ORIGINAL ARTICLE

https://doi.org/10.5005/jp-journals-11010-1111
Indian Journal of Respiratory Care
Volume 13 | Issue 2 | Year 2024

Reduced Diaphragmatic Thickness Index in Mechanically Ventilated Patients: Incidence, Risk Factors, and Impact on Weaning Outcome

Debasish Panda¹ https://orcid.org/0000-0003-0798-7728, Suresh Kumar Sundaramurthy² https://orcid.org/0000-0002-6999-8820, Lakshmi Ranganathan³ https://orcid.org/0000-0001-5486-5753, Ramesh Venkataraman⁴ https://orcid.org/0000-0003-1949-3979, Nagarajan Ramakrishnan⁵ https://orcid.org/0000-0001-5208-4013, Raymond Dominic Savio⁶ https://orcid.org/0000-0003-4851-0029

¹Department of Critical Care, Jaiprakash Hospital, Rourkela, Odisha, India

^2–6Department of Critical Care, Apollo Hospitals, Chennai, Tamil Nadu, India

Corresponding Author: Raymond Dominic Savio, Department of Critical Care, Apollo Hospitals, Chennai, Tamil Nadu, India, Phone: +91 80560 51847, e-mail: raymond.savio@gmail.com

Received: 07 January 2024; Accepted: 17 April 2024; Published on: 18 June 2024

ABSTRACT

Background: Diaphragmatic weakness (DW) is common in an intensive care unit (ICU) and diaphragmatic thickness index (DTI) using ultrasound is used as a surrogate marker for DW despite many limitations. This study aims to identify the incidence and risk factors of reduced DTI (≤30%) among patients ventilated for >48 hours and its impact on outcome of first spontaneous breathing trial (SBT).

Materials and methods: Single-center, prospective, observational study, conducted in a tertiary care ICU, over 4 months. Consecutive, eligible patients initiated on mechanical ventilation (MV) upon hospitalization and continued for >48 hours were included. Serial measurements of DTI were done once every 3 days until first SBT. Data pertaining to risk factors for DW and outcome of first SBT were documented.

Results: Ninety-two patients were included in the final analysis of the study. DTI ≤30% was identified in 43.5% of patients. Sepsis on admission (p = 0.02) and use of neuromuscular blocking (NMB) agent infusion (p = 0.028) were significantly associated with reduced DTI. Failure of first SBT was observed in 82.5% of the patients with DTI ≤30%, whereas only 25% of those with DTI ≥31% were unsuccessful [relative risk (RR)—3.3; confidence interval (CI)—2.47–1.34]. Mean DTI was significantly higher among those who succeeded their first SBT (32.9 ± 8.9) vs those who failed (19.32 ± 11.89).

Conclusion: Reduced DTI (≤30%) is common among patients mechanically ventilated for greater than 48 hours. Sepsis on admission and use of NMB agent infusion were identified as significant risk factors. DTI ≤30% was significantly associated with a failed first SBT.

How to cite this article: Panda D, Sundaramurthy SK, Ranganathan L, et al. Reduced Diaphragmatic Thickness Index in Mechanically Ventilated Patients: Incidence, Risk Factors, and Impact on Weaning Outcome. Indian J Respir Care 2024;13(2):95–100.

Source of support: Nil

Conflict of interest: None

Keywords: Diaphragmatic dysfunction, Diaphragmatic thickness index, Diaphragmatic weakness, Mechanical ventilation, Spontaneous breathing trial, Weaning

INTRODUCTION

Diaphragm is one of the important muscles of respiration which contributes to 75% of work of breathing during normal tidal ventilation. This muscle is unique in several ways and is affected by many reasons during critical illness. Recent observations suggest an incidence of diaphragmatic weakness (DW) to the tune of 40–60% in an intensive care unit (ICU). This incidence increases to 60–80% in patients receiving mechanical ventilation (MV).¹

