Insufficient oxygen delivery to cells can be regional or systemic, which is then termed shock. In shock, failure to achieve sufficient tissue oxygen delivery results in cell dysfunction and, ultimately, death. Ensuring adequate tissue oxygen delivery is a priority in critical care.

Macro- Versus Microcirculation

Macrocirculation, or perfusion through major arteries, does not always reflect blood flow at the tissue or cell level (microcirculation; arterioles, capillaries, and venules). Resuscitation guided by macrovascular parameters may lead to improper patient management and further compromise microcirculation. Various microcirculation disturbances, such as reduced capillary density, heterogeneous perfusion, or shunting, may reduce tissue perfusion despite seemingly normal macrocirculatory parameters. Finally, despite adequate oxygen delivery, cellular dysfunction, especially mitochondrial injury, may lead to a persistent inability to produce energy. Resuscitation efforts should, therefore, seek to maintain the coherence between macro- and microcirculation. The loss of hemodynamic coherence can be the result of (i) heterogeneous microcirculatory flow; (ii) reduced capillary density induced by hemodilution and anemia; (iii) microcirculatory flow reduction caused by vasoconstriction or tamponade; or (iv) tissue edema. A wide array of tools is thus paramount to successfuly optimize patient tissue perfusion.

Clinicopathologic Aids for Tissue Perfusion Monitoring

Tissue perfusion is routinely monitored via:

1.  Physical examination: This is an inexpensive approach that allows frequent patient assessment. This is, however, limited by lack of sensitivity for subtle changes and is dependent on caregiver availability.

2.  Arterial blood pressure monitoring: This can be either invasive (direct arterial blood pressure monitoring) or non-invasive (Doppler or oscillometric blood pressure monitoring).

3.  Urine output: Focuses on renal function and urine production as a surrogate for renal perfusion. This not always true, as urine output is not always correlated to renal blood flow.

4.  Clinical imaging: Ultrasound has made a tremendous improvement in the veterinary field over the past 10 years and is gaining more and more acceptance. It is a non-invasive tool that allows rapid assessment as well as evaluation of the patient's volume status in particular. Focal tissue bed perfusion can also be measured with precision.

5.  Metabolic markers such as lactate concentration or central or mixed venous oxygen concentration.

Advanced Tissue Perfusion Monitoring Techniques

Previously described techniques may not truly reflect changes in microcirculation. Direct microcirculation assessment tools can provide important information that could be used to guide resuscitation efforts.

1. Near-Infrared Spectroscopy

This technology relies on the application of different wavelengths of light to the tissue. In healthy tissues, hemoglobin, myoglobin, cytochromes, melanins, carotenes, and bilirubin alter light absorption in a concentration-dependent manner. Tissue oxygenation measurement relies on the absorption characteristics of hemoglobin in its oxygenated and deoxygenated forms.

2. Microcirculation Visualization

Direct observation of the microcirculation is a dynamic field of research. This technology is increasingly compatible with bedside testing. There are various technologies to visualize the microcirculation, such as orthogonal polarized spectroscopy imaging, sidestream dark field imaging, and incident dark field imaging (CytoCam).

3. Transcutaneous O₂ and CO₂ monitoring

Transcutaneous blood gas monitoring is noninvasive and evaluates oxygen and carbon dioxide pressures in a tissue. It detects early changes in blood gas compared to common invasive methods. This technique is more reliable and more accurate than capnography in human patients. Gas tension is measured via polarography, and the skin is heated to 43–45°C to increase transcutaneous gas diffusion.

4. Regional Capnography

The tissue-to-arterial PCO₂ gap is a reliable marker of tissue hypoperfusion. This gap can be measured using a tonometer that assess CO₂ pressure in a tissue based on the gas partial pressure equilibrium. Sublingual-arterial PCO₂ gradient has been described to have a better prognostic factor than physical markers of hypoperfusion (cardiac index, DO₂, plasma lactate). In healthy dogs under anesthesia, gastric and bladder tonometry are both correlated to sevoflurane-induced hypotension in dogs. In that study, gastric tonometry was a better reflection of global hemodynamics when compared to bladder tonometry.

