Study of Methemoglobin as a Biomarker of Tissue Hypoxia During Acute Hemodilution in Heart Surgery Patients
Condition: Other Functional Disturbances Following Cardiac Surgery
MeSH terms: Hypoxia
Study type: Observational

Summary: 
      Acute and chronic anemia continue to be associated with increased mortality in a number of
      clinical settings, including cardiac and non-cardiac surgery. However, "We have no clinical
      measures that let us know of impending insufficient oxygenation as anemia progresses" (R.B.
      Weiskopf). The current proposal is based on experimental and clinical data which suggest that
      plasma methemoglobin (MetHb) may be a sensitive biomarker of tissue hypoxia and "anemic
      stress" in surgical patients.

      Hypothesis: Increased methemoglobin is a biomarker of tissue hypoxia during acute anemia.

      Primary Objective: To demonstrate a direct relationship between decreased Hb and increased
      MetHb in patients undergoing acute hemodilution on cardiopulmonary bypass (CPB).
    

Detailed description: 
      Acute and chronic anemia continue to be associated with increased mortality in a number of
      clinical settings, including cardiac and non-cardiac surgery. 1-6 However, as recently stated
      by one of the pioneers of anemia research; Dr. R.B. Weiskopf: "We have no clinical measures
      that let us know of impending insufficient oxygenation as anemia progresses".7 Toward
      achieving this goal, we have developed experimental models to define the adaptive mechanisms
      which maintain oxygen homeostasis during acute anemia. Our research has identified that
      increased nitric oxide (NO) production by nitric oxide syntheses (NOSs) may be an important
      survival mechanism in acute anemia.3;8;9 Experimental data suggests that nNOS may promote
      survival by maintaining oxygen (O2) homeostasis during acute anemia.10 Resultant increases in
      nitric oxide (NO) contributes to adaptive cell signaling mechanisms and also increase
      oxidation of hemoglobin (Hb) to methemoglobin (MetHb).3 In addition, oxygen extraction
      results in increased levels of deoxyhemoglobin which has been proposed to act as a nitrite
      (NO2-) reductase to generate additional bioactive NO, thereby promoting vasodilation in
      hypoxic vascular beds.11-15 Thus, by more than one mechanism, increased MetHb may be
      indicative of hemoglobin desaturation, tissue hypoxia and activation of adaptive tissue
      responses to anemia. These responses may identify the threshold for local tissue hypoxia or
      "anemic stress". In attempt to determine if such mechanisms are active in humans we performed
      a retrospective study in patients undergoing cardiopulmonary bypass (CPB) during heart
      surgery to determine if plasma MetHb increased as Hb decreased during CPB. We observed an
      inverse relationship between Hb and MetHb that was independent of red blood cell transfusion
      and exogenous nitrate use
    

Intervention name(s): Brain Oximetry
Intervention type(s): Device
Intervention description(s): Non invasive brain oximeter will be applied on the patient's forehead to monitor the brain oxygen saturation throughout the surgery.
Other intervention name(s): Nonin equinox oximeter
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        heart surgery with cardiopulmonary bypass
      
Biospecimen description: 
      Plasma will be retained for analysis of plasma erythropietin, hepcidin and and
      nitrate/nitrite levels
    
Keywords: anemia; CPB; methemoglobin; hypoxia