two lines. This approach was utilized to assess diaphragmatic thickness (DT) and thickening with inspiration, in B-mode. The thickness of the diaphragm was measured bilaterally at the end of   inspiration and end-expiration. Measurements were performed three times on both sides of the diaphragm, and the best value were recorded. The change in diaphragmatic thickness (ΔTdi) during spontaneous breathing from functional residual capacity (FRC) to tidal volume (Vt) is called diaphragmatic thickness fraction (DTF). It was calculated using the formula: (end-inspiratory DT – end expiratory DT)/end expiratory DT × 100). Non-invasive mechanical ventilation (NIV) was started and set by an ICU physician.  NIV was delivered and then discontinued based on fulfilment of weaning criteria and clinical judgment. Patients were monitored and NIV gradually discontinued when there was a general improvement in the patient’s condition with RR < 25/minute, pH > 7.35, SpO2 > 90%, and FiO2 < 0.3. Switching to IMV was performed at any time by the attending physician and diaphragmatic assessment of these patients according to these indications: respiratory arrest, persistent or severe respiratory distress (respiratory pauses or gasping for air, massive aspiration, or life-threatening hypoxemia), deterioration of pH, persistent respiratory acidosis despite NIV, worsening neurologic status (deteriorating GCS or agitation), intolerance to NIV, and hemodynamic instability (without response to fluids and vasoactive drugs or severe ventricular arrhythmias)  were observed .¹⁸

Sample size calculation:

With anticipated Proportion of successful cases of NIV 60%¹⁹, the study would require a sample size of 95 patients with 95% level of confidence and 10% absolute precision.

Statistical analysis:

Data was collected by using a structured proforma. Data was entered in MS excel sheet and analysed by using SPSS 24.0 version IBM USA. Qualitative data was expressed in terms of proportions. Quantitative data was expressed in terms of Mean and Standard deviation. Association between two qualitative variables was seen by using Chi square/ Fischer’s exact test. Comparison of mean and SD between two groups was done by using unpaired t test to assess whether the mean difference between groups is significant or not. ROC curve analysis for prediction of need of invasive mechanical ventilation (IMV) based on diaphragm thickness fraction. Validity of diagnostic test was seen with calculation of sensitivity and specificity. A p value of <0.05 was considered as statistically significant whereas a p value <0.001 was considered as highly significant.

We included total 95 patients admitted to ICU with suspected acute exacerbation of COPD, were assessed for enrolment in the study. Demographic data of patients regarding Age, Gender, Comorbid conditions, Precipitating factors, GCS and Respiratory rate between the groups with DI and No DI were found to be insignificant. (Table 1)

Table 1 Demographic parameters

Data is represented by Mean ± SD, Numbers & Percentage, p = < 0.05 is significant

DI- Diaphragmatic Impairement, DM- Diabetes Melliteus, HTN- Hypertension, IHD- Ischemic heart disease, CKD- Chronic kidney disease, DHF- Diastolic heart failure, ACS- Acute coronary syndrome, GCS- Glassgow coma scale, ICU – Intensive Care Unit

Figure 1 shows the agreement (sensitivity and specificity) data after plotting Receiver Operating Characteristic (ROC) curve for Diaphragm Thickness Fraction (DTF) to predict the need of IMV after NIV failure in the patients. On the right side, cut-off value of DTF (< 31.88%) will give 100% sensitivity and 20.9% specificity to predict the need of IMV. On the Left side, cut-off value of DTF (< 28.22%) will give 100% sensitivity and 20.9% specificity to predict the need of IMV.

Figure 1. ROC curve analysis for prediction of need of invasive mechanical ventilation (IMV) based on diaphragm thickness fraction

Table 2 shows the association between DTF and MV. Use of invasive mechanical ventilation was done in 43 patients. Out of 43 patients that were put on IMV support, 34 patients were below the cut-off value. Whereas, 9 patients were above the cut off value. All the 52 patients, who got successfully weaned off from NIV were above the cut-off value.

Table 2. Diaphragmatic thickness fraction and requirement of mechanical ventilation

Data is represented by numbers and percentage. p value <0.05 is considered significant.

Right & left Diaphragmatic thickness fraction is in percentages. IMV- Invasive mechanical ventilation, NIV- Non-invasive mechanical ventilation

Table 3. shows the mean duration of IMV in deceased (34) and survived patients (9) were 8.56+/-2.11 and 2.78+/-0.83 days respectively and it is statistically significant. It indicates that the people with severe diaphragmatic impairment required IMV for many days

Table 3 Duration of invasive ventilation with respect to outcome

Data is represented by Numbers, Mean ± SD, p value < 0.05 is considered significant

Table 4. shows the mean duration of ICU stay in patients with DI and no DI were 9.95± 2.46 vs 5.37 ± 1.17 days and it is statistically significant. With regards to outcome, all patients with no DI survived. In patients with DI, 9 survived and 34 patients were deceased. The outcome of the patients was clinically significant.

