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# Monitoring tissue perfusion

Alexandra Nectoux, Guillaume Hoareau

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Alexandra Nectoux, Guillaume Hoareau. Monitoring tissue perfusion. Advanced Monitoring and Procedures for Small Animal Emergency and Critical Care, Second Edition. Edited by Jamie M. Burkitt Creedon and Harold Davis. John Wiley & Sons, Inc., 2022. hal-05079360

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# Monitoring Tissue Perfusion

Clinicopathologic Aids and Advanced Techniques

Alexandra Nectoux and Guillaume L. Hoareau

Cells depend on oxygen delivery for energy production to maintain homeostasis. Failure to achieve sufficient tissue oxygen delivery results in cell dysfunction and ultimately death. Insufficient oxygen delivery to cells can be focal (e.g. ischemic limb, infarcted spleen) or systemic, which is then termed shock.

Whether hypoxia is focal or systemic, restoring adequate tissue oxygen delivery is a cornerstone of resuscitation. Oxygen delivery to tissues depends on arterial oxygen content and tissue perfusion. This chapter focuses on the importance of monitoring tissue perfusion (Table 19.1).

## Clinical Monitoring of Tissue Perfusion

### Physical Examination

Physical examination is an inexpensive and rapid way to monitor a patient's perfusion serially. Assessment of global perfusion, a core part of a triage examination, should include evaluation of mentation, heart rate, pulse quality, extremity-to-core temperature difference, mucous membrane color, and capillary refill time. This focused assessment of a patient's circulatory function provides a global evaluation of tissue perfusion and assists in the diagnosis of shock. The evaluation of circulatory function by physical examination may also help in the diagnosis of focal perfusion disturbances such as an ischemic limb if the femoral pulse is absent, for instance.

### Arterial Blood Pressure Monitoring

Systemic arterial blood pressure measurement is also commonly used to monitor a patient's cardiovascular status. Unfortunately, normal blood pressure does not indicate adequate capillary perfusion and thus cannot guarantee adequate oxygen delivery to cells. First, microcirculatory

disturbances may persist despite normal macrocirculatory parameters such as blood pressure (i.e. hemodynamic incoherence). Second, normal systemic arterial blood pressure does not equate to normal blood flow since profound vasoconstriction, for instance, may result in normal or even high systemic blood pressure in the face of reduced blood flow. Conversely, vasodilation may result in increased blood flow despite a reduction in blood pressure. Such decrease in systemic vascular resistance is often associated with increased cardiac output in the hyperdynamic phase of sepsis.

Blood pressure measurement can be either non-invasive (oscillometric, Doppler, or pressure wave analysis technologies; see Chapter 14) or invasive. Invasive blood pressure monitoring depends on direct pressure measurement within the lumen of an artery. Most systems rely on pressure wave transmission through a column of water to a pressure transducer (see Chapter 12), though solid-state blood pressure transducing catheters are also available.

Regardless of the method of acquisition, arterial blood pressure can be used to calculate cavity or organ-specific perfusion pressures. Clinical interventions or research applications often rely on myocardial, cerebral, abdominal, or spinal perfusion pressures, which are the driving pressures for blood from the arterial to the venous sides of organs. The use of such perfusion pressures in clinical practice as resuscitation endpoints has been studied in various settings. Myocardial perfusion pressure (diastolic aortic pressure minus central venous pressure) and cerebral perfusion pressure (CPP; mean arterial pressure [MAP] minus intracranial pressure) are critical prognostic indicators in cardiopulmonary resuscitation (CPR). Data summarized in current veterinary CPR guidelines suggest that myocardial perfusion pressures above 20 mmHg are associated with increased likelihood of return of spontaneous circulation [1]. Post-cardiac arrest CPP was higher in
<table><caption>**Table 19.1** Summary of commonly available tissue perfusion monitoring tools.</caption><thead><tr><th>Clinicopathologic aids</th><th></th><th>Advanced techniques</th><th></th></tr></thead><tbody><tr><td>Physical examination</td><td></td><td>Near-infrared spectroscopy</td><td></td></tr><tr><td>Arterial blood pressure</td><td>Diastolic, mean, systolic</td><td>Microcirculation visualization</td><td>Orthogonal polarized spectroscopy</td></tr><tr><td></td><td>Perfusion pressures</td><td></td><td>Sidestream dark field</td></tr><tr><td>Urine output</td><td></td><td></td><td>Incident dark-field</td></tr><tr><td>Clinical imaging</td><td>Transcutaneous ultrasound</td><td>Transcutaneous O<sub>2</sub> and CO<sub>2</sub></td><td></td></tr><tr><td></td><td>Transesophageal echocardiography</td><td>Regional capnography</td><td></td></tr><tr><td rowspan="6">Metabolic biomarkers</td><td>Lactate concentration</td><td>Thermography</td><td></td></tr><tr><td>Lactate clearance</td><td>Cutaneous laser Doppler</td><td></td></tr><tr><td>Oxygen extraction ratio</td><td>Urine oxygen partial pressure</td><td></td></tr><tr><td>SmvO<sub>2</sub></td><td>Microdialysis</td><td></td></tr><tr><td>ScvO<sub>2</sub></td><td></td><td></td></tr><tr><td>PCO<sub>2</sub> gradients</td><td></td><td></td></tr></tbody></table>

