This retrospective study describes the clinical course, ICU management, and outcome of 54 ILD patients requiring IMV for ARF at a tertiary-referral institution. Both in-hospital and one -year mortality was high, and no difference was found in the primary outcome. Higher ventilator support requirements, vasopressor use, high dose steroids, and the IPF subtype were associated with worse in hospital mortality. The IPF subtype, ILD exacerbation as cause of ARF, no past history of CTDs, presence of SVT, vasopressor use were independent predictors of one-year mortality.
One prior study has described the in-hospital and one-year mortality of ILD patients experiencing ARF, requiring IMV, as 53% and 59%, respectively(6). Our study demonstrated a 63% in-hospital mortality and 82.5% one-year mortality. Differences in mortality rates are likely in part to the fact that our study had a large percentage of patients that were transferred from an outside hospital; which may reflect patients with worse prognosis having failed to respond to initial medical care prior to transfer. NIPPV trialed prior to IMV was found to have higher mortality in the study by Fernandez-Perez(6). Others have suggested that patients receiving an NIPPV trial prior to IMV have worse clinical outcomes(15). Patients trialed on NIPPV prior to IMV is not a standardized intervention and there is no recognized definition of what time duration of NIPPV trial is needed before it can be considered as failure. Our study found no significant difference for in-hospital mortality and one-year mortality in general between the two cohorts. With the exception of sarcoidosis patients with ILD-ARF, in-patient mortality was high and more studies are needed to validate this finding regarding sarcoid patients experiencing ARF. An age of 65 years or older had a worse one-year mortality in patients trialed on NIPPV prior to IMV in comparison to those undergoing only IMV. This proposes an ethical dilemma for critical care physicians because, in general, mortality is high for ILD-ARF patients who fail a NIPPV trial and it is unclear if IMV is even worthwhile after NIPPV failure. IMV is often an intervention that has been considered futile if transplantation is not an option for patients with advanced underlying ILD; this has most commonly been discussed in IPF patients (6,16–18). However, NIPPV trial prior to IMV initiation may identify a subset of patients who are responders and avoid need for IMV altogether.
Fernandez-Perez described that the ventilator settings which correlated with increased mortality were higher PEEP, lower tidal volume, and higher FiO2(6). They also found higher documented mean, plateau, and peak airway pressures and lower PaO2/FiO2 ratios were associated with increased mortality. Our study supported that higher PEEP settings and higher FiO2 were associated with increased in-hospital mortality. These findings were also associated with decreased one-year survival starting from day of intubation. This suggests that ARF-ILD patients requiring IMV are subject to increased risks of barotrauma, volutrauma, and cellular injury related to hyperoxia/free radical damage. Statistical differences in tidal volume settings, recorded peak airway pressures, and recorded PaO2/FiO2 ratios between our study and the Fernandez-Perez study is likely related to power. Additionally, lower tidal volume requirements to maintain plateau pressures suggests higher disease burden and poor compliance that is prognostically concerning. It is reasonable for physicians caring for ILD-ARF patients requiring IMV to adopt mechanical ventilator strategies from ARDS protocols that incorporate using the lowest possible tidal volumes and PEEP settings (19–21). FiO2 should also be aggressively titrated to the lowest possible setting to avoid hyperoxic acute lung injury(22).
PH and its effect on the primary study outcome was unclear. Our study did not support that PH impacts mortality or morbidity in ILD-ARF. Saydain et al also found no difference in systolic pulmonary artery pressures between survivors and non-survivors(17). Zafrani et al did find that PH was a determinant for in-hospital and one year mortality(7). IMV in patients with severe PH should be avoided if possible due to potential complications of hemodynamic instability(23). Right heart catheterization (RHC) remains the diagnostic modality for PH and is not commonly done in this cohort of patients. No study has evaluated IMV outcomes of ILD patients with PH diagnosed by RHC.
Zafrani et al found that corticosteroid therapy was potentially of benefit during ILD-ARF in patients admitted to the ICU(7). About 41% of our cohort received high dose steroids during their ICU course compared with 65% in the Zafrani et al study. In their study, patients with less fibrosis on chest CT scan were noted to have better response to steroids and earlier treatment with corticosteroids was associated with an improved mortality. Our study found that high dose corticosteroid therapy (pulse or stress dosing) was associated with increased mortality. The reason for differences in these findings were difficult to determine as it was unclear what the different subtypes of ARF were in their cohort. Our cohort had ARF primarily from pneumonia/sepsis and ILD exacerbations and all of our patients underwent IMV, whereas Zafrani et al had only 61% of patients treated with IMV during their ICU course(7). It is difficult to compare their cohort with ours as all our patients required IMV for respiratory support, implying that our cohort had higher all-cause disease burden. Fernandez-Perez found that high dose corticosteroid therapy had no significant effect on ILD-ARF patients requiring IMV(6). It remains unclear what the effect of high dose corticosteroid therapy is in patients ILD-ARF requiring IMV.
SVT, aside from sinus tachycardia, was associated with higher in-hospital (p= 0.06) and one-year mortality (p=0.037). There is limited data on the epidemiology of AAs in ILD patients. Studies in IPF have demonstrated that SVTs are common(24,25). SVT can be difficult to manage in ILD-ARF because: (1) there is no standardized approach to management in this cohort and (2) it is difficult to assess if SVT is the primary cause of ARF or if the SVT is secondary to the underlying etiology of ARF.
Our study has several limitations that could have influenced our findings. Our study is limited in its retrospective study design and by low power, thus necessitating the need for further investigations to validate our discovered associations. Due to reliance of the diagnosis of ILD and ARF from ICD coding and EMR investigation, it is possible that we missed patients who were not coded properly. Additionally, EMR charting was not always reliable for data extraction and some patients had missing values when analyzing potential determinants of mortality which could have impacted statistical significance. Our conclusions cannot be generalized to all ILD patients, because our study does not include ILD-ARF patients who may have not received IMV due to either the decision for palliative care interventions, death while on NIPPV, or improvement with NIPPV trial. Using cutoffs of patients on IMV for ³24 hours may have missed ILD patients that were too ill for inclusion. Our strict inclusion criteria may have also contributed to lower power. Finally, our study is only representative of one health system and may be subject to limitations related to individualized institutional cultural practices.