Chronic dysglycemia and risk of SARS-CoV-2 associated respiratory failure in hospitalized patients.

BACKGROUND: Diabetes is common among patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced respiratory failure. We aimed to investigate the relationship between different stages of chronic dysglycemia and development of respiratory failure in hospitalized SARS-CoV-2 positive patients. METHODS: In this retrospective observational study, we included 385 hospitalized SARS-CoV-2 positive patients at Karolinska University Hospital, Sweden with an HbA1c test obtained within 3 months before admission. Based on HbA1c level and previous diabetes history, we classified patients into the following dysglycemia categories: prediabetes, unknown diabetes, controlled diabetes, or uncontrolled diabetes. We used multivariable logistic regression analysis adjusted for age, sex, and body mass index, to assess the association between dysglycemia categories and development of SARS-CoV-2-induced respiratory failure. RESULTS: Of the 385 study patients, 88 (22.9%) had prediabetes, 68 (17.7%) had unknown diabetes, 36 (9.4%) had controlled diabetes, and 83 (21.6%) had uncontrolled diabetes. Overall, 299 (77.7%) patients were admitted with or developed SARS-CoV-2-induced respiratory failure during hospitalization. In multivariable logistic regression analysis compared with no chronic dysglycemia, prediabetes (OR 14.41, 95% CI 5.27-39.43), unknown diabetes (OR 15.86, 95% CI 4.55-55.36), and uncontrolled diabetes (OR 17.61, 95% CI 5.77-53.74) was independently associated with increased risk of SARS-CoV-2-induced respiratory failure. CONCLUSION: In our cohort of hospitalized SARS-CoV-2 positive patients with available HbA1c data, prediabetes, undiagnosed diabetes, and poorly controlled diabetes were associated with a markedly increased risk of SARS-CoV-2-associated respiratory failure.

Awake prone positioning in patients with hypoxemic respiratory failure due to COVID-19: the PROFLO multicenter randomized clinical trial.

BACKGROUND: The effect of awake prone positioning on intubation rates is not established. The aim of this trial was to investigate if a protocol for awake prone positioning reduces the rate of endotracheal intubation compared with standard care among patients with moderate to severe hypoxemic respiratory failure due to COVID-19. METHODS: We conducted a multicenter randomized clinical trial. Adult patients with confirmed COVID-19, high-flow nasal oxygen or noninvasive ventilation for respiratory support and a PaO2/FiO2 ratio ≤ 20 kPa were randomly assigned to a protocol targeting 16 h prone positioning per day or standard care. The primary endpoint was intubation within 30 days. Secondary endpoints included duration of awake prone positioning, 30-day mortality, ventilator-free days, hospital and intensive care unit length of stay, use of noninvasive ventilation, organ support and adverse events. The trial was terminated early due to futility. RESULTS: Of 141 patients assessed for eligibility, 75 were randomized of whom 39 were allocated to the control group and 36 to the prone group. Within 30 days after enrollment, 13 patients (33%) were intubated in the control group versus 12 patients (33%) in the prone group (HR 1.01 (95% CI 0.46-2.21), P = 0.99). Median prone duration was 3.4 h [IQR 1.8-8.4] in the control group compared with 9.0 h per day [IQR 4.4-10.6] in the prone group (P = 0.014). Nine patients (23%) in the control group had pressure sores compared with two patients (6%) in the prone group (difference - 18% (95% CI - 2 to - 33%); P = 0.032). There were no other differences in secondary outcomes between groups. CONCLUSIONS: The implemented protocol for awake prone positioning increased duration of prone positioning, but did not reduce the rate of intubation in patients with hypoxemic respiratory failure due to COVID-19 compared to standard care. TRIAL REGISTRATION: ISRCTN54917435. Registered 15 June 2020 ( https://doi.org/10.1186/ISRCTN54917435 ).

Characteristics and outcomes of patients with COVID-19 admitted to ICU in a tertiary hospital in Stockholm, Sweden.

