Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05822570 |
| Other study ID # |
O2DO2 in LTX |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
May 1, 2023 |
| Est. completion date |
December 31, 2024 |
Study information
| Verified date |
April 2023 |
| Source |
Medical University Innsbruck |
| Contact |
lukas gasteiger |
| Phone |
0043-512-504-22400 |
| Email |
Lukas.gasteiger[@]tirol-kliniken.at |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Hemoglobin (Hb) is the molecule responsible for the transport of oxygen (O2) to the tissues
in mammals.
The p50 and the Hill coefficient (HC) best describe the ODC. The interaction between Hb and
O2 can be influenced by many agents and conditions like temperature, pH, pCO2 and
2,3-diphosphoglycerate (2,3-DPG).
During liver transplantation numerous profound physiological changes occur, linked to the
different stages of the surgical procedure.
Previous studies in humans and animals undergoing liver transplantation have shown that while
the ODC seems preserved during preparation and the anhepatic phase, a left shift of the ODC
occurs after reperfusion . This left shift of the ODC could imply a decreased release of
oxygen to the tissues, probably worsening hemodynamic instability.
With this pilot study the investigator aim to measure ODCs at baseline and at different
stages during orthotopic liver transplantation in patients in order to get deeper
understanding of oxygen delivery and supply during liver transplantation surgery.
Description:
Hemoglobin (Hb) is the molecule responsible for the transport of oxygen (O2) to the tissues
in mammals.
First described by Bohr at the beginning of the 20th century, the interaction between oxygen
and hemoglobin is represented by the oxygen-hemoglobin dissociation curve (ODC), which has a
sigmoid shape. The p50 and the Hill coefficient (HC) best describe the ODC. The p50
represents the partial pressure of O2 at which the 50% of Hb is saturated with O2, and the
Hill coefficient represents the maximal steepness of the curve in the logarithmic Hill plot.
The interaction between Hb and O2 can be influenced by many agents and conditions like
temperature, pH, pCO2 and 2,3-diphospoglycerate (2,3-DPG)(1). An increase in p50 indicates a
shift of the ODC to the right and a decrease in Hb-O2 affinity, whereas a decrease of the p50
indicates a shift of the ODC to the left and an increased affinity .
Liver disease, in particular liver cirrhosis, is thought to influence the ODC in many ways, a
right shift due to a stimulation in the production of 2,3-DPG has been described. Also
Caldwell et al. showed a right shift of the ODC for cirrhotic patients, although they
couldn't demonstrate the reason for this shift and only postulated that the acid-base balance
in the red blood cell or the cation concentration could be abnormal in these patients.
Patients with End Stage Liver Disease (ESLD) show an hyperdynamic circulation, an adaptive
reaction to a possible occult ischemia and splanchnic vasodilatation (8). Under physiological
conditions, the oxygen consumption (VO2) is independent of oxygen delivery (DO2). When DO2
decreases under a critical level, oxygen extraction from hemoglobin can increase to maintain
VO2. Under this critical DO2 level, as oxygen extraction has reached its maximum, VO2 will
decrease, this state is called physiological oxygen supply dependency. It has been postulated
that in some diseases and conditions, such as ARDS, sepsis, acute liver failure or extensive
surgery, a pathological oxygen supply dependency may exist. When considering the whole oxygen
supply, it has to be taken into account that measurements of DO2 and VO2 alone don't
acknowledge the impact of the ODC on the effective delivery of oxygen in the tissue. Also
under normal conditions where DO2 and VO2 are in the normal range, the oxygen extraction rate
could be impaired by changes in the ODC. Orthotopic liver transplantation (OLT) is an
important step in the therapy of end stage liver disease and represent a complex
intervention, both from the surgical and anesthesiologic point of view. During liver
transplantation numerous profound physiological changes occur, linked to the different stages
of the surgical procedure. At first, in the preparation phase, the native liver and the
vessels are dissected and bleeding may occur. In the second phase of OLT the inferior vena
cava will be clamped, with resulting hemodynamic instability from reduced preload and
congestion in the inferior part of the body. During this so called anhepatic phase lactate
and other metabolisms end products accumulate. After anastomosis of the vena cava and the
portal vein, the reperfusion phase begins. Here, due to the return in the circulation of
acidotic blood and accumulated metabolites from the inferior part of the body, profound
hemodynamic instability with decreased blood pressure can be observed. Previous studies in
humans and animals undergoing liver transplantation have shown that while the ODC seems
preserved during preparation and the anhepatic phase, a left shift of the ODC occurs after
reperfusion . This left shift of the ODC could imply a decreased release of oxygen to the
tissues, probably worsening hemodynamic instability.
With this pilot study the investigator aim to measure ODCs at baseline and at different
stages during orthotopic liver transplantation in patients in order to get deeper
understanding of oxygen delivery and supply during liver transplantation surgery.
