Acute Respiratory Failure Learning Guide

Preferred Method of Contact:

Faculty Name: Tom Corbridge Email

Phase: 3 Module: CCC Element/Thread: Lecture #, Week #, or Date:

Learning Activity Title: Acute respiratory failure
Learning Activity Type: Overhead projector or white board

Phone: Email: Campus Address:

Contact Info: 312 908 8163 tcc734@northwestern.edu 240 E. Huron, M336
312 503 3121

Relevance:
Understanding the determinants of PaO2 and PaCO2 is crucial to the assessment and management of patients with acute and
chronic hypoxemia, including patients with pneumonia, pulmonary edema, asthma, COPD, interstitial lung disease and drug
overdose.

Learning Objectives:

1. Write the alveolar gas equation, MSK1a, c

2. Calculate the A a difference on room air and the ratio of PaO 2 to FiO2 in an intubated patient on supplemental
oxygen and describe how this informs clinical practice, MSK1a, c, MSK3a, d
3. Recite common causes of hypoxemia and separate those that elevate A a (or lower PaO 2/FiO2), and those that
do not, MSK3a, d
4. Describe the subset of hypoxemic patients with acute hypoxemic respiratory failure, MSK3a, d
5. Derive the PaCO2 equation and describe how it informs clinical practice, MSK1a, d
6. Recite causes of hypercapnia and hypocapnia, MSK3a, d
7. Describe the Haldane effect, MSK1a, d, MSK 3a, d

Preparatory Work:
Reading this learning guide

Essential Post-Session Work:

Practice questions

Outline:
Attached

Summary Learning Points: Summarize the essential 3-5 learning points/concepts from the lecture and pre-/post-session work.
1. Alveolar O2 (PAO2) is the driving pressure for oxygenation of the mixed venous blood entering alveolar-capillary
units. At sea level with FiO2 0.21, PaCO2 of 40 mmHg and R of 0.8, PAO2 is 100mmHg as determined by the
alveolar gas equation.
2. The A - a difference speaks to the health of the lung and its ability to oxygenate. Small differences are seen in
health; large differences are seen in illnesses that interfere with the lungs ability to oxygenate blood.
3. Intrapulmonary shunt conditions with V/Q zero units include pneumonia, pulmonary edema (cardiogenic and non-
cardiogenic), alveolar hemorrhage and atelectasis/collapse of alveolar units. Intracardiac shunts include patent
foramen ovale with right to left atrial flow and ASD with Eisenmengers physiology. Patients refractory to
supplemental oxygen typically have large shunts; patients with lower shunt fractions are less hypoxemic and
arterial oxygenation improves with supplemental oxygen.
4. Asthma, COPD and pulmonary embolism cause low V/Q units (but not zero) and hypoxemia that responds to
 supplemental oxygen.
5. Diffusion limitation results in hypoxemia. Examples include idiopathic pulmonary fibrosis and emphysema.
6. Lowering mixed venous oxygen saturation lowers PaO 2 in the setting of an abnormal lung, but has little effect
when the lung is normal. There are 4 main causes of low venous saturation: low cardiac output, anemia, low
arterial oxygen saturation and high oxygen consumption by tissues.
7. Hypoventilation and altitude are important causes of hypoxemia with a normal A-a difference .
8. PaCO2 is directly proportional to the amount of CO2 produced by metabolism and delivered to the lungs (VCO 2)
and inversely proportional to alveolar ventilation (VA).
. . . . . .
9. VA = VE VD, where VA is alveolar ventilation, VE is minute ventilation and VD is dead space or wasted
ventilation. Note VD with a dot over the V = VD without the dot X RR:
.
VD has units of ml/min. VD has units of ml.

10. Hypercapnia can occur from an increase in CO 2 production (eg, hypermetabolism, over
feeding), a decrease in respiratory rate X tidal volume (VE) or an increase in the dead
space to tidal volume ratio (as might happen in pulmonary embolism or emphysema), or
combinations thereof.
11. Rapid shallow breathing is not a great way to clear CO 2 because shallow breaths elevate Vd/Vt.
12. Hypercapnia can stem from an imbalance between neuromuscular strength or respiratory drive and the load on
the respiratory system, which is influenced by airway resistance, respiratory system compliance and respiratory
rate.
13. Deoxygenation of blood increases its ability to carry carbon dioxide; conversely oxygenated blood has a reduced
capacity for carbon dioxide. This property of hemoglobin was described by John Scott Haldane.

