PATHOPHYSIOLOGY OF ACUTE RESPIRATORY

FAILURE

Dr. Andrew Ferguson 

Consultant in Anaesthetics &  Intensive Care MedicineCraigavon Area Hospital, U.K.

 http://www.slideshare.net/fergua

• 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.

INTRODUCTION

• Gas exchangeo O2 & CO2 transporto Hypoxia & hypercapniao Hyper- and hypobaric scenarios

• Functions of Hbo In O2 and CO2 carriageo 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

o Acute & chronic ventilatory failureo Effects of O2 therapy

• Non-respiratory functions of the lungs

RESPIRATORY PHYSIOLOGY CURRICULUM

• 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

OVERVIEW

• pO2 < 8 kPa (60 mmHg) on room air and/or• pCO2 > 6 kPa (45 mmHg)

• Type I = primarily hypoxaemia• Type II = primarily hypercapnia • Type III = perioperative (atelectasis)• Type IV = shock (hypoperfusion)

WHAT IS RESPIRATORY FAILURE?

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 SpO2 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, pCO2 6.1 kPa, pO2 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.

CASE SCENARIO

• Mechanisms of hypoxia• Work of breathing• Dead space and alveolar ventilation• Hypoxic pulmonary vasoconstriction• Alveolar gas composition & alveolar-arterial O2 difference• Shunt and V/Q mismatch• Effects of anaesthesia on all of these• Effects of mechanical ventilation on all of these

KEY PHYSIOLOGY RELEVANT TO THIS CASE

• Gather your thoughts then proceed…

WHY IS JOHN HYPOXAEMIC?

• Ventilation-perfusion (V/Q) mismatcho E.g. secretions or bronchial constriction, emphysema, PE,

pulmonary arterial vasospasmo At least partially O2 responsive

• Shunto E.g. collapsed or flooded alveolio Typically poorly responsive to O2

• Alveolar hypoventilationo See alveolar gas equation in subsequent slides

• Reduced inspired partial pressure of O2o e.g. altitude, industrial accident, fire

• Diffusion impairmento Rarely a major contributor

MECHANISMS OF HYPOXAEMIA

Many of these are associated with a fall in FRC (functional residual capacity)

RESPONSE TO INCREASED FIO2 IN SHUNT

Shunt fraction (%)

Alveolar pO2

As shunt fraction increases,higher inspired (and alveolar) pO2 has less and less effecton arterial pO2

• Gather your thoughts then proceed…

WHAT ABOUT JOHN’S BREATHING PATTERN?

• Increased respiratory muscle worko Increases O2 consumption (can be dramatic)o May exceed ability to deliver and so precipitate cardiac ischaemia

• Rapid shallow breathing o Increased dead-space/tidal volume (VD/VT) ratio

• Turbulent flowo In rapid shallow breathing & bronchospasmo Requires greater work for same flow

• Bronchospasmo Gas trapping and auto-PEEPo Requires increased work of breathing including expiratory

IMPACT OF RESPIRATORY PATTERNS

• f/VT = respiratory rate divided by tidal volume (in litres)• Significant increase in work of breathing above f/VT = 60-70

o Corresponds to rate of 30 with tidal volume 0.5Lo Hence common use of rate > 30 as predictor of severity

RAPID SHALLOW BREATHING: F/VT RATIO

WORK OF BREATHING: P-V CURVE

• Gather your thoughts then proceed…

HOW DO YOU WORK OUT DEAD-SPACE?