PCO₂, partial pressure of carbon dioxide; SmvO₂, mixed venous hemoglobin oxygen saturation; ScvO₂, central venous hemoglobin oxygen saturation.

survivors than nonsurvivors following cardiac arrest [2] and CPP optimization is an area of active research. Abdominal perfusion pressure (MAP minus intra-abdominal pressure) is a significant focus for the management of abdominal compartment syndrome, although studies suggest that it should not be used as a resuscitation endpoint [3]. Spinal cord perfusion pressures (MAP minus intraspinal pressure, between the dura and the surface of the cord) over 50 mmHg have been associated with favorable neurological outcomes following traumatic spinal cord compression [4, 5]. The concept of perfusion pressure further supports why a resuscitation strategy solely based on MAP may not maintain adequate perfusion to individual organs (e.g. two patients may have identical MAPs but vastly different intra-abdominal pressures, and hence will have different abdominal tissue perfusion pressures).

## Urine Output

Quantification of urine output reflects renal perfusion through glomerular filtration, tubular reabsorption, and patency of the urinary tract. Urine output is part of the essential monitoring of critically ill patients, especially those with particular risk for acute kidney injury. Urine output can be quantified hourly or less frequently, depending on the patient's status. Urine output is an integral factor in fluid therapy planning and overall patient care. It can be easily and precisely measured by placing a urethral catheter connected to a closed collection system. Normal urine output is 1–2 ml/kg/hour in dogs and cats. Oliguria is defined

as a urine output less than 0.5 ml/kg/hour [6] and anuria is the absence of urine production. A urine output above the normal range is considered polyuria. In human medicine, plasma renin concentration is well correlated to urine output and represents a useful tool to assess tissue perfusion [7]; however, it is not always increased in response to ischemia-reperfusion injury. For instance, pigs subjected to hemorrhagic shock and endovascular aortic occlusion developed increased serum angiotensin II concentration without significant changes in circulating levels of renin [8].

## Clinical Imaging

Imaging tools routinely used in the hospital can be used to some extent to monitor cardiovascular status. Various approaches may assess cardiac filling and systolic function. Different point-of-care ultrasound protocols have been described in the veterinary literature [9]. Tissue perfusion to a specific organ can be confirmed using Doppler ultrasound, but this remains a diagnostic rather than a monitoring tool. Transesophageal echocardiography (TEE), whereby an ultrasound probe is inserted near the heart through the esophagus, is gaining popularity in human emergency medicine and has been used extensively in people undergoing anesthesia. In the human emergency room, TEE has proved a valuable tool in CPR and can assist in improving hand or chest compression device placement to increase stroke volume and optimize perfusion [10]. TEE is also often used to monitor and optimize perfusion in patients undergoing extracorporeal membrane oxygenation [11].
## Standard Clinicopathologic/Metabolic Markers of Tissue Perfusion

Metabolic markers of tissue perfusion are another crucial part of patient management and provide information regarding systemic or organ-specific perfusion derangements.