BACKGROUND: Information on characteristics and outcomes of intensive care unit (ICU) patients with COVID-19 remains limited. We examined characteristics, clinical course and early outcomes of patients with COVID-19 admitted to ICU. METHODS: We included all 260 patients with COVID-19 admitted to nine ICUs at the Karolinska University Hospital (Stockholm, Sweden) between 9 March and 20 April 2020. Primary outcome was in-hospital mortality among patients with definite outcomes (discharged from ICU or death), as of 30 April 2020 (study end point). Secondary outcomes included ICU length of stay, the proportion of patients receiving mechanical ventilation and renal replacement therapy, and hospital discharge destination. RESULTS: Of 260 ICU patients with COVID-19, 208 (80.0%) were men, the median age was 59 (IQR 51-65) years, 154 (59.2%) had at least one comorbidity, and the median duration of symptoms preceding ICU admission was 11 (IQR 8-14) days. Sixty-two (23.8%) patients remained in ICU at study end point. Among the 198 patients with definite outcomes, ICU length of stay was 12 (IQR, 6-18) days, 163 (82.3%) received mechanical ventilation, 28 (14.1%) received renal replacement therapy, 60 (30.3%) died, 62 (31.3%) were discharged home, 47 (23.7%) were discharged to ward, and 29 (14.6%) were discharged to another health care facility. On multivariable logistic regression analysis, older age and admission from the emergency department was associated with higher mortality. CONCLUSION: This study presents detailed data on clinical characteristics and early outcomes of consecutive patients with COVID-19 admitted to ICU in a large tertiary hospital in Sweden.

Standardized Unloading of Respiratory Muscles during Neurally Adjusted Ventilatory Assist: A Randomized Crossover Pilot Study.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Currently, there is no standardized method to set the support level in neurally adjusted ventilatory assist (NAVA). The primary aim was to explore the feasibility of titrating NAVA to specific diaphragm unloading targets, based on the neuroventilatory efficiency (NVE) index. The secondary outcome was to investigate the effect of reduced diaphragm unloading on distribution of lung ventilation. METHODS: This is a randomized crossover study between pressure support and NAVA at different diaphragm unloading at a single neurointensive care unit. Ten adult patients who had started weaning from mechanical ventilation completed the study. Two unloading targets were used: 40 and 60%. The NVE index was used to guide the titration of the assist in NAVA. Electrical impedance tomography data, blood-gas samples, and ventilatory parameters were collected. RESULTS: The median unloading was 43% (interquartile range 32, 60) for 40% unloading target and 60% (interquartile range 47, 69) for 60% unloading target. NAVA with 40% unloading led to more dorsal ventilation (center of ventilation at 55% [51, 56]) compared with pressure support (52% [49, 56]; P = 0.019). No differences were found in oxygenation, CO2, and respiratory parameters. The electrical activity of the diaphragm was higher during NAVA with 40% unloading than in pressure support. CONCLUSIONS: In this pilot study, NAVA could be titrated to different diaphragm unloading levels based on the NVE index. Less unloading was associated with greater diaphragm activity and improved ventilation of the dependent lung regions.

Opioid use following cardio-thoracic intensive care: risk factors and outcomes: a cohort study.

Opioid misuse has become a serious public health problem. Patients admitted to cardio-thoracic critical care are usually exposed to opioids, but the incidence and effects of chronic opioid use are not known. The primary objective was to describe opioid use after admission to a cardio-thoracic intensive care unit. Secondary objectives were to identify factors associated with chronic opioid usage and analyze risk of death. This cohort study included all cardio-thoracic ICU care episodes in Sweden between 2010 and 2018. Among the 34,200 patients included in the final study cohort, 4050 developed persistent opioid use after ICU care. Younger age, preadmission opioid use, female sex, presence of comorbidities and earlier year of ICU admission were all found to be associated with persistent opioid use. The adjusted hazard ratio for mortality between 6 and 18 months after admission among individuals with persistent opioid use was 2.2 (95% CI 1.8-2.6; P < 0.001). For opioid-naïve patients before ICU admission, new onset of chronic opioid usage was significant during the follow-up period of 24 months. Despite the absence of conclusive evidence supporting extended opioid treatment, the average opioid consumption remains notably elevated twelve months subsequent to cardio-thoracic ICU care.

