Central Hemodynamics and Oxygen Transport in Patients With Acute Respiratory Distress Syndrome Caused by Covid-19 and Their Impact on the Course and Outcomes of the Disease

Abstract

The aim. Determine hemodynamic status and its impact on oxygen transport, frequency of adverse events and outcomes in patients with severe SARS-CoV-2 associated with acute respiratory distress syndrome (ARDS).
 Materials and methods. A single-center prospective comparative study was conducted with 29 patients enrolled over the period of July—October 2020 who suffered a severe course of coronavirus disease and bilateral pneumonia associated with ARDS. Based on the estimated cardiac index (CI), patients were allocated to two groups: Group 1 included 14 patients with severe ARDS and CI 1.9 [1.5–2.5] L/min/m2, whereas Group 2 included 15 patients with CI 4.2 [3.2–8.1] L/min/m2 (p=0.001). Patient`s intensive care was regulated by the relevant orders of the Ministry of Health of Ukraine. Statistical analysis of the results was carried out using Statistica 10 software. Statistical significance of parameters was assessed using the non-parametric Wilcoxon criterion. Results were considered significant at p values <0.05. Data are presented as M [25–75]. Relative risk (RR) and odds ratio (OR) of adverse events were calculated.
 Results. The severe course of coronavirus disease is associated with significant oxygen transport disorders that increase with hypovolemia. Despite the increase in oxygen delivery in the group with normal CI its high tissue extraction remained, which may be a sign of development mitochondrial distress.
 Conclusions. Patients admitted to the ICU with severe COVID-19 may be in a state of hypovolemia and require individual assessment of hemodynamic status and the appointment of infusion therapy. Increased oxygen delivery in patients with normal cardiac index was associated with decreased adverse events rate and statistically significant decrease of mortality rate

Biomarkers of mitochondrial dysfunction in acute respiratory distress syndrome: A systematic review and meta-analysis

“…Biomarkers of mitochondrial dysfunction reported in the included studies were: mitochondrial DNA (mtDNA) (eight studies) ( 6 , 10 – 16 ) glutathione coupled mediators [(referenced retrospectively, glutathione, glutanation, glutathione S -transferase (GST), L-gluatamate and glutathione perosidase)] (five studies) ( 17 – 21 ), lactate (three studies) ( 20 , 22 , 23 ), malondialdehyde (MDA) (three studies) ( 17 , 24 , 25 ), metabolic signaling pathways and mediators [(referenced retrospectively: Nicotinamide adenine dinucleotide (NADH), N-terminal peptide FMNPLAQ - also known as NADH2, glyceraldehyde-3-phosphate dehydrogenase-like 6 (GAPDHL6), sirtuin enrichment, xanthine and hypoxanthine)] (four studies) ( 26 – 29 ), oxidative stress associated markers [(hydrogen peroxide (H 2 O 2 ), super oxidase dismutase (SOD), ascorbate, alpha tocopherol, beta-carotene and retinol] (three studies) ( 24 , 30 , 31 ) ( Table 3 ). Notably, multiple studies reported more than one biomarker, as recorded in Tables 2 – 5 .…”

“…Seven studies (41%) reported numerical trends toward association of higher levels of mitochondrial biomarkers with higher mortality, however the association did not reach statistical significance, or insufficient numerical information was provided ( 17 , 23 , 27 , 29 – 32 ). Positively but non-significantly associated with mortality biomarkers consisted of: xanthine ( 30 ), glutathione, MDA ( 17 ), ascorbate, alpha-tocopherol ( 31 ), GAPDHL6 ( 27 ), glutathione peroxidase (selenium) ( 21 ), mediators of sirtuin signaling pathway, mediators of oxidative phosphorylation ( 29 ) and lactate ( 23 ).…”

“…The biomarker are as follows: MDA ( 17 , 24 ), glutathione ( 17 ), ascorbate, alpha-tocopherol ( 30 ), GSH, N-acetylcysteine ( 18 ), metabolite ion chromatograph ( 20 ), and mtDNA ( 12 , 13 , 16 , 33 ). One study showed an opposing finding, with decreased biomarker levels in association with ARDS disease progression, reporting higher lactate levels in non-ARDS compare to ARDS ( 23 ).…”

“…To reflect the biological differences between biomarkers measured in the systemic circulation vs. lung compartment, peripheral blood, arterial blood and plasma were combined for comparison under the category “blood based biomarkers” and biomarkers measured in the BAL or ELF were combined under the category “BAL based biomarkers”. Eight out of ten studies were eligible for this comparison ( 6 , 10 , 13 , 14 , 16 , 23 , 24 , 29 ). Several studies provided information on multiple biomarkers, Faust et al, and Nakahira et al, reported data from two cohorts, the data on different biomarkers and different cohorts were included in meta-analysis separately ( Figure 2 ).…”

“…MDA was measured in both BAL and plasma; this variation could be driving the lack of conclusive results. Interestingly, studies which investigated the levels of lactate, another metabolite indirectly representative of mitochondrial (20,22,23). As there is no consistency across all three studies, it is plausible that metabolites such as MDA and lactate are not useful as prospective biomarkers for ARDS clinical outcomes (53).…”