Met-Hemoglobin Is a Biomarker for Poor Oxygen Delivery in Infants Following Surgical Palliation

Abstract

Background:

Infants with cyanotic congenital heart disease demonstrate wide fluctuations in hemoglobin (Hb), oxygen saturation, and cardiac output following palliation. Methemoglobin (Met-Hb), the product of Hb oxidation, may represent a compensatory mechanism during hypoxia and may be utilized as a biomarker.

Methods:

Arterial and venous Met-Hb levels were obtained from infants requiring palliation. The primary outcome was to describe the relationship between Met-Hb and other indices of tissue oxygenation (venous saturation, estimated arteriovenous oxygen difference [Est AV-Diff], and lactate). Secondary outcomes were to determine the impact of elevated Met-Hb levels ≥1.0% and the effect of red blood cell (RBC) transfusion on Met-Hb levels.

Results:

Fifty infants and 465 Met-Hb values were studied. Venous Met-Hb levels were significantly higher than arterial levels (venous: 0.84% ± 0.36% vs arterial: 0.45% ± 0.18%; P < .001). Venous Met-Hb demonstrated a significant inverse relationship with venous oxygen saturation (R = −0.6; P < .001) and Hb (R = −0.3, P < .001) and a direct relationship with the Est AV-Diff (R = 0.3, P < .001). A total of 129 (29.6%) venous Met-Hb values were elevated (≥1.0%) and were associated with significantly lower Hb and venous saturation levels and higher Est AV-Diff and lactate levels. Methemoglobin levels decreased significantly following 65 RBC transfusions (0.94 ± 0.40 vs 0.77 ± 0.34; P < .001). Linear mixed models demonstrated that higher venous Met-Hb levels were associated with lower measures of tissue oxygenation and not related to any preoperative clinical differences.

Conclusion:

Methemoglobin may be a clinically useful marker of tissue oxygenation in infants following surgical palliation.

Keywords

blood transfusion blood hypoxia/reoxygenation infants

Get full access to this article

View all access options for this article.

References

Ranucci

Isgro

Carlucci

. Central venous oxygen saturation and blood lactate levels during cardiopulmonary bypass are associated with outcome after pediatric cardiac surgery. Crit Care. 2010;14(4):R149.

Schumacher

Reichel

Vlasic

. Rate of increase in serum lactate level risk stratifies infants after surgery for congenital heart disease. J Thorac Cardiovasc Surg. 2014;148(2):589–595.

Charpie

Dekeon

Goldberg

. Serial blood lactate measurements predict early outcome after neonatal repair or palliation for complex congenital heart disease. J Thorac Cardiovasc Surg. 2000;120(1):73–80.

Murtuza

Wall

Reinhardt

. The importance of blood lactate clearance as a predictor of early mortality following the modified Norwood procedure. Eur J Cardiothorac Surg. 2001;40(5):1207–1214.

Kalyanaraman

DeCampli

Campbell

. Serial blood lactate levels as a predictor of mortality in children after cardiopulmonary bypass surgery. Pediatr Crit Care Med. 2008;9(3):285–288.

Willems

Harrington

Lacroix

. Comparison of two red-cell transfusion strategies after pediatric cardiac surgery: a subgroup analysis. Crit Care Med. 2010;38(2):649–656.

de Gast-Bakker

de Wilde

Hazekamp

. Safety and effects of two red blood cell transfusion strategies in pediatric cardiac surgery patients: a randomized controlled trial. Intensive Care Med. 2013;39(11):2011–2019.

Lacroix

Hébert

Hutchison

. Transfusion strategies for patients in pediatric intensive care units. N Engl J Med. 2007;356(16):1609–1619.

Cholette

Swartz

Rubenstein

. Outcomes using a conservative versus liberal red blood cell transfusion strategy in infants requiring cardiac operation. Ann Thorac Surg. 2017;103(1):206–214.

10.

Cholette

Rubenstein

Alfieris

. Children with single ventricle physiology do not benefit from higher hemoglobin levels post cavopulmonary connection: results of a prospective, randomized controlled trial of a restrictive versus liberal red-cell transfusion strategy. Pediatr Crit Care Med. 2011;12(1):39–45.

11.

Said

Rogers

Doctor

. Red cell physiology and signaling relevant to the critical care setting. Curr Opin Pediatr. 2015;27(3):267–276.

12.

Doctor

Stamler

. Nitric oxide transport in blood: a third gas in the respiratory cycle. Compr Physiol. 2011;1(1):541–568.

13.

Luchsinger

Rich

Gow

Williams

Stamler

Singel

. Routes to S-nitroso-hemoglobin formation with heme redox and preferential reactivity in the beta subunits. Proc Natl Acad Sci U S A. 2003;100(2):461–466.

14.

Angelo

Singel

Stamler

. An S-nitrosothiol (SNO) synthase function of hemoglobin that utilizes nitrite as a substrate. Proc Natl Acad Sci U S A. 2006;103(22):8366–8371.

15.

Hare

GMT

Tsui

AKY

Crawford

Patel

. Is methemoglobin an inert bystander, biomarker, or a mediator of oxidative stress—The example of anemia. Redox Biol. 2013;1:65–69.

16.

Hare

Romaschin

. Plasma Methemoglobin as a potential biomarker of anemic stress in humans. Can J Anaesth. 2012;59(4):348–356.

17.

Williams

Mickell

Young

Shapiro

Lofland

. Methemoglobin levels during prolonged combined nitroglycerin and sodium nitroprusside infusions in infants after cardiac surgery. J Cardiothorac Vasc Anesth. 1994;8(6):658–662.

18.

Hermon

Burda

Golej

. Methemoglobin formation in children with congenital heart disease treated with inhaled nitric oxide after cardiac surgery. Intensive Care Med. 2003;29(3):447–452.

19.

Kocsi

Demeter

Fogas

. Central venous oxygen saturation is a good indicator of altered oxygen balance in isovolemic anemia. Acta Anaesthesiol Scan 2012;56(3):291–297.

20.

De Cort

Innes

Barstow

. Cardiac output, oxygen consumption and arteriovenous oxygen difference following a sudden rise in exercise in humans. J Physiol. 1991;441:501–512.

21.

Von Roedem

Buriko

Prittie

Lamb

. Investigation of iron status and markers of inflammation in anaemic and non-anaemic hospitalized cats. J Small Anim Pract. 2017;58(6):323–329.

22.

Martin-Montalvo

Sun

Dias-Ruiz

. Cytochrome b5 reductase and the control of lipid metabolism and healthspan. NPJ Aging Mech Dis. 2016;12(2):1–12.

23.

Hare

GMT

Han

Leshchyshyn

. Potential biomarkers of tissue hypoxia during acute hemodilutional anemia in cardiac surgery: a prospective study to assess tissue hypoxia as a mechanism of organ injury. Can J Anesth. 2018;65(8):901–913.

24.

Zaouter

Zavorsky

. The measurement of carboxyhemoglobin and methemoglobin using an non-invasive pulse CO-oximeter. Resp Physiol Neurobiol. 2012;182(2-3):88–92.