iScience (Aug 2023)
Methemoglobin as a marker of acute anemic stress in cardiac surgery
- Nikhil Mistry,
- Gregory M.T. Hare,
- Nadine Shehata,
- Robert S. Kramer,
- Hosam F. Fawzy,
- Robert A. Baker,
- Paula Carmona,
- Richard Saczkowski,
- Daniela Filipescu,
- Christella S. Alphonsus,
- Antoine Rochon,
- Alexander J. Gregory,
- Boris Khanykin,
- Jonathan D. Leff,
- Eva Mateo,
- Dimos Karangelis,
- Juan C. Tellez,
- Tarit Saha,
- Dennis T. Ko,
- Duminda N. Wijeysundera,
- Subodh Verma,
- C. David Mazer
Affiliations
- Nikhil Mistry
- Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada; Department of Anesthesia, St. Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada
- Gregory M.T. Hare
- Department of Anesthesia, St. Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada; Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, ON, Canada; Department of Physiology, University of Toronto, Toronto, ON, Canada; Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada; Corresponding author
- Nadine Shehata
- Division of Hematology, Sinai Health System, Department of Medicine, University of Toronto, Toronto, ON, Canada
- Robert S. Kramer
- Maine Medical Center Cardiovascular Institute, Portland, ME, USA
- Hosam F. Fawzy
- Department of Cardiothoracic Surgery, Faculty of Medicine, University of Tanta, Tanta, Egypt
- Robert A. Baker
- Cardiac Surgery Research and Perfusion, Flinders University and Flinders Medical Centre, Adelaide, SA, Australia
- Paula Carmona
- Cardiovascular-Anesthesia and Intensive Care. University Hospital La Fe, Valencia, Spain
- Richard Saczkowski
- Department of Cardiac Sciences, Perfusion Services, Kelowna General Hospital, Kelowna, BC, Canada
- Daniela Filipescu
- University of Medicine and Pharmacy Carol Davila, Emergency Institute for Cardiovascular Diseases “Prof. Dr. C.C. Iliescu”, Bucharest, Romania
- Christella S. Alphonsus
- Department of Anaesthesia and Perioperative Medicine, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa
- Antoine Rochon
- Montreal Heart Institute, Montreal, QC, Canada
- Alexander J. Gregory
- Department of Anesthesiology, Perioperative and Pain Medicine and Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
- Boris Khanykin
- Cardiothoracic Anesthesiology Department, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
- Jonathan D. Leff
- Montefiore-Einstein Center for Heart and Vascular Care, New York City, NY, USA
- Eva Mateo
- Hospital General Universitario de València, València, Spain
- Dimos Karangelis
- Department of Cardiothoracic Surgery, Democritus University of Thrace, Alexandroupolis, Greece
- Juan C. Tellez
- Marly Clinic, Bogotá, Cundinamarca, Colombia
- Tarit Saha
- Department of Anesthesiology and Perioperative Medicine, Kingston General Hospital, Kingston, ON, Canada
- Dennis T. Ko
- Schulich Heart Program, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada; Institute of Health Policy Management, and Evaluation, University of Toronto, Toronto, ON, Canada; ICES, Toronto, ON, Canada
- Duminda N. Wijeysundera
- Department of Anesthesia, St. Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada; Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, ON, Canada; Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada; Institute of Health Policy Management, and Evaluation, University of Toronto, Toronto, ON, Canada; ICES, Toronto, ON, Canada
- Subodh Verma
- Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada; Division of Cardiac Surgery, St. Michael’s Hospital, Department of Surgery, University of Toronto, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada
- C. David Mazer
- Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada; Department of Anesthesia, St. Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada; Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, ON, Canada; Department of Physiology, University of Toronto, Toronto, ON, Canada; Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Unity Health Toronto, Toronto, ON, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada; Corresponding author
- Journal volume & issue
-
Vol. 26,
no. 8
p. 107429
Abstract
Summary: Biological evidence supports plasma methemoglobin as a biomarker for anemia-induced tissue hypoxia. In this translational planned substudy of the multinational randomized controlled transfusion thresholds in cardiac surgery (TRICS-III) trial, which included adults undergoing cardiac surgery requiring cardiopulmonary bypass with a moderate-to-high risk of death, we investigated the relationship between perioperative hemoglobin concentration (Hb) and methemoglobin; and evaluated its association with postoperative outcomes. The primary endpoint was a composite of death, myocardial infarction, stroke, and severe acute kidney injury at 28 days. We observe weak non-linear associations between decreasing Hb and increasing methemoglobin, which were strongest in magnitude at the post-surgical time point. Increased levels of post-surgical methemoglobin were associated with a trend toward an elevated risk for stroke and exploratory neurological outcomes. Our generalizable study demonstrates post-surgical methemoglobin may be a marker of anemia-induced organ injury/dysfunction, and may have utility for guiding personalized approaches to anemia management. Clinicaltrials.gov registration NCT02042898.