Diaphragmatic weakness has been shown to be a consequence of inactivity or disuse which happens during controlled MV. This specific phenomenon is referred to as the ventilator-induced diaphragmatic dysfunction (VIDD). In addition to this, DW can also be the result of systemic inflammatory response and oxidative stress during sepsis and other risk factors such as malnutrition, hyperglycemia, dyselectrolytemia, use of drugs with neuromuscular toxicity, etc. (ICU-acquired DW).²^-⁴ This has a negative impact on the capacity of respiratory muscles to compensate for a heightened demand during a critical ailment, thereby resulting in respiratory failure and added morbidity and mortality.⁵

Diaphragmatic function is important in determining weaning outcome, and therefore, the recovery from a critical illness.³^-⁸ Therefore early recognition of DW can help optimize treatment strategy and potentially prognosticate patient outcomes.⁹

Many modalities have been evaluated in the recent past to assess DW. These include assessment of ventilator parameters such as maximal inspiratory pressure (MIP), negative inspiratory force (NIF), rapid shallow breathing index (RSBI), and imaging modalities such as diaphragmatic fluoroscopy and diaphragmatic ultrasound. However, to date, the transdiaphragmatic twitch pressure in response to phrenic nerve stimulation continues to remain the gold standard for assessment of DW.¹⁰^-¹² Nevertheless, diaphragmatic ultrasound is evolving as the preferred bedside tool, considering that it is noninvasive, inexpensive, easily available, repeatable, and allows for serial assessments.¹³ Ultrasound-based assessments for diaphragmatic function commonly include diaphragmatic thickness index (DTI), diaphragm excursion (DE), and diaphragm contraction velocity.¹³^-¹⁸ The major drawback of all these measurements is that they are observer dependent and are not standalone markers. Among the three indices used to evaluate DW, DTI has been shown to have the highest specificity and sensitivity.¹⁸ Considerable clinical interest has emerged in identification of DW as this could allow for real-time modification of risk factors where feasible.

Our objectives therefore were to assess the incidence of a reduced DTI of ≤30% in our ICU setting among medical and surgical patients who required invasive MV for greater than 48 hours and until their first SBT, to determine risk factors for DTI ≤30% and observe the impact of reduced DTI (≤30%) on the outcome of first attempt at a spontaneous breathing trial (SBT).

MATERIALS AND METHODS

This was a single-center, prospective, observational study conducted in the 24-bed multidisciplinary critical care unit (MDCCU) of a tertiary care, teaching hospital over a period of 4 months, from February to May 2018 (both inclusive). All consecutive adult patients admitted to the MDCCU and initiated on invasive MV upon hospitalization [either in emergency room (ER) or MDCCU] were screened by the investigator for possible inclusion to the study.

Inclusion Criteria

All consecutive adult patients initiated on MV upon hospitalization (ER or MDCCU) to the study center and who continued to require MV for >48 hours.

Exclusion Criteria

Invasive MV prior to hospitalization.
Known neuromuscular disorder.
Nonvisualization of diaphragm by ultrasonography (USG).
Surgical dressing at site of USG assessment.
Gastric, esophageal, and thoracic surgery.
Patients receiving comfort care.

Data pertaining to demographics, severity of illness [Acute Physiology and Chronic Health Evaluation (APACHE) IV score] and provisional diagnosis of the screened patients were documented. Those patients who had a continued requirement for invasive MV beyond 48 hours and satisfied the inclusion criteria were enrolled for the study and followed up further. Serial USG assessments for DTI were performed in these patients once every 3 days until first SBT. This was carried out only by the primary investigator to avoid any interobserver variability. A DTI of ≤30% was identified as an operational cutoff for possible DW based on previous studies.¹⁸

Additional data such as duration on controlled mechanical ventilation (CMV) in hours, duration of continuous sedation infusion in hours, use of corticosteroids for any reason and duration, use of neuromuscular blocking (NMB) infusion of any duration, use of colistin, and the occurrence of hyperglycemia (described as daily mean blood sugar level ≥200 mg/dL on any single day during study period) were prospectively observed and documented during the study period. The outcome of the first SBT was recorded as either a success or failure based on standard guidelines. Patients were followed up only until the first SBT. All data was sourced from the patient’s active inhospital treatment and monitoring records. The study was approved by the institutional review board and was done following ethical standards.

Mechanical ventilation, weaning, and all other interventions and care process were in accordance to standard operating protocols (SOP) of the unit.

