TISSUE PERFUSION

1. BLOOD LACTATE
2. MIXED VENOUS OXYGEN SATURATION
3. TISSUE Pco2 MONITORING (TONOMETERY)
4. NEAR INFRARED SPECTROSCOPY
(OPTICAL MONITORING METHODS)
 BLOOD LACTATE
• HISTORY
• LACTATE METABOLISM
• MEASUREMENT OF LACTATE
• HYRELACTATEIMA AND CAUSES
• LACTATE IN SEPSIS
 HISTORY
• 1922: Otto Meyerhoff and Archibald V. Hill win
Nobel prize for energy capabilities of
carbohydrate metabolism
• Accepted that lactate production causes
acidosis
 HISTORY
• Late 1950s: Huckabee established:
Hypoperfusion → Lactic Acidosis

• 1976: Cohen and Woods:

↓ Tissue Oxygenation → Lactic acidosis
 Normal lactate production
• Glycolysis in the cytoplasm produces the
intermediate metabolite pyruvate.
• Under aerobic conditions, pyruvate is converted
to acetyl CoA to enter the Kreb’s cycle.
• Under anaerobic conditions, pyruvate is
converted by lactate dehydrogenase (LDH) to
lactic acid .
• In aqueous solutions, lactic acid dissociates
almost completely to lactate and H+ (pKa at
pH7.4 is 3.9)
REGULATION OF PATHWAY
 REGULATION OF PATHWAY
• Thiamine (cofactor of PDH) Deficiency- lactate production

• Oral biguanides/ Hypoglycemic- inhibit renal and hepatic

gluconeogenesis which supplies NAD+ for lactate to pyruvate
conversion.
 Normal lactate metabolism
• The liver removes 70% of lactate. Uptake involves both a mono-
carboxylate transporter and the less efficient process of diffusion
(Important at concentration >2 mmol/l)

• Mitochondria-rich tissues such as skeletal and cardiac myocytes

and proximal tubule cells remove the rest of the lactate by
converting it to pyruvate.

• Less than 5% of lactate is renally excreted.

Normal lactate metabolism
 Measurement of lactate
1.Spectrophotometric analysers measure lactate in
deproteinized blood by using LDH to oxidize lactate in the
presence of nicotinamide dinucleotide (NAD+) to pyruvate.
Light at 340 nm is used to measure the dihydro nicotinamide
adenine dinucleotide (NADH) formed.

2. Lactate measurements obtained from blood gas analysers

use a modified amperometric cell. The cell contains the
enzyme lactate oxidase, which produces hydrogen peroxide
from lactate. The hydrogen peroxide is oxidized at a platinum
anode producing a current proportional to the lactate
concentration.
 Measurement of lactate
• The amperometric cell reads 13% higher than the
spectrophotometric analyser; correcting for haematocrit
reduces this difference.

• In vitro red cell glycolysis leads to false elevation of whole

blood lactate.

• Specimens that are not immediately analysed should be

stabilized. This can be achieved by cooling, protein
precipitation or by addition of glycolytic inhibitors.
 Measurement of lactate
3. Lactate Pro 2- A blood lactate test meter speedily measures
lactate with only a small sample of blood. Only a 0.3µl blood
sample is required. Speedy measurements in 15 sec.
 Arterial vs Venous lactate
• Arterial lactate – Reflect net body lactate.
• Venous lactate- net lactate balance of specific portion of the
circulation drained by the vessel.
( Beware of prolong venous occlusion)
(Beware of struggling during sampling)
 TYPES OF LACTATE
• Lactate exists in two isomers:
• L-lactate and D-lactate.
• Current lactate measurements only include L-lactate
(the primary isomer produced in humans)
• D-lactate is produced by bacteria in the human colon
when they are exposed to large amounts of unabsorbed
carbohydrates.
• In the setting of alteration in the intestinal flora and a
high carbohydrate load (such as in short bowel
syndrome) there will be an excess production of D-
lactate, which can cross into the bloodstream and
potentially cause neurologic symptoms.
 Definitions
• Normal lactate: 0.3-1.3 mmol/L
– Unstressed: 0.5-1 mmol/L
– Stressed: < 2 mmol/L
• Hyperlactatemia: 2-5 mmol/L
• Lactic acidosis: usually > 5 mmol/L with
associated metabolic acidosis ( pH≤ 7.35 or
base deficit of >6 mmol/l)
• Huckabee and Weil over five decades ago.

