Impact of High-Flow Nasal Cannula Use in Subjects With COVID-19 ARDS at High Altitudes: Clinical Presentation and Prognostic Factors.

BACKGROUND: High-flow nasal cannula (HFNC) reduces the need for intubation in adult subject with acute respiratory failure. Changes in hypobaric hypoxemia have not been studied for subject with an HFNC in ICUs at altitudes > 2,600 m above sea level. In this study, we investigated the efficacy of HFNC treatment in subjects with COVID-19 at high altitudes. We hypothesized that progressive hypoxemia and the increase in breathing frequency associated with COVID-19 in high altitudes affect the success of HFNC therapy and may also influence the performance of the traditionally used predictors of success and failure. METHODS: This was a prospective cohort study of subjects >18 y with a confirmed diagnosis of COVID-19-induced ARDS requiring HFNC who were admitted to the ICU. Subjects were followed up during the 28 d of HFNC treatment or until failure. RESULTS: One hundred and eight subjects were enrolled. At admission to the ICU, FIO2 delivery between 0.5-0.8 (odds ratio 0.38 [95% CI 0.17-0.84]) was associated with a better response to HFNC therapy than oxygen delivery on admission between 0.8-1.0 (odds ratio 3.58 [95% CI 1.56-8.22]). This relationship continued during follow-ups at 2, 6, 12, and 24 h, with a progressive increase in the risk of failure (odds ratio 24 h 13.99 [95% CI 4.32-45.26]). A new cutoff for the ratio of oxygen saturation (ROX) index (ROX ≥ 4.88) after 24 h of HFNC administration was demonstrated to be the best predictor of success (odds ratio 11.0 [95% CI 3.3-47.0]). CONCLUSIONS: High-altitude subjects treated with HFNC for COVID-19 showed a high risk of respiratory failure and progressive hypoxemia when FIO2 requirements were > 0.8 after 24 h of treatment. In these subjects, personalized management should include continuous monitoring of individual clinical conditions (such as oxygenation indices, with cutoffs adapted to those corresponding to high-altitude cities).

Low Serum Erythropoietin Levels are Associated with Fatal COVID‐19 Cases at 4,150 meters above sea level

Previous studies suggested that erythropoietin (EPO) may protect against severe COVID‐19‐induced injuries, ultimately preventing mortality. This hypothesis is based on the fact that, in addition to promoting the increase in red blood cells, EPO is an anti‐inflammatory, anti‐apoptotic and protective factor in several non‐erythropoietic tissues. Furthermore, EPO promotes nitric oxide production in the hypoxic lung and stimulates ventilation by interacting with the respiratory centers of the brainstem. Given that EPO in the blood is increased at high‐altitude, we evaluated the serum levels of EPO in critical patients with COVID‐19 at “Hospital Agramont” in the city of El Alto (4,150 masl) in Bolivia. A total of 16 patients, 15 men, one woman, with a mean age of 55.8 ± 8.49 years, admitted to the Intensive Care Unit were studied. All patients were permanent residents of El Alto, with no travel history below 3,000 masl for at least one year. Blood samples were collected upon admission to the ICU. Serum EPO concentration was assessed using an ELISA kit, and a standard technique determined hemoglobin concentration. Only half of the observed patients survived the disease. Remarkably, fatal cases showed 2.5 times lower serum EPO than survivors (2.78 ± 0.8643 mU/ml vs 7.06 ± 2.713 mU/ml;p = 0.0096), and 1.24 times lower hemoglobin levels (13.96 ± 2.56 g/dL vs 17.41 ± 1.61 g/dL;p = 0.0159). While the number of cases evaluated in this work is low, our findings strongly warrant further investigation of EPO levels in COVID‐19 patients at high and low altitudes. Our results also support the hypothesis that exogenous EPO administration could help critically ill COVID‐19 patients overcome the disease.

