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

doi:10.1016/j.isci.2023.107429

Methemoglobin as a marker of acute anemic stress in cardiac surgery

iScience. 2023 Jul 20;26(8):107429. doi: 10.1016/j.isci.2023.107429. eCollection 2023 Aug 18.

Authors

Nikhil Mistry^{1

2}, Gregory M T Hare^{2

3

4

5}, Nadine Shehata⁶, Robert S Kramer⁷, Hosam F Fawzy⁸, Robert A Baker⁹, Paula Carmona¹⁰, Richard Saczkowski¹¹, Daniela Filipescu¹², Christella S Alphonsus¹³, Antoine Rochon¹⁴, Alexander J Gregory¹⁵, Boris Khanykin¹⁶, Jonathan D Leff¹⁷, Eva Mateo¹⁸, Dimos Karangelis¹⁹, Juan C Tellez²⁰, Tarit Saha²¹, Dennis T Ko^{22

23

24}, Duminda N Wijeysundera^{2

3

5

23

24}, Subodh Verma^{5

25

26}, C David Mazer^{1

2

3

4

5

26}

Affiliations

¹ Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada.
² Department of Anesthesia, St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.
³ Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, ON, Canada.
⁴ Department of Physiology, University of Toronto, Toronto, ON, Canada.
⁵ Li Ka Shing Knowledge Institute of St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.
⁶ Division of Hematology, Sinai Health System, Department of Medicine, University of Toronto, Toronto, ON, Canada.
⁷ Maine Medical Center Cardiovascular Institute, Portland, ME, USA.
⁸ Department of Cardiothoracic Surgery, Faculty of Medicine, University of Tanta, Tanta, Egypt.
⁹ Cardiac Surgery Research and Perfusion, Flinders University and Flinders Medical Centre, Adelaide, SA, Australia.
¹⁰ Cardiovascular-Anesthesia and Intensive Care. University Hospital La Fe, Valencia, Spain.
¹¹ Department of Cardiac Sciences, Perfusion Services, Kelowna General Hospital, Kelowna, BC, Canada.
¹² University of Medicine and Pharmacy Carol Davila, Emergency Institute for Cardiovascular Diseases "Prof. Dr. C.C. Iliescu", Bucharest, Romania.
¹³ Department of Anaesthesia and Perioperative Medicine, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa.
¹⁴ Montreal Heart Institute, Montreal, QC, Canada.
¹⁵ Department of Anesthesiology, Perioperative and Pain Medicine and Libin Cardiovascular Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
¹⁶ Cardiothoracic Anesthesiology Department, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
¹⁷ Montefiore-Einstein Center for Heart and Vascular Care, New York City, NY, USA.
¹⁸ Hospital General Universitario de València, València, Spain.
¹⁹ Department of Cardiothoracic Surgery, Democritus University of Thrace, Alexandroupolis, Greece.
²⁰ Marly Clinic, Bogotá, Cundinamarca, Colombia.
²¹ Department of Anesthesiology and Perioperative Medicine, Kingston General Hospital, Kingston, ON, Canada.
²² Schulich Heart Program, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
²³ Institute of Health Policy Management, and Evaluation, University of Toronto, Toronto, ON, Canada.
²⁴ ICES, Toronto, ON, Canada.
²⁵ Division of Cardiac Surgery, St. Michael's Hospital, Department of Surgery, University of Toronto, Toronto, ON, Canada.
²⁶ Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.

Abstract

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.

Keywords: Cardiovascular medicine; Health sciences; Public health; Surgery.

Associated data

ClinicalTrials.gov/NCT02042898