Monitors of Hypoxia

Circulation, local Disturbances

Clinical Assesment of Tissue Hypoxia

1 Largely Indirect2 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 Arterial Oxygen Content = CaO2 Vol%2 Venous Oxygen Content = CvO2 Vol%3 A-V Content Difference4 Oxygen Delivery ml/min5 Oxygen Extraction %6 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 >> hypoxanthine3 Reperfusion:

– Reactive oxygen and nitrogen species– Hypoxanthine + O2 >> xanthine + H2O2

Oxygen and HypoxiaMonitoring – 2.

Oxygen Dynamics

1 Oxygen Delivery = DO22 Oxygen Consumption = VO23 Oxygen Debt = Cumulative Oxygen Uptake (consumption) deficit over time4 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 monitors1. Lactate level (arterial or central venous)

Prognostic valueSensitive but not specific (blood lactate may increase e.g. in sepsis without other evidence

of tissue hypoperfusion)2. Base deficit

Normal value = clearance of lactic acidNot sensitive / specific

3. Other monitorsSvO2, VO2 and DO2Not specific /sensitive

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 PiCO2Stomach perfusion: specific & sensitiveGlobal 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

IndicationsIntensive careNeuro-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 factorsDependence of electrode currents on tissue temperature,Errors in ptiO2 readings due to tissue trauma, edema by electrode insertionIntravascular 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

2E

1E

2emissionE h

xE

1E

2E

3E

4E

0E

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 fluorochrome2 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

Microscope CameraTime codegenerator

Framegrabber

Imageprocessingcomputer

Recordingdevice

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 TonometryWhy 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

Background1. 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

IndicationsNIRS may be applied to almost any organIt is mainly used in studies investigating cerebral or muscle oxygenation after different types of hypoxic injuries.LimitationsInability to make quantitative measurements (because of the contamination of light by scatter and absorption).

Monitors of Hypoperfusion-associated Hypoxia 2.

Systemic CirculationAcid-base Balance in Clinical Practice

Blood Gases – the Basics

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Blood Gases = Acid-Base Balance

1. pH = negative logarithm of H+ ion concentration2. 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.

H+

pH concentration7.0 1/10 000 0007.1 1/12 589 2547.2 1/15 848 9317.3 1/19 952 6237.4 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 kidneysCO2 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 indicated4. 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

MalnutritionDelayed wound healing

Reduced ventilatory capacity Reduced immunity and increased risk of infection

Nutritional assessmentClinical 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, parenteralUse 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 nutritionHyperosmotic 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 nutritionHyperosmolar, 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 Cl- 15 mmol Mg2+ 13 mmol Ca2+ 30 mmol PO42- 0.4 mmol Zn2+ Water and fat soluble vitamins Trace elements