**6. Indirect methods**

## **6.1. Measuring elements of tissue oxygenation**

There are quite some methodologies available for estimating or measuring tissue oxygenation at the different levels.

Central venous oxygen saturation (ScvO2 ) and mixed venous oxygen saturation (SvO2 ).

They provide knowledge of the patient's oxygen delivery, oxygen consumption, and cardiac output. ScvO2 > 70% or SvO2 > 65% is recommended for critical patients [30]. SvO2 is an adaptive variable depending on four elementary-regulated components: the real O<sup>2</sup> consumption, SaO2 , haemoglobin and cardiac output. Consequently, SvO2 (or its surrogate ScvO2 ) is widely fluctuating. Thus, when normal, those parameters cannot rule out any impairment in tissue oxygenation related to an impaired microcirculation [31].

#### **6.2. Near-infrared spectroscopy (NIRS)**

NIRS has been developed as a non-invasive diagnostic tool for measurement of regional haemoglobin oxygen saturation in a particular organ. NIRS is mainly used in the evaluation of cerebral oxygenation in cardiac, non-cardiac surgery and traumatic intensive care patients. The NIRS signal is restricted to vessels that have a diameter of less than 1 mm, and this technique is not suitable for states of heterogeneous blood flow [32]. Tissue O2 saturation (StO2 ) mostly describes the saturation of all vessels, while total tissue haemoglobin (HbT) and the tissue haemoglobin index (THI) indicate the amount of blood present in the tested region. Brain venous blood is primarily responsible for a decrease in brain saturation and predominantly results from a local increase in oxygen extraction. During haemorrhage the arterial component preserved while venous part decreases markedly. On the other hand, in trauma patients, StO2 is altered only in the severe cases and in other forms show low sensitivity [33]. NIRS-derived dynamic measurements (vaso-occlusive test, VOT) demonstrated profound alterations in microvascular reactivity. The NIRS technique is done for a brief episode of forearm ischemia induced by transient inflation of a cuff determines changes in StO<sup>2</sup> . Some indices can be measured during this test, but the most important is the ascending slope reflecting microvascular reactivity. The severity of these alterations in microvascular reactivity is associated with organ dysfunction and mortality [34].

#### **6.3. Tissue CO2 (gastric tonometry, veno-arterial CO2 gradient, transcutaneous CO2 )**

Tissue PCO<sup>2</sup> (PtCO<sup>2</sup> ) has been measured in the stomach, sublingual area, and earlobe. Tissue PCO<sup>2</sup> has three major elements: VCO<sup>2</sup> , PaCO<sup>2</sup> , and tissue blood flow. Normally, an increase in tissue metabolism (VCO2) increases tissue perfusion and decreases PCO<sup>2</sup> . When PaCO<sup>2</sup> is constant, and PtCO<sup>2</sup> is increased, there is an inadequate relationship between metabolism and tissue perfusion. Normal tissue-arterial CO<sup>2</sup> gradient (PCO<sup>2</sup> gap) <7 mmHg. Elevated PCO<sup>2</sup> gaps may signify either flow stagnation or tissue hypoxia [35]. Importantly, there is an inverse relationship between microvascular perfusion and the PCO<sup>2</sup> gap. PtCO<sup>2</sup> consequently represents a good assessment of tissue perfusion.

Microcirculatory alterations in critically ill patients may play a role in the development of organ dysfunction. Video microscopic techniques and tissue PCO2 measurements can be used to evaluate microvascular perfusion. But, microcirculation monitoring is not yet part of routine clinical practice.

