Residual radiological opacities correlate with disease outcomes in ICU-treated COVID-19.

Background: Few studies consider both radiological and functional outcomes in COVID-19 survivors treated in the intensive care unit (ICU). We investigated clinical findings and pulmonary abnormalities on chest computed tomography (CT) and compared outcomes of severe versus mild-moderate acute respiratory distress syndrome (ARDS) on long-term follow-up. Methods: This longitudinal cohort study included 118 COVID-19 patients (median age, 58 years; 79% men). Thoracic CT scans were performed 4, 10, and 22 months after hospital discharge. Two independent blinded radiologists analyzed the 10 months scans and scored the radiology findings semi-quantitatively, as no/minor versus widespread opacities [low-radiology opacity grade (ROG) versus high-ROG]. ARDS severity was based on the PaO2/FiO2 ratio. The 6 min walk test (6MWT) was performed after 3 and 9 months, and lung diffusion capacity for carbon monoxide (DLCO) and lung volume measurement after 9 and 15 months. Dynamic spirometry was done at all time points. Residual symptoms and health-related quality-of-life (HRQL) were evaluated using validated questionnaires. Results: At 10 months, most patients (81/118; 69%) were classified as high-ROG, of which 70% had severe ARDS during hospitalisation; 69% of those with mild-moderate ARDS also had high-ROG. Patients with high-ROG had longer ICU stay and lower PaO2/FiO2 during hospitalisation (p < 0.01). At 9 months follow-up, patients with high-ROG had smaller lung volumes as % of predicted values [mean (±CI): 80 (77-84) vs. 93 (88-98) (p < 0.001)], lower DLCO as % of predicted values [74 (70-78) vs. 87 (82-92) (p < 0.001)], lower oxygen saturation during 6MWT (p = 0.02), and a tendency to more severe dyspnoea (p = 0.07), but no difference was found in HRQL compared with no/minor ROG (p = 0.92). A higher opacity score was related to lower DLCO at follow-up (r = -0.48, p < 0.001, Spearman rank test). Severe ARDS patients had slightly more severe fatigue at 9 months compared to mild-moderate, but no differences in dyspnoea or lung function at follow-up. Fibrotic-like changes were found in 93% of patients examined with CT scans at 2 years (55/118; 47%). Severe ARDS could predict widespread opacities (ROG > 25%) in most patients at follow-up at 10 months (AUC 0.74). Conclusion: Residual radiological abnormalities in ICU-treated COVID-19 patients, evaluated for up to 2 years, relate to persisting symptoms and impaired lung function, demanding careful follow-up regardless of ARDS severity at hospitalisation.

Effect of external dead space removal on CO2 homeostasis in mechanically ventilated adult Covid-19 patients.

BACKGROUND: Patients with Covid-19 respiratory failure present with hypoxemia, often in combination with hypercapnia. In this prospective, observational study we examined the effect of removing external dead space (DS) on CO2 -homeostasis in mechanically ventilated Covid-19 patients. In addition, volumetric capnography was validated for its ability to estimate external DS volume using in vitro measured DS volumes as reference. METHODS: In total, 10 patients with acute respiratory distress syndrome from Covid-19 were included. Volumetric capnography, mechanical ventilation, and arterial blood gas data were analyzed before and after removal of external DS and analyzed for potentially significant changes in response to DS removal. Measurements of external DS were obtained in circuit using volumetric capnography and compared to actual measured DS volumes off the circuit. RESULTS: After the removal of external DS, the alveolar minute ventilation and CO2 elimination improved, notwithstanding unchanged respiratory rate and tidal volumes. The increase in CO2 elimination was associated with a decrease in arterial CO2 partial pressure (PaCO2 ). The volumetric capnography method for assessment of external DS showed a low bias of -9 mL (lower limit of agreement -40, 95% CI -60 to -20 mL, upper limit of agreement 21 mL, 95% CI: 1-40 mL) and a percentage error of 48% compared to absolute values measured in vitro. CONCLUSION: Removal of external DS increased alveolar minute ventilation and CO2 elimination in Covid-19 patients with respiratory failure in the current study. This was associated with a decrease in PaCO2 . This may indicate a decreased CO2 production due to decreased work of breathing and more effective gas-exchange in response to DS removal. In addition, volumetric capnography appears to be a clinically feasible method for continuous measurement of external DS in the current study and may be of value in optimizing ventilator treatment.

Widespread Parenchymal Abnormalities and Pulmonary Embolism on Contrast-Enhanced CT Predict Disease Severity and Mortality in Hospitalized COVID-19 Patients.

