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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
Krebs 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 0.3l 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 Llactate (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 Dlactate, 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, 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 hypoperfusion/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 sepsisassociated hyperlactatemia

Accelerated aerobic glycolysis induced by sepsisassociated 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
2 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

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 HendersonHasselbach 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 (PgmCO2PaCO2) has been proposed as


an alternative measure of tissue perfusion that is less
influenced by the systemic acidbase 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 24mins.

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 valuesusing
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 NIRS1. Non invasive


2. Requiring no specialized skill
3. Cost effective (Edmonds et al - $375 per pt, not
used $3569 (43hr - $83/hr)
Limitations4. Sensor can be applied only to skin that does not
have hair follicles ( leaves several area of brain
unmonitored)
5. Electrical interphase- electrocautry - interfere
with the reading