Evaluation of diaphragm thickness to predict intubation requirement and mortality in critical COVID-19 patients

Discussion

Despite the decrease in mortality rates thanks to vaccination programs, the COVID-19 pandemic has not ended yet, and its impact continues. Therefore, identifying risk factors during ICU admission is crucial to prevent adverse outcomes in critical cases. In this study, we evaluated DT on thorax CTs obtained at ICU admission in critical COVID-19 cases and observed that low DT was associated with high MV requirement and mortality. Thorax CT is commonly used to evaluate lung parenchymal involvement in COVID-19 before ICU admission, but DT is not routinely examined in these CT scans. Evaluating the diaphragm, which is the major muscle of respiration, can prove valuable in predicting poor prognosis at an early phase.

Diaphragm thickness can decrease due to various reasons, and invasive MV requirement is higher among patients with low DT due to insufficient respiratory compensation.⁹ Although low DT is not a direct diaphragmatic pathology, increased respiratory workload could disrupt ventilation. A study evaluating respiratory muscles and the diaphragm reported a DT of 4.1-4.4 mm in healthy adults.¹¹ Our analysis of the ability to predict DT revealed a cut-off value of 3.35 mm (95% CI, sensitivity 75.00, specificity 57.89) for invasive MV requirement and 3.275 mm (95% CI, sensitivity 72.00, specificity 61.36) for mortality. Therefore, assessing DT at ICU admission can enable prompt detection of patients who might benefit from close monitoring and early intervention. Furthermore, actions to counteract sarcopenia, application of respiratory physiotherapy, and optimization of nutrition to prevent diaphragm dysfunction can prevent adverse outcomes. In a study evaluating the value of DT to predict reintubation in extubated ICU cases, Ni et al¹² reported that a value of ≥1.55 mm decrease in DT was statistically significant for increased reintubation and mortality.

Diaphragm thickness can be examined using various imaging methods. Thorax CT and USG are the primary methods used to observe the diaphragm. Recently, USG has been widely carried out in ICU patients thanks to its bedside application and ease of use. Various non-COVID-19 studies have emphasized the efficacy of USG in evaluating diaphragmatic weakness associated with critical respiratory disease.^13,14 However, USG evaluation is dependent on the physician and can considerably vary, and, unlike CT, it does not allow for visualization of the entire diaphragm.¹⁵ In a prospective study evaluating diaphragmatic excursion with USG carried out within the first 12 hours of ICU hospitalization in critically ill COVID-19 patients, it was reported that low diaphragmatic excursion was significant in predicting the need for intubation and mortality. However, because a single doctor in this study carried out the diaphragm evaluation, it was stated that further studies are needed to determine a diaphragmatic excursion cut-off value for mortality and predicting the intubation requirement.¹⁶ Furthermore, the radiologist’s close contact with the patient during USG imaging poses a risk of COVID-19 transmission. Therefore, it can be more practical to evaluate DT on thorax CT, which is routinely obtained in critical COVID-19 cases.

There is no consensus on where to measure DT on a CT scan. In a relevant study by Ufuk et al,¹⁷ CT scans were evaluated by 4 radiologists, and the diaphragm crura were measured at 5 different points. According to the best intra-observer and inter-observer agreement, the authors recommended measuring celiac artery outlet level for maximum DT and the upper level of the L1 vertebral body for the anterior DT.¹⁷ Another CT study suggested using the method of drawing the line at the celiac artery level and the anterior border of the vertebral canal in axial images and measuring from the point on axial and coronal images where the line intersects with the other lines coming from the both sides of the diaphragm on the transverse plan.¹⁸ In light of the literature, we measured diaphragmatic crura at the origin of the celiac artery and recorded measurements for each crus at the anterior and middle aspect of the vertebral body on axial images.

Although there are no direct indications for diaphragmatic dysfunction in COVID-19, studies have shown that increased oxidative stress and elevated cytokine levels in critical non-COVID-19 patients can cause diaphragm dysfunction in the event of systemic inflammation.¹⁹ Coronavirus disease-19 is known to cause hyperinflammation and cytokine storm; thus, pro-inflammatory cytokines could cause sarcolemma damage and diaphragm atrophy by proteolysis.²⁰ This is one of the main reasons we investigated diaphragm dysfunction in patients with COVID-19 in the present study.

Neutrophil-to-lymphocyte ratio is a laboratory parameter that becomes elevated in systemic inflammation and has been associated with infection and sepsis-related mortality.^21,22 As it is a part of routine hemogram tests, this parameter can be easily evaluated. There are many studies underlining the importance of NLR, ANC, and IL-6 levels in determining disease severity and estimating prognosis in COVID-19. Increased NLR and IL-6 levels, especially in the hyperinflammatory phase, are reported to be indicators of mortality.^23-25 In our study, high NLR was found to be significant for mortality, and high NLR, ANC, and IL-6 for invasive MV requirement. Evaluating NLR levels together with DT can provide accuracy in predicting mortality in COVID-19 cases.

To the best of our knowledge, there is limited information in the literature on evaluating DT with thorax CT in critical COVID-19. A pilot study evaluating DT with USG in COVID-19 patients stated that a DT value of <2.2 mm occurring in the first 36 hours of hospitalization poses a risk in terms of intubation and adverse outcomes. Furthermore, low DT and lymphopenia were indicated as independent variables to estimate mortality. However, the study involved non-critical patients rather than ICU patients.⁹ The value of our investigation lies in the fact that our study population consisted of ICU patients, that is, severe cases for whom the risk factors for MV requirement and adverse outcomes are directly related.

Published studies on DT evaluation by CT in the ICU have generally focused on intubated patients. For instance, Lee et al¹⁸ examined thorax CTs obtained 18.4±14.9 days apart during the ICU stay of patients receiving MV and measured a mean left side DT of 3.8±0.6 and right side DT of 3.9±0.8 mm, in the first scans, and 3.4±0.6 and 3.5±0.9 mm, in the second scans (p<0.05). The authors concluded that MV causes a reduction of DT in critical patients. Various studies, including studies on animal models, have revealed that pressures during MV cause diaphragm fiber injury, resulting in decreased DT.^26,27 In our study, we excluded patients who were intubated in the emergency clinic or another service before ICU admission to rule out this known effect of MV on DT. Patients with chronic respiratory diseases such as COPD and asthma were also excluded because the focus of our study was COVID-19.

Evaluating DT to detect high-risk cases before ICU admission can allow for controlled use of the practices linked with diaphragm dysfunction, such as sedation and steroid usage, and thus prevent muscle weakness leading to respiratory failure.^28,29 Furthermore, taking measures such as optimization of nutrition and respiratory physiotherapy in cases at risk of diaphragmatic atrophy during ICU stay can reduce invasive MV requirement and adverse outcomes.