Pathophysiology of hypoxic respiratory failure

PATHOPHYSIOLOGY OF ACUTE RESPIRATORY FAILURE Dr. Andrew Ferguson Consultant in Anaesthetics & Intensive Care Medicine Craigavon Area Hospital, U.K. http://www.slideshare.net/fergua

INTRODUCTION
This is a tutorial covering the pathophysiology of hypoxaemic respiratory failure, and reviewing how this information can be used to support a rational management plan.
Although this tutorial is primarily aimed at anaesthesia residents in the early part of their career, it should be useful to medical students and to doctors from other specialties who encounter these patients or are interested in understanding some of the underlying physiology.
This tutorial is an introduction to the topic, and although detailed in some areas it does not attempt to be an exhaustive reference. You should refer to standard texts and to the literature for further information.

RESPIRATORY PHYSIOLOGY CURRICULUM
Gas exchange
O 2 & CO 2 transport
Hypoxia & hypercapnia
Hyper- and hypobaric scenarios
Functions of Hb
In O 2 and CO 2 carriage
In acid-base equilibrium
Pulmonary ventilation: volumes, flows, dead-space
Effects of IPPV on the lungs (and the heart)
Mechanics of ventilation & V/Q abnormalities
Control of breathing
Acute & chronic ventilatory failure
Effects of O 2 therapy
Non-respiratory functions of the lungs

OVERVIEW
Definition of respiratory failure
Case scenario (running through the tutorial)
Mechanisms of hypoxia
Respiratory patterns and work of breathing
Definitions and calculation of dead-space
Alveolar-arterial oxygen difference and the alveolar gas equation
Venous admixture, V/Q mismatch, shunt and the shunt equation
Lung volume, compliance, and functional residual capacity
The importance of mean airway pressure
Recruitment as a component of the ventilatory strategy

WHAT IS RESPIRATORY FAILURE?
pO 2 < 8 kPa (60 mmHg) on room air and/or
pCO 2 > 6 kPa (45 mmHg)
Type I = primarily hypoxaemia
Type II = primarily hypercapnia
Type III = perioperative (atelectasis)
Type IV = shock (hypoperfusion)

CASE SCENARIO John is a 43 year old with mild asthma. He attends the Emergency Department with a 72 hour history of myalgias and fever, with increasing dyspnoea and a productive cough. His room air SpO 2 is 84% and his respiratory rate is 37/minute and shallow. He is using his accessory muscles and there is evidence of muscle use on exhalation. ABG shows pH 7.34, pCO 2 6.1 kPa, pO 2 7.8 kPa on room air He is sweaty and tiring rapidly. You detect crepitations at his right lung base and widespread wheeze. CXR confirms a right lower zone infiltrate.

KEY PHYSIOLOGY RELEVANT TO THIS CASE
Mechanisms of hypoxia
Work of breathing
Dead space and alveolar ventilation
Hypoxic pulmonary vasoconstriction
Alveolar gas composition & alveolar-arterial O 2 difference
Shunt and V/Q mismatch
Effects of anaesthesia on all of these
Effects of mechanical ventilation on all of these

WHY IS JOHN HYPOXAEMIC?
Gather your thoughts then proceed…

MECHANISMS OF HYPOXAEMIA
Ventilation-perfusion (V/Q) mismatch
E.g. secretions or bronchial constriction, emphysema, PE, pulmonary arterial vasospasm
At least partially O 2 responsive
Shunt
E.g. collapsed or flooded alveoli
Typically poorly responsive to O 2
Alveolar hypoventilation
See alveolar gas equation in subsequent slides
Reduced inspired partial pressure of O 2
e.g. altitude, industrial accident, fire
Diffusion impairment
Rarely a major contributor
Many of these are associated with a fall in FRC (functional residual capacity)

RESPONSE TO INCREASED FIO 2 IN SHUNT Shunt fraction (%) Alveolar pO 2 As shunt fraction increases, higher inspired (and alveolar) pO 2 has less and less effect on arterial pO 2

WHAT ABOUT JOHN’S BREATHING PATTERN?

