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

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. WijeysunderaSubodh Verma, C. David Mazer

College of Medicine and Public Health

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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.

Original language	English
Article number	107429
Number of pages	12
Journal	iScience
Volume	26
Issue number	8
Early online date	20 Jul 2023
DOIs	https://doi.org/10.1016/j.isci.2023.107429
Publication status	Published - 18 Aug 2023

Keywords

Cardiovascular medicine
Health sciences
Public health
Surgery

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.isci.2023.107429Licence: CC BY-NC-ND

Final published versionFinal published version, 1.23 MBLicence: CC BY-NC-ND

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Mistry, N., Hare, G. M. T., Shehata, N., Kramer, R. S., Fawzy, H. F., Baker, R. A., Carmona, P., Saczkowski, R., Filipescu, D., Alphonsus, C. S., Rochon, A., Gregory, A. J., Khanykin, B., Leff, J. D., Mateo, E., Karangelis, D., Tellez, J. C., Saha, T., Ko, D. T., ... Mazer, C. D. (2023). Methemoglobin as a marker of acute anemic stress in cardiac surgery. iScience, 26(8), Article 107429. https://doi.org/10.1016/j.isci.2023.107429

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title = "Methemoglobin as a marker of acute anemic stress in cardiac surgery",

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",

author = "Nikhil Mistry and Hare, {Gregory M.T.} and Nadine Shehata and Kramer, {Robert S.} and Fawzy, {Hosam F.} and Baker, {Robert A.} and Paula Carmona and Richard Saczkowski and Daniela Filipescu and Alphonsus, {Christella S.} and Antoine Rochon and Gregory, {Alexander J.} and Boris Khanykin and Leff, {Jonathan D.} and Eva Mateo and Dimos Karangelis and Tellez, {Juan C.} and Tarit Saha and Ko, {Dennis T.} and Wijeysundera, {Duminda N.} and Subodh Verma and Mazer, {C. David}",

year = "2023",

month = aug,

day = "18",

doi = "10.1016/j.isci.2023.107429",

language = "English",

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Mistry, N, Hare, GMT, Shehata, N, Kramer, RS, Fawzy, HF, Baker, RA, Carmona, P, Saczkowski, R, Filipescu, D, Alphonsus, CS, Rochon, A, Gregory, AJ, Khanykin, B, Leff, JD, Mateo, E, Karangelis, D, Tellez, JC, Saha, T, Ko, DT, Wijeysundera, DN, Verma, S & Mazer, CD 2023, 'Methemoglobin as a marker of acute anemic stress in cardiac surgery', iScience, vol. 26, no. 8, 107429. https://doi.org/10.1016/j.isci.2023.107429

TY - JOUR

T1 - Methemoglobin as a marker of acute anemic stress in cardiac surgery

AU - Mistry, Nikhil

AU - Hare, Gregory M.T.

AU - Shehata, Nadine

AU - Kramer, Robert S.

AU - Fawzy, Hosam F.

AU - Baker, Robert A.

AU - Carmona, Paula

AU - Saczkowski, Richard

AU - Filipescu, Daniela

AU - Alphonsus, Christella S.

AU - Rochon, Antoine

AU - Gregory, Alexander J.

AU - Khanykin, Boris

AU - Leff, Jonathan D.

AU - Mateo, Eva

AU - Karangelis, Dimos

AU - Tellez, Juan C.

AU - Saha, Tarit

AU - Ko, Dennis T.

AU - Wijeysundera, Duminda N.

AU - Verma, Subodh

AU - Mazer, C. David

PY - 2023/8/18

Y1 - 2023/8/18

N2 - 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.

AB - 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.

KW - Cardiovascular medicine

KW - Health sciences

KW - Public health

KW - Surgery

UR - http://www.scopus.com/inward/record.url?scp=85169817701&partnerID=8YFLogxK

UR - http://purl.org/au-research/grants/NHMRC/1085942

U2 - 10.1016/j.isci.2023.107429

DO - 10.1016/j.isci.2023.107429

M3 - Article

AN - SCOPUS:85169817701

SN - 2589-0042

VL - 26

JO - iScience

JF - iScience

IS - 8

M1 - 107429

ER -

Methemoglobin as a marker of acute anemic stress in cardiac surgery

Abstract

Keywords

UN SDGs

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