Monitors of Hypoxia
Circulation, local Disturbances
Clinical Assesment of Tissue Hypoxia
1 Largely Indirect
2 based on measuring aspects of whole body oxygen transport and uptake:
- clinical examination of the patient
- oxygen delivery from the inspiratory gases to the alveoli
- oxygenation of arterial blood
- delivery of oxygen to the tissues
- oxygen uptake
- lactate and assessment of regional PCO2 and pH
Oxygen Delivery and Consumption …
Several Formulas are Deployed
1
2
3
4
5
6
Arterial Oxygen Content = CaO2 Vol%
Venous Oxygen Content = CvO2 Vol%
A-V Content Difference
Oxygen Delivery ml/min
Oxygen Extraction %
Oxygen Consumption
– ml/min
– ml/Kg
Oxygen Delivery
1 Which factors determine O2 delivery?
– Hgb
– Cardiac Output
– SaO2
1 DO2 (ml/min/m2) = CI(L/min/m2) x CaO2 (ml/L)
= CI(L/min/m2) x (1.34 x [Hb](g/L) x SaO2 + 0.0031 x PaO2 (kPa)}
CaO2=Arterial Oxygen Content in Vol%
Hb x 1.34 x (SaO2/100) + (PaO2 x 0.0031)
Oxygen Delivery
CaO2=Arterial Oxygen Content in Vol% =
Hb x 1.34 x (SaO2/100) + (PaO2 x 0.0031)
CvO2=Venous Oxygen Content in Vol%=
Hb x 1.34 x (SvO2/100) + (PvO2 x 0.0031)
CaO2-CvO2 = arterial/venous oxygen content gradient in Vol%= 5 Vol
Oxygen Delivery Pathophysiology: Reduced ATP
1 Altered Na+-K+ ATPase activity
– Cellular swelling/dysfunction
2 Ca++ influx
– Activates phospholipases, ATPase, proteases
3 Decreased antioxidant defenses
– Decreased glutathione
Oxygen Delivery Pathophysiology
1 Inflammatory cell “priming”
2 ATP metabolism
– ADP >> AMP >> hypoxanthine
3 Reperfusion:
– Reactive oxygen and nitrogen species
– Hypoxanthine + O2 >> xanthine + H2O2
Oxygen and Hypoxia
Monitoring – 2.
Oxygen Dynamics
1
2
3
4
Oxygen Delivery = DO2
Oxygen Consumption = VO2
Oxygen Debt = Cumulative Oxygen Uptake (consumption) deficit over time
Oxygen Extraction Ratio
Extraction is never 100% in any tissue; the extraction capability differs between tissues
Oxygen Dynamics Pathophysiology
1 Normal DO2: 520-570 ml/min/m2
1 Critical DO2 : when aerobic >> anaerobic metabolism
• hallmark = lactic acid
• elevated P(tissue)CO2
1 Oxygen debt develops
1 ATP depletion
– Mitochondrial dysfunction
1 If oxygen extraction exceeds 0.65-0.75 for a prolonged time in acutely ill patients,
inadequate tissue oxygenation and organ dysfunction is likely.
Oxygen Consumption
Derived from the Fick equation (remember: this method calculates the arterial and venous
oxygen content difference and multiplies that value by the CO):
VO2 (ml/min) = (CaO2-CvO2) x CO
If Hgb, CO and A/V saturations are known, VO2 may be calculated without knowing the PO2
values (dissolved O2 normally contributes < 0.3 Vol% of the arterial O2 content):
VO2 (ml/min) = Hb x 1.34 x [(SaO2-SvO2)/100] x CO
The basal oxygen consumption may vary due to a variety of factors
Assessment of Oxygen Requirements
1 The only proper method is via the Fick equation.
2 Patients
- in the OR
- intubated,
- chemically paralyzed
- artificially ventilated
- hypothermic (7% additional reduction / 1oC hypothermia)
will have approx. 30% metabolic requirements than at a steady state; thus 250 ml/min Vol% is
reduced to 170 ml/min.