Guiding Questions:

1. A 44 year-old man presents to NMH with heroin overdose. An arterial blood gas demonstrates a PaO 2 of 40
mmHg, a PaCO2 of 60 mmHg and a pH of 7.24. The most likely cause of hypoxemia is:
a) aspiration pneumonitis
b) hypoventilation
c) hypoventilation with aspiration pneumonitis
d) pneumothorax
Ans: c

2. Which of the following statements is true regarding a patient with a large intrapulmonary shunt?
a) hypoxemia is relatively responsive to supplemental oxygen.
b) a drop in mixed venous oxygen saturation is unlikely to worsen hypoxemia.
c) hypoxemia occurs with a decreased P/F ratio
d) hypoxemia occurs with a normal A a difference
Ans: c

3. A 29 year-old medical student is camping at an altitude of 10,000 feet where the barometric pressure reads 530
mmHg. Her resting respiratory rate is slightly increased, which she believes correctly is her body's attempt to
elevate PAO2 and thereby PaO2. Assuming she has a PaCO2 of 28, an A-a difference of < 10 mmHg and a normal
value for R, which of the following is the best estimate of her PaO 2?
a) 82 mmHg
b) 75 mmHg
c) 64 mmHg
d) 53 mmHg
Ans: c

4. A patient with a long-standing history of alcohol abuse is intubated and mechanically ventilated on 100%
 supplemental oxygen (FiO2 1.0) for pneumonia. His arterial saturation is 87 to 88% (which gives him a PaO 2 of ~
53 mmHg). His mixed venous saturation is 75%. Assuming that the blood leaving the remaining "normal" alveolar
capillary units has a venous sat of 100%, what is the percent of the cardiac output that goes through V/Q zero
(shunt) units?
a) 20%
b) 30%
c) 40%
d) 50%
Ans: d

5. The same patient in question 4 develops an acute upper GI bleed from alcoholic gastritis. The venous saturation
falls from 75% to 60%. Assuming all other cardiopulmonary parameters remain the same, what would happen to
the patient's arterial saturation?
a) it would increase to 90%
b) it would decrease to 85%
c) it would decrease to 80%
d) it would decrease to 75%
Ans: c

6. Four 30 year-old patients are being evaluated for respiratory distress in a Florida emergency department. Room
air arterial blood gases are measured in each. Which patient most likely has pneumonia?
a) PaO2 100 PaCO2 32 pH 7.47
b) PaO2 95 PaCO2 36 pH 7.43
c) PaO2 90 PaCO2 28 pH 7.43
d) PaO2 85 PaCO2 44 pH 7.35
Ans: c

7. Which of the following would decrease PaCO2?

a) an increase in CO2 production
b) a decrease in minute ventilation
c) an increase in the dead space to tidal volume ratio
d) an increase in alveolar ventilation
Ans: d

8. A 72 year-old man with severe smoking-related emphysema presents with severe acute breathlessness from
pulmonary embolism. He is anti-coagulated with low molecular weight heparin and subsequently intubated and
mechanically ventilated for acute hypercapnic respiratory failure. He is afebrile. He has decreased breath sounds
with expiratory phase prolongation and faint expiratory wheezes. PaO 2 is 90 mmHg on 30% supplemental
oxygen. PaCO2 is 60 mmHg with a respiratory rate of 20/min and a tidal volume of 600ml.

These data suggest:

a) increased CO2 production
b) increased dead space
c) decreased dead space to tidal volume ratio
d) increased alveolar ventilation
Ans: b

9. An elderly woman with a history of depression, anxiety and metastatic colon cancer is evaluated in hospital for
tachypnea (respiratory rate, 30/min). The house officer concludes that the patient has a respiratory alkalosis and
prescribes a benzodiazepine for perceived hyperventilation/anxiety. Using the PaCO 2 equation, explain why this
is potentially a critical error.

Further Study:
Pulmonary Physiology by Michael Levitsky, 8th ed,
 .
Under steady state conditions O2 in = O2 OUT + the amount of oxygen consumed (VO2): re-written and re-arranged:
. . .
FiO2 (Patm - PH2O) VA = PAO2 VA + VO2

PAO2 = (Patm - PH2O)FiO2 - PaCO2 / R, which is a simplified and clinically useful version of the alveolar gas equation.
. . . .
. . . .
For those of you who want to derive this equation please note that R = VCO 2/VO2 and PaCO2 ~ VCO2 / VA.

