Study of Methemoglobin as a Biomarker of Tissue Hypoxia During Acute Hemodilution in Heart Surgery Patients
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| ClinicalTrials.gov Identifier: NCT01883713 |
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Recruitment Status :
Completed
First Posted : June 21, 2013
Last Update Posted : April 17, 2018
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Sponsor:
Unity Health Toronto
Information provided by (Responsible Party):
Unity Health Toronto
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Brief 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).
| Condition or disease | Intervention/treatment |
|---|---|
| Other Functional Disturbances Following Cardiac Surgery | Device: Brain Oximetry |
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
| Study Type : | Observational |
| Actual Enrollment : | 68 participants |
| Observational Model: | Cohort |
| Time Perspective: | Prospective |
| Official Title: | A Prospective Analysis of Methemoglobin as a Biomarker of Tissue Hypoxia During Acute Hemodilutional Anemia in Patients Undergoing Heart Surgery |
| Study Start Date : | January 2013 |
| Actual Primary Completion Date : | August 2016 |
| Actual Study Completion Date : | August 2016 |
Resource links provided by the National Library of Medicine
| Group/Cohort | Intervention/treatment |
|---|---|
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Heart surgery during CPB
All patients undergoing heart surgery using cardiopulmonary bypass who have a pre-operative Hb value greater than 90 g/L, no evidence of hypoxemia (SaO2 > 90%) and no history of congenital methemoglobinemia. Exclusion criteria will include severe hypoxemia, acute or chronic renal failure requiring dialysis, emergency surgery or the lack of a PA catheter. Non invasive brain oximetry will be used to assess the brain oxygen tension during surgical procedure.
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Device: Brain Oximetry
Non invasive brain oximeter will be applied on the patient's forehead to monitor the brain oxygen saturation throughout the surgery.
Other Name: Nonin equinox oximeter |
Primary Outcome Measures :
- Arterial methemoglobin levels [ Time Frame: 18 months ]To determine if there is an association between increased methemoglobin and tissue hypoxia following heart surgery
Secondary Outcome Measures :
- Cerebral tissue oxygen saturation [ Time Frame: 18 months ]
- Plasma erythropoietin levels [ Time Frame: 18 months ]
- Plasma nitrate/nitrite levels [ Time Frame: 18 months ]
- Plasma hepcidin levels [ Time Frame: 18 months ]Relationship between plasma hepcidin levels and hemoglobin levels
Other Outcome Measures:
- Adverse outcomes including mortality, myocardial infarction, low output syndrome, stroke and renal dysfunction [ Time Frame: 18 months ]
Biospecimen Retention: Samples With DNA
Plasma will be retained for analysis of plasma erythropietin, hepcidin and and nitrate/nitrite levels
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| Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
| Sampling Method: | Non-Probability Sample |
Study Population
heart surgery with cardiopulmonary bypass
Criteria
Inclusion Criteria:
- patients undergoing heart surgery using cardiopulmonary bypass at St. Michael's Hospital who have a pre-operative Hb value greater than 90 g/L, no evidence of hypoxemia (SaO2 > 90%) and no history of congenital methemoglobinemia.
Exclusion Criteria:
- severe hypoxemia, acute or chronic renal failure requiring dialysis, emergency surgery or the lack of a PA catheter (current standard of care at St. Michael's Hospital is to insert a PA catheter in > 90% of patients).
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01883713
Locations
| Canada, Ontario | |
| St. Michael's Hospital | |
| Toronto, Ontario, Canada, M5B 1W8 | |
Sponsors and Collaborators
Unity Health Toronto
Investigators
| Principal Investigator: | Gregory Hare, MD, PhD | Unity Health Toronto |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Unity Health Toronto |
| ClinicalTrials.gov Identifier: | NCT01883713 |
| Other Study ID Numbers: |
REB# 12-015 |
| First Posted: | June 21, 2013 Key Record Dates |
| Last Update Posted: | April 17, 2018 |
| Last Verified: | April 2018 |
Keywords provided by Unity Health Toronto:
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anemia CPB methemoglobin hypoxia |
Additional relevant MeSH terms:
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Hypoxia Signs and Symptoms, Respiratory |