Long-term outcome of COVID-19 patients treated with helmet noninvasive ventilation vs. high-flow nasal oxygen: a randomized trial

Background: Long-term outcomes of patients treated with helmet noninvasive ventilation (NIV) are unknown: safety concerns regarding the risk of patient self-inflicted lung injury and delayed intubation exist when NIV is applied in hypoxemic patients. We assessed the 6-month outcome of patients who received helmet NIV or high-flow nasal oxygen for COVID-19 hypoxemic respiratory failure. Methods: In this prespecified analysis of a randomized trial of helmet NIV versus high-flow nasal oxygen (HENIVOT), clinical status, physical performance (6-min-walking-test and 30-s chair stand test), respiratory function and quality of life (EuroQoL five dimensions five levels questionnaire, EuroQoL VAS, SF36 and Post-Traumatic Stress Disorder Checklist for the DSM) were evaluated 6 months after the enrollment. Results: Among 80 patients who were alive, 71 (89%) completed the follow-up: 35 had received helmet NIV, 36 high-flow oxygen. There was no inter-group difference in any item concerning vital signs (N = 4), physical performance (N = 18), respiratory function (N = 27), quality of life (N = 21) and laboratory tests (N = 15). Arthralgia was significantly lower in the helmet group (16% vs. 55%, p = 0.002). Fifty-two percent of patients in helmet group vs. 63% of patients in high-flow group had diffusing capacity of the lungs for carbon monoxide < 80% of predicted (p = 0.44); 13% vs. 22% had forced vital capacity < 80% of predicted (p = 0.51). Both groups reported similar degree of pain (p = 0.81) and anxiety (p = 0.81) at the EQ-5D-5L test; the EQ-VAS score was similar in the two groups (p = 0.27). Compared to patients who successfully avoided invasive mechanical ventilation (54/71, 76%), intubated patients (17/71, 24%) had significantly worse pulmonary function (median diffusing capacity of the lungs for carbon monoxide 66% [Interquartile range: 47–77] of predicted vs. 80% [71–88], p = 0.005) and decreased quality of life (EQ-VAS: 70 [53–70] vs. 80 [70–83], p = 0.01). Conclusions: In patients with COVID-19 hypoxemic respiratory failure, treatment with helmet NIV or high-flow oxygen yielded similar quality of life and functional outcome at 6 months. The need for invasive mechanical ventilation was associated with worse outcomes. These data indicate that helmet NIV, as applied in the HENIVOT trial, can be safely used in hypoxemic patients. Trial registration Registered on clinicaltrials.gov NCT04502576 on August 6, 202

Mitochondrial damage and metabolic compensatory mechanisms induced by hyperoxia in U-937 cell line

Experimental hyperoxia represents a suitable in vitro model to study some pathogenic mechanisms related to oxidative stress. Moreover, it allows the investigation of the molecular pathophysiology underlying oxygen therapy and toxicity. In this study, a modified experimental set up was adopted to accomplish a model of moderate hyperoxia (50% O 2, 96 h culture) to induce oxidative stress in the human leukemia cell line, U-937. Spectrophotometric measurements of mitochondrial respiratory enzyme activities, NMR spectroscopy of culture media, determination of antioxidant enzyme activities, and cell proliferation and differentiation assays were performed. The data showed that moderate hyperoxia in this myeloid cell line causes: i) intriguing alterations in the mitochondrial activities at the levels of succinate dehydrogenase and succinate-cytochrome c reductase; ii) induction of metabolic compensatory adaptations, with significant shift to glycolysis; iii) induction of different antioxidant enzyme activities; iv) significant cell growth inhibition and v) no significant apoptosis. This work will permit better characterization the mitochondrial damage induced by hyperoxia. In particular, the data showed a large increase in the succinate cytochrome c reductase activity, which could be a fundamental pathogenic mechanism at the basis of oxygen toxicity