Statistical Analysis

Data for all parameters were analyzed using Statistical Package for the Social Sciences (SPSS) 20.0 (SPSS, IBM, United States). Discrete variables were summarized as percentages and frequencies. Continuous variables were summarized as mean and standard deviation (SD). t-tests were used for the comparison of groups and proportions. Determination of risk factor for a reduction in DTI was carried out employing logistic regression analysis and the results are presented as odds ratio (OR) and corresponding 95% confidence intervals (CIs). A p-value < 0.05 was considered to be statistically significant.

Diaphragm Thickness Index Assessment

Ultrasonography assessment was done in all patients in the semirecumbent position using Sonosite edge (w/L38xi). While the diaphragm can be visualized on both right and left sides, the right side was preferred for measurements because of good acoustic window. Diaphragm was viewed using the linear high frequency probe (5–12 Hz) placed perpendicular to the chest wall in 8th–9th intercostal space between the anterior and midaxillary line (near the zone of apposition of diaphragm to chest wall). Diaphragmatic thickness was measured at end inspiration and at end expiration using M-mode (Fig. 1). The average of three measurements was taken for both inspiratory and expiratory diaphragmatic thickness. All the assessments were done by a single observer to avoid interobserver variation.¹⁹^,²⁰ DTI was calculated using the formula given below:

Fig. 1: M-mode USG showing diaphragmatic thickness assessment in inspiration (A) and expiration (B)

RESULTS

One hundred and fifty-six patients who were intubated and initiated on MV upon hospitalization, during the study period, were screened on the 1st day of ICU stay. Fifty-seven patients required invasive MV for <48 hours. The remaining 99 patients were included in the study. Follow-up was incomplete in seven (four patients died and three were transferred to a different hospital during the study period). Study analysis was completed in 92 patients (Fig. 2). Table 1 presents the baseline characteristics of the patients enrolled.

**Table 1:** Baseline characteristics of study population
Characteristics	Values
Age	56.6 ± 18.9 years
Male:female	56.2:43.8%
Mean APACHE IV score	94.1 ± 28.4
Sepsis on admission	61.9%

Fig. 2: Study flowchart

Reduced DTI of ≤30% was identified in 40 out of 92 (43.5%) patients. The use of CMV for >72 hours, use of continuous sedation for >72 hours, use of NMB agent infusion irrespective of duration, the use of any steroid or colistin irrespective of dose and duration, occurrence of hyperglycemia, severity of illness (APACHE IV score), and presence of sepsis on admission were the risk factors analyzed. An increased risk for reduced DTI was however observed only with sepsis on admission (OR 6, p = 0.02, 95% CI: 1.31–27.6) and the use of NMB infusion (OR 16, p = 0.028, 95% CI: 1.48–211.1) as seen in Table 2.

**Table 2:** Risk factors for DW as operationalized using DTI ≤30%
Variables	Value	p-value	OR	Lower 95% CI	Upper 95% CI
APACHE IV score	94.1 ± 28.4 (mean ± SD)	0.45	1.01	0.99	1.03
Sepsis on admission	61.9%	0.02*	6.04	1.32	27.70
CMV duration >72 hours	38.0%	0.87	1.00	0.98	1.03
Continued sedation >72 hours	35.9%	0.48	1.01	0.98	1.04
NMB infusion used (irrespective of duration)	20.7%	0.03*	16.85	1.34	211.16
Hyperglycemia occurrence	44.6%	0.71	1.25	0.37	4.19
Colistin used	28.3%	0.25	2.81	0.48	16.27
Steroid used	45.7%	0.96	0.97	0.22	4.16

*, significant risk factor for DW (p < 0.05)

Thirty-three patients (82.5%) with DTI ≤30% failed their first SBT, whereas only 13 (25%) with DTI ≥31% failed the first SBT with a relative risk (RR) of 3.3 (p < 0.001; 95% CI 2.47–1.34, Fig. 3). The mean DTI was 19.32 ± 11.89 among patients who failed the first SBT compared to 32.9 ± 8.9 in those who succeeded (p < 0.001) (Fig. 4).