Lung impedance changes during awake prone positioning in COVID-19. A non-randomized cross-over study.

BACKGROUND: The effects of awake prone positioning (APP) on respiratory mechanics in patients with COVID-19 are not well characterized. The aim of this study was to investigate changes of global and regional lung volumes during APP compared with the supine position using electrical lung impedance tomography (EIT) in patients with hypoxemic respiratory failure due to COVID-19. MATERIALS AND METHODS: This exploratory non-randomized cross-over study was conducted at two university hospitals in Sweden between January and May 2021. Patients admitted to the intensive care unit with confirmed COVID-19, an arterial cannula in place, a PaO2/FiO2 ratio <26.6 kPa (<200 mmHg) and high-flow nasal oxygen or non-invasive ventilation were eligible for inclusion. EIT-data were recorded at supine baseline, at 30 and 60 minutes after APP-initiation, and 30 minutes after supine repositioning. The primary outcomes were changes in global and regional tidal impedance variation (TIV), center of ventilation (CoV), global and regional delta end-expiratory lung-impedance (dEELI) and global inhomogeneity (GI) index at the end of APP compared with supine baseline. Data were reported as median (IQR). RESULTS: All patients (n = 10) were male and age was 64 (47-73) years. There were no changes in global or regional TIV, CoV or GI-index during the intervention. dEELI increased from supine reference value 0 to 1.51 (0.32-3.62) 60 minutes after APP (median difference 1.51 (95% CI 0.19-5.16), p = 0.04) and returned to near baseline values after supine repositioning. Seven patients (70%) showed an increase >0.20 in dEELI during APP. The other EIT-variables did not change during APP compared with baseline. CONCLUSION: Awake prone positioning was associated with a transient lung recruiting effect without changes in ventilation distribution measured with EIT in patients with hypoxemic respiratory failure due to COVID-19.

Improved oxygenation in prone positioning of mechanically ventilated patients with COVID-19 acute respiratory distress syndrome is associated with decreased pulmonary shunt fraction: a prospective multicenter study.

BACKGROUND: Prone position is used in acute respiratory distress syndrome and in coronavirus disease 2019 (Covid-19) acute respiratory distress syndrome (ARDS). However, physiological mechanisms remain unclear. The aim of this study was to determine whether improved oxygenation was related to pulmonary shunt fraction (Q's/Q't), alveolar dead space (Vd/Vtalv) and ventilation/perfusion mismatch (V'A/Q'). METHODS: This was an international, prospective, observational, multicenter, cohort study, including six intensive care units in Sweden and Poland and 71 mechanically ventilated adult patients. RESULTS: Prone position increased PaO2:FiO2 after 30 min, by 78% (83-148 mm Hg). The effect persisted 120 min after return to supine (p < 0.001). The oxygenation index decreased 30 min after prone positioning by 43% (21-12 units). Q's/Q't decreased already after 30 min in the prone position by 17% (0.41-0.34). The effect persisted 120 min after return to supine (p < 0.005). Q's/Q't and PaO2:FiO2 were correlated both in prone (Beta -137) (p < 0.001) and in the supine position (Beta -270) (p < 0.001). V'A/Q' was unaffected and did not correlate to PaO2:FiO2 (p = 0.8). Vd/Vtalv increased at 120 min by 11% (0.55-0.61) (p < 0.05) and did not correlate to PaO2:FiO2 (p = 0.3). The ventilatory ratio increased after 30 min in the prone position by 58% (1.9-3.0) (p < 0.001). PaO2:FiO2 at baseline predicted PaO2:FiO2 at 30 min after proning (Beta 1.3) (p < 0.001). CONCLUSIONS: Improved oxygenation by prone positioning in COVID-19 ARDS patients was primarily associated with a decrease in pulmonary shunt fraction. Dead space remained high and the global V'A/Q' measure could not explain the differences in gas exchange.