Oxygen Therapy
Face masks: oxygen mixes with air drawn in through holes in the body of the mask. Expired air is
exhausted through the holes. The percentage of oxygen administered depends on the flow rate
from the outlet.
Nasal prongs: plastic prongs designed to fit into the nostrils.
Monitors of Hypoperfusion-associated Hypoxia
Low-tech monitors
1. Lactate level (arterial or central venous)
Prognostic value
Sensitive but not specific (blood lactate may increase
of tissue hypoperfusion)
2. Base deficit
Normal value = clearance of lactic acid
Not sensitive / specific
3. Other monitors
SvO2, VO2 and DO2
Not specific /sensitive
e.g. in sepsis without other evidence
Monitors of Hypoperfusion
High-tech monitors
1.a. Tissue oxygen tension
1.b. Fiberoptic pulmonary artery catheters to monitor SvO2 changes on-line
2. Tonometry (pHi)
Measures gastric/sigmoid mucosal pH via PiCO2
Stomach perfusion: specific & sensitive
Global perfusion: not specific & sensitive
3. Near-infrared spectroscopy (NIRS)
1. Tissue Oxygen Tension
The Clark electrode: a forerunner of today’s biosensors
Tissue Oxygen Tension
The ptiO2 values correspond to O2 availability on a cellular level and provide information about
O2 supply and utilization in specific tissue beds.
The ptiO2 is relatively constant, lower (approx. 1 ml kg–1 min–1, compared with overall body
average of approx. 4 ml kg–1 min–1); thus PTO2 in s.c. tissue is a highly sensitive indicator of
tissue perfusion.
Tissue Oxygen Tension
A. The original polarographic technique (Tissue Oxymeter)
- an oxygen-permeable catheter (ID: 0.8 mm) is introduced via a 14 G i.v. cannula into the s.c.
tissue of the deltoid region of the upper arm or the surgical wound.
- hypoxic saline, obtained by bubbling N gas through normal saline for 5–10 min, is introduced
into the tube.
- this is allowed to equilibrate with tissue O2 for 15–20 min, then the saline is sampled for partial
pressure in tissues (ptiO2).
B. Miniaturized, implantable Clark electrodes
- to measure ptiO2 in organs, and body fluids directly and continuously.
Tissue Oxygen Tension
Indications
Intensive care
Neuro-surgical procedures (absolute level of oxygenation was a reliable predictor of neurological
outcome)
Monitoring muscle partial pressure of oxygen (early and reliable indicator of stagnant blood flow
and tissue dysoxia after hemorrhage, resuscitation, and shock)
Measuring ptiO2 in malignant tumours in order to define hypoxic cell radioresistance.
Limiting factors
Dependence of electrode currents on tissue temperature,
Errors in ptiO2 readings due to tissue trauma, edema by electrode insertion
Intravascular misplacement.
Diagnostic Techniques for Assessment of Organ Perfusion
Divided upon the information acquired:
(1) Anatomy of the major vessels (angiography,
duplex ultrasound, MRA , CT angiography)
(2) Flow patterns (duplex ultrasound),
(3) Flow volume (MRA)
(4) Organ Perfusion (i.e. mucosa)
- mucosal laser Doppler flowmetry
- endoluminal pulse oximetry
- endoscopy with intravital microscopy
(5) Assessment of actual ischaemia irrespective of flow
- tonometry
Reginal Red Blood Cell Perfusion Monitor
Laser-Doppler Flowmetry
Indication: intra-cranial monitoring, stroke, ischemic brain damage, tumour angiogenesis, flaps,
peripheral vascular diseases, diabetes, wound heeling, dermatology
Endoscopy + Intravital Fluorescence Microscopy
Fluorochromes can, once reached by radiation, partially absorb light and partially send it back:
the re-emitted radiation has a lower energy than that of the incident one and, thus, a longer
wavelength.
