Abstract
The imbalance of oxygen delivery and oxygen consumption resulting in insufficient tissue oxygenation is pathognomonic for all forms of shock. Mitochondrial function plays an important role in the cellular oxygen metabolism and has been shown to impact a variety of diseases in the intensive care setting, specifically sepsis. Clinical assessment of tissue oxygenation and mitochondrial function remains elusive. The in vivo protoporphyrin IX-triplet state lifetime technique (PpIX-TSLT) allows the direct, non-invasive measurement of mitochondrial oxygen tension (mitoPO2) in the human skin. Our recently established measurement protocol for the Cellular Oxygen Metabolism (COMET) Monitor, a novel device employing the PpIX-TSLT, additionally allows the evaluation of oxygen consumption (mitoVO2) and delivery (mitoDO2). In the intensive care setting, these variables might provide new insight into mitochondrial oxygen metabolism and especially mitoDO2 might be a surrogate parameter of microcirculatory function. However, the feasibility of the PpIX-TSLT in critically ill patients has not been analyzed systematically. In this interim study analysis, we evaluated PpIX-TSLT measurements of 40 patients during the acute phase of sepsis. We assessed (a) potential adverse side effects of the method, (b) the rate of analyzable measurements, (c) the stability of mitoPO2, mitoVO2, and mitoDO2, and (d) potential covariates. Due to excessive edema in patients with sepsis, we specifically analyzed the association of patients' hydration status, assessed by bioimpedance analysis (BIA), with the aforementioned variables. We observed no side effects and acquired analyzable measurements sessions in 92.5% of patients (n = 37/40). Different measures of stability indicated moderate to good repeatability of the PpIX-TSLT variables within one session of multiple measurements. The determined limits of agreement and minimum detectable differences may be helpful in identifying outlier measurements. In conjunction with signal quality they mark a first step in developing a previously unavailable standardized measurement quality protocol. Notably, higher levels of hydration were associated with lower mitochondrial oxygen tension. We conclude that COMET measurements are viable in patients with sepsis. To validate the clinical and diagnostic relevance of the PpIX-TSLT using the COMET in the intensive care setting, future studies in critically ill patients and healthy controls are needed.
Highlights
Sepsis is defined as a life-threatening host response toward infection resulting in organ dysfunction [1]
Of 332 screened patients, 45 patients with sepsis were enrolled in the study
After excluding patients who withdrew consent, died before the measurement or had contraindications, protoporphyrin IX (PpIX)-TSLT measurements were performed on 40 patients. 37 patients with reliable PpIX-TSLT measurements were included in the primary analysis
Summary
Sepsis is defined as a life-threatening host response toward infection resulting in organ dysfunction [1]. Despite advances in the pathophysiological understanding of this condition, research has not led to significant changes in sepsis therapy. It remains one of the most prevalent critical conditions worldwide with only supportive therapy. A major hallmark of sepsis and septic shock in particular is disturbed tissue oxygenation. Surrogate parameters of tissue oxygenation have been shown to be of limited reliability. Goal-directed therapy, focusing on central venous oxygen saturation as a surrogate parameter of tissue oxygenation, for example, has shown no overall benefit in a recent meta-analysis [2] leaving clinicians without any evidence on which to base their decisions. There is a need for new research into the direct measurement of tissue oxygenation
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