PAO2 is alveolar PO2, Patm is barometric pressure, PH2O is water vapor pressure, VA is alveolar ventilation, and R is the
respiratory quotient. Remember that Patm at sea level is 760 mmHg and that PH 2O is generally viewed as a constant (47
mmHg) reflecting the addition of water vapor to inspired air through mucosal humidification. FiO 2 (the fraction of inspired
oxygen) on room air = 0.21. R is the ratio of ratio of carbon dioxide production to oxygen consumption. Its value changes
with substrate utilization: carbohydrates = 1.0; proteins = 0.8; fats = 0.7; the usual mixed American diet = 0.8. If your ratio
is less than 1 it means that you expire slightly less gas than you inspire because more gas is taken up than is given up
with each breath. Thus under normal conditions at sea level we have:

PAO2 = (760 - 47) 0.21 - 40/0.8 = 100 mmHg

The altitude at the lakefront in Chicago is ~ 600, which lowers Patm in Chicago to approximately 744 mmHg.

In health the venous blood returning to the lung through the pulmonary artery (called the mixed venous O 2 or MvO2) has a
partial pressure of 40 to 45 mmHg and saturation between 70 and 75%. This blood is re-oxygenated in pulmonary
capillaries adjacent to alveoli to a value that is quite close to PAO 2. Thus the difference between the calculated PAO2 and
the PaO2 measured via an arterial blood gas sample (called the A - a difference) is small. In fact it is less than 10 mmHg in
a healthy young individual. In the above example with PAO 2 of 100 mmHg, if PaO2 is 95 mmHg then the A - a difference is
5 mmhg. The A - a difference normally increases with age by the equation:

A - a difference = 2.5 + 0.25 (age)

The A - a difference normally increases with supplemental oxygenthus the A - a difference analysis is MOST useful in
the assessment of patients breathing room/ambient air (FiO 2 0.21). In patients requiring an endotracheal tube,
mechanical ventilation and supplemental oxygen the strategy that best describes the severity of hypoxemia is the ratio of
PaO2 to FiO2 (P/F). Note that the FiO2 is known during invasive mechanical ventilation, but when supplemental oxygen
delivered by face-mask or nasal cannula the FiO2 is not known exactly, which limits precise calculation. Regardless of
FiO2, a P/F > 450 is generally viewed as normal. The lower the P/F the more severe is the hypoxemia. The P/F ratio is
important in the diagnosis of the acute respiratory distress syndrome (ARDS). Of course, other conditions such as
pneumonia and asthma lower this ratio. Understand that conditions that elevate A a on room air lower P/F on
supplemental oxygen.

Evaluation of hypoxemia: In common clinical practice, low oxygen saturation by pulse oximetry is often the starting
point. In patients breathing room air (FiO2 0.21), calculate the difference between the arterial PO 2 (PaO2) (drawn from the
patient) and the predicted/calculated PO2 in the alveolus (PAO2note the capital A). PAO2 cannot be directly measured
it is calculated from the simplified alveolar gas equation above.

The A - a difference widens when there is lung disease and the lung is less able to oxygenate venous blood. There are
three main pathophysiologic states that cause hypoxemia and widen the A - a difference (or drop P/F on supplemental
oxygen):

1) Shunt: intrapulmonary shunt (pus, water, blood, atelectasis) and right to left intracardiac shunt (patent foramen ovale,
ASD and AV malformations): Here there is no ventilation to perfused lung units so the ratio of ventilation (V) to perfusion
(Q) is zero in these units. In patients with a large shunt (say 50% of the cardiac output goes through shunt units),
increasing the fraction of inspired oxygen does not significantly improve PaO 2 (these patients are oxygen unresponsive).
Patients with smaller shunt fractions (say a 10% shunt from pneumonia) will be less hypoxemic and respond to
supplemental oxygen.

2) Low V/Q (low but not zero): Here ventilation is decreased (but not absent) to perfused lung units (as in asthma and
COPD) or Q is increased for a given V (as in pulmonary embolism). In patients with low V/Q increasing the fraction of
inspired oxygen increases PaO2 (these patients are oxygen responsive).
3) Diffusion limitation: Increased interstitial thickening (e.g., pulmonary fibrosis) or decreased area available for diffusion
(e.g., emphysema) can result in hypoxemia.

The volume of gas diffusing through tissue barrier Vgas = [A X D X (P1 P2)]/T, where A is surface area, T is the
thickness of the barrier, D is the diffusion coefficient of the gas (D ~ solubility/the square root of the molecular weight), and
P1 P2 is the partial pressure difference of the gas across the barrier. Emphysema lowers A; pulmonary fibrosis
increases T.