These authors proposed that elevated blood

lactate levels during experimental and clinical
shock states served as a measure of the
degree of oxygen deficit and the severity of
injury.
 Lactate use during stress
• During exercise, ß adrenergic stimulation,
elevated afterload, fast pacing and shock.
 SOURCE OF LACTATE IN SEPSIS
• Tissue hypoxia
• Mitochondrial dysfunction
• Pyruvate dehydrogenase inactivity
• DO2-VO2 mismatch

Dysoxia/tissue hypoxia/tissue hypo-perfusion/anaerobic

glycolysis’ theoryof SAHL

• The physiologic source of lactate generation during sepsis is

currently a matter of debate and research.
• Recent data suggest that other potential non hypoxic causes
could contribute to SAHL.
Alternative explanations for sepsis-
associated hyperlactatemia
• Accelerated aerobic glycolysis induced by sepsis-associated
inflammation has been proposed as a more likely explanation for
SAHL.
• This theory holds that an altered metabolic state occurs when
the rate of carbohydrate metabolism (pyruvate formation)
exceeds the oxidative capacity of the mitochondria.
• This increases cellular pyruvate concentration, which in turn
increases lactate production by a mass effect.

• Endogenous/exogenous catecholamines are highly correlated

with hyperlactatemia in sepsis. Through ß2 –receptor stimulation
They increase the activity of theNa/K-ATPase pump
 Where does lactate come from in
sepsis?
• Lungs changed from uptake to lactate production after
induction of endotoxemia.

• Muscle and liver lactate fluxes were neutral.

• Lactate uptake occurred in the gut and kidneys before and

after endotoxemia.
 The concept of lactate clearance
• 2004 Nguyen and colleagues reported that 'lactate clearance‘
defined as the percentage decrease in lactate from emergency
department presentation to 6 hours later, was an independent
predictor of mortality.
• Jones and colleagues extended the concept of targeting
resuscitation in sepsis to achieve a ‘lactate clearance’ of at least
10% as a marker of restoration of oxygen delivery to the tissues
with resuscitation treatment.
• The most recent Surviving Sepsis Campaign guidelines
recommend 'targeting resuscitation to normalize lactate in
patients with elevated lactate levels as a marker of tissue
hypoperfusion' (grade 2C)
• The term ‘clearance’ in relation to lactate is scientifically and
pharmacokinetically incorrect.

• Clearance represents the removal of a substance from a unit of

volume over a unit of time, typically expressed in milliliters per
minute.

• Logically, it is impossible to know if the rate and/or amount of

decline in SAHL is due to increased removal, decreased
production, dilution because of fluid administration during
resuscitation or all the above in variable combinations.
– Both initial high blood lactate and duration of
high blood lactate affect the outcome.

– Serial measurement allows assessment of

response to treatment.

– Initial fluid therapy may “wash out” lactate from

tissue leading to transient increase in lactate.
MIXED VENOUS OXYGEN
SATURATION
• Oxygen Delivery (DO2 )is the amount of oxygen
delivered or transported to the tissues in one
minute.
• Oxygen Delivery (DO2)= Arterial oxygen content
(CaO2) X Cardiac output (CO)

• 1.34-1.39 amount of O2 that can combine with 1 gram of haemoglobin

• 0.0031: solubility coefficient of O in the plasma*
• Oxygen Consumption (VO2)- Amount of oxygen used
by the tissue ie systemic gas exchange.
 Mixed Venous Oxygen saturation
(SvO2 ):
• Drawn from the pulmonary artery port of the pulmonary
artery catheter. Captures blood from the superior and inferior
vena cavae and the coronary sinus to reflect a true mixture of
all of the venous blood coming back to the right side of the
heart.

• Reflects the amount of oxygen "leftover" after all of the

tissues of the body have extracted oxygen but before the
blood is re-oxygenated at the lung

• Is the "Gold Standard" for assessment of oxygen extraction

• Normal value is 60-80%
• Techniques of measurement
1. Intermittent blood sampling – Co-oximetry
2. Indwelling Fiber optic catheter – oxygen saturation of
venous blood can be measure continuously.

