ABSTRACT
BACKGROUND: While antibiotic therapy is advocated to improve outcomes in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) whenever mechanical ventilation is required, the evidence relies on small studies carried out before the era of widespread antibiotic resistance. Furthermore, the impact of systematic antibiotic therapy on successful weaning from mechanical ventilation was never investigated accounting for the competitive risk of death. The aim of the study was to assess whether early antibiotic therapy (eABT) increases successful mechanical ventilation weaning probability as compared to no eABT, in patients with AECOPD without pneumoniae, using multivariate competitive risk regression. METHODS: Retrospective analysis of patients admitted in 2 intensive care units (ICU) from 2012 to 2020 for AECOPD without pneumonia and requiring mechanical ventilation. eABT was defined as any anti-bacterial chemotherapy introduced during the first 24 h after ICU admission. The primary outcomes were the adjusted subdistribution hazard ratio (SHR) of the probability of being successfully weaned from mechanical ventilation (i.e. non-invasive and invasive ventilation) according to eABT status and accounting for the competitive risk of death. RESULTS: Three hundred and ninety-one patients were included, of whom 66% received eABT. eABT was associated with a lower probability of successful liberation from mechanical ventilation when accounting for the competing risk of death in multivariate analyses (SHR 0.71 [95% confidence interval, 0.57-0.89], p < 0.01), after adjustment with covariates of disease severity. This association was present in all subgroups except in patients under invasive mechanical ventilation on ICU day-1, in patients with ICU day-1 worst PaCO2 > 74 torr (median value) and in patients with a documented bacterial bronchitis at ICU admission. Ventilator-free days at day 28, ICU-free days at day 28 and invasive mechanical ventilation-free days at day 28, were significantly lower in the eABT group, while there was no significant difference in mortality at day 28 between patients who received eABT and those who did not. CONCLUSIONS: eABT was independently associated with a lower probability of being successfully weaned from mechanical ventilation, suggesting that the clinician decision to overrule systematic administration of eABT was not associated with a detectable harm in AECOPD ICU patients without pneumonia.
ABSTRACT
BACKGROUND: Protracted viral shedding is common in hospitalized patients with COVID-19 pneumonia, and up to 40% display signs of pulmonary fibrosis on computed tomography (CT) after hospital discharge. We hypothesized that COVID-19 patients with acute respiratory failure (ARF) who die in intensive care units (ICU) have a lower viral clearance in the respiratory tract than ICU patients discharged alive, and that protracted viral shedding in respiratory samples is associated with patterns of fibroproliferation on lung CT. We, therefore, conducted a retrospective observational study, in 2 ICU of Lyon university hospital. RESULTS: 129 patients were included in the study, of whom 44 (34%) died in ICU. 432 RT-PCR for SARS-CoV-2 were performed and 137 CT scans were analyzed. Viral load was significantly higher in patients deceased as compared to patients alive at ICU discharge (p < 0.001), after adjustment for the site of viral sampling and RT-PCR technique. The median time to SARS-CoV-2 negativation on RT-PCR was 19 days [CI95 %:15-21] in patients alive at ICU discharge and 26 days [CI95 %:17-infinity] in non-survivors at ICU discharge. Competitive risk regression identified patients who died in ICU and age as independent risk factors for longer time to SARS-CoV-2 negativation on RT-PCR, while antiviral treatment was independently associated with shorter time. None of the CT scores exploring fibroproliferation (i.e., bronchiectasis and reticulation scores) were significantly associated with time to SARS-CoV-2 negativation. CONCLUSIONS: Viral load in respiratory samples is significantly lower and viral shedding significantly shorter in ICU survivors of COVID-19 associated acute respiratory failure. Protracted viral shedding is unrelated to occurrence of fibrosis on lung CT.
ABSTRACT
PURPOSE: Mechanical ventilation with ultra-low tidal volume (VT) during ARDS may reduce alveolar strain, driving pressure and hence ventilator-induced lung injury, with the main drawback of worsening respiratory acidosis. We hypothesized that VT could be reduced down to 4 ml/kg, with clinically significant decrease in driving pressure, without the need for extracorporeal CO2 removal, while maintaining pH > 7.20. METHODS: We conducted a non-experimental before-and-after multicenter study on 35 ARDS patients with PaO2/FiO2 ≤ 150 mmHg, within 24 h of ARDS diagnosis. After inclusion, VT was reduced to 4 ml/kg and further adjusted to maintain pH ≥ 7.20, respiratory rate was increased up to 40 min-1 and PEEP was set using a PEEP-FiO2 table. The primary judgment criterion was driving pressure on day 2 of the study, as compared to inclusion. RESULTS: From inclusion to day 2, driving pressure decreased significantly from 12 [9-15] to 8 [6-11] cmH2O, while VT decreased from 6.0 [5.9-6.1] to 4.1 [4.0-4.7] ml/kg. On day 2, VT was below 4.2 ml/kg in 65% [CI95% 48%-79%], and below 5.25 ml/kg in 88% [CI95% 74%-95%] of the patients. 2 patients (6%) developed acute cor pulmonale after inclusion. Eleven patients (32%) developed transient severe acidosis with pH < 7.15. Fourteen patients (41%) died before day 90. CONCLUSION: Ultra-low tidal volume ventilation may be applied in approximately 2/3 of moderately severe-to-severe ARDS patients, with a 4 cmH2O median reduction in driving pressure, at the price of transient episodes of severe acidosis in approximately 1/3 of the patients.
