Incidence and Prognostic Significance of Hypoxemia in Fibrotic Interstitial Lung Disease: An International Cohort Study.

BACKGROUND: Hypoxemia is a cardinal feature of fibrotic interstitial lung disease (ILD). The incidence, progression, and prognostic significance of hypoxemia in patients with fibrotic ILD currently is unknown. RESEARCH QUESTION: What are the epidemiologic features of hypoxemia and its additive prognostic value in a current risk prediction model of fibrotic ILD? METHODS: We identified 848 patients with fibrotic ILD (258 with idiopathic pulmonary fibrosis [IPF]) in five prospective ILD registries from Australia, Canada, and Switzerland. Cumulative incidence of exertional and resting hypoxemia from the time of diagnosis was estimated at 1-year intervals in patients with baseline 6-min walk tests, adjusted for competing risks of death and lung transplantation. Likelihood ratio tests were used to determine the prognostic significance of exertional and resting hypoxemia for 1-year mortality or transplantation when added to the ILD-GAP model. The cohort was divided into derivation and validation subsets to evaluate performance characteristics of the extended model (the ILD-GAP-O2 model), which included oxygenation status as a predictor. RESULTS: The 1-, 2-, and 5-year overall cumulative incidence was 6.1%, 17.3%, and 40.1%, respectively, for exertional hypoxemia and 2.4%, 5.6%, and 16.5%, respectively, for resting hypoxemia, which were significantly higher in patients with IPF compared with patients without IPF (P < .001 for both). Addition of exertional or resting hypoxemia to the ILD-GAP model improved 1-year mortality and transplantation prediction (P < .001 for both). The ILD-GAP-O2 model showed improved discrimination (C-index, 0.80 vs 0.75) and model fit (Akaike information criteria, 400 vs 422) in the validation cohort, with comparable calibration. INTERPRETATION: Patients with IPF have higher cumulative incidence of exertional and resting hypoxemia than patients without IPF. The extended ILD-GAP-O2 model provides additional risk stratification for 1-year prognosis in fibrotic ILD.

The Role of Midodrine for Hypotension Outside of the Intensive Care Unit.

Midodrine is an oral, peripherally acting alpha-adrenergic agonist. After gaining Food and Drug Administration (FDA) approval in 1996 for orthostatic hypotension, its use has evolved to target vasoplegic conditions such as intradialytic hypotension in the end-stage renal disease population, refractory ascites in cirrhotic patients to support diuresis, and in hepatorenal syndrome. Upon oral ingestion, the drug undergoes enzymatic hydrolysis to an active metabolite, desglymidodrine. Its use has been well tolerated at 2.5 mg, 5 mg, and 10 mg oral doses. The most frequently occurring side effects relate directly to its sympathomimetic profile and include piloerection, scalp pruritis, generalized paresthesias, and urinary retention. The vasoplegic profile of sepsis would be a potential target for midodrine therapy. While its use to mediate recovery from septic shock has been suggested, there is a paucity of clinical data supporting its use. Such therapy may be uniquely appropriate in septic patients who are not candidates for intensive care unit (ICU) level of care.