### Lactate

Plasma lactate concentration has long been used for the monitoring of systemic or focal (e.g. limb) ischemia. Lactate production has traditionally been classified as type A (insufficient oxygen delivery) or B (increased lactate production in the face of adequate oxygen availability) [12]. Type A hyperlactatemia has been further characterized as relative, from increased oxygen demand (e.g. in exercise, shivering, seizure) or absolute, from decreased oxygen delivery (e.g. in hypoperfusion, severe anemia, severe hypoxemia). Type B hyperlactatemia has been observed with certain diseases (e.g. lymphoma, pheochromocytoma), toxins or drugs (e.g. glucocorticoids, xylitol, metformin), or congenital metabolism disorders. Spurious readings can be observed with ethylene glycol intoxication [13]. Much of the evidence about the usefulness of plasma lactate concentration in veterinary medicine has originated from studies of gastric dilation volvulus. While measurements at single time points do not always provide meaningful information, serial plasma lactate concentration measurements may better correlate with outcome. Lactate concentration-derived parameters such as time to lactate less than 2 mmol/l and lactate clearance can differentiate between survivors and non-survivors in dogs diagnosed with shock [14, 15].

Lactate measurement may also reflect locoregional hypoxia in patients with various conditions. Venous lactate concentration measured from a limb with suspected ischemia may be higher than that of the systemic circulation [16, 17]. Similarly, lactate concentration measured in cerebrospinal fluid reflects the magnitude of spinal cord [18, 19] or cerebral ischemia [20].

### Blood Gas Parameters and Oxygen Extraction Ratio

Under baseline physiologic conditions, oxygen is delivered to cells in excess of metabolic demand. When tissue oxygen delivery is decreased, cells and therefore organs can increase the fraction of oxygen they consume from the arterial supply to a higher percentage of the oxygen being delivered. Thus, oxygen consumption remains independent of oxygen supply over a wide range of normal to lower-than-normal-but-adequate oxygen delivery. This principle can be quantified by calculating the oxygen extraction ratio (OER; Box 19.1)

A mixed venous sample is obtained from the pulmonary artery via a pulmonary artery catheter and comprises a

### Box 19.1 Calculating the Oxygen Extraction Ratio

$$ \text{OER}(\%) = (\text{CaO}_2 - \text{CmvO}_2) \div \text{CaO}_2 $$

$$ \text{CaO}_2 = [1.34 \times \text{Hb} \times \text{SaO}_2] + [0.003 \times \text{PaO}_2] $$

$$ \text{CmvO}_2 = [1.34 \times \text{Hb} \times \text{SmvO}_2] + [0.003 \times \text{PmvO}_2] $$

CaO₂, arterial oxygen content, ml/dl

CmvO₂, mixed venous oxygen content, ml/dl

Hb, hemoglobin concentration, g/dL

OER, oxygen extraction ratio

PaO₂, partial pressure of arterial oxygen, mmHg

PmvO₂, partial pressure of microvascular venous oxygen, mmHg

SaO₂, oxygen saturation

SmvO₂, mixed venous oxygen saturation

combination of cranial and caudal vena cava blood along with coronary sinus blood; thus, mixed venous blood is the most globally representative venous blood sample obtainable. This mixed venous sample better reflects systemic venous oxygen content than central venous blood acquired from the jugular vein or vena cava.

While OER increases in shock states to compensate for reduced oxygen delivery, in more severe shock states, cells have extracted nearly all oxygen in the capillary blood, OER stops increasing, and oxygen consumption becomes dependent on oxygen delivery. Scientists have argued that the relationship between oxygen consumption and delivery is actually linear in certain conditions, which would dictate that oxygen consumption would always depend directly (linearly) on oxygen delivery [21, 22]. Extraction ratios can be calculated for specific tissue beds via selective sampling of arterial and venous blood. For example, renal arterial and venous blood can be sampled to calculate the renal OER. This approach is generally limited to the research setting.

The balance between oxygen delivery and oxygen consumption is often evaluated via analysis of central venous (cranial caval, most often) saturation of oxygen (ScvO₂), as it is a single number and thus eliminates the need for calculations. ScvO₂ can be measured via blood gas analysis or continuous fiber tip spectrophotometry. ScvO₂ was part of the early goal-directed therapy protocol for the management of septic shock in people [23]. In a study of dogs with sepsis or septic shock associated with pyometra, a goal-directed resuscitation therapy guided by physical examination, ScvO₂, lactate concentration, and base deficit showed that ScvO₂ and base deficit were superior to lactate in predicting survival [24]. Importantly, in critically ill people, there is no uniform correlation between lactate concentration and ScvO₂ [25, 26]. In isolated studies, resuscitative efforts in patients with early sepsis aiming at improving
lactate clearance or normalizing ScvO₂ did not yield significant survival benefit [27]. However, a meta-analysis reported superiority of lactate clearance-driven algorithms when compared to those aiming at improving ScvO₂ [28].

