MitoPO2 guided resuscitation to prevent shock during cardiac surgery

In the Netherlands, 14,500 patients undergo cardiac surgery annually.
Approximately 36% of all patients undergoing cardiac surgery develop
multiple-organ failure, in particular acute kidney injury (AKI). This lengthens
hospital stay and significantly hinders recovery. Central in the aetiology of
organ failure is circulatory shock, where organs do not receive an adequate
supply of oxygen rich blood, leading to organ failure. Shock is challenging to
treat peri-operatively as there is no marker which measures the oxygen supply
to tissue directly. As a result, patients are often under or over-resuscitated,
both associated with organ failure and death. Currently, indirect and markers
are used to guide treatment of shock, however
these markers are unspecific. Disturbances in the microcirculation create a
dissociation between these indirect markers and the true tissue oxygenation
inside organs. These limitations highlight the need for the direct measurement
of tissue oxygenation. The recent development of the protoporphyrin-IX delayed
lifetime technique allows non-invasive bedside measurement of the mitochondrial
oxygen tension in the cell (mitoPO2). The mitochondria are the most downstream
of oxygen supply and demand balance and its value is therefore applicable
regardless of the status of other macro- and microcirculatory variables. We
have recently shown that a low mitoPO2 is a highly accurate early independent
predictor of the occurrence of AKI after cardiac surgery. As such, mitoPO2
could be the ideal marker for personalized resuscitation, particularly
benefitting female patients. The hypothesis is that the use of mitoPO2 to guide
shock treatment will reduce the incidence of organ failure after cardiac
surgery as compared to the use of conventional monitoring. In a randomized
clinical trial in 160 cardiac surgery patients, a mitoPO2-based algorithm to
guide administration of fluids and vaso-active agents will be compared to
monitoring using conventional parameters for the incidence of AKI , cardiac
injury and functional outcome.

To compare the use of mitoPO2 with the use of conventional markers in guiding
interventions to treat shock in patients undergoing cardiac surgery

single center open label randomized controlled superiority trial

Use of mitoPO2 to guide therapy for shock during and 24 hours after cardiac
surgery in the intervention group compared to use of standard monitoring to
guide therapy in the control group

The subjects receive usual care and do not require deviation from standard
protocol, regardless of their allocation. The COMET*s intraoperative
non-invasive measurements are regarded as safe and do not result in any
increased risk. Administration of a 5-aminolevulinic acid patch to the shoulder
that is necessary for the mitoPO2 measurement causes slight local erythema, but
no other reactions. Non-invasive measurements of mitoPO2 intra operatively and
post operatively use a sensor placed on the skin. Blood samples for monitoring
and kidney biomarkers are taken from an existing arterial catheter amounting to
12ml of blood drawn per patient. Treatment decisions follow algorithms
according to the discretion of medical specialists and in line with current
guidelines. Possible benefits in the intervention group include a reduced
incidence of organ dysfunction and acute kidney injury in the investigational
arm.