5. Thermography

Thermography is a reproducible, non-invasive, rapid imaging technique to measure the heat emitted by a surface. A recent publication in cats showed that infrared thermography had a high accuracy in diagnosing arterial thromboembolism. The technique could also be used to evaluate reperfusion, as evidenced by an increase in thermal signature at the time of return of blood flow. This is a promising technique for clinical practice application to assess peripheral macrocirculation; however, further studies are needed to evaluate the ability to monitor microcirculation.

6. Cutaneous Laser Doppler

This technology can be used to monitor both blood flow and endothelial dysfunction. The laser Doppler probe (LDP) is placed on an area of clipped and cleaned skin with adhesive tape. The LDP emits laser beams and records signals that are generated by refracted beams. The refraction is created by the flow of blood cells, which is a function of blood flow in the tissue under the probe. The machine provides a computer-generated flow unit, which is proportional to how much blood flow the probe is sensing. The probe evaluates flow at a depth of approximately 1 mm, therefore providing information about arteriole, capillary, and venule flow. After a few minutes, the probe is heated to a temperature of 42°C (107.6°F). In health, this rise in temperature leads to an increase in blood flow, mostly mediated by NO, which is reflected by an increase in flow units. In dysfunctional endothelium, this rise is blunted as a result of decreased NO synthesis or bioavailability. It can be argued that this technique only provides information about the microcirculation immediately under the skin rather than throughout the body. In the research setting, CLDF has been used in dog models for assessing wound healing, grafting, etc. Laser Doppler technology has also been applied to non-cutaneous tissues. Clinical reports of the use of LDF in dogs are limited. LDF has been used to measure capillary flow in the gastric mucosa of dogs with gastric dilation-volvulus. Intra-operative LDF technology has successfully measured spinal blood flow in canine patients with intervertebral disk disease. Spinal cord blood flow is increased immediately following decompression was not correlated with the degree of compression on magnetic resonance imaging or neurological outcome 24 hours following surgery. The same group more recently used the same technology to demonstrate that durotomy did not increase spinal cord blood flow following spinal decompression in dogs with intervertebral disk disease.

7. Urine Partial Pressure of Oxygen

Perfusion to the kidney can be derived from oxygen partial pressure in the urine, assuming there is no change in arterial oxygen content. This technology has been developed in animals and utilized in humans. Current technologies rely on either a probe immersed in urine (whether in the bladder or a urine collection system) or optical fiber than can measure urine oxygen partial pressure without contact with the urine. Alterations in global hemodynamics translate into changes in urine oxygen partial pressure. In sheep, resuscitation from septic shock with fluids and norepinephrine outlined the positive correlation between urine oxygen tension and renal medullary blood flow. Studies in rabbits have also suggested the potential for urine PO₂ to predict the risk of acute kidney injury. Nonetheless, this technology relies on the absence of oligo-anuria.

8. Microdialysis

Microdialysis is another tool to monitor cell function and changes in perfusion. A microdialysis catheter (outer diameter from 0.24 to 0.5 mm and length from 1 to 10 mm) is inserted in the tissue of interest or inside a blood vessel and then connected to a syringe pump. Similar to hemodialysis, the tip of the microdialysis catheter will allow for solute exchange across a permeable membrane. Upon equilibrium, the concentration of markers of cell metabolism and hypoxia (lactate, glutamate, glucose, glycerol, pyruvate, and urea) in the dialysate reflect that of the interstitium. The clinical use of microdialysis is especially relevant for neuro-intensive care patients. Microdialysis can be inserted in the spinal cord or in the brain. Brain perfusion monitoring via microdialysis has been recommended as part of the management of humans with traumatic brain injury and subdural hematoma.