Partial pressure of carbon dioxide (PCO₂) can be measured on mixed or central venous blood to calculate the tension difference with that of arterial blood (Pv-aCO₂) [29]. Pv-aCO₂ depends mostly on cardiac output and systemic CO₂ production and is not reflective of tissue hypoxemia; rather it reflects the adequacy of venous blood flow to remove the CO₂ produced in the tissues, an approximation of tissue perfusion. Pv-aCO₂ could be used to guide resuscitation in conjunction with other markers of tissue perfusion, in particular ScvO₂, to match oxygen delivery to CO₂ production. A Pv-aCO₂ greater than 6 mmHg may suggest insufficient resuscitation.

More sophisticated calculations leveraging arterial and venous O₂ and CO₂ contents may refine the specificity of tissue perfusion monitoring. In patients with septic shock, following restoration of MAP, increased Pv-aCO₂ correlated with lower tissue oxygen saturation, a reflection of global flow. PcvaCO₂/CavO₂ ratio (where PcvaCO₂ is the central venous-to-arterial carbon dioxide difference and CavO₂ is the arterial-venous oxygen content difference) was a good indicator of local oxygen consumption and microvascular dysfunction [30].

## Advanced Tissue Perfusion Monitoring Techniques

The previously described techniques may not reflect changes in microcirculation. Direct microcirculation assessment tools can provide important information to guide resuscitation. Unfortunately, these techniques sometimes require expensive, large, or impractical tools, and are thus primarily used in laboratory or research settings at this time.

### Near-Infrared Spectroscopy

Spectroscopy is optical monitoring that relies on the application of different wavelengths of light to tissue. In healthy tissues, hemoglobin, myoglobin, cytochromes, melanins, carotenes, and bilirubin absorb light in a concentration-dependent manner. Tissue oxygenation measurement relies on the distinct light wavelength absorption characteristics of hemoglobin in its oxygenated and deoxygenated forms.

Near-infrared spectroscopy (NIRS) is an optical monitoring technique that relies on the Beer-Lambert law correlating the concentration of a substance to its light absorption. NIRS assesses oxygen saturation of hemoglobin in the capillaries of a tissue (StO₂) and can detect oxygenation disorders

before pulse oximetry, plasma lactate concentration, or physical examination [31]. Assuming no significant change in arterial oxygen content, a decrease in tissue oxygenation directly reflects reduced perfusion. StO₂ is mostly measured in peripheral muscle or brain with dedicated probes; since it measures local oxygen saturation, readings depend on probe location [32, 33]. Moreover, changes in blood volume in brain tissue, peripheral vasoconstriction, pain, hypothermia, as well as hypovolemia, meaningfully influence the intravascular compartment and alter readings. In the human literature, several studies showed that tissue desaturation in the frontal cortex of the brain and peripheral muscles (thenar, leg, and masseter muscles) was associated with poor outcomes [34, 35]. However, these results remain controversial [36]. In pigs exposed to various cardiovascular derangements, NIRS readings from the pelvic limbs showed good agreement with more invasive parameters [22]. NIRS evaluation of cerebral blood flow has been described in dogs in an experimental setting, where the probe was applied directly onto the skull [37]. Non-invasive NIRS readings have been reported in healthy conscious and unconscious Chihuahuas [38]. StO₂ declines in various states of shock in canine patients [39, 40]. StO₂ readings were associated with disease severity but did not predict survival [40]. Care providers should consider establishing clear protocols, as various factors such as probe location may introduce variability in the readings. For instance, in healthy dogs, the sartorius muscle provides a good assessment of tissue oxygen saturation and could be consistently used [41]. Similar to many other monitoring devices, there can be significant variability in readings when using different NIRS devices [42].

### Microcirculation Visualization

Direct observation of the microcirculation is a dynamic field of research that has rendered this approach more available for clinical use, even in veterinary medicine. There are various technologies to visualize the microcirculation. The following devices are listed from oldest to newest:

#### Orthogonal Polarized Spectroscopy Imaging

Two polarizers oriented perpendicularly to one another are respectively used to emit and collect light on a specific tissue region. The light collected passes through a spectral filter to isolate the wavelength region and linearly polarize it. A beam splitter reflects the light toward the target tissue, and an objective lens focuses the light onto a region of approximately 1 mm in diameter. The device then generates an image of the illuminated region. Contrast is obtained from the absorption of linearly polarized light by both oxygenated and deoxygenated hemoglobin in the blood. Subsequently, red blood cells in the microcirculation
appear black on the white background of the surrounding tissue, which creates a high-contrast image. This technique was first described in the human literature in comparison with a standard fluorescence method [43]. A study established baseline values in 15 healthy dogs and assessed the reproducibility of this technique [44], but it offers a limited field of view, as only a focal area of tissue can be visualized.

