First year medical school lecture on the above

1. Jim Lavelle, MD
Associate Professor of Medicine
Division of Pulmonary Sciences and
Critical Care Medicine

2.  Understand the types, pathophysiology, and
use of arterial blood gases in the diagnosis
and management of respiratory failure.
 Understand four key ventilator settings.
 Know the definition, pathogenesis, and
predisposing conditions of ARDS, along with
the management strategies that improve
survival.
 Learn a touch about shock.

3. Hypercapneic
Chronic
Hypoxemic
Acute

4. Hypercapneic
Hypoxemic

5.  Ventilation/perfusion mismatch
 Impaired gas diffusion
 Alveolar hypoventilation
 High altitude
Copyright 2012 Society of CriticalCare Medicine
Etiology: Any process that limits diffusion orV/Q matching
to the point that oxygen saturation is reduced.

6. Shunt
Normal
Dead Space
Ventilation/perfusion mismatch

7.  Impaired gas diffusion
 Alveolar hypoventilation
 High altitude
Copyright 2012 Society of CriticalCare Medicine
Alveolar
hypoventilation
O2
CO2
Impaired diffusion
High altitude
Excess CO2 –
“No room” for O2
Lower barometric
pressure – less O2

8.  Etiology: Any process that impairs
ventilation.
 Can’t breathe vs won’t breathe.
 Can’t breathe: Asthma, COPD, upper airway
obstruction, severe burn (chest wall restriction),
trauma, neuromuscular.
 Won’t breathe: Respiratory drive issues, central
hypoventilation, oversedation, brain injury,
seizure.

9. You only need to know about two for the
purpose of this lecture:
1. Tidal volume ( 𝑉𝑡)
2. Respiratory rate (𝑓)
𝑉𝑒 = 𝑉𝑡 × 𝑓
𝑉𝑎 = 𝑉𝑡 − 𝑉𝑑 × 𝑓
N.B. Alveolar ventilation ( 𝑉𝑎) ultimately determines the
PaCO2. Do not discount the importance of dead space.

10. Any process that reduces
perfusion to ventilated
alveoli increases physiologic
dead space.
• Hypovolemia
• Decreased cardiac output
• Pulmonary embolus
• High airway pressures

11.  Physical examination.
 Chest imaging (usually start with an Xray).
 Arterial blood gas.
Every patient, every time.

12.  Standard notation: pH/pCO2/pO2
 Calculate alveolar/arterial oxygen difference
(A-a DO2) using alveolar gas equation:
PAO2=(Pbar-PH2O) x FIO2-PaCO2/RQ
A-a DO2= PAO2-PaO2
 Typical values:
 RQ = 0.8
 Pbar=760 (sea level) or 630 (Denver)
 FIO2= 21% at room air
 PH2O=47

13. Calculate the A-a DO2:
7.36/36/65 on room air in Denver
PAO2=(Pbar-PH2O) x FIO2-PaCO2/RQ
PAO2=(630-47)x 0.21-36/0.8
PAO2=77
A-a DO2= PAO2-PaO2
A-a DO2= 77-65
A-a DO2= 12

14.  Sometimes referred to as a gradient. It is a
difference, not a gradient.A gradient is a
change over a defined distance or time.This
is a difference between discrete
compartments.
 A normal A-a DO2 reflects normal gas
exchange. Hypoxemia in the setting of a
normal A-a DO2 is due to one of three things:
PAO2=(Pbar-PH2O) x FIO2-PaCO2/RQ

15. Hypercapneic
Chronic
Hypoxemic
Acute

16. ChronicAcute

17.  Chronicity of hypoxemic respiratory failure is
based entirely on medical history and clinical
context.
 Patient with chronic lung disease on 2 liters per
minute nasal cannula oxygen at home.
▪ Comes in with saturation of 92% on 2L?
▪ Comes in with saturation of 82% on 2L, 92% on 6L?
 Long-term smoker who hasn’t seen a doctor in 40
years comes in with obvious emphysema on Xray,
saturating 82% on room air, 92% on 4L?

18.  Using simple compensation rules, it is
possible to tell from the blood gas and serum
bicarbonate (HCO3
-) the acuity or chronicity
of a ventilatory process.
 We will focus on respiratory acidosis (note the
parallel between respiratory acidosis and
hypercapneic respiratory failure).