IMPACT OF RESPIRATORY PATTERNS
Increased respiratory muscle work
Increases O 2 consumption (can be dramatic)
May exceed ability to deliver and so precipitate cardiac ischaemia
Rapid shallow breathing
Increased dead-space/tidal volume (VD/VT) ratio
Turbulent flow
In rapid shallow breathing & bronchospasm
Requires greater work for same flow
Bronchospasm
Gas trapping and auto-PEEP
Requires increased work of breathing including expiratory

RAPID SHALLOW BREATHING: F/VT RATIO
f/VT = respiratory rate divided by tidal volume (in litres)
Significant increase in work of breathing above f/VT = 60-70
Corresponds to rate of 30 with tidal volume 0.5L
Hence common use of rate > 30 as predictor of severity

WORK OF BREATHING: P-V CURVE

HOW DO YOU WORK OUT DEAD-SPACE?

RESPIRATORY DEAD-SPACE
Anatomical
Conducting airway volume = around 150 ml (2ml/kg ideal BW)
Increased by:
Rapid shallow breathing (as above)
Very high VT (pull on trachea and bronchi increases volume)
Decreased by:
Head-down position (compresses conducting airways)
Measured by Fowler’s method
Physiological
Alveolar dead-space = alveoli ventilated but not perfused
Physiological dead-space = alveolar + anatomical = 170 ml
Measured by Bohr’s method using Bohr equation

IMPLICATIONS OF DEAD-SPACE VOLUME
Impacts on effective alveolar ventilation
Alveolar minute ventilation = (VT – VD) x resp. rate
Increased dead-space
Decreases effective alveolar ventilation
Increases pCO 2
Increases work of breathing

FOWLER’S (1948) METHOD (ANATOMICAL D-S)

FOWLER’S METHOD

FOWLER’S METHOD
Area under the exhalation curve = C exp x (V exp – V d )
Because the upstroke is not vertical the separation of Vexp and Vd is found by dropping a perpendicular so that area A = area B
Where this hits the volume axis = anatomical dead-space

BOHR EQUATION You might want to get coffee….we are going to derive the Bohr equation and there are some mathematics and mental gymnastics involved! You have been warned! And yes…it does have some clinical relevance…read on!

BOHR EQUATION (PHYSIOLOGICAL D-S)
Let’s start with the fact that exhaled tidal volume is made up of dead-space volume plus some alveolar volume
VT = V d + V alv [re-arranged to V alv = VT – V d ]
The amount of a gas exhaled will be the sum of the amount in the alveolar portion plus the amount in dead-space (we use CO 2 )
The amount of gas = volume x concentration
SO… VT x C exp = V d x C d + V alv x C alv & for CO 2 C d is near zero
SO… VT x C exp = V alv x C alv and V alv = VT – V d
SO… VT x C exp = (VT - V d ) x C alv
SO… VT x C exp = (VT x C alv ) – (V d x C alv )
Rearranging gives (V d x C alv ) = (VT x C alv ) – (VT x C exp )

BOHR EQUATION
SO V d x C alv = VT (C alv – C exp ) leading to VD/VT = (C alv -C exp )/C alv
Using partial pressures, VD/VT = (P Alv CO 2 -P E CO 2 )/(P Alv CO 2 )
It is then assumed that P Alv CO 2 = PaCO 2 (arterial)
SO finally
VD/VT = (PaCO 2 -P E CO 2 )/PaCO 2 (norm = 0.2-0.3)
and all are measurable so you can now work out the physiological dead-space of your patients!
REMEMBER the application of this: The larger the gap between PaCO 2 and ETCO 2 the greater the physiological dead-space

JOHN IS STILL ALIVE…JUST!
You got pretty worried and intubated John before he collapsed. After 10 minutes on the ventilator with PEEP 5, VT 550 and FiO 2 0.8 John’s ABG shows:
pH 7.30, pCO 2 6.6 kPa, pO 2 8.6 kPa
A nurse has just done the FCCS course and asks you 2 questions:
how much of the hypoxia is due to the CO 2 retention?
What is John’s A-aDO 2 ?

ALVEOLAR-ARTERIAL OXYGEN DIFFERENCE
The easy bit…
The difference is normally quite small (<15 mmHg or 2 kPa)
It increases with age by 1 mmHg for every decade above 18 years
If a patient has hypoxia with a normal A-aDO 2 the cause is either:
Hypoventilation (hypercapnia), or
Breathing a gas with low pO 2
If the A-aDO 2 is elevated the hypoxia is pulmonary in origin
i.e. pulmonary system (vessels, alveoli etc.)
The harder bit…
Assumes that we know the O 2 concentration in the alveoli

