Individualized mechanical ventilation in a shared ventilator setting: limits, safety and technical details.

The COVID-19 pandemic has resulted in an increased need for ventilators. The potential to ventilate more than one patient with a single ventilator, a so-called split ventilator setup, provides an emergency solution. Our hypothesis is that ventilation can be individualized by adding a flow restrictor to limit tidal volumes, add PEEP, titrate FiO2 and monitor ventilation. This way we could enhance optimization of patient safety and clinical applicability. We performed bench testing to test our hypothesis and identify limitations. We performed a bench testing in two test lungs: (1) determine lung compliance (2) determine volume, plateau pressure and PEEP, (3) illustrate individualization of airway pressures and tidal volume with a flow restrictor, (4a) illustrate that PEEP can be applied and individualized (4b) create and measure intrinsic PEEP (4c and d) determine PEEP as a function of flow restriction, (5) individualization of FiO2. The lung compliance varied between 13 and 27 mL/cmH2O. Set ventilator settings could be applied and measured. Extrinsic PEEP can be applied except for settings with a large expiratory time. Volume and pressure regulation is possible between 70 and 39% flow restrictor valve closure. Flow restriction in the tested circuit had no effect on the other circuit or on intrinsic PEEP. FiO2 could be modulated individually between 0.21 and 0.8 by gradually adjusting the additional flow, and minimal affecting FiO2 in the other circuit. Tidal volumes, PEEP and FiO2 can be individualized and monitored in a bench testing of a split ventilator. In vivo research is needed to further explore the clinical limitations and outcomes, making implementation possible as a last resort ventilation strategy.

Fatal lymphocytic cardiac damage in coronavirus disease 2019 (COVID-19): autopsy reveals a ferroptosis signature.

AIMS: Cardiovascular complications, including myocarditis, are observed in coronavirus disease 2019 (COVID-19). Major cardiac involvement is a potentially lethal feature in severe cases. We sought to describe the underlying pathophysiological mechanism in COVID-19 lethal cardiogenic shock. METHODS AND RESULTS: We report on a 48-year-old male COVID-19 patient with cardiogenic shock; despite extracorporeal life support, dialysis, and massive pharmacological support, this rescue therapy was not successful. Severe acute respiratory syndrome coronavirus 2 RNA was detected at autopsy in the lungs and myocardium. Histopathological examination revealed diffuse alveolar damage, proliferation of type II pneumocytes, lymphocytes in the lung interstitium, and pulmonary microemboli. Moreover, patchy muscular, sometimes perivascular, interstitial mononuclear inflammatory infiltrates, dominated by lymphocytes, were seen in the cardiac tissue. The lymphocytes 'interlocked' the myocytes, resulting in myocyte degeneration and necrosis. Predominantly, T-cell lymphocytes with a CD4:CD8 ratio of 1.7 infiltrated the interstitial myocardium, reflecting true myocarditis. The myocardial tissue was examined for markers of ferroptosis, an iron-catalysed form of regulated cell death that occurs through excessive peroxidation of polyunsaturated fatty acids. Immunohistochemical staining with E06, a monoclonal antibody binding to oxidized phosphatidylcholine (reflecting lipid peroxidation during ferroptosis), was positive in morphologically degenerating and necrotic cardiomyocytes adjacent to the infiltrate of lymphocytes, near arteries, in the epicardium and myocardium. A similar ferroptosis signature was present in the myocardium of a COVID-19 subject without myocarditis. In a case of sudden death due to viral myocarditis of unknown aetiology, however, immunohistochemical staining with E06 was negative. The renal proximal tubuli stained positively for E06 and also hydroxynonenal (4-HNE), a reactive breakdown product of the lipid peroxides that execute ferroptosis. In the case of myocarditis of other aetiology, the renal tissue displayed no positivity for E06 or 4-HNE. CONCLUSIONS: The findings in this case are unique as this is the first report on accumulated oxidized phospholipids (or their breakdown products) in myocardial and renal tissue in COVID-19. This highlights ferroptosis, proposed to detrimentally contribute to some forms of ischaemia-reperfusion injury, as a detrimental factor in COVID-19 cardiac damage and multiple organ failure.

LOGIC-insulin algorithm-guided versus nurse-directed blood glucose control during critical illness: the LOGIC-1 single-center, randomized, controlled clinical trial.

OBJECTIVE: Tight blood glucose control (TGC) in critically ill patients is difficult and labor intensive, resulting in poor efficacy of glycemic control and increased hypoglycemia rate. The LOGIC-Insulin computerized algorithm has been developed to assist nurses in titrating insulin to maintain blood glucose levels at 80-110 mg/dL (normoglycemia) and to avoid severe hypoglycemia (<40 mg/dL). The objective was to validate clinically LOGIC-Insulin relative to TGC by experienced nurses. RESEARCH DESIGN AND METHODS: The investigator-initiated LOGIC-1 study was a prospective, parallel-group, randomized, controlled clinical trial in a single tertiary referral center. A heterogeneous mix of 300 critically ill patients were randomized, by concealed computer allocation, to either nurse-directed glycemic control (Nurse-C) or algorithm-guided glycemic control (LOGIC-C). Glycemic penalty index (GPI), a measure that penalizes both hypoglycemic and hyperglycemic deviations from normoglycemia, was the efficacy outcome measure, and incidence of severe hypoglycemia (<40 mg/dL) was the safety outcome measure. RESULTS: Baseline characteristics of 151 Nurse-C patients and 149 LOGIC-C patients and study times did not differ. The GPI decreased from 12.4 (interquartile range 8.2-18.5) in Nurse-C to 9.8 (6.0-14.5) in LOGIC-C (P < 0.0001). The proportion of study time in target range was 68.6 ± 16.7% for LOGIC-C patients versus 60.1 ± 18.8% for Nurse-C patients (P = 0.00016). The proportion of severe hypoglycemic events was decreased in the LOGIC-C group (Nurse-C 0.13%, LOGIC-C 0%; P = 0.015) but not when considered as a proportion of patients (Nurse-C 3.3%, LOGIC-C 0%; P = 0.060). Sampling interval was 2.2 ± 0.4 h in the LOGIC-C group versus 2.5 ± 0.5 h in the Nurse-C group (P < 0.0001). CONCLUSIONS: Compared with expert nurses, LOGIC-Insulin improved efficacy of TGC without increasing rate of hypoglycemia.