If the incident radiation is a U.V. ray, i.e. invisible, the emitted radiation can usually be seen.
Fluorescence microscopy: permits the localisation in cells or tissues of molecules labelled with
fluorochromes.
Absorption – Emission
E2
E1
Eemission  h 2
Ex
E1
E2
E3
E4
E0
Every molecule has a characteristic set of energy levels, and a set of allowed transitions between
them.
1 The emission spectrum is characteristic of the molecule, and is independent of the
excitation wavelength: a stable part of the molecular signature!
Autofluorescence
1 Most biological samples can emit fluorescence only after a labelling with fluorochromes;
in this case it is defined as INDUCED or SECONDARY FLUORESCENCE
1 Some biological samples, particularly of vegetal origin, such as cellulose, naturally emit
fluorescence: PRIMARY FLUORESCENCE or AUTOFLUORESCENCE.
Autofluorescence
1 Occasionally, an advantage: no need to add a fluorochrome
2 NADH is co-enzyme involved in metabolism, serves as universal redox currency,
carrying reducing power as hydride ions (H−).
3 NADPH and NADH emit strong fluorescence at 460 nm, NAD and NADP fluoresce three
orders of magnitude weaker.
Intensified Fluorescence Intravital Video-Microscopy System
Recording
device
Microscope
Camera
Time code
generator
Frame
grabber
Image
processing
computer
Monitor
The (fluorescent) signal is received through the microscope by the CCD camera. The image is
sent to the frame grabber to digitize the signal for image processing. The processed signal is then
sent to a monitor for display by the operator and permanently recorded for later playback and
analysis.
Polarised Light
When the quanta of all the beam light rays oscillate in parallel planes, the light beam is defined
polarised. A light beam can be polarized by passing it through an appropriate filter, the polariser.
Orthogonal Polarization Spectral Imaging (OPS technique
2. Clinical Tonometry
Why monitor mucosal PCO2?
1. The gastric mucosa is an early target of blood flow redistribution in shock, trauma, sepsis or
major surgery.
2. The small intestine is one of the first organs to suffer from hypoperfusion and one of the last to
be restored to normality by resuscitation.
3. The gastrointestinal mucosa is very sensitive to altered perfusion. Inadequate splanchnic tissue
perfusion plays a major role in the development of sepsis and multiple organ failure (MOF)
Indirect Tonometry: the Basics
1. The counter- current circulation with decreasing pO2 partial pressure towards the tip cannot
provide the tip of the villi with sufficient oxygen in the case of decreasing perfusion.
2. The mismatch between mucosal perfusion and regional metabolism leads to regional
imbalance between CO2 removal and production.
3. As a result CO2 accumulates in the mucosa. This can be detected by measuring the gastric
CO2, PgCO2.
Indirect Tonometry: the Basics
Types of Tonometers
1 PgCO2 measurement is minimally invasive. A special tonometry catheter and monitor are
used to analyze PCO2 with infrared sensor technology.
2 Saline tonometry: multiple lumen catheter includes a semi-permeable silicone balloon at
the distal end of the catheter, which is positioned in the stomach. CO2 freely equilibrates
between the gastric mucosa, the gastric lumen and the balloon.
A. A gas sample is drawn from the balloon and analyzed every 30 min (conventional tonometry);
B. Air-automated tonometry: 10 min equilibration time. This technique can significantly
improve the precision of PgCO2 determination.
Gastric Tonometry
Patients who require gastrointestinal mucosal PCO2 monitoring:
1 Trauma, major surgery e.g. cardiac patients
2 patients with hemorrhagic shock, cardiogenic shock
3 patients with severe acute respiratory failure
4 severe acute pancreatitis
5 patients with major burns
In the case of low flow states (hypovolemic, cardiogenic shock) vasoconstriction is established in
the gastric mucosa.