19.  Acute respiratory acidosis:
 [HCO3
-] ↑ 1 mEq/L : PaCO2 ↑ 10 mm Hg
 ∆ pH = 0.008 x (35- PaCO2) – Denver
 Chronic respiratory acidosis:
 [HCO3
-] ↑ 4 mEq/L : PaCO2 ↑ 10 mm Hg
 ∆ pH = 0.003 x (35- PaCO2) – Denver

20. 1. Calculate the A-aDO2 to classify hypoxemia
as due to:
a) a primary diffusion,V/Q, or shunt abnormality
b) Hypercapnea
2. Use clinical context for acute vs. chronic.
3. Determine if a respiratory acidosis is
present. If so, there is a component of
hypercapneic respiratory failure.
4. Determine acute vs. chronic by standard
compensation rules.

21.  65 year old woman with mild emphysema, no
home oxygen requirement, and 3 days of
increasing cough and wheeze presents to an
ED in Denver with shortness of breath.
 ABG: 7.28/50/30 on room air.
 Diagnosis?

22.  42 year old man with morbid obesity and
chronic low back pain. Has had worsened low
back pain the past few days, for which he has
been taking oxycodone. Brought into an ED
in Seattle after family found him very sleepy
and confused.
 ABG: 7.18/80/40 on room air.
 Diagnosis?

24.  This is a basic overview of ventilation, and will
not get into details about different modes of
ventilation or of delivery systems.
 A basic understanding of the principles of
artificial respiration is integral to the
discussion of respiratory failure andARDS.

25. You need know only two: one obvious, one not.
1. FIO2: Fraction (%) of inspired oxygen
2. PEEP: Positive end-expiratory pressure

26.  When a person with an intact, natural upper
airway breathes spontaneously, the glottis
can close to maintain end expiratory pressure
and lung inflation.
 Bypassing the glottis with an endotracheal
tube prevents this, so when the vent cycles
into exhalation, it provides an adjustable level
of back pressure to simulate glottic closure,
thus maintaining alveolar recruitment and
diffusion surface area.

27.  22 year old woman with history of asthma
comes into the UCH ED with an acute attack,
requiring intubation and mechanical
ventilation.
 What type of respiratory failure do you
expect?
 Assuming an ABG of 7.08/75/420 on vent
settings ofVT 500, RR 20, FIO2 90%, PEEP 5,
what next?

28.  7.08/75/420
 Assuming her vent settings areVT 500, RR 20,
FIO2 90%, PEEP 5, what next?
 Decrease FIO2, increase RR (orVT), treat
asthma with standard therapies (steroids,
bronchodilators, ± antibiotics).
N.B. Vent management in asthma can be complicated by incomplete
exhalation due to bronchoconstriction. As a result, simply increasing
RR is often counterproductive.The key is to maximize expiratory
time, which can be accomplished by increasing inspiratory flow or
decreasing RR. More on this later in your training.

29.  May be acute or chronic, hypercapneic or
hypoxemic, or any combination
 ABG is necessary to characterize and treat
 Ventilator settings are changed according to
the ABG findings – respiratory rate and tidal
volume to manipulate pCO2 and pH, PEEP
and FIO2 to manipulate pO2

30. Sometimes known interchangeably as ARDS, Acute Lung Injury, or ALI.

31.  Clinical definition (2012 ARDS definition task
force – “Berlin Definition”):
 Occurs within 1 week of known clinical insult or
worsening in respiratory symptoms
 Diffuse bilateral pulmonary infiltrates
 Not fully explained by cardiac failure or fluid overload
 Severity classified by PaO2:FIO2 with ≥ 5 cmH2O PEEP
PaO2:FIO2 Severity Mortality
201-300 Mild 27%
101-200 Moderate 32%
≤ 100 Severe 45%

32. Alveolar inflammation -
recruitment of inflammatory
cells:
Inflammatory cytokines
Neutrophil and inflammatory
macrophage influx
Oxidant/enzymatic damage
Loss of alveolar/capillary
barrier function
Loss of surfactant
Increased intraalveolar fluid
Ware, Matthay. NEJM, 2000.

33. •Alveolar filling with
proteinaceous edema
•Denuded basement
membrane
•“Hyaline membrane”
formation (protein
deposition)
•Neutrophilic infiltrate
•Hemorrhage
•Type II cell hyperplasia

35.  ARDS likely represents a final common pathway for
a variety of different disease processes.
 Associated conditions include: sepsis (pulmonary or
otherwise), direct inhalational or aspiration injury,
transfusions, polytrauma, fat emboli, amniotic fluid
embolus, pancreatitis.
 Most likely pathogenesis is humoral: cytokines,
activated neutrophils, other “evil humors” related to
the primary illness.

36.  Mortality rate improving, but still between
20-30%, despite recent advances.
 Historical mortality rates between 50-70%.
 Initial case series (Ashbaugh, Petty, et al.), 7
of 12 patients died (58.3%).
 Age-adjusted incidence 82.6 per 100,000
person-years. (Bernard, et al.)