Continuous renal replacement therapy in intensive care patients with COVID-19; survival and renal recovery.

BACKGROUND: Outcome for critically ill patients with COVID-19 treated with continuous renal replacement therapy (CRRT) is largely unknown. We describe mortality and renal outcome in this group. METHODS: This observational study was conducted at a university hospital in Sweden. We studied critically ill adult COVID-19 patients with Acute Kidney injury (AKI) who received CRRT. RESULTS: In 451 patients, AKI incidence was 43.7%. 18.2% received CRRT. Median age of CRRT patients was 60 years (IQR 54-65), 90% were male, median BMI was 29 (IQR 25-32), 23.2% had Diabetes, 37.8% hypertension and 6.1% chronic kidney disease prior to admission. 100% required mechanical ventilation. 8.5% received Extra Corporeal Membrane Oxygenation. Median length of stay was 23 days (IQR 15-26). ICU mortality was 39% and 90-day mortality was 45.1%. Age, baseline creatinine values and body weight change were associated with 60 days mortality. Of the survivors, no patients required dialysis at hospital discharge, 73.8% recovered renal function and a median 10.5% of body weight was lost during admission. CONCLUSIONS: Critically ill COVID-19 patients with AKI who received CRRT had a 90-day mortality of 45.1%. At follow-up, three quarters of survivors had recovered renal function. This information is important in the clinical management of COVID-19.

COVID-19 pathophysiology may be driven by an imbalance in the renin-angiotensin-aldosterone system.

SARS-CoV-2 uses ACE2, an inhibitor of the Renin-Angiotensin-Aldosterone System (RAAS), for cellular entry. Studies indicate that RAAS imbalance worsens the prognosis in COVID-19. We present a consecutive retrospective COVID-19 cohort with findings of frequent pulmonary thromboembolism (17%), high pulmonary artery pressure (60%) and lung MRI perfusion disturbances. We demonstrate, in swine, that infusing angiotensin II or blocking ACE2 induces increased pulmonary artery pressure, reduces blood oxygenation, increases coagulation, disturbs lung perfusion, induces diffuse alveolar damage, and acute tubular necrosis compared to control animals. We further demonstrate that this imbalanced state can be ameliorated by infusion of an angiotensin receptor blocker and low-molecular-weight heparin. In this work, we show that a pathophysiological state in swine induced by RAAS imbalance shares several features with the clinical COVID-19 presentation. Therefore, we propose that severe COVID-19 could partially be driven by a RAAS imbalance.

Neurally adjusted ventilatory assist and pressure support ventilation in small species and the impact of instrumental dead space.

BACKGROUND: Neurally adjusted ventilatory assist (NAVA) is a pneumatically-independent mode of mechanical ventilation controlled by diaphragm electrical activity (EAdi), and has not yet been implemented in very small species. OBJECTIVES: The aims of the study were to evaluate the feasibility of applying NAVA in very small species and to compare this to pressure support ventilation (PSV) in terms of ventilatory efficiency and breathing pattern, and evaluate the impact of instrumental dead space on breathing pattern during both modes. METHODS: Nine healthy rats (mean weight 385 +/- 4 g) were studied while breathing on PSV or NAVA, at baseline or with added dead space. RESULTS: A clear difference in breathing pattern between NAVA and PSV was observed during both baseline and dead space, where PSV - despite similar EAdi and tidal volume as during NAVA - caused shortened inspiratory time (p < 0.05) and increased the respiratory rate (p < 0.05). A higher minute ventilation (p < 0.05) in order to reach the same arterial CO(2) was observed. Ineffective inspiratory efforts occurred only during PSV and decreased with the dead space. CONCLUSION: This study demonstrates, in a small group of animals, that NAVA can deliver assist in very small species with a higher efficiency than PSV in terms of eliminating CO(2) for a given minute ventilation.