Purpose: Severe COVID-19 is associated with inflammation, thromboembolic disease, and high mortality. We studied factors associated with fatal outcomes in consecutive COVID-19 patients examined by computed tomography pulmonary angiogram (CTPA). Methods: This retrospective, single-center cohort analysis included 130 PCR-positive patients hospitalized for COVID-19 [35 women and 95 men, median age 57 years (interquartile range 51-64)] with suspected pulmonary embolism based on clinical suspicion. The presence and extent of embolism and parenchymal abnormalities on CTPA were recorded. The severity of pulmonary parenchymal involvement was stratified by two experienced radiologists into two groups: lesions affecting ≤50% or >50% of the parenchyma. Patient characteristics, radiological aspects, laboratory parameters, and 60-day mortality data were collected. Results: Pulmonary embolism was present in 26% of the patients. Most emboli were small and peripheral. Patients with widespread parenchymal abnormalities, with or without pulmonary embolism, had increased main pulmonary artery diameter (p < 0.05) and higher C-reactive protein (p < 0.01), D-dimer (p < 0.01), and troponin T (p < 0.001) and lower hemoglobin (p < 0.001). A wider main pulmonary artery diameter correlated positively with C-reactive protein (r = 0.28, p = 0.001, and n = 130) and procalcitonin. In a multivariant analysis, D-dimer >7.2 mg/L [odds ratio (±95% confidence interval) 4.1 (1.4-12.0)] and ICU stay were significantly associated with embolism (p < 0.001). The highest 60-day mortality was found in patients with widespread parenchymal abnormalities combined with pulmonary embolism (36%), followed by patients with widespread parenchymal abnormalities without pulmonary embolism (26%). In multivariate analysis, high troponin T, D-dimer, and plasma creatinine and widespread parenchymal abnormalities on CT were associated with 60-day mortality. Conclusions: Pulmonary embolism combined with widespread parenchymal abnormalities contributed to mortality risk in COVID-19. Elevated C-reactive protein, D-dimer, troponin-T, P-creatinine, and enlarged pulmonary artery were associated with a worse outcome and may mirror a more severe systemic disease. A liberal approach to radiological investigation should be recommended at clinical deterioration, when the situation allows it. Computed tomography imaging, even without intravenous contrast to assess the severity of pulmonary infiltrates, are of value to predict outcome in COVID-19. Better radiological techniques with higher resolution could potentially improve the detection of microthromboses. This could influence anticoagulant treatment strategies, preventing clinical detoriation.

Neurally adjusted ventilatory assist feasibility during anaesthesia: A randomised crossover study of two anaesthetics in a large animal model.

BACKGROUND: Spontaneous breathing during mechanical ventilation improves gas exchange by redistribution of ventilation to dependent lung regions. Neurally adjusted ventilatory assist (NAVA) supports spontaneous breathing in proportion to the electrical activity of the diaphragm (EAdi). NAVA has never been used in the operating room and no studies have systematically addressed the influence of different anaesthetic drugs on EAdi. OBJECTIVES: The aim of this study was to test the feasibility of NAVA under sedation and anaesthesia with two commonly used anaesthetics, sevoflurane and propofol, with and without remifentanil, and to study their effects on EAdi and breathing mechanics. DESIGN: A crossover study with factorial design of NAVA during sedation and anaesthesia in pigs. SETTING: University basic science laboratory in Uppsala, Sweden, from March 2009 to February 2011. ANIMALS: Nine juvenile pigs were used for the experiment. INTERVENTIONS: The lungs were ventilated using NAVA while the animals were sedated and anaesthetised with continuous low-dose ketamine combined with sevoflurane and propofol, with and without remifentanil. MAIN OUTCOME MEASURES: During the last 5  min of each study period (total eight steps) EAdi, breathing pattern, blood gas analysis, neuromechanical efficiency (NME) and neuroventilatory efficiency (NVE) during NAVA were determined. RESULTS: EAdi was preserved and normoventilation was reached with both sevoflurane and propofol during sedation as well as anaesthesia. Tidal volume (Vt) was significantly lower with sevoflurane anaesthesia than with propofol. NME was significantly higher with sevoflurane than with propofol during anaesthesia with and without remifentanil. NVE was significantly higher with sevoflurane than with propofol during sedation and anaesthesia. CONCLUSION: NAVA is feasible during ketamine-propofol and ketamine-sevoflurane anaesthesia in pigs. Sevoflurane promotes lower Vt, and affects NME and NVE less than propofol. Our data warrant studies of NAVA in humans undergoing anaesthesia.