Oxygen therapy limiting peripheral oxygen saturation to 89-93% is associated with a better survival prognosis for critically ill COVID-19 patients at high altitudes

Patients admitted to the Intensive Care Unit (ICU) with acute hypoxemic respiratory failure automatically receive oxygen therapy to improve inspiratory oxygen fraction (FiO2). Supplemental oxygen is the most prescribed drug for critically ill patients regardless of altitude of residence. In high altitude dwellers (i.e. in La Paz [»3,400 m] and El Alto [»4,150 m] in Bolivia), a peripheral oxygen saturation (SatpO2) of 89-95% and an arterial partial pressure of oxygen (PaO2) of 50-67mmHg (lower as altitude rises), are considered normal values for arterial blood. Consequently, it has been suggested that limiting oxygen therapy to maintain SatpO2 around normoxia may help avoid episodes of hypoxemia, hyperoxemia, intermittent hypoxemia, and ultimately, mortality. In this study, we evaluated the impact of oxygen therapy on the mortality of critically ill COVID-19 patients who permanently live at high altitudes. A multicenter cross-sectional descriptive observational study was performed on 100 patients admitted to the ICU at the ?Clinica Los Andes? (in La Paz city) and ?Agramont? and ?Del Norte? Hospitals (in El Alto city). Our results show that: 1) as expected, fatal cases were detected only in patients who required intubation and connection to invasive mechanical ventilation as a last resort to overcome their life-threatening desaturation;2) among intubated patients, prolonged periods in normoxia are associated with survival, prolonged periods in hypoxemia are associated with death, and time spent in hyperoxemia shows no association with survival or mortality;3) the oxygenation limits required to effectively support the intubated patients? survival in the ICU are between 89% and 93%;4) among intubated patients with similar periods of normoxemic oxygenation, those with better SOFA scores survive;and 5) a lower frequency of observable reoxygenation events is not associated with survival. In conclusion, our findings indicate that high-altitude patients entering an ICU at altitudes of 3,400 ? 4,150 m should undergo oxygen therapy to maintain oxygenation levels between 89 and 93 %.

Oxygen therapy limiting peripheral oxygen saturation to 89-93% is associated with a better survival prognosis for critically ill COVID-19 patients at high altitudes.

Patients admitted to the Intensive Care Unit (ICU) with acute hypoxemic respiratory failure automatically receive oxygen therapy to improve inspiratory oxygen fraction (FiO2). Supplemental oxygen is the most prescribed drug for critically ill patients regardless of altitude of residence. In high altitude dwellers (i.e. in La Paz [≈3,400 m] and El Alto [≈4,150 m] in Bolivia), a peripheral oxygen saturation (SatpO2) of 89-95% and an arterial partial pressure of oxygen (PaO2) of 50-67 mmHg (lower as altitude rises), are considered normal values ​​for arterial blood. Consequently, it has been suggested that limiting oxygen therapy to maintain SatpO2 around normoxia may help avoid episodes of hypoxemia, hyperoxemia, intermittent hypoxemia, and ultimately, mortality. In this study, we evaluated the impact of oxygen therapy on the mortality of critically ill COVID-19 patients who permanently live at high altitudes. A multicenter cross-sectional descriptive observational study was performed on 100 patients admitted to the ICU at the "Clinica Los Andes" (in La Paz city) and "Agramont" and "Del Norte" Hospitals (in El Alto city). Our results show that: 1) as expected, fatal cases were detected only in patients who required intubation and connection to invasive mechanical ventilation as a last resort to overcome their life-threatening desaturation; 2) among intubated patients, prolonged periods in normoxia are associated with survival, prolonged periods in hypoxemia are associated with death, and time spent in hyperoxemia shows no association with survival or mortality; 3) the oxygenation limits required to effectively support the intubated patients' survival in the ICU are between 89% and 93%; 4) among intubated patients with similar periods of normoxemic oxygenation, those with better SOFA scores survive; and 5) a lower frequency of observable reoxygenation events is not associated with survival. In conclusion, our findings indicate that high-altitude patients entering an ICU at altitudes of 3,400 - 4,150 m should undergo oxygen therapy to maintain oxygenation levels between 89 and 93 %.