Mechanisms, etiology, and management of acute hypoxemic respiratory failure

Response
Cause of A-a
Definition Etiologies PaCO2 to Treatment
hypoxemia* gradient
oxygen
V/Q mismatch Imbalance of lung Embolic disease High Typically normal Yes Supplemental
perfusion relative (venous pulmonary (unless (unless due oxygen
to ventilation: embolism, fat associated with to shunt) Treat
Low V/Q – embolism, amniotic hypoventilation underlying
Regions fluid embolism, or significant cause
underventilated malignant cells) increase in dead
relative to Pulmonary vascular space)
perfusion disease (destroys
(shunt is capillary beds and
extreme form limits perfusion to
of low V/Q alveoli)
mismatch; refer Chronic obstructive
to below) lung
High V/Q – disease/emphysema
Regions that (destroys the
are pulmonary capillary-
overventilated alveolar interface)
relative to Interstitial diseases
perfusion (eg, pulmonary
(dead space is edema, pulmonary
extreme form inflammation)
of high V/Q Low flow cardiac
mismatch) output states

Right-to-left Extreme form of Anatomic: High Normal No Oxygen;

shunt low V/Q mismatch: Cardiac shunt however, it is
Anatomic (ie, (eg, ASD, PFO, frequently
mechanical VSD) minimally
shunt) Intravascular responsive or
Physiologic (ie, shunt (pulmonary unresponsive
typically or other AVM, to oxygen
capillary shunt) hepatopulmonary Treat
syndrome) underlying
Physiologic: cause

Capillary shunt
(eg, atelectasis,
edema,
pneumonia)
Alveolar filling
disorders (eg,
fluid,
hemorrhage, pus,
cells, protein,
lipid)
Complete airway
obstruction
(including
angioedema)
 Hypoventilation Reduced minute Central neurologic Normal Elevated Yes Supplemental
ventilation "can't disease (eg, stroke, oxygen
breathe, won't sedation, (oxygen will
breathe, can't hypothyroidism) improve
breathe enough" ¶ Respiratory oxygenation
neuromuscular and but will not
chest wall diseases resolve
(eg, cervical-spine or hypercapnia)
phrenic nerve injury, Increase
Guillain-Barré minute
syndrome, bilateral ventilation
diaphragmatic (eg,
weakness) noninvasive
Airway/alveolar ventilation or
disease (acute invasive
exacerbation of ventilation)
COPD, COPD, Treat
asthma, ILD) underlying
cause

Diffusion Impairment of gas ILD High Normal Yes Supplemental

defect exchange between Lung resection (occasionally oxygen
alveoli and Emphysema normal) Treat
pulmonary Pulmonary vascular underlying
capillaries disease cause
Often overlaps
with shunt or V/Q
mismatch
pathophysiology

Reduced PiO2 Reduced PiO2 Δ Sudden change in Normal Normal or low Yes Descent if
elevation or new (if altitude is the
altitude hyperventilation cause
Reduction in present) Supplemental
pressure during air oxygen
travel in aircraft Consider
acetazolamide

Increased Reduced mixed Decreased cardiac High Normal Yes Supplemental

oxygen venous oxygen output oxygen
extraction content of blood Anemia Treat
returning to the Hypermetabolism underlying
right side of the (eg, fever, sepsis, cause
heart hyperthyroidism,
burns, trauma)

A-a gradient: alveolar-arterial gradient; PaCO2: arterial carbon dioxide tension; V/Q: ventilation/perfusion; ASD: atrial septal
defect; PFO: patent foramen ovale; VSD: ventricular septal defect; AVM: arteriovenous malformation; COPD: chronic obstructive
pulmonary disease; ILD: interstitial lung disease; PiO2: inspired oxygen tension.
* Rare causes of hypoxemia include hemoglobinopathies, cyanide toxicity, methemoglobinemia, and leukocyte larceny.
¶ Refer to UpToDate content on hypercapnia.
Δ Refer to UpToDate content on altitude.

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