Table 4. Duration of ICU stay and Outcome

Data is represented by Numbers, Mean ± SD, p value < 0.05 is considered significant

In our study, demographic parameters included Age, Gender, comorbid conditions, glassgow coma scale, respiratory rate were not statistically significant in both the groups. (Table 1)  

In our study, ROC curve analysis for prediction of need of invasive mechanical ventilation showed the DTF cut-off on right and left side of diaphragm as 31.88% and 28.2%.(Figure 1) We observed out of 43 patients that required IMV, 34 patients were below the DTF cut-off and 9 patients were above the DTF cut-off value. It showed there was a significant association between IMV and DTF cut-off values (< 0.05).(Table 2) Amr Abdalla Elsayed et al. in their study  to predict the need of IMV in AECOPD showed, the cut-off values of DTF on the right and left side as <29% and <26%.¹⁹ Qian et al. conducted a study to predict the weaning outcome from MV based on ultrasound assessment of diaphragmatic dysfunction. They concluded that both diaphragmatic excursion and DTF showed good diagnostic performance of predicting weaning outcomes. They showed DTF% cut-off values of successful and failed ventilation groups as 24.18+/-3.02 and 19.12+/-3.18.²⁰ Antenora et al. conducted a study to assess the clinical consequence of diaphragmatic dysfunction using USG in patients with AECOPD. They reported that NIV failure was found to be strongly associated with diaphragmatic dysfunction (p < 0.001, R2 = 0.27).²¹ Marchioni et al. in their prospective observational study assessed diaphragmatic impairment of AECOPD patients to predict the outcome on NIV. They conclude that there is a high risk of NIV failure and mortality if they had diaphragmatic dysfunction as assessed by USG.²² Kheir M et al. conducted a systematic review to compare ultrasonographic methods and their utility in predicting NIV outcomes. They reported that DTF of less than 20% was associated with NIV failure requiring invasive mechanical ventilation with a sensitivity of 80-84.6% and specificity 76.3-91.5%.²³

The mean duration of IMV in patients with DTF cut-off value below and above was 8.56+/-2.11 and 2.78+/-0.83 days.(Table 3) It shows that patients with severe diaphragmatic impairment were put on IMV for more days compared to the patients with mild or moderate diaphragmatic impairment. Amr Abdalla Elsayed et al^.  in his study showed that patients with diaphragmatic impairement showed longer mechanical ventilatory days compared to patients with no diaphragmatic impairement. (14.25+/-2.8 vs 6.38+/-1.90 days).¹⁹ Marchioni et al in their prospective observational study showed that patients with diaphragmatic dysfunction showed longer mechanical ventilatory days compared to patients with no diaphragmatic dysfunction. (16 vs 8 days).²² Antenora et al conducted a study to assess the clinical consequences of diaphragmatic dysfunction (DD) using USG in patients with AECOPD. They found that patients with DD have prolonged mechanical ventilation (p = 0.023, R2 = 0.15).²¹

We observed that, the mean duration of ICU stay in patients with DI and without DI were 9.95+/-2.46 and 5.37+/-1.17 days respectively. It shows that people with diaphragmatic impairement had significantly longer length of ICU stay (p<0.05). (Table 4) Amr Abdalla Elsayed et al in his study showed that, patients with diaphragmatic impairement showed longer ICU stay compared to patients with no diaphragmatic impairement. (15.8+/-3.1 vs 10.98+/-2.67 days)^19. Marchioni et al in their study showed that, patients with diaphragmatic dysfunction showed longer ICU stay compared to patients with no diaphragmatic dysfunction. (17 vs 12 days).²² Antenora et al. conducted a study on the prevalence and clinical consequences of diaphragmatic dysfunction (DD) using USG in patients with AECOPD. They found that patients DD had longer ICU stay. (p = 0.02, R2 = 0.13).²¹

We observed that out of 43 patients that were put on IMV due to diaphragmatic impairement, 34 patients got deceased and 9 patients got weaned. We observed statistically significant association between IMV and outcome in our study (p<0.05).(Table 4) It shows as the severity of DI increases; patients will have bad prognosis. Amr Abdalla Elsayed et al. showed that, “patients with diaphragmatic impairment showed higher 28-day mortality rate compared to the patients with successful NIV.¹⁹ Marchioni et al. showed that, patients with diaphragmatic dysfunction showed higher mortality compared to patients with no diaphragmatic dysfunction (10 vs 6).²²

 Limitations

USG assessment of diaphragm is a subjective technique requires lot of training. We did not compare with existing gold standard methods for diaphragm assessment like transdiaphragmatic pressure and electromyography. As, these methods are invasive and expensive.

We conclude that ultra-sound assessed Diaphragmatic thickness fraction is a good indicator in determining the diaphragmatic impairment and predicting the need for invasive mechanical ventilation in AECOPD patients with 100% sensitivity and 20.9% specificity. DI as assessed by DTF can be used as a prognostic factor for determining Invasive Mechanical Ventilatory days, ICU stay and Outcome of the patient.

Conflict of interest: Nil

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