Implications of early respiratory support strategies on disease progression in critical COVID-19: a matched subanalysis of the prospective RISC-19-ICU cohort.

Uncertainty about the optimal respiratory support strategies in critically ill COVID-19 patients is widespread. While the risks and benefits of noninvasive techniques versus early invasive mechanical ventilation (IMV) are intensely debated, actual evidence is lacking. We sought to assess the risks and benefits of different respiratory support strategies, employed in intensive care units during the first months of the COVID-19 pandemic on intubation and intensive care unit (ICU) mortality rates. Subanalysis of a prospective, multinational registry of critically ill COVID-19 patients. Patients were subclassified into standard oxygen therapy ≥10 L/min (SOT), high-flow oxygen therapy (HFNC), noninvasive positive-pressure ventilation (NIV), and early IMV, according to the respiratory support strategy employed at the day of admission to ICU. Propensity score matching was performed to ensure comparability between groups. Initially, 1421 patients were assessed for possible study inclusion. Of these, 351 patients (85 SOT, 87 HFNC, 87 NIV, and 92 IMV) remained eligible for full analysis after propensity score matching. 55% of patients initially receiving noninvasive respiratory support required IMV. The intubation rate was lower in patients initially ventilated with HFNC and NIV compared to those who received SOT (SOT: 64%, HFNC: 52%, NIV: 49%, p = 0.025). Compared to the other respiratory support strategies, NIV was associated with a higher overall ICU mortality (SOT: 18%, HFNC: 20%, NIV: 37%, IMV: 25%, p = 0.016). In this cohort of critically ill patients with COVID-19, a trial of HFNC appeared to be the most balanced initial respiratory support strategy, given the reduced intubation rate and comparable ICU mortality rate. Nonetheless, considering the uncertainty and stress associated with the COVID-19 pandemic, SOT and early IMV represented safe initial respiratory support strategies. The presented findings, in agreement with classic ARDS literature, suggest that NIV should be avoided whenever possible due to the elevated ICU mortality risk

Prevention and Intervention Studies with Telmisartan, Ramipril and Their Combination in Different Rat Stroke Models

The effects of AT1 receptor blocker, telmisartan, and the ACE inhibitor, ramipril, were tested head-to head and in combination on stroke prevention in hypertensive rats and on potential neuroprotection in acute cerebral ischemia in normotensive rats. Normotensive Wistar rats were treated s.c. 5 days prior to middle cerebral artery occlusion (MCAO) for 90 min with reperfusion. Groups (n = 10 each): (1) sham, (2) vehicle (V; 0,9% NaCl), (3) T (0,5 mg/kg once daily), (4) R (0,01 mg/kg twice daily), (5) R (0,1 mg/kg twice daily) or (6) T (0,5 mg/kg once daily) plus R (0,01 mg/kg twice daily). Twenty-four and 48 h after MCAO, neurological outcome (NO) was determined. Forty-eight h after MCAO, infarct volume by MRI, neuronal survival, inflammation factors and neurotrophin receptor (TrkB) were analysed.Stroke incidence was reduced, survival was prolonged and neurological outcome was improved in all treated SHR-SP with no differences between treated groups. In the acute intervention study, T and T+R, but not R alone, improved NO, reduced infarct volume, inflammation (TNFα), and induced TrkB receptor and neuronal survival in comparison to V.T, R or T+R had similar beneficial effects on stroke incidence and NO in hypertensive rats, confirming BP reduction as determinant factor in stroke prevention. In contrast, T and T+R provided superior neuroprotection in comparison to R alone in normotensive rats with induced cerebral ischemia

Bronchoalveolar Lavage and Blood Markers of Infection in Critically Ill Patients—A Single Center Registry Study

Microbiological sampling is an indispensable targeted antibiotic therapy for critically ill patients. Invasive respiratory sampling by bronchoalveolar lavage (BAL) can be performed to obtain samples from the lower respiratory tract. It is debated as to whether blood markers of infection can predict the outcome of BAL in a medical intensive care unit (ICU). Retrospectively, all ICU patients undergoing BAL from 2009–2018 were included. A total of 468 BAL samples from 276 patients (average age 60 years, SAPS2 47, ICU-mortality 41.7%) were analyzed. At the time of BAL, 94.4% patients were mechanically ventilated, 92.9% had suspected pneumonia, 96.2% were on antibiotic therapy and 36.3% were immunocompromised. Relevant bacteria were cultured in 114/468 (24.4%) cases of BAL. Patients with relevant bacteria in the culture had a higher ICU mortality rate (45.6 vs. 40.4%, p = 0.33) and were significantly less likely to be on a steroid (36 vs. 52%, p p < 0.01), while procalcitonin (PCT), C-reactive protein (CRP), and white blood cell (WBC) counts were similar. The area under the receiver operating curve (AUC) values for positive culture and PCT, CRP and WBC counts were low (0.53, 0.54 and 0.51, respectively). In immunocompromised patients, AUC values were higher (0.65, 0.57 and 0.61, respectively). Therefore, microbiological cultures by BAL revealed relevant bacteria in 24.4% of samples. Our data, therefore, might suggest that indication for BAL should not be based on blood markers of infection