Protocol for the MicroRESUS study: The impact of circulatory shock and resuscitation on microcirculatory function and mitochondrial respiration after cardiovascular surgery

• Published in: PloS one Vol. 17; no. 8; p. e0273349
• Main Authors: Greenwood, John C, Talebi, Fatima M, Jang, David H, Spelde, Audrey E, Kilbaugh, Todd J, Shofer, Frances S, Acker, Michael A, Augoustides, John G. T, Bakker, Jan, Meyer, Nuala J, Brenner, Jacob S, Muzykantov, Vladimir R, Abella, Benjamin S
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 26.08.2022; Public Library of Science (PLoS)
• Subjects: Abnormalities; Acidosis; Biology and Life Sciences; Biomarkers; Blood; Blood cells; Blood pressure; Blood vessels; Cardiac output; Cardiovascular system; Clinical outcomes; Consent; CPR (First aid); Critical components; Heart; Heart surgery; Hemodynamics; Human tissues; Injury analysis; Leukocytes (mononuclear); Medicine and Health Sciences; Methods; Mitochondria; Mitochondrial membranes; Observational studies; Oxygen; Oxygen saturation; Patients; Peripheral blood mononuclear cells; Physical Sciences; Physiological aspects; Pulmonary arteries; Respiration; Respirometry; Resuscitation; Shock; Shock (Circulatory); Study Protocol; Substrate inhibition; Surgery; Titration; Veins & arteries; United States; United States > US; Netherlands
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0273349

Despite current resuscitation strategies, circulatory shock and organ injury after cardiac surgery occur in 25-40% of patients. Goal-directed resuscitation after cardiac surgery has generated significant interest, but clinical practice to normalize hemodynamic variables including mean arterial pressure, cardiac filling pressures, and cardiac output may not reverse microcirculation abnormalities and do not address cellular dysoxia. Recent advances in technology have made it possible to measure critical components of oxygen delivery and oxygen utilization systems in live human tissues and blood cells. The MicroRESUS study will be the first study to measure microcirculatory and mitochondrial function in patients with circulatory shock and link these findings with clinical outcomes. This will be a prospective, observational study that includes patients undergoing elective cardiovascular surgery with cardiopulmonary bypass (CPB). Microcirculation will be quantified with sublingual incident dark field videomicroscopy. Mitochondrial respiration will be measured by performing a substrate-uncoupler-inhibitor titration protocol with high resolution respirometry on peripheral blood mononuclear cells at baseline and serial timepoints during resuscitation and at recovery as a possible liquid biomarker. Plasma samples will be preserved for future analysis to examine endothelial injury and other mechanisms of microcirculatory dysfunction. Thirty-day ventilator and vasopressor-free days (VVFDs) will be measured as a primary outcome, along with sequential organ failure assessment scores, and other clinical parameters to determine if changes in microcirculation and mitochondrial respiration are more strongly associated with clinical outcomes compared to traditional resuscitation targets. This will be the first prospective study to examine both microcirculatory and mitochondrial function in human patients with circulatory shock undergoing cardiac bypass and address a key mechanistic knowledge gap in the cardiovascular literature. The results of this study will direct future research efforts and therapeutic development for patients with shock.