Gastric tonometry works as an early warning measurement to detect gastric hypoperfusion prior
to systemic
Gastric Tonometry
1 Significance of gastric PCO2: gastric PCO2 (PgCO2) indicates the balance between CO2
production (metabolism) and removal (perfusion).
An elevated gastric PCO2, regional hypercapnia, is therefore a marker of inadequate tissue
perfusion and/or deranged metabolism.
1 Normal PgCO2value: PgCO2 approximates arterial PCO2, (PgCO2 is about 45 mmHg (6
kPa).
It is recommended to compare it with either arterial PCO2 or with end-tidal CO2.
pHi and PgCO2
1 PgCO2 might provide earlier information when compared with pHi (better therapeutic
index).
1 When DO2crit is reached, anaerobic CO2 production contributes to increased PgCO2,
while arterial pH decreases and favors a decrease in intramucosal pH (pHi). When pHi is
used to guide treatment, therapeutics might prove to be ineffective if pHi is already low.
3. Near-Infrared Spectroscopy
Near-Infrared Spectroscopy
NIRS: according to the Beer-Lambert law.
NIRS: continuous, non-invasive method applying the principles of light transmission and
absorption to determine tissue oxygen saturation.
NIRS: measures oxygenated and deoxygenated Hb as well as the redox state of cytochrome C
oxydase aa3 as an average value of arterial, venous and capillary blood.
Near-Infrared Spectroscopy
Background
1. Cytochrome aa3 (terminal cytochrome of the respiratory chain) is responsible for approx. 90%
of cellular O2 consumption through oxidative phosphorylation.
2. The redox state of cytochrome aa3 is primarily determined by available O2, → decrease in
cellular DO2 → reduction of oxidative phosphorylation and a decreased oxidation level of
cytochrome aa3.
3. Monitoring the redox state of cytochrome aa3 is a key indicator of impaired cellular oxidative
metabolism and tissue dysoxia.
Near-Infrared Spectroscopy
Indications
NIRS may be applied to almost any organ
It is mainly used in studies investigating cerebral or muscle oxygenation after different types of
hypoxic injuries.
Limitations
Inability to make quantitative measurements (because of the contamination of light by scatter and
absorption).
Monitors of Hypoperfusion-associated Hypoxia 2.
Systemic Circulation
Acid-base Balance in Clinical Practice
Blood Gases – the Basics
Every time you sign in at a Red Cross blood drive this summer, you will be automatically
registered to win $100 in FREE GAS!
Blood Gases = Acid-Base Balance
1. pH = negative logarithm of H+ ion concentration
2. pH = 6.1 + log (HCO3- / CO2)
Acid-base Balance – the Basics
Logarithmic scale = small pH change = large jump in H+ concentration. If pH changes from 7.4
to 7.0, the acidity will be 2.5x higher.
pH
7.0
7.1
7.2
7.3
7.4
H+
concentration
1/10 000 000
1/12 589 254
1/15 848 931
1/19 952 623
1/25 118 864
Acid-base Balance – the Basics
Among the buffer system of the human body bicarbonate regulates the pH of the whole system,
because it acts on two points:
HCO3- through kidneys
CO2 through the lungs: H+ + HCO3- <=> H2CO3 <=> H2O + CO2
Acid-base Balance – the Basics
Capillary blood or arterial samples can be used, in 10 min max. after sampling. If this is
impossible, the sample must be freezed.
1. Arterial sample is drawn at the pulse site at the wrist.
2. A local anesthetic at the site is applied if indicated.
3. An oxymeter clip will be placed on the finger to correlate with the blood values if further
oxygen testing is indicated
4. Pressure will be held at the site for several minutes to assure that there is no bleeding
What do the Different Numbers Mean?
Stepwise Interpretation of the Blood Gas
Summary
Arterial O2 content, perfusion pressure and blood flow are necessary prerequisites
for adequate oxygenation.