4) If any of the above three pathophysiologic states is present, then the mixed venous O 2 saturation (MvO 2) further
impacts arterial oxygen saturation (SaO 2). In common practice the central venous oxygen saturation (ScvO 2) is used as a
surrogate for MvO2, the former is sampled from a central venous catheter appropriately placed just above the right atrium,
the later requires a right heart catheter. For example, when the ScvO 2 or MvO2 falls [as may be seen with low cardiac
.
output (CO), high oxygen consumption (VO 2), anemia and low SaO2], the SaO2 falls as well (bad blood in to a bad lung
leads to bad blood out). Note that three of the four causes of low MvO2 stem from decreased oxygen delivery (DO 2) to
tissue beds.

DaO2 = CO X arterial oxygen content

Arterial oxygen content = (1.34 X Hg X SaO2) + 0.003 X PaO2
DaO2 = CO X [(1.34 X Hg X SaO2) + 0.003 X PaO2]

Conversely, if ScvO2 or MvO2 is raised (e.g., a blood transfusion is given to an anemic patient), then SaO 2 would be
expected to rise accordingly. For various reasons this may or may not happen in clinical practice.

Now consider conditions that cause hypoxemia but DO NOT elevate the A - a difference. This happens when the reason
for low PaO2 is low PAO2. To understand conditions that lower PAO2 go back to the alveolar gas equation and look at what
variables can be changed. These are listed in numbers 5 8 below.

5) Hypoventilation: Example: if a patient has a completely normal lung (and thus a normal A - a difference), and takes an
overdose of heroin that suppresses respiration, decreases minute ventilation and acutely elevates PaCO 2 to 60 mmHg (in
Chicago on room air with R = 0.8) then:

PAO2 = 75 mmHg = (760 - 47) 0.21 - 60/0.8

If the PaO2 is 68 mmHg in this patient, the A - a difference is 7 mmHg (which is normal) and the hypoxemia is explained
entirely by hypoventilation. The clinical approach here is to increase minute ventilation with the drug naloxone (the
underlying lung is probably okay). Aspiration pneumonia, heroin-induced pulmonary edema and heroin-induced asthma
are all unlikely because of the normal A - a difference. Of course, stopping heroin use isnt a bad idea either!

6) Low barometric pressure: In Denver, Patm is ~ 635 mmHg and PaO 2 can run in the 70s, normally. Know the altitude
and barometric pressure where you practice medicine!

7) Low FiO2 (below 0.21). This is rare but can occur in inhalation injuries/fires when other gases dilute the fraction of
inspired oxygen.

8) Low R. Lowering R from 1.0 to 0.7 will lower PAO 2 from 110 to 93 mmHg when Bp is 760, FiO2 is 0.21 and PaCO2 is 40
mmHg. This is not a common cause of hypoxemia in clinical practice.

What happens to the PaO2 if the ScvO2 drops in a patient with normal lungs (as may occur in numbers 5 through 8
above)? Not much! The normal lung can oxygenate very desaturated blood to achieve a normal PaO 2.

Partial pressure of carbon dioxide (PaCO2 in units of mmHg or Torr or kPA) is commonly determined by drawing an
arterial blood, most often from the radial artery. The normal value for PaCO 2 is 35-45 mmHg. The PaCO2 equation* helps
explain the normal range and the underlying mechanisms for abnormal results. The equation states that PaCO 2 is
determined by the ratio of how much is made divided by how much is eliminated following an analysis of mass
balance:
For CO2:

IN = OUT PRODUCED
. .
0 = VA PACO2 - VCO2
.
VCO2 x 0.863
PACO2 = ----------------------
.
VA
. .
The constant 0.863 is necessary to equate dissimilar units for VCO 2 (ml/min) and VA (L/min) to PACO2 pressure units
. .
(mmHg). Alveolar ventilation (VA) is the total volume of air breathed per minute (VE; minute ventilation) minus that which
.
goes to dead space ventilation per minute (VD). Dead space in healthy individuals consists mainly of large airways where
ventilation does not affect gas exchange. Patients with unhealthy lungs may ventilate alveoli that are not perfused (as in
emphysema and pulmonary embolism) creating additional dead space. Note: while the derivation of the equation is for
alveolar PCO2 (PACO2), clinical utility stems from the fact that alveolar and arterial PCO 2 (PaCO2) can be assumed to be
equal, or at least close:

Thus:
.
VCO2 x 0.863
* PaCO2 = ----------------------
.
VA
.
PaCO2 is directly proportional to the amount of CO2 produced by metabolism and delivered to the lungs (VCO 2) and
.
inversely proportional to alveolar ventilation (VA).
 .
VA is more useful in clinical practice when it is broken down into its component parts:
.
VA = RR X Vt (1 Vd/ Vt), where RR = respiratory rate, Vt = tidal volume and Vd = dead space volume with each breath)
. . .
VA = VE VD
. . . .
VA = VE (1 VD/VE)
.
VA = RR X Vt [1 (RR X Vd)/(RR X Vt)]
.
VA = RR X Vt (1 Vd/Vt)

.
VCO2 x 863
* PaCO2 = ------------------------ A VERY CLINICALLY USEFUL EQUATION!
RR X Vt (1 Vd/Vt)

Lets plug in normal values: assuming a RR of 14/min and a Vt of 500 ml during quiet breathing, only the first 350 ml of the
tidal breath reaches gas exchanging units. The last 150 cc remains within large airways (last in and first out), and these
large airways do not participate in gas exchange (they are anatomically dead spaces).
. .
Thus VA = 14 x 500 (1 - 150/500) = 7 L/min X 0.7 = 4.9 L/min. (Also note VA/Q is therefore 1).
.
If resting VCO2 is 200 ml/min then the numerator is ~ 173 L/min, and 173/4.9 ~ 35 mmHg.

The PaCO2 equation requires us to consider 3 variables when PaCO 2 is too high (> 45 mmHg) (hypercapnia) or too low
 . .
(< 35 mmHg) (hypocapnia); namely, VCO2, VE and Vd/Vt.
.
Increased VE is the most common cause of hypocapnia (respiratory alkalosis) as in:

pain, anxiety, fever, sepsis, asthma, pneumonia, pulmonary edema, pulmonary embolism, aspirin intoxication, stimulant
overdose, liver failure, pregnancy, metabolic acidosis, hyperthyroidism, psychosis and others.

For hypercapnia (respiratory acidosis) consider:

.
1) increased VCO2:
fever, excess movement, seizures, over-feeding, hypermetabolic states such as hyperthyroidism
.
2) decreased VE (most likely in clinical practice):
a) Head trauma with raised intracranial pressure
b) CNS tumor or infection (encephalitis)
c) CNS depressant drugs (opioids, benzodiazepines, barbiturates)
d) Obesity leading to hypoventilation
e) Hypothyroidism
f) Neuromuscular disease (ALS, Myasthenia, Guillan Barre, Poliomyelitis, muscular dystrophy, etc)
g) Chest wall deformity
h) Obstructive lung disease
i) Restrictive lung disease

3) increased Vd/Vt (pulmonary embolism, emphysema, pulmonary hyperinflation, use of low tidal volumes during
mechanical ventilation, and shallow breathing from illness.

Consider further that hypercapnia often reflects an imbalance between strength or drive and the load on the respiratory
system. In other words, you need adequate strength/drive for whatever load is present (representing how hard it is to
move the respiratory system). For example, a very weak patient with ALS would be expected to have a normal PaCO 2
only when the lung and chest wall are normal (a normal respiratory load). If load increases even slightly as may occur with
an upper respiratory infection, then hypercapnia may ensue. Conversely, in a very strong patient the load must be
extremely high to develop hypercapnia (example: acute severe asthma in a normally strong individual). Commonly there
is a combination of decreased strength and increased load (e.g., COPD exacerbation).

Another interesting and clinically relevant observation is that administration of supplemental oxygen therapy to some
patients with chronic obstructive lung disease (COPD) causes an increase in PaCO 2. The magnitude of this increase is
small and insignificant in some patients, but others develop critical hypercapnia and academia. This means that
supplemental oxygen must be administered very carefully and over-oxygenation must be avoided in clinical practice. The
increase in PaCO2 appears to be secondary to a worsening of ventilation and perfusion matching within the lung
secondary to impaired hypoxic pulmonary vasoconstriction, with relatively smaller contributions from the Haldane effect
(Haldane effect: deoxygenation of the blood increases its ability to carry carbon dioxide; conversely oxygenated blood has
a reduced capacity for carbon dioxide) and oxygen-induced reduction in overall minute ventilation. Similar increases in
PaCO2 have been observed in response to oxygen in patients with neuromuscular disease and obesity hypoventilation
syndrome.