ABSTRACT
INTRODUCTION: Administration of oxygen therapy is common, yet there is a lack of knowledge on its ability to prevent cellular hypoxia as well as on its potential toxicity. Consequently, the optimal oxygenation targets in clinical practice remain unresolved. The novel PpIX technique measures the mitochondrial oxygen tension in the skin (mitoPO2) which allows for non-invasive investigation on the effect of hypoxemia and hyperoxemia on cellular oxygen availability. RESULTS: During hypoxemia, SpO2 was 80 (77-83)% and PaO2 45(38-50) mmHg for 15 min. MitoPO2 decreased from 42(35-51) at baseline to 6(4.3-9)mmHg (p < 0.001), despite 16(12-16)% increase in cardiac output which maintained global oxygen delivery (DO2). During hyperoxic breathing, an FiO2 of 40% decreased mitoPO2 to 20 (9-27) mmHg. Cardiac output was unaltered during hyperoxia, but perfused De Backer density was reduced by one-third (p < 0.01). A PaO2 < 100 mmHg and > 200 mmHg were both associated with a reduction in mitoPO2. CONCLUSIONS: Hypoxemia decreases mitoPO2 profoundly, despite complete compensation of global oxygen delivery. In addition, hyperoxemia also decreases mitoPO2, accompanied by a reduction in microcirculatory perfusion. These results suggest that mitoPO2 can be used to titrate oxygen support.
ABSTRACT
Circulatory shock is the inadequacy to supply mitochondria with enough oxygen to sustain aerobic energy metabolism. A novel noninvasive bedside measurement was recently introduced to monitor the mitochondrial oxygen tension in the skin (mitoPo2). As the most downstream marker of oxygen balance in the skin, mitoPo2 may provide additional information to improve shock management. However, a physiological basis for the interpretation of mitoPo2 values has not been established yet. In this paper, we developed a mathematical model of skin mitoPo2 using a network of parallel microvessels, based on Krogh's cylinder model. The model contains skin blood flow velocity, heterogeneity of blood flow, hematocrit, arteriolar oxygen saturation, and mitochondrial oxygen consumption as major variables. The major results of the model show that normal physiological mitoPo2 is in the range of 40-60 mmHg. The relationship of mitoPo2 with skin blood flow velocity follows a logarithmic growth curve, reaching a plateau at high skin blood flow velocity, suggesting that oxygen balance remains stable while peripheral perfusion declines. The model shows that a critical range exists where mitoPo2 rapidly deteriorates if skin perfusion further decreases. The model intuitively shows how tissue hypoxia could occur in the setting of septic shock, due to the profound impact of microcirculatory disturbance on mitoPo2, even at sustained cardiac output. MitoPo2 is the result of a complex interaction between all factors of oxygen delivery and microcirculation. This mathematical framework can be used to interpret mitoPo2 values in shock, with the potential to enhance personalized clinical trial design.NEW & NOTEWORTHY This is the first paper to simulate mitochondrial oxygen tension in skin in circulatory shock. The relationships of mitoPo2 with parameters of (microcirculatory) oxygen delivery aid in the understanding of noninvasive bedside measurement of mitoPo2 values and show that mitochondrial oxygen tension is two orders of magnitude higher than classically assumed. The model can be used to enhance clinical trial design investigating mitoPo2 as a resuscitation target in circulatory shock.