Monitoring the adequacy of tissue oxygenation should always be based on clinical
assessment + comprehensive evaluation.
Extracorporal membrane oxygenization – artificial oxygen transport (DO2) and gas
exchange (ECC)
Extracorporal Membrane Oxygenization
Bubble oxygenator (Richard DeWall and C. Walton Lillehei) has a direct gas to blood interface,
thus causing contact and complement pathway activation leading to activation of C3 and C5A;
pulmonary and myocardial edema.
Membrane oxygenators eliminate direct gas to blood interfacing and emulate the O2 and CO2
transfer rates of the lungs via microporus polypropylene hollow fibers
The Membrane Lung
1 Polycarbonate/silicon envelope in spiral loop
– Blood and gas phases separated by membrane
– Permeability of CO2 > O2 (6:1 ratio)
– Variable surface area (Neonatal < Pediatric < Adult)
2 O2 and CO2 transport determined by:
– Surface area of membrane
– Membrane diffusion characteristics
– Gas diffusion gradient across membrane
3 O2 transport also determined by:
• Rate of blood flow through membrane
4 CO2 transport also determined by:
• Rate of gas flow through membrane
Surgical nutrition
Malnutrition
Delayed wound healing
Reduced ventilatory capacity
Reduced immunity and increased risk of infection
Nutritional assessment
Clinical assessment
Weight loss
10% =mild malnutrition
30% = severe malnutrition
Body mass index
Anthropometric assessment
Triceps skin fold thickness
Mid arm circumference
Hand grip strength
Blood indices
Reduced serum albumin, prealbumin or transferrin
Lymphocyte count
Methods of nutritional support: enteral, parenteral
Use gastrointestinal tract if available
Early enteral nutrition reduce post-operative morbidity
Surgical nutrition 2.
Enteral feeding
* Prevents intestinal mucosal atrophy
* Supports gut associated immunological shield
* Attenuates hypermetabolic response to injury and surgery
* Cheaper than TPN and has fewer complications
* Polymeric liquid diet
o Short peptides, medium chain triglycerides and polysaccharides
o Vitamins and trace elements
* Elemental diet
o L-amino acids, simple sugars
o Expensive and unpalatable
o High osmolarity can cause diarrhoea
* Enteral feed can be taken orally or by NGT
* Nasoenteral tube - usually fine bore
* Long term feeding can be by:
o Surgical gastrostomy, jejunostomy
o Percutaneous endoscopic gastrostomy
o Needle catheter jejunostomy
* Complications of enteral feeding
o Malposition and blockage of tube
o Gastrooesophageal reflux
o Feed intolerance
Surgical nutrition 3.
Parenteral nutrition
* Intestinal failure = „reduction in functioning gut mass below the minimal necessary for
adequate digestion and absorption of nutrients”
* Useful concept for assessing need for TPN
* Can be given by either a peripheral or central line
Indications for total parenteral nutrition
* Absolute indications
o Enterocutaneous fistulae
* Relative indications
o Moderate or severe malnutrition
o Acute pancreatitis
o Abdominal sepsis
o Prolonged ileus
o Major trauma and burns
o Severe inflammatory bowel disease
Surgical nutrition 4.
Peripheral parenteral nutrition
Hyperosmotic solution
Significant problem with thrombophlebitis
Need to change cannulas every 24-48 hours
No evidence to support it as a clinically important therapy
Composition - 12g nitrogen, 2000 Calories
Central parenteral nutrition
Hyperosmolar, low pH and irritant to vessel walls
Typical feed contains the following in 2.5L
14g nitrogen as L amino acids
250g glucose
500 ml 20% lipid emulsion
100 mmol Na+
100 mmol K+
150 mmol Cl15 mmol Mg2+
13 mmol Ca2+
30 mmol PO420.4 mmol Zn2+
Water and fat soluble vitamins
Trace elements