## Sidestream Dark Field Imaging

Sidestream dark field (SDF) imaging uses the same concept as orthogonal polarized spectroscopy imaging. In this case, the illuminated light and the reflected light travel via different pathways to not interfere with the image quality. Using a videomicroscope, a green light-emitting diode produces a light beam, which is absorbed by hemoglobin. This technique is limited to experimental use because it requires constant user interactions and long measurements to obtain only a few seconds of video for analysis [45, 46]. Despite those limitations, SDF imaging allows real-time imaging of the microvasculature and was able to demonstrate altered microcirculatory variables in dogs with hemorrhagic shock, when compared to normal dogs [47]. SDF shows an increase in vessel density in dogs receiving various rates of fluid under general anesthesia, which demonstrates the link between SDF findings and perfusion changes [48]. Finally, whereas SDF is a reliable bedside tool to assess microcirculation, it did not correlate with current standard analysis for different perfusion parameters in healthy dogs [49].

## Incident Dark Field Imaging

First described in 1970, incident dark field imaging (IDF) is similar to SDF imaging in that it uses light-emitting diodes arranged circumferentially to illuminate a target tissue. In this method, the strobe speed is significantly decreased, which induces less distortion of the red blood cells' images. The device is a small, light, handheld camera, which makes it easier for the operator to manipulate compared to the previous devices. This camera also has a higher optical resolution and a wider field of view that enable the user to identify suitable areas of microcirculation more rapidly. Additionally, in contrast to the previous device, the IDF imaging device has a dedicated integral automated software, decreasing the time needed to acquire images [50, 51]. In comparison with SDF technique, IDF showed comparable vessel detection and significantly better vessel contrast in pigs undergoing a shock state [52].

Several microcirculatory indices can be calculated by semi-automated software using the images acquired by the three previous techniques. Care providers can assess and monitor the microcirculatory system in a peripheral region using the following parameters: (i) Total vessel density, which is a measure of total vessels' length over the area

within the field of the camera; (ii) proportion of perfused vessels, which represents the proportion of perfused vessels in the field; and (iii) perfused vessel density, which is a measure of perfused vessels' length within the field. The potential clinical benefits of perfused vessel density, which is derived from total vessel density and proportion of perfused vessels, are outlined by experimental data. A normal perfused vessel density, for example, strongly correlates with tissue survival in rodents [53]. Hemodilution can decrease the perfused vessel density [54]. Finally, (iv) the microcirculatory flow index quantifies the velocity of microcirculatory perfusion.

## Transcutaneous O₂ and CO₂ Monitoring

Transcutaneous blood gas monitoring is a noninvasive and reliable technique to approximate oxygen and carbon dioxide tensions in a tissue. It detects early changes in tissue blood gases compared to invasive methods [55]. This technique is more reliable and more accurate than capnography in human patients [56]. Gas tension is measured via polarography. The skin is heated to 43-45°C to increase transcutaneous gas diffusion. Accuracy of this technique can be affected by skin thickness, peripheral vasoconstriction, hypoperfusion, or peripheral edema [57]. Consistent measurement protocols are therefore paramount for reliable measurements. Moreover, a decrease in cardiac output reduces the ability of transcutaneous partial pressure of oxygen (PtcO₂) to approximate partial pressure of oxygen (PO₂) [58], which is a significant limitation when monitoring tissue perfusion in critically ill animals. Recently, research in critically ill dogs showed that transcutaneous blood gas monitoring overestimated PaO₂ and PaCO₂ and should not be used in those patients [59]. In ventilated patients, an oxygen challenge test is performed to evaluate the change in PtcO₂ value in response to an increase in fraction of inspired oxygen. This test predicted outcome in patients with septic shock [60].

