Is a dropping mitoPO2 suggestive for the development of acute kidney injury and/or postoperative cognitive dysfunction after cardiac surgery?

Cardiac-surgery-associated acute kidney injury (CSA-AKI) is a common
complication after cardiac surgery. CSA-AKI is independently associated with
increased morbidity and mortality. Central in the development of CSA-AKI is the
imbalance between oxygen supply and demand. This is often not recognized in
time and can therefore not be prevented. Previous studies have shown the
potential of monitoring cutaneous mitochondrial oxygen tension (mitoPO2) by the
recently introduced Cellular Oxygen METabolism (COMET) (Photonics Healthcare
B.V., Utrecht).This study will investigate whether there is a correlation
between perioperative duration of low mitochondrial oxygen tension (<20 mmHg)
and CSA-AKI. Since post-operative cognitive dysfunction (POCD) after cardiac
surgery may also be caused by an oxygen deficiency in the tissue, we will
further investigate the relationship between between perioperative duration of
low mitochondrial oxygen tension (<20 mmHg) and POCD.

Primary Objective: the relation between the occurrence of CSA-AKI and the
duration of peri-operative low mitoPO2 measurements (<20 mmHg).
Secondary Objective:
- To study the relationship between the occurrence of postoperative cognitive
dysfunction (POCD) and the duration of low mitoPO2 (<20 mmHg) during and up to
48 hours after cardiac surgery.
- To study the relationship between the duration of low mitoPO2 (<20 mmHg)
during and up to 48 hours after cardiac surgery and the post-operative measured
cardiac surgery associated acute kidney injury (CSA-AKI) biomarkers: TIMP-2 and
IGFBP-7
- To study the relationship between mitoPO2 and the standard hemodynamic
monitoring parameters and other biomarkers measured during coronary artery
bypass grafting (CABG)
- To study the relationship between low mitoPO2 (<20 mmHg) during and up to 48
hours after cardiac surgery and the occurrence of delirium.
- To study the relationship between low mitoPO2 (<20 mmHg) during and up to 48
hours after cardiac surgery and the stay length in the intensive care unit
(ICU), and the stay length in the hospital.
- To monitor adverse events related to prolonged usage of the aminolevulinic
acid plasters.

Single center observational study

There are no direct benefits for the subjects enrolled in the study.

ALA is clinically used in photodynamic diagnosis and therapy of cancer.
Administration of ALA is safe, but transient local photosensitisation requires
participants to limit exposure to (sun)light 24 hours after the treatment. This
can easily be achieved by covering the site where the ALA plaster has been
placed with a light shielding plaster.

The PpIX-TSLT technique likely to be safe, proven by research on healthy
volunteers. Since the research with healthy volunteers it has safely been used
in neurosurgical patients (MEC-2015-342) , cardiothoracic surgery requiring
cardiopulmonary bypass (MEC-2017-532), in large abdominal surgery patients (MEC
2017-556) and in patients admitted to the Intensive Care Unit.(22, 26). The
possible effect of phototoxicity after PpIX induction is always potential risk,
but because the PpIX-TSLT uses short-pulsed excitation and total light dosage
less than used in photodynamic therapy, this risk is considered to be very low
(8, 27).

The COMET Sensor Holder has not been used in clinical trials before. It has to
be attached the arm of the patient peri- and post-operatively, which gives some
restrictions in freedom of movement. Since the patients are bedridden the first
days after CABG, we do expect this will cause extra burden on the patients. The
COMET Sensor Holder can potentially cause bruising or pressure ulcers from
pressure during surgery. Measures such as relieving pressure points with cotton
wool will be taken in order to prevent this.

The biomarkers are collected during standard care sampling, so this will be now
extra burden to the patient.

The psychometric tests will cost the patients time, about an hour per for all
tests, so in total three hours extra. The baseline measurements and the
measurements after one week are expected to be performed in the hospital. For
the psychometric testing after three months, a dedicated team will visit the
subject at home to keep the burden for the patients as low as possible. Since
the tests do not contain sensitive questions and the included patients and
tests can either be performed during their admission to the hospital or in
their own home at their own time, it is deemed as a small burden for the
patients.

Overall, the risks are considered negligible and the burden small.