Fig. 3: Diaphragmatic thickness index and SBT failure; *82.5% of the patients with DTI ≤30% failed their first SBT, only 25% of those with DTI ≥31% were unsuccessful with their first SBT (RR—3.3; p < 0.001; 95% CI: 2.47–1.34)

Fig. 4: Spontaneous breathing trial outcome and DTI; *difference in mean DTI was significant (p < 0.001)

DISCUSSION

Diaphragmatic weakness poses an important challenge to the process of liberation from invasive MV and is associated with increased mortality and number of days on MV.²¹^-²³ It can occur any time after intubation, as a direct repercussion of MV or as a consequence of ICU acquired weakness from various factors.²²^,²⁴ There are several means of assessing DW in the ICU and DTI using bedside ultrasound of the diaphragm has emerged as one of the commonly practiced methods for its assessment. Our study intended to analyze the incidence of a reduced DTI (≤30%), its risk factors and the ensuing impact on the outcome of first SBT among patients requiring invasive MV for greater than 48 hours.

In our cohort of patients who were initiated on MV in the hospital and also continued to require the same for >48 hours, reduced DTI of ≤30% was seen in 43.5% (n = 40/92) during the study period. Recent studies using DTI as a surrogate for DW report an incidence of 60–80% among patients requiring MV.²²^,²⁵ The study by Dres et al. concluded that DW in ICU was noticed two times more often than limb weakness. Likewise, Jung et al. reported an 80% prevalence of DW in patients with ICU-acquired weakness and stressed upon the fact that DW was more common than expected.²²^,²³ The possible reasons for a seemingly low incidence in our study could be from the nature of exclusion criteria and the fact that patients were followed up only until the first SBT. The vast majority (67.4%) had their first SBT at <6 days and another 26.1% between days 6 and 9. Of these 40 patients, 40, 47.5, and 12.5% were detected to have a reduced DTI (≤30%) on days 3, 6, and 9, respectively (from initiation of MV).

Among the various risk factors assessed, sepsis on admission (61.9%) and the use of NMB agent infusion (irrespective of duration) were significantly associated with a reduced DTI. Demoule and Amoateng-Adjepong had also demonstrated that sepsis, due to increased inflammatory infiltrates, resulting in diaphragmatic atrophy is a significant risk factor on ICU admission.⁵^,²⁴^,²⁵ Despite the fact that the diaphragm is a muscle that is highly resistant to NMB agents, Cappellini and Schepens had demonstrated that prolonged use of muscle relaxant and MV can result in disuse atrophy of diaphragmatic fibers resulting in DW.²⁶^,²⁷ Although other risk factors such as patient acuity, prolonged hyperglycemia, profound malnutrition, prolonged sedation, longer duration of MV, neurotoxic drugs like colistin, and corticosteroid therapy may lead to muscle weakness in mechanically ventilated patients in the ICU as reported by other studies, a similar association could not be established between these factors and DW (as operationalized with a DTI ≤30%) in our study.¹^,²⁸ The small sample size of our study could be the likely reason behind this inability to elicit an association between such established risk factors and impaired diaphragmatic function.

While 82.5% of the patients detected to have DTI ≤30% had failed their first SBT, only 25% of those with DTI ≥31% failed their first SBT in our study (RR 3.3). Although the relation between ICU-acquired diaphragm weakness and poor subject outcomes are often discussed, this has not been proved unequivocally. Nevertheless, there are several recent studies that are in concurrence with our finding and indicate that diaphragmatic strength could indeed be an important factor that governs weaning duration.²³^,²⁷ Further to this, Supinski and colleagues demonstrated that DW was a stronger predictor of ICU mortality than many other factors that were analyzed in mechanically ventilated patients.²⁹