THE ALVEOLAR GAS EQUATION (SIMPLE)
Assumptions
Inspired gas has no CO 2
P A CO 2 = P a CO 2
Alveolar gas is saturated with water
Simple equation: P A O 2 = P I O 2 – PaCO 2 /R where P I O 2 =FiO 2 (P atm -P H2O )
R = respiratory quotient = 0.8
P H2O = SVP of water at 37 o C = 47 mmHg or 6.25 kPa
P atm = atmospheric pressure assumed to be 760 mmHg (101 kPa)
Substituting gives:
P A O 2 = 94.75 x FiO 2 – 1.25 x PaCO 2

THE ALVEOLAR GAS EQUATION (COMPLEX) If R < 1 (and especially if FiO 2 is high) then more O 2 is taken up from the alveolus than CO 2 is released into it, and alveolar volume would fall if more gas did not move in passively from the airway to replace it. This gas moving in can increase the P A O 2 very slightly and if we want to correct for this we need to use this larger equation. OUCH! Luckily the effect is so small that in the real world we can pretty much ignore it. P A O 2 = (P atm – P H2O ) x FiO 2 – PaCO 2 /R + (FiO 2 x P a CO 2 x (1-R)/R))

Back to the A-aDO 2 A-aDO 2 = P A O 2 -P a O 2 So John, assuming R is 0.8 and breathing 80% O 2 should have an alveolar O 2 of: 94.75 x 0.8 – 1.25 x 6.6 = 75.8 – 8.25 = 67.6 kPa John’s A-aDO 2 is 67.6 – 8.6 = 59 kPa Which is WAY above the normal of 2 kPa, so his hypoxia is plainly not due to his hypercapnia!!!

So back to john’s hypoxia…
The helpful staff nurse wants to understand what’s going on in John’s lungs, since the CO 2 isn’t the main problem. You tell her that he is “shunting” which draws a puzzled look and inevitably leads to her asking you to explain. You walked into it, now you have to get yourself out!

SHUNT & VENOUS ADMIXTURE
Shunt = perfusion without ventilation i.e. V/Q = 0
Mixing of deoxygenated blood back into the arterial circulation
V/Q mismatch = imbalance of ventilation and perfusion
Venous admixture is a construct representing the amount of (deoxygenated) mixed venous blood that would have to be added to (oxygenated) pulmonary end-capillary blood to produce the A-aDO 2 that you observe in your patient, so it reflects the degree of shunting and V/Q mismatch

SHUNT
Anatomical shunts
Physiological
Thebesian veins draining from the LV walls (0.3% of cardiac output)
Bronchial veins (< 1% of cardiac output)
This blood is NOT mixed venous blood
Pathological
Congenital heart disease with right to left shunt
Pulmonary A-V shunts e.g. haemangioma
Perfusion of non-ventilated alveoli (atelectasis/flooded)
Protective mechanism = hypoxic pulmonary vasoconstriction
Diverts blood away from diseased alveoli
Not 100% effective so some flow remains
Effect diminished by disease processes and drugs (anaesthetics)

THE SHUNT EQUATION
Don’t panic….you have seen the principle before (Bohr’s)!
Let’s take it step by step:
The blood leaving the lungs (Qt) is made up of the blood that went through working lung (Qc) and the blood that shunted (Qs), so Qt (cardiac output) = Qs + Qc and so Qc = Qt – Qs
We want to know about blood flow and oxygen content, so:
The oxygen content of Qt (cardiac output) is CaO 2 (arterial)
The oxygen content of Qs (the pure shunt) is CvO 2 (mixed venous)
The oxygen content of Qc (working capillaries) is CcO 2 (pulm. capillary)
Substituting equation 1 we get Qt = Qs + (Qt - Qs)
So far so go I hope! Think that through then proceed…

THE SHUNT EQUATION OK, so we have Qt = Qs + (Qt – Qs) , but we are interested in the total O 2 running in this system, which equals flow x content Let’s add in the content and go from there: Qt.CaO 2 = Qs.CvO 2 + (Qt – Qs).CcO 2 (since Qt – Qs = Qc) Qt.CaO 2 = Qs.CvO 2 + Qt.CcO 2 – Qs.CcO 2 Arrange the equation so Qs and Qt are on opposite sides: Qs.CcO 2 – Qs.CvO 2 = Qt.CcO 2 – Qt.CaO 2 now factorise… Qs(CcO 2 – CvO 2 ) = Qt(CcO 2 – CaO 2 ) and rearrange to get Qs/Qt Shunt fraction Qs/Qt = (CcO 2 – CaO 2 ) / (CcO 2 – CvO 2 )

THE REALITY
CaO 2 results from a mixture of blood from different lung units
Some with pure shunt
Some with varying degrees of V/Q mismatch
over or under-ventilated relative to blood flow
Some with normal blood and gas flow
The impact of increasing FiO 2 on your patient will depend on their individual mix of V/Q ratios.
It’s important to realise that this is dynamic and that you can have an impact on it to improve the arterial pO 2 .