• Anatomicalo Conducting airway volume = around 150 ml (2ml/kg ideal BW)o Increased by:

Rapid shallow breathing (as above) Very high VT (pull on trachea and bronchi increases volume)

o Decreased by: Head-down position (compresses conducting airways)

o Measured by Fowler’s method• Physiological

o Alveolar dead-space = alveoli ventilated but not perfusedo Physiological dead-space = alveolar + anatomical = 170 mlo Measured by Bohr’s method using Bohr equation

RESPIRATORY DEAD-SPACE

• Impacts on effective alveolar ventilation• Alveolar minute ventilation = (VT – VD) x resp. rate• Increased dead-space

o Decreases effective alveolar ventilationo Increases pCO2o Increases work of breathing

IMPLICATIONS OF DEAD-SPACE VOLUME

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

FOWLER’S METHOD

• Area under the exhalation curve = Cexp x (Vexp – Vd)• 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

FOWLER’S METHOD

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

• Let’s start with the fact that exhaled tidal volume is made up of dead-space volume plus some alveolar volume VT = Vd + Valv [re-arranged to Valv = VT – Vd]

• 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 CO2)

• The amount of gas = volume x concentration• SO… VT x Cexp = Vd x Cd + Valv x Calv & for CO2 Cd is near zero• SO… VT x Cexp = Valv x Calv and Valv = VT – Vd

• SO… VT x Cexp = (VT - Vd) x Calv

• SO… VT x Cexp = (VT x Calv) – (Vd x Calv)• Rearranging gives (Vd x Calv) = (VT x Calv) – (VT x Cexp)

BOHR EQUATION (PHYSIOLOGICAL D-S)

• SO Vd x Calv = VT (Calv – Cexp) leading to VD/VT = (Calv-Cexp)/Calv

• Using partial pressures, VD/VT = (PAlvCO2-PECO2)/(PAlvCO2)• It is then assumed that PAlvCO2 = PaCO2 (arterial)• SO finally

VD/VT = (PaCO2-PECO2)/PaCO2 (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 PaCO2 and ETCO2 the greater the physiological dead-space

BOHR EQUATION

You got pretty worried and intubated John before he collapsed. After 10 minutes on the ventilator with PEEP 5, VT 550 and FiO2 0.8 John’s ABG shows:

pH 7.30, pCO2 6.6 kPa, pO2 8.6 kPa

A nurse has just done the FCCS course and asks you 2 questions:1. how much of the hypoxia is due to the CO2 retention?• What is John’s A-aDO2?

Gather your thoughts then proceed…

JOHN IS STILL ALIVE…JUST!

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-aDO2 the cause is either:

o Hypoventilation (hypercapnia), oro Breathing a gas with low pO2

• If the A-aDO2 is elevated the hypoxia is pulmonary in origino i.e. pulmonary system (vessels, alveoli etc.)

The harder bit…• Assumes that we know the O2 concentration in the alveoli

ALVEOLAR-ARTERIAL OXYGEN DIFFERENCE

Assumptions• Inspired gas has no CO2

• PACO2 = PaCO2

• Alveolar gas is saturated with water

Simple equation: PAO2 = PIO2 – PaCO2/R where PIO2=FiO2(Patm-PH2O)

R = respiratory quotient = 0.8PH2O = SVP of water at 37oC = 47 mmHg or 6.25 kPaPatm = atmospheric pressure assumed to be 760 mmHg (101 kPa)

Substituting gives:

PAO2 = 94.75 x FiO2 – 1.25 x PaCO2

THE ALVEOLAR GAS EQUATION (SIMPLE)

If R < 1 (and especially if FiO2 is high) then more O2 is taken up from the alveolus than CO2 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 PAO2 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.

THE ALVEOLAR GAS EQUATION (COMPLEX)

PAO2 = (Patm – PH2O) x FiO2 – PaCO2/R + (FiO2x PaCO2 x (1-R)/R))

A-aDO2 = PAO2-PaO2

So John, assuming R is 0.8 and breathing 80% O2 should have an alveolar O2 of:94.75 x 0.8 – 1.25 x 6.6 = 75.8 – 8.25 = 67.6 kPa

John’s A-aDO2 is 67.6 – 8.6 = 59 kPaWhich is WAY above the normal of 2 kPa, so his hypoxia is plainly not due to his hypercapnia!!!