• Issues- Tip position may influence signal quality (SQI) and

readings if the tip is positioned against a vessel wall.
• Fluids infused through the distal lumen may also influence SQI
and readings (e.g., lipids such as TPN or propofol, green or
blue dyes, and crystalloid infusions at high flow rates).
• Catheter kinking may also result in a high SQI.
(Both the large distal lumen and the sending/ receiving optics
reside at the tip of the catheter)
 LOW SVO2

• A low SvO2 is most suggestive of increased extraction (VO2)

• Decrease oxygen delivery (DO2)

 HIGH SVO2
• SvO2 may be FALSELY ELEVATED :

• if the tip of the pulmonary artery catheter is wedged or

distally placed or

• if excessive vacuum has been applied to the sampling

syringe. (Blood to be pulled from the pulmonary capillary into
the syringe)

• Aspiration of air into the blood gas syringe during sampling,

or the presence of an air bubble
 HIGH SVO2
• Rarely, a high SvO2 reading may indicate
failure of the cells to extract. This could occur
in end stage multi organ failure or with cell
toxins such as cyanide

• Shunting of oxygenated blood past tissue

 Central venous oxygen saturation
ScVO2
• ScvO2 usually runs 7% higher than SvO in critically ill patients.

• Reflects the amount of oxygen "leftover" that is coming from

the head and upper extremities

• Is a surrogate for SvO2 but it misses the inferior vena cava

blood (gut, kidney and low extremities) and coronary sinus.
 When the change is significant
• ScvO2 and SvO2 values are not static and fluctuate
approximately ± 5%. These values may show significant
changes with activities or interventions such as suctioning.
However the values should recover within seconds.
• Slow recovery- cardiopulmonary system struggling
• When monitoring ScvO2 clinicians should look for changes of
± 5 -10% that are sustained for more than 5 minutes and then
investigate each of the four factors that influence ScvO2
TISSUE Pco2 MONITORING
(TONOMETERY)
• Level of CO2 in a tissue is determined by
- Arterial CO2
- Blood flow to the tissue
- CO2 production by the tissue

- Tissue levels of CO2 rises early in hypoperfusion.

• Carbon dioxide production increases in hypoperfused tissue

to buffer the increase in hydrogen ions generated by the
hydrolysis of ATP during glycolysis .
• Impaired clearance of CO2 causing a further increase in tissue
CO2 concentrations.
• This impaired clearance is likely the largest contributor to
tissue hypercapnia in states of hypoperfusion .
• Gut mucosa is one of the earliest regions in the
body affected by hypoperfusion.

• Relatively easy accessibility of the gut makes

gastric tonometry an appealing choice for the
early detection of shock.
• Tonometry is based on the principle that gases will
equilibrate between semipermeable compartments over
time.

• Gastric tonometry involves placing a nasogastric tube tipped

with a fluid or air filled balloon into the lumen of the stomach
and allowing its contents to equilibrate with the fluid in the
stomach.

• This gastric fluid, in turn, is in equilibrium with the mucosal

lining the stomach. Therefore, by sampling the steady state
contents of the balloon, one can estimate the partial pressure
of CO2 in the gastric mucosa (PgmCO2).
• The original set-ups used saline in the balloon, which required
approximately 90 minutes for equilibration. Once equilibrated, the
saline was aspirated and its PCO2 was determined.
• Newer automated models use air in place of saline, which results in
shorter equilibration times (less than 20 minutes) and improved
precision.

• Many of the early studies performed with gastric tonometry used

the PgmCO2 to determine the intramucosal pH (pHi) by estimating
the tissue bicarbonate levels from serum bicarbonate and solving
the Henderson–Hasselbach equation.

• Recent focus has shifted away from this approach due to the
introduction of error by estimating intra mucosal bicarbonate from
serum bicarbonate.

• Instead, the PCO2gap (PgmCO2–PaCO2) has been proposed as an

alternative measure of tissue perfusion that is less influenced by
the systemic acid–base status.
• Currently, no standardized normal value exists for the PiCO2
gap recommended values range from 2 to 10 mm Hg (ie,
PiCO2= 50 mm Hg and PaCO2= 40 mm Hg)

• PiCO2-PaCO2gap greater than 25 to 35 mm Hg indicates the

onset of anaerobic metabolism
• The current recommendation is to maintain a gap less than 25
mm Hg in order to avoid anaerobic metabolism

• Of clinical usefulness, an increase in the gap greater than 20

mm Hg was associated with increased complications and
mortality.