EFFECTS OF MIXED V/Q RATIOS

SO BACK TO FIXING JOHN’S OXYGENATION
We’ve established John has altered V/Q and shunt
He has thick purulent lung secretions in his right lower lobe
He has bronchial oedema related to his asthma
He has been rapid shallow breathing which will have reduced his FRC and induced atelectasis, adding to his problems
What we want to do is to:
improve the V/Q mismatch
Convert areas of shunt (O 2 resistant) to V/Q mismatch (O 2 responsive)
Reverse atelectasis
And we are going to do this by
improving functional residual capacity (FRC)
RECRUITING collapsed or flooded alveoli

LUNG VOLUMES AND COMPLIANCE
Remember blowing up a balloon!
At low volume it’s stiff and really hard to inflate
In the middle all is great!
Before it bursts it gets difficult to inflate again
We want John’s lungs on the steep (compliant) part of the curve
Stiff overdistended lung Stiff atelectatic lung Pressure PEEP Peak Ventilator pressures FRC

VENTILATION TO IMPROVE OXYGENATION
Remember! Recruitment manoeuvres can reduce BP severely
Marked fall in RV preload and increase in RV afterload
More severe in hypovolaemic patients
Recruitment manoeuvre on initiation of ventilation
Manual
Inflate to given pressure (30 or 40 cmH 2 O)
Hold for 30 seconds if BP/SpO 2 maintained
Connect to ventilator
On ventilator
Ensure safe peak inspiratory pressure < 30 cmH 2 O
Ensure safe tidal volume < 6-8 ml/kg predicted body weight if lung injury
Press inspiratory hold button on ventilator (some need to be held in)
Repeat to hold breath for 30 seconds
Assumes adequate PEEP afterwards to maintain “open lung”
Recheck pressures and volumes on ventilator
Compliance may have changed

MAINTAINING FRC, AVOIDING OVERDISTENSION
All of the ventilation manoeuvres you might perform to improve oxygenation rely on an increase in MEAN AIRWAY PRESSURE which is the driver for maintenance of FRC via increased alveolar pressure
The options include:
Increasing PEEP (producing a higher baseline pressure)
Increasing peak pressure (not used often)
Not beyond 30 cmH 2 O
Maintaining safe tidal volumes (6 ml/kg PBW in lung injury)
Increasing inspiratory time
Increases inspiration:expiration time ratio (I:E) ratio
Usually in 1:2 range, increased towards 1:1 or sometimes even higher
Very prolonged inspiratory times may lead to harmful gas trapping
Increasing respiratory rate
Provided inspiratory time is not shortened too much

MEAN AIRWAY PRESSURE
O 2 is a band-aid, not a good primary therapy
Increasing FiO 2 makes the ABG look better, but does not correct the pathophysiology
Recruitment and PEEP improve V/Q and convert some of the shunt to V/Q mismatch
This allows a lower FiO 2 to achieve same pO 2 target

SO BACK TO JOHN… John has been ventilated for 2 hours. It looks like you have stabilised him!!! Initial + 1 hour Current PEEP (cmH 2 O) 8 8 10 PC (cmH 2 O) 20 16 18 Peak (cmH 2 O) 28 28 28 Mean AP (cmH 2 O) 12.5 12 14 RR / min 15 16 16 I:E ratio 1:2 1:1 1:1 FiO 2 80% 60% 60% pO 2 (kPa) 9.9 9.1 9.7 pCO 2 (kPa) 4.9 5.3 5.2

REVIEW
You have looked at a case of severe hypoxaemia
You have reviewed the mechanisms of hypoxaemia and the concepts of dead-space, alveolar gas composition, V/Q mismatch, and shunt fraction (along with their mathematics)
You have seen this information used as the physiological basis for a clinical approach to this disorder
You have seen the importance of lung recruitment and the maintenance of FRC

THANK YOU FOR TAKING THIS TUTORIAL! Please let me know if you found it helpful, or if you have other areas you would like to see covered. You can email me at: fergua at gmail.com

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Pathophysiology of hypoxic respiratory failure

by Andrew Ferguson on Mar 26, 2011

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Pathophysiology of hypoxic respiratory failure — Presentation Transcript