Back to the A-aDO2

The helpful staff nurse wants to understand what’s going on in John’s lungs, since the CO2 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!

• Gather your thoughts then proceed…

So back to john’s hypoxia…

• Shunt = perfusion without ventilation i.e. V/Q = 0o 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-aDO2 that you observe in your patient, so it reflects the degree of shunting and V/Q mismatch

SHUNT & VENOUS ADMIXTURE

• Anatomical shuntso 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

o 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)

SHUNT

Don’t panic….you have seen the principle before (Bohr’s)!

Let’s take it step by step:1. 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

1. We want to know about blood flow and oxygen content, so:o The oxygen content of Qt (cardiac output) is CaO2 (arterial)1. The oxygen content of Qs (the pure shunt) is CvO2 (mixed venous) 2. The oxygen content of Qc (working capillaries) is CcO2 (pulm. capillary)

2. Substituting equation 1 we get Qt = Qs + (Qt - Qs)

1. 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 O2 running in this system, which equals flow x content

Let’s add in the content and go from there:Qt.CaO2 = Qs.CvO2 + (Qt – Qs).CcO2 (since Qt – Qs = Qc)Qt.CaO2 = Qs.CvO2 + Qt.CcO2 – Qs.CcO2

Arrange the equation so Qs and Qt are on opposite sides:Qs.CcO2 – Qs.CvO2 = Qt.CcO2 – Qt.CaO2 now factorise…Qs(CcO2 – CvO2) = Qt(CcO2 – CaO2) and rearrange to get Qs/Qt

Shunt fraction Qs/Qt = (CcO2 – CaO2) / (CcO2 – CvO2)

THE SHUNT EQUATION

• CaO2 results from a mixture of blood from different lung units o Some with pure shunto Some with varying degrees of V/Q mismatch

over or under-ventilated relative to blood flowo Some with normal blood and gas flow

• The impact of increasing FiO2 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 pO2.

THE REALITY

EFFECTS OF MIXED V/Q RATIOS

• 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:o improve the V/Q mismatcho Convert areas of shunt (O2 resistant) to V/Q mismatch (O2 responsive)o Reverse atelectasis

And we are going to do this by• improving functional residual capacity (FRC)• RECRUITING collapsed or flooded alveoli

SO BACK TO FIXING JOHN’S OXYGENATION

• 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

LUNG VOLUMES AND COMPLIANCE

Stiff overdistended lung

Stiff atelectatic lung

Pressure

PEEP Peak Ventilator pressures

FRC

• 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 ventilationo Manual

Inflate to given pressure (30 or 40 cmH2O) Hold for 30 seconds if BP/SpO2 maintained Connect to ventilator

o On ventilator Ensure safe peak inspiratory pressure < 30 cmH2O 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

VENTILATION TO IMPROVE OXYGENATION

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)

o Not beyond 30 cmH2Oo Maintaining safe tidal volumes (6 ml/kg PBW in lung injury)

• Increasing inspiratory timeo Increases inspiration:expiration time ratio (I:E) ratioo 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

o Provided inspiratory time is not shortened too much

MAINTAINING FRC, AVOIDING OVERDISTENSION

• O2 is a band-aid, not a good primary therapy

• Increasing FiO2 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 FiO2 to achieve same pO2 target

MEAN AIRWAY PRESSURE

John has been ventilated for 2 hours. It looks like you have stabilised him!!!

SO BACK TO JOHN…Initial + 1 hour Current

PEEP (cmH2O) 8 8 10

PC (cmH2O) 20 16 18

Peak (cmH2O) 28 28 28

Mean AP (cmH2O) 12.5 12 14

RR / min 15 16 16

I:E ratio 1:2 1:1 1:1

FiO280% 60% 60%

pO2 (kPa) 9.9 9.1 9.7

pCO2 (kPa) 4.9 5.3 5.2

• 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

REVIEW

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

THANK YOU FOR TAKING THIS TUTORIAL!