37.  Treat the underlying cause of ARDS.
 Supportive care.
 Multiple clinical trials of various agents
targeting inflammation have failed to show
any benefit.
 Ventilator management may be the only
thing that helps.

39.  Patients meeting ALI/ARDS criteria
randomized to receive mechanical ventilation
at 6 cc/kg ideal body weight and plateau
pressure ≤ 30 cm H2O vs 12 cc/kg and plateau
pressure ≤ 55 cm H2O.
 Permissive hypercapnea allowed, and if
necessary, sodium bicarbonate administered
to maintain a pH ≥ 7.15.
 28 day mortality 31% in the 6 cc group, 39.8%
in the 12 cc group.

40.  The data would suggest that the key to
improving mortality in ARDS is limiting
Ventilator Induced Lung Injury.
 Mortality attributable toVentilator Induced
Lung Injury is at least 9%, based on ARMA
data.

42.  Patients with PaO2: FIO2 ≤ 150 (moderate to
severe according to Berlin definition)
randomized to prone positioning for at least
16 hours per day vs standard care.
 Patients were ventilated according to low
tidal volume parameters of ARMA.
 Protocolized trials of supination in the
intervention group after at least 16 hours of
prone ventilation.

43.  Patients in the prone group did better:
 28 day mortality 16.0% vs 32.8%
 90 day mortality 23.6% vs 41.0%
 More ventilator free days (57 vs 43) and higher likelihood of
being liberated from mechanical ventilation (80.5% vs
65%) at day 90.
 Mechanism is unclear, but theories center around
more uniform transpulmonary pressure and
distribution of alveolar stress during prone
ventilation.

44. . . . but not too deep.

45.  Clinical definition based on clinical scenario and
radiographic and ABG findings.
 Multiple predisposing factors.
 Inflammation leads to disruption of
alveolar/capillary barrier function, resulting in
alveolar flooding with fluid, red cells, and
neutrophils.
 Hyaline membrane formation with hypoxemic
respiratory failure.

46.  Supportive care
 Treat underlying condition
 Ventilator strategy is the ONLY therapeutic
intervention that improves survival:
 6 cc/kg tidal volume, plateau pressure ≤ 30 cm H2O
 Permissive hypercapnea
 Consider prone ventilation in patients with
PaO2: FIO2 ≤ 150

48.  Shock is a general state characterized by
inadequate blood flow, such that end-organ
damage or dysfunction occurs.
 Almost any organ system can be affected:
 CNS – altered mental status
 Renal – Rising creatinine, falling urine output
 General – rising lactic acid

49.  Cardiogenic – decreased cardiac output
 Hypovolemic – inadequate blood volume and
cardiac filling pressures
 Obstructive – mechanical/structural
impediment to blood flow (pulmonary
embolism, valvular disease, tamponade)
 Distributive – inappropriate vasodilation with
low systemic vascular resistance

50.  With inappropriate vasodilation, cardiac
output often increases, but at the tissue level,
perfusion is inadequate due to impaired
regulation of microvascular blood flow.
 Pathophysiology may be neurohormonal
(neurogenic or spinal shock, adrenal crisis),
inflammatory (anaphylactic, septic), or
toxin/drug mediated.

51.  Occurs in the setting of infection
 Mediated by a lot of the same processes that
contribute to ARDS – direct toxic effect of
bacterial proteins, cytokines, activation of the
coagulation cascade – which is probably why
ARDS is most often seen in the setting of
sepsis.

52. 1. Appropriate empiric antibiotics after
cultures are obtained
2. Aggressive IV fluid resuscitation
3. Vasopressors (norepinephrine, epinephrine,
phenylephrine – all agents with significant
α-adrenergic agonist properties) to maintain
adequate blood pressure – typically a mean
arterial pressure (MAP) of 65.

53.  Understand the different types of respiratory
failure and how to classify them according to
ABG analysis.
 Understand the determinants of oxygenation
and ventilation in mechanically ventilated
patients and know how to use ABG data to
manage ventilator settings.
 Understand basic pathogenesis and
definition of ARDS.

54.  Understand the basics of management of
ARDS (supportive care, treating the
underlying condition, ventilator strategy).
 Key fact hidden in this lecture:
 Before increasing a patient’s tidal volume,
based on ABG analysis, make certain that
the patient does not meet criteria for ARDS.
You might be risking your patient’s life.

55.  Evaluation of respiratory failure, every patient,
every time: chest X ray & ABG.
 Always be thinking about ARDS in your ICU
patients. Because of the different ventilator
strategy, making the diagnosis and reducing
tidal volumes early may improve survival.