Several researchers including Jung et al. and Laghi et al. concluded that many patients (up to 44%) can actually be successfully liberated from the ventilator despite the presence of diaphragmatic dysfunction.²²^,²³^,³⁰^-³² In our study, similarly not all patients with DTI ≤30% failed their first SBT. Likewise, some with DTI ≥31% (25%) also failed the first SBT, thus reinforcing the facts that DTI per se is not a fool proof way for the diagnosis of DW and that DW does not always lead to impaired weaning off the ventilator. It should be understood that while DW might limit exercise capacity, it is not the only factor impacting the weaning process. The total respiratory muscle capacity and respiratory load imbalance also contributes to weaning outcomes.⁶^,³³ In fact, the consequence of respiratory muscle dysfunction (including muscles in addition to the diaphragm), following critical illness could be of greater importance as it often correlates with poor outcomes in the long-term.⁸^,³⁴ As a corollary, it is often seen that many patients with chronic diaphragm dysfunction do not require MV.³⁵^,³⁶ Despite these findings, it should be stressed that the presence of a low DTI should not deter us from attempting an SBT.

Conceivably, the mean DTI was higher in those patients who had a successful first SBT (32.9 ± 8.9) vs those who failed (19.32 ± 11.89), with an absolute difference of almost 13 between the groups. Available evidence is in support of our finding. Many researchers including Dres et al. and Ferrari et al. demonstrated that mean DTI was higher by almost 20 (cumulative scores of all trials) in the successful weaning group compared to those in the failed weaning group.²²^,²⁷^,³⁶^-³⁸ Similarly, Jung, Spadaro, and few other researchers documented a greater mean diaphragmatic excursion (DE) in the successful weaning group than among those who failed.²³^,²⁸^,³²^,³⁷^,³⁹ In addition to DTI, there are many more newer USG-based indices that are currently being evaluated to assess respiratory muscle function such as diaphragmatic rapid shallow breathing index (D-RSBI),⁴⁰ assessment of parasternal intercostal muscle thickness fraction (PICTF)⁴¹ and abdominal expiratory muscle thickness pattern.⁴² It would be interesting to see if an integrated USG-based score for prediction of weaning outcomes will soon emerge.

As the ultrasound assessment was done by the same observer with adequate technical skills, we were able to eliminate interobserver variability and ensure reproducibility with measurements, thereby adding strength to the study. However, this research does have certain limitations. Ours was a single-center trial in a tertiary care multidisciplinary ICU and may have limitations in extrapolating the results to other clinical settings. Secondly, although ultrasound technique is easier and economical, assessment of diaphragm function was not done using magnetic impulse for the stimulation of phrenic nerve which is considered the gold standard for this purpose. Lastly, USG-guided assessment of diaphragmatic function was done when patients were on assist control or pressure support modes and not during SBT. This methodology was chosen as it would be practical and less of a strain for sick patients, however, this could underestimate the true incidence DW. We were unable to control for factors such as mode of ventilation and use of sedation and paralytic agents as occurs in a practical situation and therefore its impact on actual incidence cannot be clarified. Another intriguing reality is the interchangeable use of the term diaphragmatic dysfunction and DW, and the assumption of reduced DTI and DE to be an equivalent to DW in literature. While a reduced DTI may signal a diaphragmatic dysfunction, whether this can be labeled as “weakness” remains to be established. We also did not correlate DTI changes with other markers of respiratory muscle strength such as PImax or other weaning parameters. This could have provided us some insights into the clinical relevance of DTI changes. Nonetheless, the findings of our study reinforce the fact that patients with a DTI ≤30% have a high risk of failing their first SBT, prompting preemptive strategies such as appropriate family counseling and extubation to noninvasive ventilation of high flow nasal cannula. This, however, should not discourage from performing an SBT in the absence of other compelling contraindications.

CONCLUSION

A reduced DTI (≤30%) is common among patients who are mechanically ventilated for greater than 48 hours. Sepsis on admission and the use of NMB agents were identified as significant risk factors for reduced DTI. Patients with DTI ≤ 30% have a significantly higher risk of failing their first SBT.

ORCID

Debasish Panda https://orcid.org/0000-0003-0798-7728

Suresh Kumar Sundaramurthy https://orcid.org/0000-0002-6999-8820

Lakshmi Ranganathan https://orcid.org/0000-0001-5486-5753

Ramesh Venkataraman https://orcid.org/0000-0003-1949-3979

Nagarajan Ramakrishnan https://orcid.org/0000-0001-5208-4013

Raymond Dominic Savio https://orcid.org/0000-0003-4851-0029

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