Insufficient Cellular Oxygen in ICU Patients With Anaemia

Study Overview
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Brief Summary
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The purpose of this study is whether the mitochondrial oxygenation tension (mitoPO2) is a feasible and reliable tool in ICU patients with anaemia undergoing red cell transfusion to ultimately personalize blood transfusion decisions in the ICU.

Detailed Description
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Evidence is increasing that in some cases a Hb trigger of 7-8g/dl may be too low and te question arises whether an individualized red cell transfusion strategy may benefit critically ill patients. New studies have shown the potential of protoporphyrin IX-triple state lifetime technique to measure mitochondrial oxygenation tension (mitoPO2) in vivo, which possibly is an early indicator of oxygen disturbance in the cell and therefore a physiological trigger for red cell transfusion. The goals are: 1. Determining the feasibility of using mitoPO2 and the variability of mitoPO2 measurements in critically ill intensive care unit (ICU) patients before and after receiving a red cell transfusion 2. Describing the effects of red cell transfusion and the associated change in [Hb] on mitoPO2 and on other physiologic measures of tissue oxygenation and oxygen balance 3. Describing the association between mitoPO2 and vital organ functions. Included patients will undergo red cell transfusion as planned. However, red cell transfusion will be delayed by 2 hours. At multiple predefined moments data collection including blood samples and measurements of mitoPO2 will take place. The results of this study cannot be immediately translated to clinical practice. Using these results, the investigators will design a phase 2 diagnostic study, most probably a randomized clinical trial that will yield applied knowledge with respect to personalizing red cell transfusion. Application will be in ICU patients with anaemia who might or might not profit from red cell transfusions. It will lead to a reduction of both over- and under- transfusion.

Official Title
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Insufficient Cellular Oxygen in ICU Patients With Anaemia: the INOX ICU-2 Study

Conditions
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Critical Care, Anemia, Erythrocyte Transfusion, Oxygen, Mitochondria

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patient admitted to the ICU Hb below 6.3 mmol/l (10 g/dl) central venous catheter in situ red cell transfusion planned Exclusion Criteria: adults without a legal representative to ask for informed consent patients less than 18 years old pregnant or breast feeding women patients in need of emergency red cell transfusion e.g. bleeding not having a central venous catheter in situ porphyria and or known photodermatosis patients with an expected ICU stay <24 hours patients with hypersensitivity to the active substance or to the plaster material of ALA

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ICU patients with anaemia<br>At admission to the ICU all patients, or their legal representatives, expected to stay at the ICU for longer than 24 hours will be asked to participate in the study and will be asked informed consent. ICU patients with anaemia in whom a central venous catheter is already in place and in whom a red cell transfusion is planned, will be included in the study. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Variability of mitoPO2 | Variability of mitoPO2 before and after red cell transfusion. This will be compared to traditional parameters used to measure oxygenation and oxygen balance. | Variability of mitoPO2 will be assessed during 8 predefined moments (within a timeframe of 24 hours) in the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Organ damage | Value of mitoPO2 measurements for predicting (ischemic) organ damage | Value of mitoPO2 in predicting (ischemic) organ damage will be assessed during 8 predefined moments (within a timeframe of 24 hours) in the study | 
| Microcirculation | Association of mitoPO2 with the microcirculation | Association of the mitoPO2 with the microcirculation will be assessed during 2 predefined moments (before transfusion and 24 hours after transfusion) in the study | 
| Length of stay | Length of hospital-stay and ICu stay | Length of stay will be assessed during the 3 months follow-up time | 
| Mortality | 90-day mortality, hospital mortality and ICU mortality | Mortality will be assessed during the 3 months follow-up time | 
| Adverse events | Adverse and serious adverse events of the mitoPO2 measurements | Association of the mitoPO2 with adverse events will be assessed during 8 predefined moments (within a timeframe of 24 hours) in the study |