### **6.4. Lactate**

imaging and incident dark-field (IDF) imaging (CytoCam) provide in vivo visualisation of the microcirculation. OPS and SDF imaging have become clinically useless due to the large size, motion and pressure artefacts, operator-dependent output, and the need for offline analysis,

56 Hyperbaric Oxygen Treatment in Research and Clinical Practice - Mechanisms of Action in Focus

There are quite some methodologies available for estimating or measuring tissue oxygenation

They provide knowledge of the patient's oxygen delivery, oxygen consumption, and cardiac

fluctuating. Thus, when normal, those parameters cannot rule out any impairment in tissue

NIRS has been developed as a non-invasive diagnostic tool for measurement of regional haemoglobin oxygen saturation in a particular organ. NIRS is mainly used in the evaluation of cerebral oxygenation in cardiac, non-cardiac surgery and traumatic intensive care patients. The NIRS signal is restricted to vessels that have a diameter of less than 1 mm, and this tech-

mostly describes the saturation of all vessels, while total tissue haemoglobin (HbT) and the tissue haemoglobin index (THI) indicate the amount of blood present in the tested region. Brain venous blood is primarily responsible for a decrease in brain saturation and predominantly results from a local increase in oxygen extraction. During haemorrhage the arterial component preserved while venous part decreases markedly. On the other hand, in trauma

NIRS-derived dynamic measurements (vaso-occlusive test, VOT) demonstrated profound alterations in microvascular reactivity. The NIRS technique is done for a brief episode of fore-

ces can be measured during this test, but the most important is the ascending slope reflecting microvascular reactivity. The severity of these alterations in microvascular reactivity is associ-

arm ischemia induced by transient inflation of a cuff determines changes in StO<sup>2</sup>

, PaCO<sup>2</sup>

 **(gastric tonometry, veno-arterial CO2**

is altered only in the severe cases and in other forms show low sensitivity [33].

) has been measured in the stomach, sublingual area, and earlobe. Tissue

output. ScvO2 > 70% or SvO2 > 65% is recommended for critical patients [30]. SvO2

tive variable depending on four elementary-regulated components: the real O<sup>2</sup>

nique is not suitable for states of heterogeneous blood flow [32]. Tissue O2

, haemoglobin and cardiac output. Consequently, SvO2

oxygenation related to an impaired microcirculation [31].

) and mixed venous oxygen saturation (SvO2

(or its surrogate ScvO2

 **gradient, transcutaneous CO2**

, and tissue blood flow. Normally, an increase

).

is an adap-

) is widely

consumption,

saturation (StO2

. Some indi-

**)**

)

which takes time to produce data.

**6.1. Measuring elements of tissue oxygenation**

Central venous oxygen saturation (ScvO2

**6.2. Near-infrared spectroscopy (NIRS)**

ated with organ dysfunction and mortality [34].

has three major elements: VCO<sup>2</sup>

**6. Indirect methods**

at the different levels.

SaO2

patients, StO2

**6.3. Tissue CO2**

(PtCO<sup>2</sup>

Tissue PCO<sup>2</sup>

PCO<sup>2</sup>

Lactate in the human body is a metabolic product of anaerobic glycolysis, produced from the reduction of pyruvate by the enzyme lactate dehydrogenase, and reflects inadequate oxygen delivery. Normally, a total amount of 1500 mmol of lactate is produced daily in adult, and blood lactate levels are sustained less than 2 mmol/L. However, in the state of hypoperfusion and hypoxia, pyruvate rapidly accumulate, and its metabolism is shifted almost entirely to lactate production. The tissue hypoxia is a cause of lactate elevation and characterised by supply-dependent oxygen consumption [36]. Single measurement of lactate can only serve as a risk-stratification biomarker. Lactate clearance with its association with clinical outcome should be used during treatment to make it more clinically useful [37].

### **6.5. Microcirculation and hyperbaric oxygen therapy**

Hyperbaric oxygen therapy (HBOT) is a clinical treatment in which a patient breathes pure oxygen for a limited period of time at an increased pressure. This therapy has been suggested to improve oxygen supply to tissues and therefore improves microcirculation [38]. HBOT in patients with diabetic foot ulcer was associated with a greater reduction in the ulcer wound area than standard therapy and significantly improves the ulcers in a short term [39]. Also, HBOT which is applied in acute ischemic stroke, femoral head necrosis, and carbon monoxide intoxication aims to increase oxygen supply to the ischemic tissue and to reduce the extent of irreversible tissue damage [40–42].