## Regional Capnography

The tissue-to-arterial PCO₂ gap is a reliable marker of tissue hypoperfusion [61, 62]. This gap can be measured using a tonometer that assesses PCO₂ in a tissue based on the gas's partial pressure equilibrium. Gastric, esophageal, sublingual, cutaneous, and urinary bladder tissues have been studied in experimental animals and human patients [62, 63]. The sublingual-arterial PCO₂ gradient has been described to be a better prognostic indicator than physical markers of hypoperfusion (cardiac index, DO₂, plasma lactate) [64]. In healthy dogs under anesthesia, gastric and bladder tonometry both correlated to sevoflurane-induced hypotension in dogs [65]. In that study, gastric tonometry was a better reflection of global hemodynamics when compared to bladder tonometry.
## Thermography

Thermography is a reproducible, non-invasive, rapid imaging technique to measure the heat emitted by a surface. This method is used in human medicine to diagnose venous and arterial thromboembolism [66]. A recent publication in cats showed that infrared thermography had a high accuracy in diagnosing arterial thromboembolism [67]. The technique could also be used to evaluate repuerfusion, as evidenced by an increase in thermal signature with return of blood flow [68]. This is a promising technique for clinical practice application to assess peripheral macrocirculation; however, further studies are needed to evaluate its ability to monitor microcirculation.

## 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 generated by refracted beams. Signal 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 arteriolar, capillary, and venular 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 [69], which is reflected as an increase in flow units. If the endothelium is dysfunctional, this flow 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, cutaneous laser Doppler flowmetry has been used in dog models for assessing wound healing and grafts. Laser Doppler technology has also been applied to non-cutaneous tissues. Clinical reports of the use of laser Doppler flowmetry (LDF) in dogs are limited. LDF has been used to measure capillary flow in the gastric mucosa of dogs with gastric dilation volvulus [70]. Intra-operative LDF technology has successfully measured spinal cord blood flow in canine patients with intervertebral disc disease. Spinal cord blood flow increased immediately following decompression but did not correlate with degree of compression on magnetic resonance imaging or neurological outcome 24hours following surgery [71]. 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 disc disease [72].

## Urine Partial Pressure of Oxygen

Perfusion to the kidney can be determined from PO₂ in the urine, assuming there is no change in arterial oxygen content. This technology was developed in animals and has been used in people. Current technologies rely on either a probe immersed in urine (whether in the bladder or a urine collection system) or optical fiber that can measure urine PO₂ without contact with the urine. Alterations in global hemodynamics translate to changes in urine PO₂ [73]. In sheep, resuscitation from septic shock with fluids and norepinephrine outlined the positive correlation between urine PO₂ and renal medullary blood flow. Studies in rabbits have also suggested the potential for urine PO₂ to predict the risk of acute kidney injury [74]. This technology relies on the absence of oligoanuria.

## Microdialysis

Microdialysis is another tool to monitor cell function and changes in perfusion. A microdialysis catheter (outer diameter 0.24–0.5 mm and length 1–10 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 equilibration, the concentration of markers of cell metabolism and hypoxia (lactate, glutamate, glucose, glycerol, pyruvate, urea) in the dialysate reflect that of the interstitium. Other biomarkers such as cytokines or biomarkers of brain injury can also be retrieved, and this microdialysis sample better reflects their local concentration compared with systemic samples. Analyte concentration can then be measured on a benchtop machine. As for renal replacement therapy, membrane cutoff size impacts the nature of solutes retrieved in the dialysate [75]. This technology is currently being used in both clinical and research settings. The clinical use of microdialysis is especially relevant for neurointensive care patients. A microdialysis probe can be inserted into the spinal cord [76] or the brain [75]. Brain perfusion monitoring via microdialysis has been recommended as part of the management of people with traumatic brain injury and subdural hematoma [77]. In the laboratory, the authors have used microdialysis in various tissues, such as the kidney or liver. Furthermore, placing the microdialysis catheter in a large vessel such as the caudal vena cava allows for frequent evaluation of plasma lactate concentration without the need to remove blood from the animal.

## Conclusion

Care providers have a wide range of tools available to guide resuscitation. Optimizing tissue oxygen delivery relies on normalizing arterial oxygen content and tissue perfusion.
Owing to the limitations of markers of macrocirculation, there are ongoing efforts to refine advanced techniques to make them more suitable for clinical practice. Continuing research efforts often focus on perfusion to a specific organ (kidney, brain, heart), which may not always reflect global perfusion. Acute care providers should therefore employ a diverse range of monitoring tools to improve patient care.

## Acknowledgment

The current author and editors would like to acknowledge Dr. Brian Young's contributions to first edition of Advanced Monitoring and Procedures for Small Animal Emergency and Critical Care, upon which this chapter is based.

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