• In trauma patients, a value greater than 18 mm Hg was

predictive of multiorgan dysfunction syndrome and death.
 SUBLINGUAL TONOMETERY

• New technology for intermittent measurement of

partial pressure of sublingual carbon dioxide
(PslCO2).

• It is used as a surrogate markers of gastrointestinal

perfusion.

• Probe is placed under the tongue in contact with sub

mucosa and measurement is available in 2-4mins.
• Capno-probe consist of
disposable sensor covered with
a membrane permeable to
carbon dioxide.

• The sensor contains a

fluorescent dye that emits a light
in direct proportion to the
amount of carbon dioxide
present.

• Fibro-optic technology is used to

detect the changes in the
fluorescence and these light
signals are converted into
numeric values.
• PslCO2 greater than 70 mm Hg was 100% predictiveof
circulatory shock.
• whereas a Psl CO2 less than 70 mm Hg was predictive of
survival.
• Although the absolute PslCO2 value may have prognostic
implications, interpretation of PslCO 2 is difficult because
of the direct relationship between PaCO2 and PslCo2.

• The PslCO2-PaCO gradient may be a useful indicator of

hypo-perfusion.
• A normal PslCO2-PaCO2 gradient is less than 10 mm Hg
(eg, PslCO2=50 mm Hg and PaCO2= 40 mm Hg).
• Current evidence suggests that the clinical usefulness of PslCO2
monitoring is the rapid detection of changes in gastric perfusion
as an indicator of circulatory shock.
• The prognostic value of PslCO2 and its use as an end point of
resuscitation remain to be shown, particularly in patients with
septic shock.
1. Tactile stimuli can increase sublingual blood flow and
production of saliva, the presence of the device itself
under the tongue can increase sublingual blood flow.

2. Enteral feeding could theoretically interfere indirectly with

sublingual blood flow through reflex mechanisms
NEAR INFRARED SPECTROSCOPY
 The Beer –Lambert Law
• When a monochromatic light of initial intensity
Io passes through a solution in a transparent
vessel, some of the light is absorbed so that the
intensity of the transmitted light I is less than Io
.There is some loss of light intensity from
scattering by particles in the solution and
reflection at the interfaces, but mainly from
absorption by the solution.
• Light in near infrared spectrum has a property
of undergoing the least amount of absorption
and scattering as it passes through tissue.
• Cerebral oximeters obtain continuous, noninvasive cerebral
oxygenation values using near-infrared spectroscopy (NIRS)
technology

• In general, most cerebral oximeters can support two to four

oximeter probes with respective monitor cables.

• Oximeter probes can be placed anywhere on the head but

most commonly on the forehead, where there is the least
amount of hair.
• NIRS technique is based on the principle that deoxygenated
hemoglobin absorbs light in the range of 760 nm or lower
whereas both deoxy and oxygenated hemoglobin absorbs light
at 800 nm.

• Thus passage of two different wavelength can detect the

changes in the concentration of oxyhemoglobin and
deoxyhemoglobin.

• SRO2 = amount of oxygenated hemoglobin level by the total

hemoglobin level.
And results are displayed in percentage value.
• Cerebral NIRS devices measure mean tissue oxygen
saturation and as such, reflect haemoglobin saturation in
venous, capillary, and arterial blood comprising the
sampling volume.
• For cerebral cortex, average tissue haemoglobin is
distributed in a proportion of 70% venous and 30% arterial
based on correlations between position emission
tomography (PET) and NIRS

• The adequacy of regional cerebral perfusion should be

investigated if
1. Sro2 decreases 12-20 points from base line.
2. Sro2 is>30 points less than arterial O2 saturation.
3. If the absolute Sro2 index is <50 in patient without an intra
cardiac shunt.
• AdvantageS of NIRS-
1. Non invasive
2. Requiring no specialized skill
3. Cost effective (Edmonds et al - $375 per pt, not used $3569
(43hr - $83/hr)

Limitations-
1. Sensor can be applied only to skin that does not have hair
follicles ( leaves several area of brain unmonitored)
2. Electrical interphase- electrocautry - interfere with the
reading